@article {pmid33208178, year = {2020}, author = {Li, N and Zuo, B and Huang, S and Zeng, B and Han, D and Li, T and Liu, T and Wu, Z and Wei, H and Zhao, J and Wang, J}, title = {Spatial heterogeneity of bacterial colonization across different gut segments following inter-species microbiota transplantation.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {161}, doi = {10.1186/s40168-020-00917-7}, pmid = {33208178}, issn = {2049-2618}, support = {31630074//National Natural Science Foundation of China/ ; 31972596//National Natural Science Foundation of China/ ; S170001//Beijing Municipal Natural Science Foundation/ ; B16044//111 Project/ ; }, abstract = {BACKGROUND: The microbiota presents a compartmentalized distribution across different gut segments. Hence, the exogenous microbiota from a particular gut segment might only invade its homologous gut location during microbiota transplantation. Feces as the excreted residue contain most of the large-intestinal microbes but lack small-intestinal microbes. We speculated that whole-intestinal microbiota transplantation (WIMT), comprising jejunal, ileal, cecal, and colonic microbiota, would be more effective for reshaping the entire intestinal microbiota than conventional fecal microbiota transplantation fecal microbiota transplantation (FMT).<br><br>RESULTS: We modeled the compartmentalized colonization of the gut microbiota via transplanting the microbiota from jejunum, ileum, cecum, and colon, respectively, into the germ-free mice. Transplanting jejunal or ileal microbiota induced more exogenous microbes' colonization in the small intestine (SI) of germ-free mice rather than the large intestine (LI), primarily containing Proteobacteria, Lactobacillaceae, and Cyanobacteria. Conversely, more saccharolytic anaerobes from exogenous cecal or colonic microbiota, such as Bacteroidetes, Prevotellaceae, Lachnospiraceae, and Ruminococcaceae, established in the LI of germ-free mice that received corresponding intestinal segmented microbiota transplantation. Consistent compartmentalized colonization patterns of microbial functions in the intestine of germ-free mice were also observed. Genes related to nucleotide metabolism, genetic information processing, and replication and repair were primarily enriched in small-intestinal communities, whereas genes associated with the metabolism of essential nutrients such as carbohydrates, amino acids, cofactors, and vitamins were mainly enriched in large-intestinal communities of germ-free mice. Subsequently, we compared the difference in reshaping the community structure of germ-free mice between FMT and WIMT. FMT mainly transferred LI-derived microorganisms and gene functions into the recipient intestine with sparse SI-derived microbes successfully transplanted. However, WIMT introduced more SI-derived microbes and associated microbial functions to the recipient intestine than FMT. Besides, WIMT also improved intestinal morphological development as well as reduced systematic inflammation responses of recipients compared with FMT.<br><br>CONCLUSIONS: Segmented exogenous microbiota transplantation proved the spatial heterogeneity of bacterial colonization along the gastrointestinal tract, i.e., the microbiota from one specific location selectively colonizes its homologous gut region. Given the lack of exogenous small-intestinal microbes during FMT, WIMT may be a promising alternative for conventional FMT to reconstitute the microbiota across the entire intestinal tract. Video Abstract.}, }
@article {pmid33204401, year = {2020}, author = {Li, J and Han, J and Lv, J and Wang, S and Qu, L and Jiang, Y}, title = {Saikosaponin A-Induced Gut Microbiota Changes Attenuate Severe Acute Pancreatitis through the Activation of Keap1/Nrf2-ARE Antioxidant Signaling.}, journal = {Oxidative medicine and cellular longevity}, volume = {2020}, number = {}, pages = {9217219}, pmid = {33204401}, issn = {1942-0994}, abstract = {Objective: Severe acute pancreatitis (SAP) is a serious and life-threatening disease associated with multiple organ failure and a high mortality rate and is accompanied by distinct oxidative stress and inflammatory responses. Saikosaponin A has strong antioxidant properties and can affect the composition of gut microbiota. We sought to determine the effects of Saikosaponin A interventions on SAP by investigating the changes of gut microbiota and related antioxidant signaling.<br><br>Methods: A SAP model was established in Sprague-Dawley (SD) rats through the injection of sodium taurocholate into the biliopancreatic duct and confirmed by elevated levels of serum lipase and amylase. The model was fed a standard diet either with saline solution or with Saikosaponin A. Fecal microbiota transplantation (FMT) from Saikosaponin A-induced rats into the rat model was performed to test the effects of gut microbiota. The composition of gut microbiota was analyzed by using 16S rRNA gene sequencing. We measured apoptotic status, inflammatory biomarkers, and Keap1-Nrf2-ARE ((Kelch-like ECH-associated protein 1) nuclear factor erythroid 2-related factor 2-antioxidant response element) antioxidant signaling.<br><br>Results: Saikosaponin A intervention attenuated SAP lesions and reduced the levels of serum amylase and lipase, oxidative stress, and inflammatory responses by reducing pathological scores and affecting the serum level of oxidative and inflammatory factors. Meanwhile, the expression of Keap1-Nrf2-ARE was increased. Saikosaponin A intervention improved microbiota composition by increasing the relative abundance of Lactobacillus and Prevotella species. FMT resulted in similar results as those caused by the Saikosaponin A intervention, suggesting Saikosaponin A may exert its function via the improvement of gut microbiota composition.<br><br>Conclusions: Saikosaponin A-induced gut microbiota changes attenuate SAP progression in the rat model and may be a potential natural drug for adjuvant treatment of SAP. Further work is needed to clear up the points.}, }
@article {pmid33203880, year = {2020}, author = {Song, L and Liu, Z and Hu, HH and Yang, Y and Li, TY and Lin, ZZ and Ye, J and Chen, J and Huang, X and Liu, DT and Zhou, J and Shi, Y and Zhao, H and Xie, C and Chen, L and Song, E and Lin, SY and Lin, SC}, title = {Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {5842}, doi = {10.1038/s41467-020-19694-w}, pmid = {33203880}, issn = {2041-1723}, abstract = {Increased lipogenesis has been linked to an increased cancer risk and poor prognosis; however, the underlying mechanisms remain obscure. Here we show that phosphatidic acid phosphatase (PAP) lipin-1, which generates diglyceride precursors necessary for the synthesis of glycerolipids, interacts with and is a direct substrate of the Src proto-oncogenic tyrosine kinase. Obesity-associated microenvironmental factors and other Src-activating growth factors, including the epidermal growth factor, activate Src and promote Src-mediated lipin-1 phosphorylation on Tyr398, Tyr413 and Tyr795 residues. The tyrosine phosphorylation of lipin-1 markedly increases its PAP activity, accelerating the synthesis of glycerophospholipids and triglyceride. Alteration of the three tyrosine residues to phenylalanine (3YF-lipin-1) disables lipin-1 from mediating Src-enhanced glycerolipid synthesis, cell proliferation and xenograft growth. Re-expression of 3YF-lipin-1 in PyVT;Lpin1-/- mice fails to promote progression and metastasis of mammary tumours. Human breast tumours exhibit increased p-Tyr-lipin-1 levels compared to the adjacent tissues. Importantly, statistical analyses show that levels of p-Tyr-lipin-1 correlate with tumour sizes, lymph node metastasis, time to recurrence and survival of the patients. These results illustrate a direct lipogenesis-promoting role of the pro-oncogenic Src, providing a mechanistic link between obesity-associated mitogenic signaling and breast cancer malignancy.}, }
@article {pmid33198506, year = {2020}, author = {Duan, H and Yu, L and Tian, F and Zhai, Q and Fan, L and Chen, W}, title = {Antibiotic-induced gut dysbiosis and barrier disruption and the potential protective strategies.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-26}, doi = {10.1080/10408398.2020.1843396}, pmid = {33198506}, issn = {1549-7852}, abstract = {The oral antibiotic therapies administered widely to people and animals can cause gut dysbiosis and barrier disruption inevitably. Increasing attention has been directed toward antibiotic-induced gut dysbiosis, which involves a loss of diversity, changes in the abundances of certain taxa and consequent effects on their metabolic capacity, and the spread of antibiotic-resistant bacterial strains. Treatment with beta-lactam, glycopeptide, and macrolide antibiotics is associated with the depletion of beneficial commensal bacteria in the genera Bifidobacterium and Lactobacillus. The gut microbiota is a reservoir for antibiotic resistance genes, the prevalence of which increases sharply after antibiotic ingestion. The intestinal barrier, which comprises secretory, physical, and immunological barriers, is also a target of antibiotics. Antibiotic induced changes in the gut microbiota composition could induce weakening of the gut barrier through changes in mucin, cytokine, and antimicrobial peptide production by intestinal epithelial cells. Reports have indicated that dietary interventions involving prebiotics, probiotics, omega-3 fatty acids, and butyrate supplementation, as well as fecal microbiota transplantation, can alleviate antibiotic-induced gut dysbiosis and barrier injuries. This review summarizes the characteristics of antibiotic-associated gut dysbiosis and barrier disruption, as well as the strategies for alleviating this condition. This information is intended to provide a foundation for the exploration of safer, more efficient, and affordable strategies to prevent or relieve antibiotic-induced gut injuries.}, }
@article {pmid33198059, year = {2020}, author = {Krishnamoorthy, M and Lenehan, JG and Burton, JP and Maleki Vareki, S}, title = {Immunomodulation in Pancreatic Cancer.}, journal = {Cancers}, volume = {12}, number = {11}, pages = {}, doi = {10.3390/cancers12113340}, pmid = {33198059}, issn = {2072-6694}, support = {N/A//London Regional Cancer Program's Catalyst Grant Program, Keith Smitt Translational Research Grants./ ; }, abstract = {Pancreatic cancer has a high mortality rate, and its incidence is increasing worldwide. The almost universal poor prognosis of pancreatic cancer is partly due to symptoms presenting only at late stages and limited effective treatments. Recently, immune checkpoint blockade inhibitors have drastically improved patient survival in metastatic and advanced settings in certain cancers. Unfortunately, these therapies are ineffective in pancreatic cancer. However, tumor biopsies from long-term survivors of pancreatic cancer are more likely to be infiltrated by cytotoxic T-cells and certain species of bacteria that activate T-cells. These observations suggest that T-cell activation is essential for anti-tumor immunity in pancreatic cancers. This review discusses the immunological mechanisms responsible for effective anti-tumor immunity and how immune-based strategies can be exploited to develop new pancreatic cancer treatments.}, }
@article {pmid33198044, year = {2020}, author = {Yang, J and Fu, X and Liao, X and Li, Y}, title = {Effects of gut microbial-based treatments on gut microbiota, behavioral symptoms, and gastrointestinal symptoms in children with autism spectrum disorder: A systematic review.}, journal = {Psychiatry research}, volume = {293}, number = {}, pages = {113471}, doi = {10.1016/j.psychres.2020.113471}, pmid = {33198044}, issn = {1872-7123}, abstract = {Many studies have identified some abnormalities in gastrointestinal (GI) physiology (e.g., increased intestinal permeability, overall microbiota alterations, and gut infection) in children with autism spectrum disorder (ASD). Furthermore, changes in the intestinal flora may be related to GI and ASD symptom severity. Thus, we decided to systematically review the effects of gut microbial-based interventions on gut microbiota, behavioral symptoms, and GI symptoms in children with ASD. We reviewed current evidence from the Cochrane Library, EBSCO PsycARTICLES, PubMed, Web of Science, and Scope databases up to July 12, 2020. Experimental studies that used gut microbial-based treatments among children with ASD were included. Independent data extraction and quality assessment of studies were conducted according to the PRISMA statement. Finally, we identified 16 articles and found that some interventions (i.e., prebiotic, probiotic, vitamin A supplementation, antibiotics, and fecal microbiota transplantation) could alter the gut microbiota and improve behavioral symptoms and GI symptoms among ASD patients. Our findings highlight that the gut microbiota could be a novel target for ASD patients in the future. However, we only provided suggestive but not conclusive evidence regarding the efficacy of interventions on GI and behavioral symptoms among ASD patients. Additional rigorous trials are needed to evaluate the effects of gut microbial-based treatments and explore potential mechanisms.}, }
@article {pmid33194651, year = {2020}, author = {Chen, YC and Miao, ZF and Yip, KL and Cheng, YA and Liu, CJ and Li, LH and Lin, CY and Wang, JW and Wu, DC and Cheng, TL and Wang, JY}, title = {Gut Fecal Microbiota Transplant in a Mouse Model of Orthotopic Rectal Cancer.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {568012}, doi = {10.3389/fonc.2020.568012}, pmid = {33194651}, issn = {2234-943X}, abstract = {The gut microbiota is reported to play an important role in carcinogenesis and the treatment of CRC. SW480 and SW620 colon cancer cells integrated with infrared fluorescent proteins were injected into the rectal submucosa of nude mice. In the subsequent 30 days, we observed tumor growth weekly using an in vivo imaging system. The bacterial solution was infused anally into the mice to perform bacterial transplant. Phosphate-buffered saline, Acinetobacter lwoffii, and Bifidobacterium longum solutions were infused individually. The 16S ribosomal DNA (rDNA) and polymerase chain reaction of murine feces were investigated to confirm the colonization of target bacteria. In the SW620 orthotopic xenograft rectal cancer model, 4 of 5 mice developed rectal cancer by 30 days after submucosal injection. In the SW480 orthotopic xenograft rectal cancer model, 2 of 6 mice developed rectal cancer by 30 days after submucosal injection. For the 16S rDNA analysis, the mice receiving the bacterial solution infusion demonstrated positive findings for A. lwoffii and B. longum. With the successful establishment of a mouse model of orthotopic rectal cancer and transplant of target bacteria, we can further explore the relationship between gut microbiota and CRC. The role of fecal microbiota transplant in the treatment and alleviation of adverse events of chemotherapy in CRC could be clarified in subsequent studies.}, }
@article {pmid33193813, year = {2020}, author = {Tian, Y and Zuo, L and Guo, Q and Li, J and Hu, Z and Zhao, K and Li, C and Li, X and Zhou, J and Zhou, Y and Li, XA}, title = {Potential role of fecal microbiota in patients with constipation.}, journal = {Therapeutic advances in gastroenterology}, volume = {13}, number = {}, pages = {1756284820968423}, doi = {10.1177/1756284820968423}, pmid = {33193813}, issn = {1756-283X}, abstract = {Background: We evaluated the safety and efficacy of fecal microbiota transplantation (FMT) for chronic functional constipation (CFC) ineffectively treated by conventional constipation medication.<br><br>Methods: Thirty-four patients with CFC underwent FMT treatment (three rounds, via gastroscopy). Clinical scales, including the Wexner constipation score as the main index of efficiency, were completed at baseline; after each treatment, and at 2 and 3 months of follow up. Secondary evaluation indices included the self-assessment of constipation symptoms, patient assessment constipation quality-of-life questionnaire, Bristol stool form scale, and Zung's self-rating depression and anxiety scales. Gastrointestinal motility, motilin, gastrin, nitric oxide (NO), and 5-hydroxytryptamine (5-HT) were assessed before and after treatment. Intestinal flora changes were assessed by 16S ribosomal ribonucleic acid (rRNA) sequencing.<br><br>Results: There were no serious adverse reactions. The clinical cure rate was 73.5% (25/34), clinical remission rate was 14.7% (5/34), and the inefficiency rate was 11.8% (4/34). Clinical scale data indicated that the FMT treatment was effective. Furthermore, FMT treatment promoted intestinal peristalsis, increased gastrointestinal motility, and increased serum NO and 5-HT levels. The 16S rRNA sequencing data indicated that high abundances of Bacteroides, Klebsiella, Megamonas, Erysipelotrichaceae and Epulopiscium may be the cause of constipation, and high abundances of Prevotella, Acidaminococcus and Butyricimonas may be the main factors in curing constipation.<br><br>Conclusion: Treatment with FMT regulates the intestinal microflora and changes the abundance of CFC-associated bacterial flora to improve constipation.}, }
@article {pmid33193352, year = {2020}, author = {Schmidt, CJ and Wenndorf, K and Ebbers, M and Volzke, J and Müller, M and Strübing, J and Kriebel, K and Kneitz, S and Kreikemeyer, B and Müller-Hilke, B}, title = {Infection With Clostridioides difficile Attenuated Collagen-Induced Arthritis in Mice and Involved Mesenteric Treg and Th2 Polarization.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {571049}, doi = {10.3389/fimmu.2020.571049}, pmid = {33193352}, issn = {1664-3224}, abstract = {Objectives: Rheumatoid arthritis is an autoimmune disease with multifactorial etiopathogenesis. Among the environmental factors, mucosal infections and the inducing pathobionts are gaining increasing attention. We here set out to explore the gut-joint-axis and the impact of Clostridioides difficile infection on subsequent arthritis.<br><br>Methods: We combined C. difficile infection in DBA/1J × B10.Q F1 mice with collagen induced arthritis (CIA). Mice were infected via oral gavage and infection was monitored by weight loss, colonic histology, and antibodies against bacteria. Scoring of arthritis was performed macroscopically. Intestinal microbiomes were analyzed and immune responses were monitored via quantification of transcription factor-specific mRNA isolated from the inguinal and mesenteric lymph nodes.<br><br>Results: Infection with C. difficile VPI 10463 resulted in significant weight loss and severe colitis yet accelerated the reversal towards the original microbiome after antibiotic treatment. Spontaneous clearance of VPI 10463 infection reduced the incidence of subsequent CIA and led to mesenteric Treg and Th2 polarization. However, this attenuating effect was abrogated if VPI 10463 was eradicated via vancomycin followed by fecal microbiota transplantation. Moreover, VPI 10463 infection following the onset of CIA lacked therapeutic potential.<br><br>Conclusion: Our results demonstrate that infection with C. difficile VPI10463 induced an inflammation of the gut that protected from subsequent arthritis development in mice. Both, microbial changes to the gut and immune cell mobilization and/or polarization may have contributed to arthritis protection. The prospect of potential therapeutic benefits resulting from C. difficile infections or some byproduct thereof call for further experiments that help elucidate exact mechanisms.}, }
@article {pmid33193273, year = {2020}, author = {Geng, ST and Zhang, ZY and Wang, YX and Lu, D and Yu, J and Zhang, JB and Kuang, YQ and Wang, KH}, title = {Regulation of Gut Microbiota on Immune Reconstitution in Patients With Acquired Immunodeficiency Syndrome.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {594820}, doi = {10.3389/fmicb.2020.594820}, pmid = {33193273}, issn = {1664-302X}, abstract = {Human immunodeficiency virus type 1 (HIV-1) infection of CD4+ T cells in the gut plays an insidious role in acquired immunodeficiency syndrome (AIDS) pathogenesis. Host immune function is closely related to gut microbiota. Changes in the gut microbiota cause a different immune response. Previous studies revealed that HIV-1 infection caused changes in gut microbiota, which induced immune deficiency. HIV-1 infection results in an abnormal composition and function of the gut microbiota, which may disrupt the intestinal epithelial barrier and microbial translocation, leading to long-term immune activation, including inflammation and metabolic disorders. At the same time, an abnormal gut microbiota also hinders the effect of antiviral therapy and affects the immune reconstruction of patients. However, studies on the impact of the gut microbiota on immune reconstitution in patients with HIV/AIDS are still limited. In this review, we focus on changes in the gut microbiota caused by HIV infection, as well as the impact and regulation of the gut microbiota on immune function and immune reconstitution, while we also discuss the potential impact of probiotics/prebiotics and fecal microbiota transplantation (FMT) on immune reconstitution.}, }
@article {pmid33190214, year = {2020}, author = {Zhou, Y and Ni, X and Duan, L and Niu, L and Liu, Q and Zeng, Y and Wang, Q and Wang, J and Khalique, A and Pan, K and Jing, B and Zeng, D}, title = {Lactobacillus plantarum BSGP201683 Improves the Intestinal Barrier of Giant Panda Microbiota-Associated Mouse Infected by Enterotoxigenic Escherichia coli K88.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12602-020-09722-y}, pmid = {33190214}, issn = {1867-1314}, support = {31970503//National Natural Science Foundation of China/ ; CPF2014-15//Chengdu Giant Panda Breeding Research Foundation/ ; 201906910016//China Scholarship Council/ ; }, abstract = {Giant pandas often suffered from gastrointestinal disease, especially the captive sub-adult one. Our study aims to investigate whether L. plantarum G83, a good panda-derived probiotic, can improve the intestinal barrier against the enterotoxigenic Escherichia coli K88 (E. coli K88) infection in giant panda microbiota-associated mice (GPAM). We treated SPF mice with antibiotics cocktail and transplanted the giant panda intestinal microbiota to set up a GPAM. Our results demonstrated that the microbiota of GPAM changed over time and was relatively stable in the short-term experiment (2-4 weeks). Whereafter, the GPAM pretreated with L. plantarum G83 for 15 days and infected with enterotoxigenic E. coli K88. The result indicated that the number of Bifidobacteria spp. increased in GPAM-G and GPAM-GE groups; the Lactobacillus spp. only increased in the GPAM-G group. Although the abundance of Enterobacteriaceae spp. only decreased in the GPAM-G group, the copy number of Escherichia coli in the GPAM-E group was significantly lower than that in the other groups. Meanwhile, the L. plantarum G83-induced alteration of microbiota could increase the mRNA expression of Claudin-1, Zo-1, and Occludin-1 in the GPAM-G group in the ileum; only Occludin-1 was increased in the GPAM-GE group. The sIgA in the ileum showed a positive response, also the result of body weight and histology in both the GPAM-G and GPAM-GE group. These results indicated that the L. plantarum G83 could improve the intestinal barrier to defense the enterotoxigenic E. coli K88 invasion.}, }
@article {pmid33187097, year = {2020}, author = {Nourrisson, C and Brunet, J and Flori, P and Moniot, M and Bonnin, V and Delbac, F and Poirier, P}, title = {Comparison of DNA Extraction Methods and Real-Time PCR Assays for the Detection of Blastocystis sp. in Stool Specimens.}, journal = {Microorganisms}, volume = {8}, number = {11}, pages = {}, doi = {10.3390/microorganisms8111768}, pmid = {33187097}, issn = {2076-2607}, abstract = {Diagnosis of Blastocystis in stool may be challenging, as microscopic examination and culture-based methods have demonstrated low sensitivity. Molecular detection assays are now available for this enteric parasite, based on &quot;in-house&quot; or commercial-developed techniques. The aim of this study was to assess and compare the performance of (i) two DNA extraction methods (manual versus automated), and (ii) four qPCR assays (three &quot;in-house&quot; and one commercialized), for detection of Blastocystis sp. in human stools. One hundred and forty stools were included, among which 76 were confirmed to be positive for Blastocystis. The manual DNA extraction method allowed for the identification of significantly more positive specimens than the automated method (p < 0.05). In particular, specimens with a low parasite load were negative when DNA was extracted with the automated process. The four qPCR assays also had variable performances, with the commercialized assay being the most sensitive (84%) but the least specific (82%). Overall, for all qPCR assays, the specificity decreased when the sensitivity increased. Blastocystis' subtype, notably the subtype 4, influenced these performances. Our results indicate that the positivity rate for the detection of Blastocystis in stools could be variable according to the DNA extraction method and the qPCR assay used. These pitfalls need to be considered for the selection of method and interpretation of results, particularly considering the search of this intestinal parasite in a donor before fecal microbiota transplantation.}, }
@article {pmid32066789, year = {2020}, author = {van der Eijk, JAJ and Rodenburg, TB and de Vries, H and Kjaer, JB and Smidt, H and Naguib, M and Kemp, B and Lammers, A}, title = {Early-life microbiota transplantation affects behavioural responses, serotonin and immune characteristics in chicken lines divergently selected on feather pecking.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {2750}, pmid = {32066789}, issn = {2045-2322}, mesh = {Aggression/psychology ; Animal Welfare ; Animals ; Antibodies/*blood ; Anxiety/immunology/*microbiology/physiopathology ; Bacteria/classification/immunology ; *Behavior, Animal ; Chickens/blood/genetics/immunology/*microbiology ; Corticosterone/blood ; Feathers ; Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome/*immunology ; Genotype ; Male ; Serotonin/blood ; Time Factors ; }, abstract = {Gut microbiota influences host behaviour and physiology, such as anxiety, stress, serotonergic and immune systems. These behavioural and physiological characteristics are related to feather pecking (FP), a damaging behaviour in chickens that reduces animal welfare and productivity. Moreover, high FP (HFP) and low FP (LFP) lines differed in microbiota composition. However, it is unknown whether microbiota can influence the development of FP. For the first time, we identified the effects of microbiota transplantation on FP, and behavioural and physiological characteristics related to FP. HFP and LFP chicks received sterile saline (control), HFP or LFP microbiota transplantation during the first two weeks post-hatch. Microbiota transplantation influenced behavioural responses of the HFP line during treatment and of the LFP line after treatment. In both lines, homologous microbiota transplantation (i.e., receiving microbiota from their line) resulted in more active behavioural responses. Furthermore, microbiota transplantation influenced immune characteristics (natural antibodies) in both lines and peripheral serotonin in the LFP line. However, limited effects on microbiota composition, stress response (corticosterone) and FP were noted. Thus, early-life microbiota transplantation had immediate and long-term effects on behavioural responses and long-term effects on immune characteristics and peripheral serotonin; however, the effects were dependent on host genotype. Since early-life microbiota transplantation influenced behavioural and physiological characteristics that are related to FP, it could thus influence the development of FP later in life.}, }
@article {pmid33176177, year = {2020}, author = {Zhang, Y and Xie, B and Chen, X and Zhang, J and Yuan, S}, title = {A key role of gut microbiota-vagus nerve/spleen axis in sleep deprivation-mediated aggravation of systemic inflammation after LPS administration.}, journal = {Life sciences}, volume = {}, number = {}, pages = {118736}, doi = {10.1016/j.lfs.2020.118736}, pmid = {33176177}, issn = {1879-0631}, abstract = {AIMS: Sleep deprivation (SD) correlates with exacerbated systemic inflammation after sepsis. However, the underlying mechanisms remain unclear. This study aimed to evaluate the roles and mechanisms of SD in inflammatory organ injury after lipopolysaccharide (LPS) administration.<br><br>MAIN METHODS: Mice were intraperitoneally injected with LPS followed by 3 consecutive days of SD. The pseudo germ-free (PGF) mice received fecal microbiota transplant by being gavaged with supernatant from fecal suspension of septic mice with or without SD. The subdiaphragmatic vagotomy (SDV) or splenectomy was performed 14 days prior to LPS injection or antibiotics administration.<br><br>KEY FINDINGS: Post-septic SD increased the plasma levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), reduced IL-10 plasma level, increased spleen weight, and promoted inflammatory injury of the lung, liver and kidney. The relative abundance of Proteobacteria and its subgroups were increased after post-septic SD. PGF mice transplanted with fecal bacteria from septic mice subjected to SD developed splenomegaly, systemic inflammation, organ inflammation and damage as their donors did. Intriguingly, SDV abolished the aggravated effects of SD on splenomegaly and inflammatory organ injury in septic mice received SD or in PGF mice transplanted with fecal bacteria from septic mice subjected to SD. Furthermore, splenectomy also abrogated the increase in IL-6 and TNF-α plasma levels and the decrease in IL-10 plasma level in PGF mice transplanted with fecal bacteria from septic mice subjected to SD.<br><br>SIGNIFICANCE: Gut microbiota-vagus nerve axis and gut microbiota-spleen axis play key roles in modulating systemic inflammation induced by SD after LPS administration.}, }
@article {pmid33175698, year = {2020}, author = {Ademe, M}, title = {Benefits of fecal microbiota transplantation: A comprehensive review.}, journal = {Journal of infection in developing countries}, volume = {14}, number = {10}, pages = {1074-1080}, doi = {10.3855/jidc.12780}, pmid = {33175698}, issn = {1972-2680}, abstract = {A growing body of literatures showed the interaction of dysbiotic gut with a wide range of disorders, and the clinical use of fecal microbiota transplantation (FMT) shifted from infectious disease to non-communicable disorders. Despite the promising therapeutic benefits of FMT, the exact mechanisms through which fecal recipients benefit from the fecal intervention are not well understood. However, owing to the advantages of having a healthy gut microbiome, possible mechanisms of actions of FMT has been described. On the one hand, through direct ecological competition, FMT may potentially stimulate decolonization of pathogenic microorganisms and increase host resistance to pathogens. Moreover, following dysbiosis, abnormal microbial colonization of the gastrointestinal tract may also cause excessive or dysregulated immune response, resulting in chronic inflam-mation and the development of mucosal lesions. In this regard, repopulating gut microbiome through FMT helps to restore immune function and reduce host damage. On the other hand, FMT helps to restore essential metabolites used for host metabolism, including short-chain fatty acids (SCFA), antimicrobial peptides (AMP), bacteriocins and bile acids. Therefore, in this review, the existing evidences regarding the mechanisms of action, current opportunities and challenges of FMT will be described.}, }
@article {pmid33172329, year = {2020}, author = {Kim, S and Lee, JY and Shin, SG and Kim, JK and Silwal, P and Kim, YJ and Shin, NR and Kim, PS and Won, M and Lee, SH and Kim, SY and Sasai, M and Yamamoto, M and Kim, JM and Bae, JW and Jo, EK}, title = {ESRRA (estrogen related receptor alpha) is a critical regulator of intestinal homeostasis through activation of autophagic flux via gut microbiota.}, journal = {Autophagy}, volume = {}, number = {}, pages = {}, doi = {10.1080/15548627.2020.1847460}, pmid = {33172329}, issn = {1554-8635}, abstract = {The orphan nuclear receptor ESRRA (estrogen related receptor alpha) is critical in mitochondrial biogenesis and macroautophagy/autophagy function; however, the roles of ESRRA in intestinal function remain uncharacterized. Herein we identified that ESRRA acts as a key regulator of intestinal homeostasis by amelioration of colonic inflammation through activation of autophagic flux and control of host gut microbiota. Esrra-deficient mice presented with increased susceptibility to dextran sodium sulfate (DSS)-induced colitis with upregulation of intestinal inflammation. In addition, esrra-null mice had depressed AMP-activated protein kinase phosphorylation (AMPK), lower levels of TFEB (transcription factor EB), and accumulation of SQSTM1/p62 (sequestosome 1) with defective mitochondria in intestinal tissues. Esrra-deficient mice showed distinct gut microbiota composition and significantly higher microbial diversity than wild-type (WT) mice. Cohousing or fecal microbiota transplantation from WT mice to Esrra-deficient mice ameliorated DSS-induced colitis severity. Importantly, patients with ulcerative colitis (UC) had significantly decreased ESRRA expression in intestinal mucosal tissues that correlated with disease activity, suggesting clinical relevance of ESRRA in UC. Taken together, our results show that ESRRA contributes to intestinal homeostasis through autophagy activation and gut microbiota control to protect the host from detrimental inflammation and dysfunctional mitochondria.}, }
@article {pmid30928978, year = {2020}, author = {Gorbovskaya, I and Kanji, S and Liu, JCW and MacKenzie, NE and Agarwal, SM and Marshe, VS and Sriretnakumar, V and Verdu, EF and Bercik, P and De Palma, G and Hahn, MK and Müller, DJ}, title = {Investigation of the Gut Microbiome in Patients with Schizophrenia and Clozapine-Induced Weight Gain: Protocol and Clinical Characteristics of First Patient Cohorts.}, journal = {Neuropsychobiology}, volume = {79}, number = {1}, pages = {5-12}, doi = {10.1159/000494696}, pmid = {30928978}, issn = {1423-0224}, mesh = {Adult ; Animals ; Antipsychotic Agents/*adverse effects ; Clozapine/*adverse effects ; Disease Models, Animal ; Drug-Related Side Effects and Adverse Reactions/*therapy ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Prospective Studies ; Schizophrenia/*drug therapy/*microbiology ; Weight Gain/*drug effects ; }, abstract = {BACKGROUND: Emerging evidence suggests an important role of the human gut microbiome in psychiatry and neurodevelopmental disorders. An increasing body of literature based on animal studies has reported that the gut microbiome influences brain development and behavior by interacting with the gut-brain axis. Furthermore, as the gut microbiome has an important role in metabolism and is known to interact with pharmaceuticals, recent evidence suggests a role for the microbiome in antipsychotic-induced metabolic side effects in animals and humans.<br><br>PURPOSE: Here we present the protocol for a two-phase study investigating the gut microbiome in healthy controls and in patients with schizophrenia treated with antipsychotics.<br><br>METHODS: Phase I of our study involves humans exclusively. We recruit 25 patients who are chronically treated with clozapine and compare them with 25 healthy controls matched for age, sex, BMI, and smoking status. A second cohort consists of 25 patients newly starting on clozapine, and a third cohort includes 25 antipsychotic-naive patients. The patients in the second cohort and third cohort are prospectively assessed for up to 6 and 12 weeks, respectively. Phase II of this study will incorporate microbiota humanized mouse models to examine the influence of human fecal transplant on metabolic parameters and the gut-brain axis. Progress and Future Directions: We are underway with the first participants enrolled in all phase I treatment cohorts. This study will contribute to elucidating the role of the gut microbiome in schizophrenia and metabolic side effects. In addition, its results may help to explore potential therapeutic targets for antipsychotic-induced metabolic side effects.}, }
@article {pmid33166939, year = {2020}, author = {Singh, R and Zogg, H and Wei, L and Bartlett, A and Ghoshal, UC and Rajender, S and Ro, S}, title = {Gut Microbial Dysbiosis in the Pathogenesis of Gastrointestinal Dysmotility and Metabolic Disorders.}, journal = {Journal of neurogastroenterology and motility}, volume = {}, number = {}, pages = {}, doi = {10.5056/jnm20149}, pmid = {33166939}, issn = {2093-0879}, abstract = {Of all microorganisms in the human body, the largest and most complex population resides in the gastrointestinal (GI) tract. The gut microbiota continuously adapts to the host environment and serves multiple critical functions for their hosts, including regulating host immunity, procuring energy from food, and preventing the colonization of pathogens. Mounting evidence has suggested gut microbial imbalance (dysbiosis) as a core pathophysiology in the development of GI motility and metabolic disorders, such as irritable bowel syndrome and diabetes. Current research has focused on discovering associations between these disorders and gut microbial dysbiosis; however, whether these associations are a consequence or cause is still mostly unexplored. State-of-the-art studies have investigated how gut microbes communicate with our body systems through microbiota-derived metabolites and how they are able to modulate host physiology. There is now mounting evidence that alterations in the composition of small intestinal microbes have an association with GI dysmotility and metabolic disorders. Although treatment options for gut microbial dysbiosis are currently limited, antibiotics, fecal microbiota transplantation, probiotics, and dietary interventions are currently the best options. However, treatment with broad-spectrum antibiotics has been viewed with skepticism due to the risk of developing antibiotic resistant bacteria. In order to elucidate the cellular and molecular pathways underlying gut microbiotahost crosstalk and for the development of a powerful platform for future therapeutic approaches; studies are warranted. Here, we review recent literature on gut microbial alterations and/or interactions involved in the pathophysiology of GI dysmotility and metabolic disorders.}, }
@article {pmid33166735, year = {2020}, author = {Koszewiczz, M and Jaroch, J and Brzecka, A and Ejma, M and Budrewicz, S and Mikhaleva, LM and Muresanu, C and Schield, P and Somasundaram, SG and Kirkland, CE and Avila-Rodriguez, M and Aliev, G}, title = {Dysbiosis is one of the risk factor for stroke and cognitive impairment and potential target for treatment.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {105277}, doi = {10.1016/j.phrs.2020.105277}, pmid = {33166735}, issn = {1096-1186}, abstract = {Above 50 millions people have different forms of cognitive impairment basically caused by neurodegenerative diseases, such as Alzheimer disease, Parkinson disease, and cerebrovascular diseases, mostly stroke. Often these coexistence and exacerbate one another. The damaged area in the post-stroke dementia may lead to the additional neurodegenerative lesions. Gut microbiome functions like an endocrine organ by generating bioactive metabolites, can directly or indirectly impact human physiology. An alteration in the composition and function of intestinal flora, i.e. gut dysbiosis, is involved in neurodegenerative and cerebrovascular diseases. Additionally, gut dysbiosis may accelerate the progression of the cognitive impairment in the course of these diseases. Dysbiosis may result from obesity; metabolic, cardiovascular, and sleep disorders; or lack of physical activity. They may coexist in various patterns in older people, enhancing the risk, incidence, and progression of cerebrovascular lesions, neurodegenerative disorders, and cognitive impairment, creating a vicious circle. Recently, several metabolites produced by gut microbiota from dietary metabolism, e.g. trimethylamine,/trimethylamine N-oxide, short-chain fatty acids, secondary bile acids have been linked to neurodegenerative and cerebrovascular diseases. New treatment modalities, including prebiotic and probiotics, may normalize the gut microbiota composition, change the brain-gut barrier and decrease the risk of the pathology development. Fecal microbiota transplantation, sometimes with combination with other methods, is used for remodeling and replenishing the symbiotic gut microbiome. The promising field of research is associated with basic findings of bidirectional communication between body organs and gut microbiota that open the possibilities of pharmacological treatments of many clinical situations. The authors present the role of gut microbiota in physiology, and the novel therapeutic targets in modulation of intestinal microbiota Personalized therapies based on their personal genome make up could offer benefits by modulating microbiota cross-talk with brain and cardiovascular system. A healthy lifestyle, including pre and probiotic nutrition is generally recommended. Prevention may also be enhanced by correcting gut dysbiosis resulting a reduced risk of post-stroke cognitive impairment including dementia.}, }
@article {pmid33163830, year = {2020}, author = {Witjes, JJ and Smits, LP and Pekmez, CT and Prodan, A and Meijnikman, AS and Troelstra, MA and Bouter, KEC and Herrema, H and Levin, E and Holleboom, AG and Winkelmeijer, M and Beuers, UH and van Lienden, K and Aron-Wisnewky, J and Mannisto, V and Bergman, JJ and Runge, JH and Nederveen, AJ and Dragsted, LO and Konstanti, P and Zoetendal, EG and de Vos, W and Verheij, J and Groen, AK and Nieuwdorp, M}, title = {Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis.}, journal = {Hepatology communications}, volume = {4}, number = {11}, pages = {1578-1590}, doi = {10.1002/hep4.1601}, pmid = {33163830}, issn = {2471-254X}, abstract = {The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant-based, low-animal-protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. We therefore performed a double-blind randomized controlled proof-of-principle study in which individuals with hepatic steatosis on ultrasound were randomized to two study arms: lean vegan donor (allogenic n = 10) or own (autologous n = 11) FMT. Both were performed three times at 8-week intervals. A liver biopsy was performed at baseline and after 24 weeks in every subject to determine histopathology (Nonalcoholic Steatohepatitis Clinical Research Network) classification and changes in hepatic gene expression based on RNA sequencing. Secondary outcome parameters were changes in intestinal microbiota composition and fasting plasma metabolomics. We observed a trend toward improved necro-inflammatory histology, and found significant changes in expression of hepatic genes involved in inflammation and lipid metabolism following allogenic FMT. Intestinal microbial community structure changed following allogenic FMT, which was associated with changes in plasma metabolites as well as markers of . Conclusion: Allogenic FMT using lean vegan donors in individuals with hepatic steatosis shows an effect on intestinal microbiota composition, which is associated with beneficial changes in plasma metabolites and markers of steatohepatitis.}, }
@article {pmid33163828, year = {2020}, author = {Acharya, C and Bajaj, JS}, title = {Transmitting Diet-Related Microbial Benefit through Fecal Microbiota Transplant in NASH: Can Microbiota Cut Through the Fat?.}, journal = {Hepatology communications}, volume = {4}, number = {11}, pages = {1559-1561}, doi = {10.1002/hep4.1596}, pmid = {33163828}, issn = {2471-254X}, }
@article {pmid33162889, year = {2020}, author = {Xue, A and Qian, X and Gao, X and Wang, P and Wang, L and Zheng, C and Huang, Z and Hu, W and Shi, J and Huang, Y}, title = {Fecal Microbial Signatures Are Associated With Engraftment Failure Following Umbilical Cord Blood Transplantation in Pediatric Crohn's Disease Patients With IL10RA Deficiency.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {580817}, doi = {10.3389/fphar.2020.580817}, pmid = {33162889}, issn = {1663-9812}, abstract = {Objectives: Umbilical cord blood transplantation (UCBT) is associated with a relatively high rate of engraftment failure. This study aimed at exploring whether any fecal microbiota could be associated with engraftment failure following UCBT in Crohn's disease patients with IL10RA deficiency.<br><br>Methods: Thirteen patients were recruited and their 230 fecal samples were collected longitudinally from immediately before conditioning chemotherapy to 8 weeks post the UCBT. The V3-V4 regions of the bacterial 16S rRNA gene were amplified by PCR and sequenced, followed by bioinformatics analyses.<br><br>Results: Following the UCBT, 7 out of 13 patients achieved neutrophil and platelet engraftment with a median of 21 and 28 days, respectively (S group), while 6 patients failed to achieve engraftment (F group). In comparison with that in the S group, significantly lower Shannon diversity values on the UCBT day (P = 0.0176) and less abundance of Bifidobacterium longum, Bifidobacterium pseudolongum, Enterobacteriaceae_538000, and one taxon of Lachnospiraceae family was detected in the F group, accompanied by significantly higher abundances of four taxa including Lautropia, Pseudomonas, and species Microvirgula aerodenitrificans during the chemotherapy period as well as UCBT. The abundances of thirty OTUs were correlated significantly with clinical indices.<br><br>Conclusions: Microbial indicators of reduced diversity of microbiota and signatures of specific bacterial abundances, such as a lower abundance of Bifidobacterium longum, for engraftment failure would require validation. These indicators may help for the risk stratification in patients with IL10RA deficiency undergoing UCBT.}, }
@article {pmid33160712, year = {2020}, author = {Aira, A and Arajol, C and Casals-Pascual, C and González-Suárez, B and Martí, S and Domínguez, MÁ and Guardiola, J and Soriano, Á and , }, title = {Recommendations for stool donor selection for fecal microbiota transplant. Consensus document endorsed by the Catalan Society of Digestology, Catalan Society of Infectious diseases and Clinical microbiology and the GEMBIOTA group from Spanish Society of Infectious Diseases and Clinical Microbiology.}, journal = {Enfermedades infecciosas y microbiologia clinica}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.eimc.2020.09.002}, pmid = {33160712}, issn = {1578-1852}, abstract = {Fecal microbiota transplantation (FMT) is an effective and safe treatment to treat recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and based on scientific knowledge. Selection of the fecal microbiota donor is a key point of the process to ensure recipient safety. It is necessary to have protocols of action that allow clinicians to act with the maximum guarantees and to minimize the risks of the procedure. For this reason, a multidisciplinary working group has been set up in Cataluña with the aim of establishing recommendations for the selection of the fecal microbiota donor.}, }
@article {pmid33159210, year = {2020}, author = {Zellmer, C and Sater, MRA and Huntley, MH and Osman, M and Olesen, SW and Ramakrishna, B}, title = {Shiga Toxin-Producing Escherichia coli Transmission via Fecal Microbiota Transplant.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa1486}, pmid = {33159210}, issn = {1537-6591}, abstract = {Fecal microbiota transplantation (FMT) is recommended therapy for multiply recurrent Clostridioides difficile infection. We report adverse events in 7 patients who received FMT from a stool donor who was colonized with Shiga toxin-producing Escherichia coli (STEC). No patients died of FMT-transmitted STEC. Improved screening can likely avoid future transmission.}, }
@article {pmid33158078, year = {2020}, author = {Souai, N and Zidi, O and Mosbah, A and Kosai, I and Manaa, JE and Mokhtar, NB and Asimakis, E and Stathopoulou, P and Cherif, A and Tsiamis, G and Kouidhi, S}, title = {Impact of the Post-Transplant Period and Lifestyle Diseases on Human Gut Microbiota in Kidney Graft Recipients.}, journal = {Microorganisms}, volume = {8}, number = {11}, pages = {}, doi = {10.3390/microorganisms8111724}, pmid = {33158078}, issn = {2076-2607}, support = {KA107//Erasmus+/ ; }, abstract = {Gaining long-term graft function and patient life quality remain critical challenges following kidney transplantation. Advances in immunology, gnotobiotics, and culture-independent molecular techniques have provided growing insights into the complex relationship of the microbiome and the host. However, little is known about the over time-shift of the gut microbiota in the context of kidney transplantation and its impact on both graft and health stability. Here we aimed to characterize the structure of gut microbiota within stable kidney graft recipients. We enrolled forty kidney transplant patients after at least three months of transplantation and compared them to eighteen healthy controls. The overall microbial community structure of the kidney transplanted group was clearly different from control subjects. We found lower relative abundances of Actinobacteria, Bacteroidetes, and Verrucomicrobia within the patient group and a higher abundance of Proteobacteria compared to the control group. Both richness and Shannon diversity indexes were significantly lower in the kidney graft recipients than in healthy controls. Post-graft period was positively correlated with the relative abundance of the Proteobacteria phylum, especially Escherichia.Shigella genus. Interestingly, only Parabacteroides was found to significantly differentiate patients that were not suffering from lifestyle diseases and those who suffer from post-graft complications. Furthermore, network analysis showed that the occurrence of lifestyle diseases was significantly linked with a higher number of negative interactions of Sutterella and Succinivibrio genera within patients. This study characterizes gut microbiome fluctuation in stable kidney transplant patients after a long post-allograft period. Analysis of fecal microbiota could be useful for nephrologists as a new clinical tool that can improve kidney allograft monitoring and outcomes.}, }
@article {pmid33156122, year = {2020}, author = {Adelman, MW and Woodworth, MH and Shaffer, VO and Martin, GS and Kraft, CS}, title = {Critical Care Management of the Patient with Clostridioides difficile.}, journal = {Critical care medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/CCM.0000000000004739}, pmid = {33156122}, issn = {1530-0293}, abstract = {OBJECTIVES: To review published clinical evidence on management of Clostridioides difficile infection in critically ill patients.<br><br>DATA SOURCES: We obtained relevant studies from a PubMed literature review and bibliographies of reviewed articles.<br><br>STUDY SELECTION: We selected English-language studies addressing aspects of C. difficile infection relevant to critical care clinicians including epidemiology, risk factors, diagnosis, treatment, and prevention, with a focus on high-quality clinical evidence.<br><br>DATA EXTRACTION: We reviewed potentially relevant studies and abstracted information on study design, methods, patient selection, and results of relevant studies. This is a synthetic (i.e., not systematic) review.<br><br>DATA SYNTHESIS: C. difficile infection is the most common healthcare-associated infection in the United States. Antibiotics are the most significant C. difficile infection risk factor, and among antibiotics, cephalosporins, clindamycin, carbapenems, fluoroquinolones, and piperacillin-tazobactam confer the highest risk. Age, diabetes mellitus, inflammatory bowel disease, and end-stage renal disease are risk factors for C. difficile infection development and mortality. C. difficile infection diagnosis is based on testing appropriately selected patients with diarrhea or on clinical suspicion for patients with ileus. Patients with fulminant disease (C. difficile infection with hypotension, shock, ileus, or megacolon) should be treated with oral vancomycin and IV metronidazole, as well as rectal vancomycin in case of ileus. Patients who do not respond to initial therapy should be considered for fecal microbiota transplant or surgery. Proper infection prevention practices decrease C. difficile infection risk.<br><br>CONCLUSIONS: Strong clinical evidence supports limiting antibiotics when possible to decrease C. difficile infection risk. For patients with fulminant C. difficile infection, oral vancomycin reduces mortality, and adjunctive therapies (including IV metronidazole) and interventions (including fecal microbiota transplant) may benefit select patients. Several important questions remain regarding fulminant C. difficile infection management, including which patients benefit from fecal microbiota transplant or surgery.}, }
@article {pmid33155639, year = {2020}, author = {Allegretti, JR and Kelly, CR and Grinspan, A and Mullish, BH and Hurtado, J and Carrellas, M and Marcus, J and Marchesi, JR and McDonald, JAK and Gerardin, Y and Silverstein, M and Pechlivanis, A and Barker, GF and Miguens Blanco, J and Alexander, JL and Gallagher, KI and Pettee, W and Phelps, E and Nemes, S and Sagi, SV and Bohm, M and Kassam, Z and Fischer, M}, title = {Inflammatory Bowel Disease Outcomes Following Fecal Microbiota Transplantation for Recurrent C. difficile Infection.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izaa283}, pmid = {33155639}, issn = {1536-4844}, abstract = {BACKGROUND: Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding worsening of IBD activity; however, prospective data among IBD patients are limited.<br><br>METHODS: Secondary analysis from an open-label, prospective, multicenter cohort study among IBD patients with 2 or more CDI episodes was performed. Participants underwent a single FMT by colonoscopy (250 mL, healthy universal donor). Secondary IBD-related outcomes included rate of de novo IBD flares, worsening IBD, and IBD improvement-all based on Mayo or Harvey-Bradshaw index (HBI) scores. Stool samples were collected for microbiome and targeted metabolomic profiling.<br><br>RESULTS: Fifty patients enrolled in the study, among which 15 had Crohn's disease (mean HBI, 5.8 ± 3.4) and 35 had ulcerative colitis (mean partial Mayo score, 4.2 ± 2.1). Overall, 49 patients received treatment. Among the Crohn's disease cohort, 73.3% (11 of 15) had IBD improvement, and 4 (26.6%) had no disease activity change. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement, 29.4% (11 of 34) had no change, and 4% (1 of 34) experienced a de novo flare. Alpha diversity significantly increased post-FMT, and ulcerative colitis patients became more similar to the donor than Crohn's disease patients (P = 0.04).<br><br>CONCLUSION: This prospective trial assessing FMT in IBD-CDI patients suggests IBD outcomes are better than reported in retrospective studies.}, }
@article {pmid33155247, year = {2020}, author = {Kaźmierczak-Siedlecka, K and Vitale, E and Makarewicz, W}, title = {COVID-19 - gastrointestinal and gut microbiota-related aspects.}, journal = {European review for medical and pharmacological sciences}, volume = {24}, number = {20}, pages = {10853-10859}, doi = {10.26355/eurrev_202010_23448}, pmid = {33155247}, issn = {2284-0729}, abstract = {OBJECTIVE: The aim of this review paper was to discuss the gut microbiota-related aspects of COVID-19 patients. We presented the faecal-oral transmission of SARS-CoV-2, gut microbiota imbalance, and fecal microbiota transplantation as a hidden source of this virus.<br><br>MATERIALS AND METHODS: We analyzed the available literature (PubMed, Embase, Google Scholar databases) regarding COVID-19 and gut microbiota related aspects.<br><br>RESULTS: The gastrointestinal symptoms, such as nausea, vomiting, diarrhea, abdominal discomfort/pain, may occur in these patients. Notably, these symptoms may contribute to the severity of COVID-19. Recent several studies have revealed a new SARS-CoV-2 transmission possibility, opening a fresh view on COVID-19. It is observed the possibility of SARS-CoV-2 transmission via faecal-oral route. Fecal microbiota transplantation may be a hidden source of SARS-CoV-2. Additionally, the pharmacological treatment of COVID-19 and other factors may significantly alter the composition of gut microbiota. Among others, loss of bacterial diversity, the decrease of commensal microbes as well as the increase of opportunistic pathogens are observed.<br><br>CONCLUSIONS: The alterations of gut microbiota in COVID-19 patients consequently may lead to the development of gut dysbiosis-related diseases even after recovery from COVID-19. Therefore, it is recommended to screen stool samples taken from recovered patients at least 35 days after clearance of virus from respiratory tract. Before 35 days period, SARS-CoV-2 may still be detected in feces. It is also recommended to screen the composition as well as the activity of gut microbiota to assess its balance. In the case of gut dysbiosis, there should be introduced an appropriate method of its modulation. Additionally, all the fecal samples which are prepared for fecal microbiota transplantation should be tested for SARS-CoV-2 to provide protection for its recipients.}, }
@article {pmid33153085, year = {2020}, author = {Borsom, EM and Lee, K and Cope, EK}, title = {Do the Bugs in Your Gut Eat Your Memories? Relationship between Gut Microbiota and Alzheimer's Disease.}, journal = {Brain sciences}, volume = {10}, number = {11}, pages = {}, doi = {10.3390/brainsci10110814}, pmid = {33153085}, issn = {2076-3425}, support = {CTR040636//Arizona Alzheimer's Consortium DHS/ ; }, abstract = {The human microbiota is composed of trillions of microbial cells inhabiting the oral cavity, skin, gastrointestinal (GI) tract, airways, and reproductive organs. The gut microbiota is composed of dynamic communities of microorganisms that communicate bidirectionally with the brain via cytokines, neurotransmitters, hormones, and secondary metabolites, known as the gut microbiota-brain axis. The gut microbiota-brain axis is suspected to be involved in the development of neurological diseases, including Alzheimer's disease (AD), Parkinson's disease, and Autism Spectrum Disorder. AD is an irreversible, neurodegenerative disease of the central nervous system (CNS), characterized by amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Microglia and astrocytes, the resident immune cells of the CNS, play an integral role in AD development, as neuroinflammation is a driving factor of disease severity. The gut microbiota-brain axis is a novel target for Alzheimer's disease therapeutics to modulate critical neuroimmune and metabolic pathways. Potential therapeutics include probiotics, prebiotics, fecal microbiota transplantation, and dietary intervention. This review summarizes our current understanding of the role of the gut microbiota-brain axis and neuroinflammation in the onset and development of Alzheimer's disease, limitations of current research, and potential for gut microbiota-brain axis targeted therapies.}, }
@article {pmid31719078, year = {2019}, author = {Quraishi, MNN and Yalchin, M and Blackwell, C and Segal, J and Sharma, N and Hawkey, P and McCune, V and Hart, AL and Gaya, D and Ives, NJ and Magill, L and Loi, S and Hewitt, C and Gerasimidis, K and Loman, NJ and Hansen, R and McMullan, C and Mathers, J and Quince, C and Crees, N and Iqbal, T}, title = {STOP-Colitis pilot trial protocol: a prospective, open-label, randomised pilot study to assess two possible routes of faecal microbiota transplant delivery in patients with ulcerative colitis.}, journal = {BMJ open}, volume = {9}, number = {11}, pages = {e030659}, pmid = {31719078}, issn = {2044-6055}, support = {MR/M50161X/1/MRC_/Medical Research Council/United Kingdom ; MR/M501621/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; Aged ; Clinical Protocols ; Colitis, Ulcerative/*therapy ; Double-Blind Method ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Middle Aged ; Outcome Assessment, Health Care ; Pilot Projects ; Prospective Studies ; United Kingdom ; Young Adult ; }, abstract = {INTRODUCTION: Imbalance of the gut microbiome is key to the pathogenesis of ulcerative colitis (UC). Faecal microbiota transplant (FMT) is the transfer of homogenised and filtered faeces from a healthy individual to the gastrointestinal tract of a patient with disease. Published datasets show a positive signal for the use of FMT to treat UC, but the optimal route and dose of FMT remain unanswered.<br><br>METHODS AND ANALYSIS: This prospective, multi-centre open-label, randomised pilot study will assess two possible routes of FMT delivery, via the nasogastric (NG) route or by delivery to the COLON, in 30 patients with active UC recruited from three sites in the UK. Stool will be collected from healthy screened donors, processed, frozen and stored under a Medicines and Healthcare products Regulatory Agency (MHRA) &quot;specials&quot; manufacturing licence held at the University of Birmingham Microbiome Treatment Centre. Thawed FMT samples will be administered to patients either via eight nasogastric infusions given initially over 4 days starting on the day of randomisation, and then again for 4 days in week 4 for foregut delivery (total of 240 g of stool) or via one colonoscopic infusion followed by seven weekly enemas according to the hindgut protocol (total of 360 g of stool). Patients will be followed up weekly for 8 weeks, and then at 12 weeks. The aims of this pilot study are (1) to determine which FMT administration route (NG or COLON) should be investigated in a randomised double-blind, placebo-controlled trial and (2) to determine if a full randomised controlled trial is feasible. The primary outcome will be a composite assessment of both qualitative and quantitative data based on efficacy (clinical response), acceptability and safety. At the end of the pilot study, decisions will be made regarding the feasibility of a full randomised double-blind, placebo-controlled trial and, if deemed feasible, which route of administration should be used in such a study.<br><br>ETHICS AND DISSEMINATION: Ethical approval for this study has been obtained from the East Midlands-Nottingham Research Ethics Committee (REC 17/EM/0274). At the end of the study, findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals.<br><br>TRIAL REGISTRATION NUMBER: ISRCTN74072945.}, }
@article {pmid33151664, year = {2020}, author = {Shi, L and Zheng, J and Yan, S and Li, Y and Wang, Y and Liu, X and Xiao, C}, title = {Exposure to Perfluorooctanoic Acid Induces Cognitive Deficits via Altering Gut Microbiota Composition, Impairing Intestinal Barrier Integrity, and Causing Inflammation in Gut and Brain.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.0c05834}, pmid = {33151664}, issn = {1520-5118}, abstract = {Perfluorooctanoic acid (PFOA) is an eight-carbon perfluoroalkyl chemical and has been detected widely in many media. Although the toxic effect of PFOA has been confirmed, the influence on gut and brain has not been cleared. Male C57BL/6J mice were exposed to different concentrations (0, 0.5, 1, and 3 mg/Kg (bw)/day of PFOA for 35 days in this work. The results indicate that exposure to PFOA could damage intestinal barrier integrity and impair the synaptic structure. PFOA exposure also caused inflammation in gut and brain by increasing lipopolysaccharide, tumor necrosis factor-α, interleukin-1 beta, and cyclooxygenase-2 and decreasing interleukin-10. Interestingly, fecal microbiota transplantation treatment could attenuate a series of PFOA-induced changes to a certain extent. The results suggest that exposure to PFOA has potential deleterious effects on gut and brain, and inflammation may play an essential role in evaluating the influence induced by PFOA exposure.}, }
@article {pmid33151137, year = {2020}, author = {Keller, JJ and Ooijevaar, RE and Hvas, CL and Terveer, EM and Lieberknecht, SC and Högenauer, C and Arkkila, P and Sokol, H and Gridnyev, O and Mégraud, F and Kump, PK and Nakov, R and Goldenberg, SD and Satokari, R and Tkatch, S and Sanguinetti, M and Cammarota, G and Dorofeev, A and Gubska, O and Ianiro, G and Mattila, E and Arasaradnam, RP and Sarin, SK and Sood, A and Putignani, L and Alric, L and Baunwall, SM and Kupcinskas, J and Link, A and Goorhuis, AG and Verspaget, HW and Ponsioen, C and Hold, GL and Tilg, H and Kassam, Z and Kuijper, EJ and Gasbarrini, A and Mulder, CJ and Williams, HR and Vehreschild, MJ}, title = {A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group.}, journal = {United European gastroenterology journal}, volume = {}, number = {}, pages = {2050640620967898}, doi = {10.1177/2050640620967898}, pmid = {33151137}, issn = {2050-6414}, abstract = {BACKGROUND: Fecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of feces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council.<br><br>OBJECTIVE: Several European and international consensus statements concerning fecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document.<br><br>METHODS: Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about fecal microbiota transplantation.<br><br>RESULTS: A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening.<br><br>CONCLUSION: The implementation of fecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor feces preparations for patients.}, }
@article {pmid33130602, year = {2020}, author = {Nagy, GG and Tudlik, Z and Gergely, L and Kónya, J and Orosi, P and Rákóczi, É and Szabó, J and Várvölgyi, C and Vitális, E and Paragh, G}, title = {Reconsidering the technical aspects and quality management background of faecal microbiota transplantation due to the novel coronavirus pandemic.}, journal = {Orvosi hetilap}, volume = {161}, number = {44}, pages = {1858-1871}, doi = {10.1556/650.2020.32023}, pmid = {33130602}, issn = {1788-6120}, mesh = {Betacoronavirus ; Clostridium Infections/*therapy ; Clostridium difficile ; *Coronavirus ; Coronavirus Infections/epidemiology/*prevention &amp; control ; Fecal Microbiota Transplantation/methods/*standards ; Humans ; Hungary ; Pandemics ; Pneumonia, Viral/epidemiology/*prevention &amp; control ; Quality Improvement ; Treatment Outcome ; }, abstract = {Összefoglaló. A székletmikrobiota-transzplantáció (faecalismikrobiota-transzplantáció - FMT) a Clostridioides difficile fertőzés (CDI) kezelésében nemzetközileg széles körben elfogadott, megfelelő szakmai háttér mellett végezve biztonságos, potenciálisan életmentő, költséghatékony, valamint a hospitalizációs idő és az orvos-beteg találkozások jelentős redukálására képes eljárás. Az FMT elvégzésére egyes országokban magas szintű minőségirányítási háttérrel működő, célfeladatra szerveződött donor- és székletbankok rendezkedtek be. Máshol, így például hazánkban, az eljáráshoz az egyértelmű jogi szabályozási környezet, a standardizált technológiai háttér és a finanszírozás hiánya miatt nem egységes a hozzáférés. Régóta időszerű továbbá, hogy a heterogén, nemegyszer háztartási eszközökkel előkészített beavatkozások helyett a nemzetközi és legújabban már a hazai ajánlásokban is megfogalmazott, a betegbiztonságot legjobban garantáló elvárások mellett történjen a széklettranszplantáció. Az új koronavírus (SARS-CoV-2) okozta pandémia megjelenése erőteljes szakmai érv országos szinten az FMT minőségirányítási környezetének és technológiai hátterének újragondolására, mert a SARS-CoV-2 egyszerre jelent kockázatot a CDI miatt kórházban kezelt sérülékeny betegpopulációnak, és egyben veszélyezteti az FMT biztonságosságát mind a recipiens, mind pedig az eljárást végző egészségügyi személyzet tekintetében. Ezekre a szakmai és társadalmi kihívásokra reagálva, a széles körű beteghozzáférés és a legmagasabb szintű betegbiztonság garantálására, a Debreceni Egyetemen új eljárásrendet dolgoztunk ki az FMT végzésére. Ezen eljárásrendnek a COVID-19-pandémia miatt módosított, a fagyasztottgraftbank üzemeltetése és a rendszerszemlélet tekintetében releváns elemeit ismertetjük. Javasolt, hogy országos szinten hasonló, megfelelő minőségirányítási és technológiai környezettel, a SARS-CoV-2-fertőzés kizárását is integráló donorszűrési rendszerrel, továbbá fagyasztottgraft-banki háttérrel működő laboratóriumok vegyenek részt a széklettranszplantációk végzésében. Felmerül továbbá, hogy az eljárást a számos analógia és a donor-recipiens koncepció alapján a sejt- és szövettranszplantációkra vonatkozó szabályozórendszer keretei közé ajánlott beágyazni. Orv Hetil. 2020; 161(44): 1858-1871. Summary. Stool transplantation (faecal microbiota transplantation - FMT) is a widely accepted, potentially life-saving, cost-effective medical intervention for the treatment of Clostridioides difficile infection (CDI), which has an acceptable safety profile if performed with an appropriate professional background. FMT can significantly reduce hospitalization time and the number of patient visits. National donor and stool banks with high-standard quality management systems were established in certain countries for supporting the procedures. In other regions, including Hungary, patient access is not uniform due to the lack of clear legal regulations, standardized technology or financial reimbursement. It has been expected for a long time to replace the heterogenous techniques, occasionally utilizing household equipment with a technology providing improved patient safety and fulfilling international and recently published local FMT guidelines. The emergence of the novel coronavirus (SARS-CoV-2) pandemic is a very powerful argument in favour of urgently reconsidering the quality management and technological background of FMT procedures. SARS-CoV-2 is a major threat to the vulnerable patients suffering from CDI and also impose risks for the recipient and healthcare personnel involved in carrying out the transplantation. New FMT guidelines were implemented at the University of Debrecen to address these professional and public challenges, to provide wide patient access and to guarantee the highest achievable patient safety. Relevant elements of this new protocol are presented, focusing on a systemic quality management approach, on the operation of a frozen stool bank and on a modified donor screening algorithm taking the risks of COVID-19 into consideration. We suggest that laboratories with proper quality assurance and technological conditions, implementing SARS-CoV-2 donor screening and operating a frozen graft bank should participate in faecal microbiota transplantations. It is also recommended that, based on the analogies and the similar donor-recipient concept, FMT should be embedded under the organ tissue and cell transplantation polices in Hungary. Orv Hetil. 2020; 161(44): 1858-1871.}, }
@article {pmid31957588, year = {2019}, author = {Ossorio, PN and Zhou, Y}, title = {FMT and Microbial Medical Products: Generating High-Quality Evidence through Good Governance.}, journal = {The Journal of law, medicine &amp; ethics : a journal of the American Society of Law, Medicine &amp; Ethics}, volume = {47}, number = {4}, pages = {505-523}, doi = {10.1177/1073110519897727}, pmid = {31957588}, issn = {1748-720X}, mesh = {Biological Products/*therapeutic use ; *Clinical Trials as Topic ; *Data Accuracy ; Drug Approval/*legislation &amp; jurisprudence ; *Fecal Microbiota Transplantation ; Government Regulation ; Humans ; Policy ; United States ; United States Food and Drug Administration/legislation &amp; jurisprudence ; }, abstract = {This article argues that current data for the safety and efficacy of fecal microbiota transplants as a treatment for any indication, including recurrent Clostridioides difficile infection, is low-quality. It develops a governance proposal that encourages production of high-quality evidence by incentivizing well-designed RCTs of stool and stoolderived microbial products. The proposal would require that FDA change its current enforcement approach, but it would not require any change in statutes or regulations.}, }
@article {pmid31957585, year = {2019}, author = {Hoffmann, DE}, title = {Introduction: The Promise and Challenges of Microbiome-Based Therapies.}, journal = {The Journal of law, medicine &amp; ethics : a journal of the American Society of Law, Medicine &amp; Ethics}, volume = {47}, number = {4}, pages = {476-481}, doi = {10.1177/1073110519897725}, pmid = {31957585}, issn = {1748-720X}, mesh = {Clinical Trials as Topic ; *Dissent and Disputes ; Fecal Microbiota Transplantation/ethics/*trends ; Female ; *Government Regulation ; Humans ; Male ; Microbiota ; *Policy ; United States ; United States Food and Drug Administration/*legislation &amp; jurisprudence ; Vagina/microbiology ; }, }
@article {pmid33145316, year = {2020}, author = {Wang, D and Hao, H and Li, X and Wang, Z}, title = {The effect of intestinal flora on immune checkpoint inhibitors in tumor treatment: a narrative review.}, journal = {Annals of translational medicine}, volume = {8}, number = {17}, pages = {1097}, doi = {10.21037/atm-20-4535}, pmid = {33145316}, issn = {2305-5839}, abstract = {Tremendous progress has been achieved in understanding of the interaction between tumor microenvironment and intestinal flora in the past decades. Immune checkpoint inhibitors (ICIs) are a promising treatment strategy for advanced tumors, most prominently cytotoxic T-lymphocyte-associated protein (CTLA-4) and programmed cell death protein-1 (PD-1), its major ligand PD-L1, its beneficial to part of the population and obtaining excellent clinical results. However, the majority of patients do not respond or develop early progressive disease. Reached consensus by experts currently believe that the intestinal flora plays an important role in the explanation of the limited therapeutic effect of ICIs, there are differences in the composition of intestinal flora between patients with good response and patients with poor response, cloned mice by fecal microbiota transplantation (FMT) proved that the mice with transplanted feces from patients with good response can reduce tumor volume and obtain a better progress free survival (PFS). Therefore, &quot;beneficial bacteria&quot; seem to be enriched in the intestinal flora of patients who are well-responsive to ICIs and can be potentially used as a marker and cancer immunotherapeutic adjuvant of ICIs. In this review, we aim to summarize some of the studies demonstrating intestinal flora on tumor immunotherapy through anti-PD1, anti-PD-L1, anti-CTLA-4 and discuss possible mechanisms of this effect.}, }
@article {pmid33139601, year = {2020}, author = {Gesualdo, M and Rizzi, F and Bonetto, S and Rizza, S and Cravero, F and Saracco, GM and De Angelis, CG}, title = {Pancreatic Diseases and Microbiota: A Literature Review and Future Perspectives.}, journal = {Journal of clinical medicine}, volume = {9}, number = {11}, pages = {}, doi = {10.3390/jcm9113535}, pmid = {33139601}, issn = {2077-0383}, abstract = {Gut microbiota represent an interesting worldwide research area. Several studies confirm that microbiota has a key role in human diseases, both intestinal (such as inflammatory bowel disease, celiac disease, intestinal infectious diseases, irritable bowel syndrome) and extra intestinal disorders (such as autism, multiple sclerosis, rheumatologic diseases). Nowadays, it is possible to manipulate microbiota by administering prebiotics, probiotics or synbiotics, through fecal microbiota transplantation in selected cases. In this scenario, pancreatic disorders might be influenced by gut microbiota and this relationship could be an innovative and inspiring field of research. However, data are still scarce and controversial. Microbiota manipulation could represent an important therapeutic strategy in the pancreatic diseases, in addition to standard therapies. In this review, we analyze current knowledge about correlation between gut microbiota and pancreatic diseases, by discussing on the one hand existing data and on the other hand future possible perspectives.}, }
@article {pmid32047093, year = {2020}, author = {Haifer, C and Kelly, CR and Paramsothy, S and Andresen, D and Papanicolas, LE and McKew, GL and Borody, TJ and Kamm, M and Costello, SP and Andrews, JM and Begun, J and Chan, HT and Connor, S and Ghaly, S and Johnson, PD and Lemberg, DA and Paramsothy, R and Redmond, A and Sheorey, H and van der Poorten, D and Leong, RW}, title = {Australian consensus statements for the regulation, production and use of faecal microbiota transplantation in clinical practice.}, journal = {Gut}, volume = {69}, number = {5}, pages = {801-810}, doi = {10.1136/gutjnl-2019-320260}, pmid = {32047093}, issn = {1468-3288}, mesh = {Australia ; Clostridium Infections/*therapy ; Consensus ; Donor Selection ; Fecal Microbiota Transplantation/*methods ; Female ; Health Facilities/statistics &amp; numerical data ; Humans ; Male ; *Practice Guidelines as Topic ; Treatment Outcome ; }, abstract = {OBJECTIVE: Faecal microbiota transplantation (FMT) has proved to be an extremely effective treatment for recurrent Clostridioides difficile infection, and there is interest in its potential application in other gastrointestinal and systemic diseases. However, the recent death and episode of septicaemia following FMT highlights the need for further appraisal and guidelines on donor evaluation, production standards, treatment facilities and acceptable clinical indications.<br><br>DESIGN: For these consensus statements, a 24-member multidisciplinary working group voted online and then convened in-person, using a modified Delphi approach to formulate and refine a series of recommendations based on best evidence and expert opinion. Invitations to participate were directed to Australian experts, with an international delegate assisting the development. The following issues regarding the use of FMT in clinical practice were addressed: donor selection and screening, clinical indications, requirements of FMT centres and future directions. Evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.<br><br>RESULTS: Consensus was reached on 27 statements to provide guidance on best practice in FMT. These include: (1) minimum standards for donor screening with recommended clinical selection criteria, blood and stool testing; (2) accepted routes of administration; (3) clinical indications; (4) minimum standards for FMT production and requirements for treatment facilities acknowledging distinction between single-site centres (eg, hospital-based) and stool banks; and (5) recommendations on future research and product development.<br><br>CONCLUSIONS: These FMT consensus statements provide comprehensive recommendations around the production and use of FMT in clinical practice with relevance to clinicians, researchers and policy makers.}, }
@article {pmid31852769, year = {2020}, author = {El-Salhy, M and Hatlebakk, JG and Gilja, OH and Bråthen Kristoffersen, A and Hausken, T}, title = {Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study.}, journal = {Gut}, volume = {69}, number = {5}, pages = {859-867}, pmid = {31852769}, issn = {1468-3288}, mesh = {Adult ; Donor Selection ; Double-Blind Method ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Irritable Bowel Syndrome/microbiology/physiopathology/*therapy ; Male ; Middle Aged ; Patient Satisfaction/*statistics &amp; numerical data ; Prognosis ; Recovery of Function ; Reference Values ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {OBJECTIVE: Faecal microbiota transplantation (FMT) from healthy donors to patients with irritable bowel syndrome (IBS) has been attempted in two previous double-blind, placebo-controlled studies. While one of those studies found improvement of the IBS symptoms, the other found no effect. The present study was conducted to clarify these contradictory findings.<br><br>DESIGN: This randomised, double-blind, placebo-controlled study randomised 165 patients with IBS to placebo (own faeces), 30 g FMT or 60 g FMT at a ratio of 1:1:1. The material for FMT was obtained from one healthy, well-characterised donor, frozen and administered via gastroscope. The primary outcome was a reduction in the IBS symptoms at 3 months after FMT (response). A response was defined as a decrease of 50 or more points in the total IBS symptom score. The secondary outcome was a reduction in the dysbiosis index (DI) and a change in the intestinal bacterial profile, analysed by 16S rRNA gene sequencing, at 1 month following FMT.<br><br>RESULTS: Responses occurred in 23.6%, 76.9% (p<0.0001) and 89.1% (p<00.0001) of the patients who received placebo, 30 g FMT and 60 g FMT, respectively. These were accompanied by significant improvements in fatigue and the quality of life in patients who received FMT. The intestinal bacterial profiles changed also significantly in the groups received FMT. The FMT adverse events were mild self-limiting gastrointestinal symptoms.<br><br>CONCLUSIONS: FMT is an effective treatment for patients with IBS. Utilising a well-defined donor with a normal DI and favourable specific microbial signature is essential for successful FMT. The response to FMT increases with the dose. Trial registration www.clinicaltrials.gov (NCT03822299) and www.cristin.no (ID657402).}, }
@article {pmid31767915, year = {2019}, author = {Nadatani, Y and Watanabe, T and Suda, W and Nakata, A and Matsumoto, Y and Kosaka, S and Higashimori, A and Otani, K and Hosomi, S and Tanaka, F and Nagami, Y and Kamata, N and Taira, K and Yamagami, H and Tanigawa, T and Hattori, M and Fujiwara, Y}, title = {Gastric acid inhibitor aggravates indomethacin-induced small intestinal injury via reducing Lactobacillus johnsonii.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {17490}, pmid = {31767915}, issn = {2045-2322}, mesh = {Animals ; Disease Models, Animal ; Dysbiosis/*chemically induced/microbiology ; Fecal Microbiota Transplantation ; High-Throughput Nucleotide Sequencing ; Humans ; Indomethacin/administration &amp; dosage/*adverse effects ; Injections, Intraperitoneal ; Intestine, Small/drug effects/*injuries/microbiology ; Lactobacillus johnsonii/drug effects/*isolation &amp; purification/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Proton Pump Inhibitors/administration &amp; dosage/*adverse effects ; Pyrroles/administration &amp; dosage/adverse effects ; RNA, Ribosomal, 16S/genetics ; Rabeprazole/administration &amp; dosage/adverse effects ; Sequence Analysis, DNA ; Sulfonamides/administration &amp; dosage/adverse effects ; }, abstract = {Proton pump inhibitors (PPIs) alter the composition of the intestinal microbiome, exacerbating indomethacin (IND)-induced small intestinal damage. Vonoprazan fumarate inhibits gastric acid secretion using a different mechanism from PPIs. We investigated the effects of both drugs on the intestinal microbiome and IND-induced small intestinal damage. We sought to clarify whether PPI-induced dysbiosis and worsening of the damage were due to a specific drug class effect of PPIs. Rabeprazole administration increased operational taxonomic unit numbers in the small intestines of C57BL/6 J mice, whereas the difference was not significant in the vonoprazan-treated group but exhibited a trend. Permutational multivariate analysis of variance of the unweighted UniFrac distances showed significant differences between vehicle- and vonoprazan- or rabeprazole-treated groups. L. johnsonii was the predominant microbial species, and the population ratio decreased after vonoprazan and rabeprazole administration. The vonoprazan- and rabeprazole-treated groups showed increased IND-induced damage. This high sensitivity to IND-induced damage was evaluated by transplantation with contents from the small intestine of mice treated with either vonoprazan or rabeprazole. Supplementation of L. johnsonii orally in mice treated with rabeprazole and vonoprazan prevented the increase in IND-induced small intestinal damage. In conclusion, both rabeprazole and vonoprazan aggravated NSAID-induced small intestinal injury by reducing the population of L. johnsonii in the small intestine via suppressing gastric acid secretion.}, }
@article {pmid33136284, year = {2020}, author = {Gomaa, EZ}, title = {Human gut microbiota/microbiome in health and diseases: a review.}, journal = {Antonie van Leeuwenhoek}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10482-020-01474-7}, pmid = {33136284}, issn = {1572-9699}, abstract = {The human gut microbiota has received considerable interest in the recent years and our knowledge of the inhabitant species and their potential applications is increased particularly after the development of metagenomic studies. Gut microbiota is highly diverse and harboring trillions of microorganisms in human digestive system. The shaping and multiplication of gut microbiome starts at birth, while the modification of their composition depends mainly on various genetic, nutritional and environmental factors. The modification in the composition and function of the gut microbiota can change intestinal permeability, digestion and metabolism as well as immune responses. The pro inflammatory state caused by alternation of gut microbiota balance lead to the onset of many diseases ranging from gastrointestinal and metabolic conditions to immunological and neuropsychiatric diseases. In this context, the present review clarifies the role of gut microbiota in maintaining host health and investigates how nutritional and environmental factors affect the gut microbial structure and function. In addition, many therapeutic strategies of gut microbiota aimed at modulating and restoring of the intestinal ecosystem balance have been surveyed.}, }
@article {pmid33136261, year = {2020}, author = {Aira, A and Rubio, E and Vergara Gómez, A and Fehér, C and Casals-Pascual, C and González, B and Morata, L and Rico, V and Soriano, A}, title = {rUTI Resolution After FMT for Clostridioides difficile Infection: A Case Report.}, journal = {Infectious diseases and therapy}, volume = {}, number = {}, pages = {}, doi = {10.1007/s40121-020-00365-8}, pmid = {33136261}, issn = {2193-8229}, abstract = {Clostridioides difficile infection (CDI) is the leading cause of nosocomial infectious diarrhea. Fecal microbiota transplantation (FMT) is a successful treatment for recurrent CDI (rCDI), and in some patients FMT has been associated with the resolution of recurrent urinary tract infections (rUTI). Recent evidence suggests that the origin of most bacterial infections in the urinary tract is the gut. Thus, the possibility of using FMT to displace pathogens commonly involved in rUTIs has major therapeutic implications. We report the case of a 93-year-old female patient with a rCDI and rUTI that underwent FMT and reported a complete clinical resolution of CDI; unexpectedly, no new symptomatic UTI episodes were diagnosed post-FMT. We characterized the gut microbiota of the stool donor and of the patient before and after the procedure. Our patient presented a dysbiosis with clear predominance of Enterobacteriaceae (74%) before FMT, which was significantly reduced to 0.07% after FMT. These findings were maintained for almost a year. We also observed an increase in microbial diversity indices compared with the pre-FMT sample reaching diversity values comparable to the donor stool samples. We reasoned that the disappearance of UTIs in our patient resulted from the reduction of Enterobacteriaceae in the gut microbiota. Our findings support previous evidence suggesting the potential of FMT for rUTI, particularly in cases due to multi-drug resistant pathogens where conventional antibiotic treatment is not an option.}, }
@article {pmid33134739, year = {2020}, author = {Dong, LT and Espinoza, HV and Espinoza, JL}, title = {Emerging superbugs: The threat of Carbapenem Resistant Enterobacteriaceae.}, journal = {AIMS microbiology}, volume = {6}, number = {3}, pages = {176-182}, doi = {10.3934/microbiol.2020012}, pmid = {33134739}, issn = {2471-1888}, abstract = {Carbapenem-resistant Enterobacteriaceae (CRE) are gram-negative bacteria that are resistant to carbapenems, a group of antibiotics considered as the last-resource for the treatment of infections caused by multidrug-resistant bacteria. CRE constitutes a major threat to health care systems because infections caused by these pathogens are difficult to treat and are commonly associated with high mortality due to the limited availability of effective antibiotics. While infection prevention and timely detection are of vital importance to control CRE infections, developing new and effective anti-CRE therapies is also crucial. Accumulating evidence indicates that gut microbiota alteration (dysbiosis) is associated with an increased intestinal colonization with CRE and consequently with higher risk of developing CRE infections. Importantly, therapeutic interventions aimed to modify the gut microbiota composition via fecal microbiota transplantation (FMT) have been explored in various clinical settings with some of them showing promising results, although larger clinical trials are needed to confirm the efficacy of this strategy. Here, we highlight the challenges associated with the emergence of CRE infections.}, }
@article {pmid33133183, year = {2020}, author = {Ye, ZN and Xia, HH and Zhang, R and Li, L and Wu, LH and Liu, XJ and Xie, WR and He, XX}, title = {The Efficacy of Washed Microbiota Transplantation on Helicobacter pylori Eradication: A Pilot Study.}, journal = {Gastroenterology research and practice}, volume = {2020}, number = {}, pages = {8825189}, doi = {10.1155/2020/8825189}, pmid = {33133183}, issn = {1687-6121}, abstract = {Aim: The fecal microbiota transplantation by washed preparation was recently coined as washed microbiota transplantation (WMT). This pilot study is aimed at exploring the feasibility and efficacy of WMT on Helicobacter pylori eradication.<br><br>Methods: Consecutive patients who had been treated with WMT for various indications and who were positive for H. pylori infection before WMT treatment but had never received eradication therapy for H. pylori infection were invited to take a follow-up 13C-urea breath test. The associations of demographic, clinical factors, and laboratory indicators for gastric function and intestinal barrier function with the therapeutic effect were determined.<br><br>Results: A total of 32 eligible patients were included, and the overall H. pylori eradication rate was 40.6% (13/32). Patients with H. pylori eradication had a higher pepsinogen ratio (PGR) than those without (13.00 ± 6.97vs.8.31 ± 3.733; P = 0.02). Female patients had a higher, albeit not statistically significant, eradication rate than male patients (53.85% vs. 31.58%; P = 0.208). Compared with lower gastrointestinal tract delivery route, middle gastrointestinal tract delivery route seems to be a more suitable way for the treatment of H. pylori infection (58.33% vs 16.67%; P = 0.152). There was no significant difference in other demographic and clinical factors between patients with and without H. pylori eradication.<br><br>Conclusion: H. pylori infection is eradicated in a proportion of patients who have received WMT. An increased pre-WMT PGR appears to be associated with the therapeutic effect. Further studies are required to confirm the efficacy of WMT, especially in combination with currently recommended regimens in randomized controlled trials.}, }
@article {pmid33132658, year = {2020}, author = {Wen, Q and Liu, KJ and Cui, BT and Li, P and Wu, X and Zhong, M and Wei, L and Tu, H and Yuan, Y and Lin, D and Hsu, WH and Wu, DC and Yin, H and Zhang, FM}, title = {Impact of cap-assisted colonoscopy during transendoscopic enteral tubing: A randomized controlled trial.}, journal = {World journal of gastroenterology}, volume = {26}, number = {39}, pages = {6098-6110}, doi = {10.3748/wjg.v26.i39.6098}, pmid = {33132658}, issn = {2219-2840}, abstract = {BACKGROUND: Colonic transendoscopic enteral tubing (TET) requires double cecal intubation, raising a common concern of how to save cecal intubation time and make the tube stable. We hypothesized that cap-assisted colonoscopy (CC) might reduce the second cecal intubation time and bring potential benefits during the TET procedure.<br><br>AIM: To investigate if CC can decrease the second cecal intubation time compared with regular colonoscopy (RC).<br><br>METHODS: This prospective multicenter, randomized controlled trial was performed at four centers. Subjects ≥ 7 years needing colonic TET were recruited from August 2018 to January 2020. All subjects were randomly assigned to two groups. The primary outcome was the second cecal intubation time. Secondary outcomes included success rate, insertion pain score, single clip fixation time, purpose and retention time of TET tube, length of TET tube inserted into the colon, and all procedure-related (serious) adverse events.<br><br>RESULTS: A total of 331 subjects were randomized to the RC (n = 165) or CC (n = 166) group. The median time of the second cecal intubation was significantly shorter for CC than RC (2.2 min vs 2.8 min, P < 0.001). In patients with constipation, the median time of second cecal intubation in the CC group (n = 50) was shorter than that in the RC group (n = 43) (2.6 min vs 3.8 min, P = 0.004). However, no difference was observed in the CC (n = 42) and RC (n = 46) groups of ulcerative colitis patients (2.0 min vs 2.5 min, P = 0.152). The insertion pain score during the procedure in CC (n = 14) was lower than that in RC (n = 19) in unsedated colonoscopy (3.8 ± 1.7 vs 5.4 ± 1.9; P = 0.015). Multivariate analysis revealed that only CC (odds ratio [OR]: 2.250, 95% confidence interval [CI]: 1.161-4.360; P = 0.016) was an independent factor affecting the second cecal intubation time in difficult colonoscopy. CC did not affect the colonic TET tube's retention time and length of the tube inserted into the colon. Moreover, multivariate analysis found that only endoscopic clip number (OR: 2.201, 95%CI: 1.541-3.143; P < 0.001) was an independent factor affecting the retention time. Multiple regression analysis showed that height (OR: 1.144, 95%CI: 1.027-1.275; P = 0.014) was the only independent factor influencing the length of TET tube inserted into the colon in adults.<br><br>CONCLUSION: CC for colonic TET procedure is a safe and less painful technique, which can reduce cecal intubation time.}, }
@article {pmid33131919, year = {2020}, author = {Chaitman, J and Gaschen, F}, title = {Fecal Microbiota Transplantation in Dogs.}, journal = {The Veterinary clinics of North America. Small animal practice}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cvsm.2020.09.012}, pmid = {33131919}, issn = {1878-1306}, abstract = {In people, fecal microbiota transplantation is recognized as the best treatment modality for recurrent Clostridioides difficile infection in people, and its value is currently investigated in the treatment of other diseases associated with an abnormal gut microbiome. In dogs, intestinal dysbiosis has been documented in many acute and chronic digestive diseases as well as in diseases of other organ systems. There are only few published studies evaluating the benefits of fecal microbiota transplantation (FMT) in canine gastrointestinal disorders. They provide evidence that FMT may be beneficial in the treatment of acute intestinal diseases and hope that the technique might also be useful for the management of chronic enteropathies.}, }
@article {pmid33131263, year = {2020}, author = {Pietro Merli,  and Lorenza Putignani,  and Annalisa Ruggeri,  and Federica Del Chierico,  and Livia Gargiullo,  and Federica Galaverna,  and Stefania Gaspari,  and Daria Pagliara,  and Alessandra Russo,  and Stefania Pane,  and Luisa Strocchio,  and Mattia Algeri,  and Francesca Rea,  and Erminia Francesca Romeo,  and Paola Bernaschi,  and Andrea Onetti Muda,  and Bruno Dallapiccola,  and Franco Locatelli, }, title = {Decolonization of multi-drug resistant bacteria by fecal microbiota transplantation in five pediatric patients before allogeneic hematopoietic stem cell transplantation: gut microbiota profiling, infectious and clinical outcomes.}, journal = {Haematologica}, volume = {105}, number = {11}, pages = {2686-2690}, doi = {10.3324/haematol.2019.244210}, pmid = {33131263}, issn = {1592-8721}, }
@article {pmid32852834, year = {2020}, author = {Ianiro, G and Porcari, S and Ford, AC and Gasbarrini, A and Cammarota, G}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome-room for improvement.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {52}, number = {5}, pages = {923-924}, doi = {10.1111/apt.15923}, pmid = {32852834}, issn = {1365-2036}, mesh = {Colonoscopy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; }, }
@article {pmid32852821, year = {2020}, author = {Lahtinen, P and Jalanka, J and Hartikainen, A and Mattila, E and Hillilä, M and Punkkinen, J and Koskenpato, J and Anttila, VJ and Tillonen, J and Satokari, R and Arkkila, P}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome-room for improvement. Authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {52}, number = {5}, pages = {925-926}, doi = {10.1111/apt.15942}, pmid = {32852821}, issn = {1365-2036}, mesh = {Colonoscopy ; Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome/therapy ; }, }
@article {pmid32232453, year = {2020}, author = {Ransom, EM and Burnham, CD and Jones, L and Kraft, CS and McDonald, LC and Reinink, AR and Young, VB}, title = {Fecal Microbiota Transplantations: Where Are We, Where Are We Going, and What Is the Role of the Clinical Laboratory?.}, journal = {Clinical chemistry}, volume = {66}, number = {4}, pages = {512-517}, doi = {10.1093/clinchem/hvaa021}, pmid = {32232453}, issn = {1530-8561}, support = {U01 AI124255/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Clinical Laboratory Techniques/economics ; Clostridium Infections/microbiology/*therapy ; Donor Selection ; Expert Testimony ; Fecal Microbiota Transplantation/*adverse effects/economics/*methods ; Humans ; Transplantation, Homologous ; }, }
@article {pmid33123253, year = {2020}, author = {Wang, J and Yang, HR and Wang, DJ and Wang, XX}, title = {Association between the gut microbiota and patient responses to cancer immune checkpoint inhibitors.}, journal = {Oncology letters}, volume = {20}, number = {6}, pages = {342}, pmid = {33123253}, issn = {1792-1074}, abstract = {Studies are increasingly investigating the association between the gut microbiota and the outcomes of immunotherapy in patients with cancer. Notably, certain studies have demonstrated that the gut microbiota serves a key role in regulating a patient's response to immunotherapy. In the present review, the potential associations between the gut microbiota, and cancer, host immunity and cancer immunotherapy are reviewed. Furthermore, the effects of fecal microbiota transplantation, antibiotics, probiotics, prebiotics, synbiotics, components of traditional Chinese medicine and various lifestyle factors on the gut microbiota and cancer immunotherapy outcomes are discussed. Certain dominant bacterial groups in the context of cancer immunotherapy and certain effective methods for optimizing immunotherapy by regulating the gut microbiota have been identified. Further investigation may enable the rapid conversion of these discoveries into practical products and clinically applicable methods.}, }
@article {pmid33122357, year = {2020}, author = {Guo, H and Chou, WC and Lai, Y and Liang, K and Tam, JW and Brickey, WJ and Chen, L and Montgomery, ND and Li, X and Bohannon, LM and Sung, AD and Chao, NJ and Peled, JU and Gomes, ALC and van den Brink, MRM and French, MJ and Macintyre, AN and Sempowski, GD and Tan, X and Sartor, RB and Lu, K and Ting, JPY}, title = {Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites.}, journal = {Science (New York, N.Y.)}, volume = {370}, number = {6516}, pages = {}, doi = {10.1126/science.aay9097}, pmid = {33122357}, issn = {1095-9203}, abstract = {Ionizing radiation causes acute radiation syndrome, which leads to hematopoietic, gastrointestinal, and cerebrovascular injuries. We investigated a population of mice that recovered from high-dose radiation to live normal life spans. These &quot;elite-survivors&quot; harbored distinct gut microbiota that developed after radiation and protected against radiation-induced damage and death in both germ-free and conventionally housed recipients. Elevated abundances of members of the bacterial taxa Lachnospiraceae and Enterococcaceae were associated with postradiation restoration of hematopoiesis and gastrointestinal repair. These bacteria were also found to be more abundant in leukemia patients undergoing radiotherapy, who also displayed milder gastrointestinal dysfunction. In our study in mice, metabolomics revealed increased fecal concentrations of microbially derived propionate and tryptophan metabolites in elite-survivors. The administration of these metabolites caused long-term radioprotection, mitigation of hematopoietic and gastrointestinal syndromes, and a reduction in proinflammatory responses.}, }
@article {pmid33121693, year = {2020}, author = {Cheng, YW and Fischer, M}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis. Are We Ready for Primetime?.}, journal = {Gastroenterology clinics of North America}, volume = {49}, number = {4}, pages = {739-752}, doi = {10.1016/j.gtc.2020.08.006}, pmid = {33121693}, issn = {1558-1942}, abstract = {&quot;Patients with inflammatory bowel disease, including ulcerative colitis (UC) and Crohn disease, have altered gut microbiomes. The success of fecal microbiota transplantation (FMT) in the treatment of Clostridioides difficile infection, a disease that is also marked by dysbiosis, has spurred research in applying FMT to UC. So far, 3 randomized controlled trials have demonstrated benefit in mild to moderate UC disease course after FMT. However, important questions regarding optimal stool preparation, route, and frequency of administration, as well as characteristics of the stool donor and recipient still remain.&quot;}, }
@article {pmid30944372, year = {2019}, author = {Larsen, OFA and Koning, AHJ and van der Spek, PJ and Claassen, E}, title = {Towards a rational design of faecal transplant analogues.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {5558}, doi = {10.1038/s41598-019-42043-x}, pmid = {30944372}, issn = {2045-2322}, mesh = {Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Microbial Consortia ; Models, Biological ; }, abstract = {Faecal transplants (microbiota transfer) have shown to be promising therapies having a wide range of therapeutic applications. However, current safety considerations hamper further valorisation. As such, well designed faecal transplant analogues provide an interesting alternative to minimize possible safety aspects. However, to date little knowledge on how to rationally design such analogues exists. Here, we show by applying first order basic graph theory that such analogues dedicated to restoring a specific physiological functionality (a microbial guild) should consist of 5-6 species to maximize stability, efficiency, and minimize safety issues and production costs.}, }
@article {pmid33118360, year = {2020}, author = {Silva, JC and Ponte, A and Mota, M and Pinho, R and Vieira, N and Oliveira, R and Mota-Carvalho, N and Gomes, AC and Afecto, E and Carvalho, J}, title = {Fecal microbiota transplantation in the intestinal decolonization of carbapenamase-producing enterobacteriaceae.}, journal = {Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva}, volume = {112}, number = {}, pages = {}, doi = {10.17235/reed.2020.7150/2020}, pmid = {33118360}, issn = {1130-0108}, abstract = {BACKGROUND AND AIMS: fecal microbiota transplantation (FMT) is effective for recurrent Clostridium difficile infection (CDI). Intestinal decolonization of carbapenamase-producing enterobacteriaceae (CPE) can prevent transmission and infection by these agents. The aim of this study was to assess CPE decolonization after FMT.<br><br>METHODS: this was a case-series study that consecutively included all CPE-carriers that underwent FMT between 2014 and 2019. The indications included refractory/recurrent CDI and CPE-decolonization.<br><br>RESULTS: out of 21 CPE-carriers, eight were excluded due to incomplete post-FMT testing. CPE decolonization was confirmed in 76.9 % (n = 10). The median decolonization time was 16-weeks (IQR-23) and ranged from two to 53 weeks.<br><br>CONCLUSION: FMT may be used in the clinical practice for CPE-decolonization as an alternative to combined antibiotic regimens.}, }
@article {pmid33117731, year = {2020}, author = {Li, Q and Jin, M and Liu, Y and Jin, L}, title = {Gut Microbiota: Its Potential Roles in Pancreatic Cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {572492}, doi = {10.3389/fcimb.2020.572492}, pmid = {33117731}, issn = {2235-2988}, abstract = {Pancreatic cancer is considered a lethal disease with a low survival rate due to its late-stage diagnosis, few opportunities for resection and lack of effective therapeutic strategies. Multiple, highly complex effects of gut microbiota on pancreatic cancer have been recognized as potential strategies for targeting tumorigenesis, development and treatment in recent decades; some of the treatments include antibiotics, probiotics, and fecal microbiota transplantation. Several bacterial species are associated with carcinogenesis of the pancreas, while some bacterial metabolites contribute to tumor-associated low-grade inflammation and immune responses via several proinflammatory factors and signaling pathways. Given the limited evidence on the interplay between gut microbiota and pancreatic cancer, risk factors associated with pancreatic cancer, such as diabetes, chronic pancreatitis and obesity, should also be taken into consideration. In terms of treatment of pancreatic cancer, gut microbiota has exhibited multiple effects on both traditional chemotherapy and the recently successful immunotherapy. Therefore, in this review, we summarize the latest developments and advancements in gut microbiota in relation to pancreatic cancer to elucidate its potential value.}, }
@article {pmid33117316, year = {2020}, author = {Dai, X and Hou, H and Zhang, W and Liu, T and Li, Y and Wang, S and Wang, B and Cao, H}, title = {Microbial Metabolites: Critical Regulators in NAFLD.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {567654}, doi = {10.3389/fmicb.2020.567654}, pmid = {33117316}, issn = {1664-302X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease throughout the world. The relationship between gut microbiota and NAFLD has been extensively investigated. The gut microbiota is involved in the regulation of NAFLD by participating in the fermentation of indigestible food, interacting with the intestinal mucosal immune system, and influencing the intestinal barrier function, leading to signaling alteration. Meanwhile, the microbial metabolites not only affect the signal transduction pathway in the gut but also reach the liver far away from gut. In this review, we focus on the effects of certain key microbial metabolites such as short-chain fatty acids, trimethylamine-N-oxide, bile acids, and endogenous ethanol and indole in NAFLD, and also summarize several potential therapies targeting the gut-liver axis and modulation of gut microbiota metabolites including antibiotics, prebiotics, probiotics, bile acid regulation, and fecal microbiota transplantation. Understanding the complex interactions between microbial metabolites and NAFLD may provide crucial insight into the pathogenesis and treatment of NAFLD.}, }
@article {pmid33116952, year = {2020}, author = {Kullar, R and Tran, MN and Goldstein, EJC}, title = {Investigational Treatment Agents for Recurrent Clostridioides difficile Infection (rCDI).}, journal = {Journal of experimental pharmacology}, volume = {12}, number = {}, pages = {371-384}, doi = {10.2147/JEP.S242959}, pmid = {33116952}, issn = {1179-1454}, abstract = {Clostridioides difficile infection (CDI) is a major cause of nosocomial diarrhea that is deemed a global health threat. C. difficile strain BI/NAP1/027 has contributed to the increase in the mortality, severity of CDI outbreaks and recurrence rates (rCDI). Updated CDI treatment guidelines suggest vancomycin and fidaxomicin as initial first-line therapies that have initial clinical cure rates of over 80%. Unacceptably high recurrence rates of 15-30% in patients for the first episode and 40% for the second recurrent episode are reported. Alternative treatments for rCDI include fecal microbiota transplant and a human monoclonal antibody, bezlotoxumab, that can be used in patients with high risk of rCDI. Various emerging potential therapies with narrow spectrum of activity and little systemic absorption that are in development include 1) Ibezapolstat (formerly ACX-362E), MGB-BP-3, and DS-2969b-targeting bacterial DNA replication, 2) CRS3213 (REP3123)-inhibiting toxin production and spore formation, 3) ramizol and ramoplanin-affecting bacterial cell wall, 4) LFF-571-blocking protein synthesis, 5) Alanyl-L-Glutamine (alanylglutamine)-inhibiting damage caused by C. difficile by protecting intestinal mucosa, and 6) DNV3837 (MCB3681)-prodrug consisting of an oxazolidinone-quinolone combination that converts to the active form DNV3681 that has activity in vitro against C. difficile. This review article provides an overview of these developing drugs that can have potential role in the treatment of rCDI and in lowering recurrence rates.}, }
@article {pmid33116044, year = {2020}, author = {Han, Y and Wu, L and Ling, Q and Wu, P and Zhang, C and Jia, L and Weng, H and Wang, B}, title = {Intestinal Dysbiosis Correlates With Sirolimus-Induced Metabolic Disorders in Mice.}, journal = {Transplantation}, volume = {}, number = {}, pages = {}, doi = {10.1097/TP.0000000000003494}, pmid = {33116044}, issn = {1534-6080}, abstract = {BACKGROUND: Long-time use of pharmacological immunosuppressive agents frequently leads to metabolic disorders. Most studies have focused on islet toxicity leading to post-transplantation diabetes mellitus. In contrast, the link between intestinal dysbiosis and immunosuppressive drug-induced metabolic disorders remains unclear.<br><br>METHODS: We established a mouse model of metabolic abnormality via sirolimus treatment. Fecal microbiota was examined using 16S rRNA gene MiSeq sequencing. Intestinal barrier function was assessed using fluorescein isothiocyanate-dextran assay and mucus immunostaining. Systemic inflammation was determined using a multiplexed fluorescent bead-based immunoassay.<br><br>RESULTS: Sirolimus induced dyslipidemia and glucose intolerance in mice in a dose-dependent manner. Interestingly, the clinical-mimicking dose of sirolimus altered the intestinal microbiota community, which was characterized by the enrichment of Proteobacteria, depletion of Akkermansia, and potential function shifts to those involved in lipid metabolism and the immune system. In addition, the clinical-mimicking dose of sirolimus reduced the thickness of the intestinal mucosal layer, increased the intestinal permeability, and enriched the circulating pro-inflammatory factors, including IL-12, IL-6, MCP-1, GM-CSF, and IL-1β. Our results showed a close association between intestinal dysbiosis, intestinal barrier failure, systemic inflammation, and metabolic disorders. Furthermore, we demonstrated that oral intervention in the gut microbiota by Lactobacillus rhamnosus HN001 protected against intestinal dysbiosis, especially by depleting the LPS-producing Proteobacteria, and attenuated the sirolimus-induced systemic inflammation, dyslipidemia, and insulin resistance.<br><br>CONCLUSION: Our study demonstrated a potentially causative role of intestinal dysbiosis in sirolimus-induced metabolic disorders, which will provide a novel therapeutic target for transplant recipients.}, }
@article {pmid33094595, year = {2020}, author = {Poortmans, P and Kindt, S}, title = {Diagnostic approach to chronic diarrhoea and recent insights in treatment of functional diarrhoea including irritable bowel syndrome.}, journal = {Acta gastro-enterologica Belgica}, volume = {83}, number = {3}, pages = {461-474}, pmid = {33094595}, issn = {1784-3227}, mesh = {Bile Acids and Salts ; *Diarrhea/diagnosis/etiology/therapy ; Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome/diagnosis/therapy ; Parasympatholytics ; }, abstract = {Chronic diarrhoea is a common clinical problem with a plethora of possible causes and underlying pathophysiological mechanisms. The value of diagnostic assessment by laboratory testing, stool analysis, evaluation of bile acid malabsorption, endoscopy, breath testing and radiological imaging techniques is discussed. The decision to focus investigations on excluding certain pathologies remains a matter of clinical judgement. Functional diarrhoea and irritable bowel syndrome (IBS) being the most frequent causes of chronic diarrhoea, recent insights in the role of dietary management, management of dysbiosis by pre-, proand antibiotics and faecal microbiota transplantation, as well as targeted treatment by spasmolytics, 5-HT3 receptor antagonists and eluxadoline will be reviewed.}, }
@article {pmid33111793, year = {2020}, author = {Luz, MRMPD and Waizbort, RF}, title = {[Fecal microbiota transplants in the treatment of pseudomembranous colitis (1958-2013): priority of discovery and thought styles in the academic literature].}, journal = {Historia, ciencias, saude--Manguinhos}, volume = {27}, number = {3}, pages = {859-878}, doi = {10.1590/S0104-59702020000400009}, pmid = {33111793}, issn = {1678-4758}, abstract = {In 1958, Eiseman and contributors published the first scientific paper reporting the use of fecal microbiota transplant for treating pseudomembranous colitis. The relevance of this innovative paper was only acknowledged in 1990. The academic literature on the theme is characterized by a narrative that has undergone successive revisions. We suggest that such revisions were based on claims of priority of scientific discoveries, as described by Merton. The revival of fecal microbiota transplants is interpreted as a process of genesis of a scientific fact, as defined by Fleck: there is a switch from a thought style based on the use of antibiotics to treat infectious diseases to another that accepts the ecological relations between hosts, vectors and parasites.}, }
@article {pmid33110112, year = {2020}, author = {Kazemian, N and Ramezankhani, M and Sehgal, A and Khalid, FM and Kalkhoran, AHZ and Narayan, A and Wong, GK and Kao, D and Pakpour, S}, title = {The trans-kingdom battle between donor and recipient gut microbiome influences fecal microbiota transplantation outcome.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {18349}, doi = {10.1038/s41598-020-75162-x}, pmid = {33110112}, issn = {2045-2322}, abstract = {Fundamental restoration ecology and community ecology theories can help us better understand the underlying mechanisms of fecal microbiota transplantation (FMT) and to better design future microbial therapeutics for recurrent Clostridioides difficile infections (rCDI) and other dysbiosis-related conditions. In this study, stool samples were collected from donors and rCDI patients one week prior to FMT (pre-FMT), as well as from patients one week following FMT (post-FMT). Using metagenomic sequencing and machine learning, our results suggested that FMT outcome is not only dependent on the ecological structure of the recipients, but also the interactions between the donor and recipient microbiomes at the taxonomical and functional levels. We observed that the presence of specific bacteria in donors (Clostridioides spp., Desulfovibrio spp., Odoribacter spp. and Oscillibacter spp.) and the absence of fungi (Yarrowia spp.) and bacteria (Wigglesworthia spp.) in recipients prior to FMT could predict FMT success. Our results also suggested a series of interlocked mechanisms for FMT success, including the repair of the disturbed gut ecosystem by transient colonization of nexus species followed by secondary succession of bile acid metabolizers, sporulators, and short chain fatty acid producers.}, }
@article {pmid31784432, year = {2019}, author = {Pai, N and Popov, J and Hill, L and Hartung, E}, title = {Protocol for a double-blind, randomised, placebo-controlled pilot study for assessing the feasibility and efficacy of faecal microbiota transplant in a paediatric Crohn's disease population: PediCRaFT Trial.}, journal = {BMJ open}, volume = {9}, number = {11}, pages = {e030120}, pmid = {31784432}, issn = {2044-6055}, mesh = {Administration, Oral ; Adolescent ; Child ; Child, Preschool ; Colonoscopy/methods ; Crohn Disease/microbiology/*therapy ; Double-Blind Method ; Feasibility Studies ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Pilot Projects ; Research Design ; Treatment Outcome ; }, abstract = {INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory condition with transmural involvement of the gastrointestinal tract. Extraintestinal manifestations are common, and the disease burden on patients and the healthcare system is significant. While treatment options have expanded in recent years, they have mainly focused on dampening the immune response, thus carrying notable risks associated with long-term immunosuppression. Faecal microbiota transplant (FMT) targets inflammatory bowel disease (IBD) by modifying intestinal dysbiosis. Limited adult and paediatric data have demonstrated a favourable response to FMT in IBD; however, no randomised controlled trial has yet been published in paediatrics. This double-blind, randomised, placebo-controlled pilot study will assess feasibility and efficacy outcomes of FMT in a paediatric CD population.<br><br>METHODS AND ANALYSIS: Forty-five patients between the ages of 3 and 17 years, with established CD or IBD unclassified, will be enrolled 2:1 to undergo FMT intervention or placebo control. Participants will undergo a colonoscopic infusion to the terminal ileum at baseline, followed by oral capsules two times per week for 6 weeks. Outcomes will be measured throughout the intervention period and 18 weeks of subsequent follow-up. Primary outcomes will assess feasibility, including patient recruitment, sample collection and rates of adverse events. Secondary outcomes will address clinical efficacy, including change in clinical response, change in urine metabolome and change in microbiome.<br><br>ETHICS AND DISSEMINATION: Ethics approval from the local hospital research ethics board was obtained at the primary site (McMaster Children's Hospital, Hamilton), with ethics pending at the secondary site (Centre Hospitalier Universitaire-Sainte-Justine, Montréal). RBX7455 and RBX2660 are human donor-sourced, microbiota-based therapeutic formulations. Both RBX7455 and RBX2660 are currently undergoing clinical trials to support potential US Food and Drug Administration approval. Approval to conduct this paediatric clinical trial was obtained from Health Canada's Biologics and Genetic Therapies Directorate. The results of this trial will be published in peer-reviewed journals and will help inform a large, multicentre trial in the future.<br><br>TRIAL REGISTRATION NUMBER: NCT03378167; pre-results.}, }
@article {pmid33106983, year = {2020}, author = {Dembrovszky, F and Gede, N and Szakács, Z and Hegyi, P and Kiss, S and Farkas, N and Molnár, Z and Imrei, M and Dohos, D and Péterfi, Z}, title = {Fecal Microbiota Transplantation May Be the Best Option in Treating Multiple Clostridioides difficile Infection: A Network Meta-Analysis.}, journal = {Infectious diseases and therapy}, volume = {}, number = {}, pages = {}, doi = {10.1007/s40121-020-00356-9}, pmid = {33106983}, issn = {2193-8229}, support = {GINOP-2.3.2-15-2016-00048//European Regional Development Fund/ ; EFOP-3.6.2-16-2017-00006//European Regional Development Fund/ ; }, abstract = {INTRODUCTION: Clostridioides difficile (formerly Clostridium) infection (CDI) is the most common cause of healthcare-associated diarrhea with high mortality and recurrence rate; furthermore, the treatment of recurrent cases is a challenge. In this network meta-analysis, we aimed to compare all available therapies against multiple recurrent CDI (mrCDI) and rank them by efficacy.<br><br>METHODS: After a systematic search, randomized controlled trials (RCT) with any interventions against mrCDI were included. Data were extracted to the study database using Excel. Risk of bias assessment was performed with the Cochrane RoB 2 tool. The primary outcome was the clinical cure of CDI and the secondary outcome was the recurrence of CDI. A Bayesian method was performed to investigate the efficacy rank order of therapies. We registered our protocol with the Prospero Center for Reviews and Dissemination (registration no. CRD42020160365).<br><br>RESULTS: Six RCTs with seven interventions were included in the quantitative synthesis. According to the surface under the cumulative ranking curve values, fecal microbiota transplantation (FMT) after a short course of vancomycin therapy (83%) shows the highest efficacy for clinical cure. Tolevamer and vancomycin + FMT seemed to be the most effective in preventing recurrence (87% and 75%, respectively).<br><br>CONCLUSION: Vancomycin + FMT is perhaps the most effective option for the treatment and prevention of mrCDI, while tolevamer is also effective in preventing recurrence.}, }
@article {pmid33102769, year = {2020}, author = {Gill, M and Blacketer, C and Chitti, F and Telfer, K and Papanicolas, L and Dann, LM and Tucker, EC and Bryant, RV and Costello, SP}, title = {Physician and patient perceptions of fecal microbiota transplant for recurrent or refractory Clostridioides difficile in the first 6 years of a central stool bank.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {4}, number = {5}, pages = {950-957}, doi = {10.1002/jgh3.12396}, pmid = {33102769}, issn = {2397-9070}, abstract = {Background and Aim: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent or refractory Clostridioides difficile infection (rCDI). Despite inclusion in society guidelines, the uptake of FMT therapy has been variable. Physician and patient attitudes may be a barrier to evidence-based uptake of therapies; however, data assessing attitudes regarding FMT for rCDI are limited.<br><br>Methods: The South Australian FMT for CDI database prospectively recorded patient outcomes of FMT for CDI from August 2013 to January 2019. A total of 93 consecutive patients who underwent FMT for rCDI in South Australia were invited to participate in a 20-question survey regarding the patient experience of FMT. All gastroenterologists and infectious disease physicians practicing in South Australia were invited to participate in an online survey comprised of 22 questions that addressed referral experience, indications for referral, perceived risks, and regulation and funding.<br><br>Results: Fifty-four patients (54/93, 58%) returned the survey, of whom 52 (96%) would recommend FMT to others, and 51 (94%) were satisfied with treatment outcome. Fifty physicians returned the online survey (50/100, 50%), of whom 23 (46%) were concerned about disease transmission risk, and 15 (30%) believed that the risk of FMT would outweigh the benefit. Infectious diseases physicians and advanced trainees had significantly greater concern regarding the potential alteration of the microbiome than gastroenterology physicians and advanced trainees (8/17 (47%) vs 6/33 (18%); P = 0.047).<br><br>Conclusion: Despite high levels of patient-reported satisfaction following FMT, physician-reported reservations exist and may present a barrier to uptake of this therapy.}, }
@article {pmid33102555, year = {2020}, author = {Rossi, G and Pengo, G and Galosi, L and Berardi, S and Tambella, AM and Attili, AR and Gavazza, A and Cerquetella, M and Jergens, AE and Guard, BC and Lidbury, JA and Stainer, JM and Crovace, AM and Suchodolski, JS}, title = {Effects of the Probiotic Mixture Slab51® (SivoMixx®) as Food Supplement in Healthy Dogs: Evaluation of Fecal Microbiota, Clinical Parameters and Immune Function.}, journal = {Frontiers in veterinary science}, volume = {7}, number = {}, pages = {613}, doi = {10.3389/fvets.2020.00613}, pmid = {33102555}, issn = {2297-1769}, abstract = {The gut microbiota plays a crucial role in several physiologic functions of the host. In humans and animals, manipulation of the intestinal microbiota by oral administration of probiotic lactic acid bacteria plays a significant role in modulating the immune system. The aim of this study was to evaluate the safety of the probiotic mixture Slab51® and the capacity of this mixture to stimulate immune function in healthy dogs. Twenty dogs were divided in two groups and received a control diet or the same diet supplemented with a dose of 400 billion cfu of lyophilized bacteria for a period of 60 days. Body weight, food intake, body condition score (BCS), fecal score (FSS), fecal immunoglobulin IgA concentration, plasma IgG concentration, and fecal microbiota composition were monitored. Weight, food intake, BCS, FSS, and biochemical parameters remained unchanged during the treatment in both groups of animals. The fecal microbiota showed a significant decrease in the abundance of Clostridium perfringens and a significant increase in the abundance of beneficial Bifidobacterium and Lactobacillus organisms (p < 0.05). Fecal IgA and plasma IgG levels were significantly higher in the group receiving the probiotic compared to healthy controls. These data show that dietary supplementation with the probiotic mixture Slab51® is safe and well-tolerated, modulating the composition of the intestinal microbiota, and enhancing specific immune functions in healthy dogs.}, }
@article {pmid33102406, year = {2020}, author = {Koo, H and Crossman, DK and Morrow, CD}, title = {Strain Tracking to Identify Individualized Patterns of Microbial Strain Stability in the Developing Infant Gut Ecosystem.}, journal = {Frontiers in pediatrics}, volume = {8}, number = {}, pages = {549844}, doi = {10.3389/fped.2020.549844}, pmid = {33102406}, issn = {2296-2360}, abstract = {Stable microbe and host interactions are established during the development of the infant gut microbial community that provide essential functions for the efficient digestion of food, immune development, and resistance to colonization with pathogens. To further delineate the stability of the gut microbial community during this time, we have used microbial strain tracking analysis with published longitudinal metagenomic data sets to identify strains that persist in the developing infant gut ecosystem. In the first study, 17 infants were evaluated that had not received antibiotics for 3 years after birth. An infant specific pattern was seen for stable and unstable microbial strains during this time, with only one infant having no stable strains identified out of available strains during the first 3 years. Strain tracking was also applied to follow microbes in a separate set of 14 infants that had multiple doses of antibiotics over the 3 years. In 10 out of 14 infants given multiple antibiotics during the first 3 years, we identified a unique pattern of transient strains that appeared after multiple antibiotic treatments for a short time compared to that in infants not on antibiotics. In a second, independent study, we selected a subset of 9 infants from a previously published study consisting of high-density longitudinal fecal sampling to analyze the gut microbial strain stability of Bacteroides vulgatus and Bifidobacterium adolescentis for up to 6 years following birth. Individual specific patterns were found consisting of varying dominant microbial strains that were independent of antibiotic exposure and birth mode. Our analysis demonstrates an individual specific inherent variability of extinction and persistence of microbial strains in the infant gut community during a time of development that is critical for interactions necessary for establishing normal metabolism and the development of the host immune response.}, }
@article {pmid33098239, year = {2020}, author = {Li, W and Chen, C and Chen, M and Zhang, X and Ji, Q and Wang, Y and Zheng, Q and Tan, S and Gao, X and Lu, Y}, title = {Salted and Unsalted Zhàcài (Brassica juncea var. tumida) Alleviated High-Fat Diet-Induced Dyslipidemia by Regulating Gut Microbiota: A Multiomics Study.}, journal = {Molecular nutrition &amp; food research}, volume = {}, number = {}, pages = {e2000798}, doi = {10.1002/mnfr.202000798}, pmid = {33098239}, issn = {1613-4133}, abstract = {SCOPE: Zhàcài, a salting-processed Brassica juncea var. tumida vegetable, is widely consumed as a pickle, but little is known about the health benefits of both salted and unsalted Zhàcài as a whole food.<br><br>METHODS AND RESULTS: The preventive effects of salted and unsalted Zhàcài against dyslipidemia wereassessed in high-fat diet (HF)-fed mice. HF intake for 12 continuous weeks caused dyslipidemia in mice, as evidenced by the elevations in serum total triglyceride, total cholesterol and low-density lipoprotein cholesterol levels by 30%, 66% and 117%, respectively. Metabolomics analysis and the 16S rRNA genes sequencing suggested that dietary administration of salted and unsalted Zhàcài (2.5% w/w) alleviates HF-induced dyslipidemia, metabolic disorders of short-chain fatty acids, and disturbance of intestinal flora in mice. These positive effects of unsalted Zhàcài werestronger than those of salted Zhàcài. Moreover, fecal bacteria transplantation confirmed the antidyslipidemia of Zhàcài.<br><br>CONCLUSION: These results suggest that consumption of Zhàcài may prevent HF-induced dyslipidemia by regulating gut microbiota. This article is protected by copyright. All rights reserved.}, }
@article {pmid31061423, year = {2019}, author = {García-Fernández, S and Frentrup, M and Steglich, M and Gonzaga, A and Cobo, M and López-Fresneña, N and Cobo, J and Morosini, MI and Cantón, R and Del Campo, R and Nübel, U}, title = {Whole-genome sequencing reveals nosocomial Clostridioides difficile transmission and a previously unsuspected epidemic scenario.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {6959}, doi = {10.1038/s41598-019-43464-4}, pmid = {31061423}, issn = {2045-2322}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Child ; Child, Preschool ; Clostridium Infections/epidemiology/microbiology/therapy/*transmission ; Clostridium difficile/drug effects/*genetics/isolation &amp; purification ; Fecal Microbiota Transplantation/methods ; Female ; *Genetic Variation ; *Genome, Bacterial ; Humans ; Male ; Middle Aged ; Whole Genome Sequencing/*methods ; Young Adult ; }, abstract = {To trace the routes and frequencies of transmission of Clostridioides difficile in a tertiary-care hospital in Madrid (Spain), we sequenced the genomes from all C. difficile isolates collected over 36 months (2014-2016) that were indistinguishable from any other isolate by PCR ribotyping. From a total of 589 C. difficile infection cases, we cultivated and PCR-ribotyped 367 C. difficile isolates (62%), of which 265 were genome-sequenced. Based on close relatedness of successively collected isolates (≤2 SNPs difference in their genomes), whole-genome sequencing revealed a total of 17 independent, putative transmission clusters, caused by various C. difficile strains and each containing 2 to 18 cases, none of which had been detected previously by standard epidemiological surveillance. Proportions of linked isolates varied widely among PCR ribotypes, from 3% (1/36) for ribotype 014/020 to 60% (12/20) for ribotype 027, suggesting differential aptitudes for nosocomial spread. Remarkably, only a minority (17%) of transmission recipients had direct ward contact to their presumed donors and specific C. difficile genome types frequently went undetectable for several months before re-emerging later, suggesting reservoirs for the pathogen outside of symptomatic patients. Taken together, our analysis based on genome sequencing suggested considerable within-hospital epidemic spread of C. difficile, even though epidemiological data initially had been inconspicuous.}, }
@article {pmid33087514, year = {2020}, author = {Kang, DW and Adams, JB and Vargason, T and Santiago, M and Hahn, J and Krajmalnik-Brown, R}, title = {Distinct Fecal and Plasma Metabolites in Children with Autism Spectrum Disorders and Their Modulation after Microbiota Transfer Therapy.}, journal = {mSphere}, volume = {5}, number = {5}, pages = {}, pmid = {33087514}, issn = {2379-5042}, abstract = {Accumulating evidence has strengthened a link between dysbiotic gut microbiota and autism. Fecal microbiota transplant (FMT) is a promising therapy to repair dysbiotic gut microbiota. We previously performed intensive FMT called microbiota transfer therapy (MTT) for children with autism spectrum disorders (ASD) and observed a substantial improvement of gastrointestinal and behavioral symptoms. We also reported modulation of the gut microbiome toward a healthy one. In this study, we report comprehensive metabolite profiles from plasma and fecal samples of the children who participated in the MTT trial. With 619 plasma metabolites detected, we found that the autism group had distinctive metabolic profiles at baseline. Eight metabolites (nicotinamide riboside, IMP, iminodiacetate, methylsuccinate, galactonate, valylglycine, sarcosine, and leucylglycine) were significantly lower in the ASD group at baseline, while caprylate and heptanoate were significantly higher in the ASD group. MTT drove global shifts in plasma profiles across various metabolic features, including nicotinate/nicotinamide and purine metabolism. In contrast, for 669 fecal metabolites detected, when correcting for multiple hypotheses, no metabolite was significantly different at baseline. Although not statistically significant, p-cresol sulfate was relatively higher in the ASD group at baseline, and after MTT, the levels decreased and were similar to levels in typically developing (TD) controls. p-Cresol sulfate levels were inversely correlated with Desulfovibrio, suggesting a potential role of Desulfovibrio on p-cresol sulfate modulation. Further studies of metabolites in a larger ASD cohort, before and after MTT, are warranted, as well as clinical trials of other therapies to address the metabolic changes which MTT was not able to correct.IMPORTANCE Despite the prevalence of autism and its extensive impact on our society, no U.S. Food and Drug Administration-approved treatment is available for this complex neurobiological disorder. Based on mounting evidences that support a link between autism and the gut microbiome, we previously performed a pioneering open-label clinical trial using intensive fecal microbiota transplant. The therapy significantly improved gastrointestinal and behavioral symptoms. Comprehensive metabolomic measurements in this study showed that children with autism spectrum disorder (ASD) had different levels of many plasma metabolites at baseline compared to those in typically developing children. Microbiota transfer therapy (MTT) had a systemic effect, resulting in substantial changes in plasma metabolites, driving a number of metabolites to be more similar to those from typically developing children. Our results provide evidence that changes in metabolites are one mechanism of the gut-brain connection mediated by the gut microbiota and offer plausible clinical evidence for a promising autism treatment and biomarkers.}, }
@article {pmid32820707, year = {2020}, author = {Yiu, JHC and Chan, KS and Cheung, J and Li, J and Liu, Y and Wang, Y and Fung, WWL and Cai, J and Cheung, SWM and Dorweiler, B and Wan, EYF and Tso, P and Xu, A and Woo, CW}, title = {Gut Microbiota-Associated Activation of TLR5 Induces Apolipoprotein A1 Production in the Liver.}, journal = {Circulation research}, volume = {127}, number = {10}, pages = {1236-1252}, doi = {10.1161/CIRCRESAHA.120.317362}, pmid = {32820707}, issn = {1524-4571}, abstract = {RATIONALE: Dysbiosis of gut microbiota plays an important role in cardiovascular diseases but the molecular mechanisms are complex. An association between gut microbiome and the variance in HDL-C (high-density lipoprotein-cholesterol) level was suggested in a human study. Besides, dietary fat was shown to increase both HDL-C and LDL-C (low-density lipoprotein-cholesterol) levels. We speculate that certain types of gut bacteria responding to dietary fat may help to regulate HDL-C level and potentially affect atherosclerotic development.<br><br>OBJECTIVE: We aimed to investigate whether and how high-fat diet (HFD)-associated gut microbiota regulated HDL-C level.<br><br>METHODS AND RESULTS: We found that HFD increased gut flagellated bacteria population in mice. The increase in HDL-C level was adopted by mice receiving fecal microbiome transplantation from HFD-fed mouse donors. HFD led to increased hepatic but not circulating flagellin, and deletion of TLR5 (Toll-like receptor 5), a receptor sensing flagellin, suppressed HFD-stimulated HDL-C and ApoA1 (apolipoprotein A1) levels. Overexpression of TLR5 in the liver of TLR5-knockout mice was able to partially restore the production of ApoA1 and HDL-C levels. Mechanistically, TLR5 activation by flagellin in primary hepatocytes stimulated ApoA1 production through the transcriptional activation responding to the binding of NF-κB (nuclear factor-κB) on Apoa1 promoter region. Furthermore, oral supplementation of flagellin was able to stimulate hepatic ApoA1 production and HDL-C level and decrease atherosclerotic lesion size in apolipoprotein E-deficient (Apoe-/-) mice without triggering hepatic and systemic inflammation. The stimulation of ApoA1 production was also seen in human ApoA1-transgenic mice treated with oral flagellin.<br><br>CONCLUSIONS: Our finding suggests that commensal flagellated bacteria in gut can facilitate ApoA1 and HDL-C productions in liver through activation of TLR5 in hepatocytes. Hepatic TLR5 may be a potential drug target to increase ApoA1.}, }
@article {pmid32356701, year = {2020}, author = {Ciocan, D and Cassard, AM}, title = {[Intestinal bacteria involved in nutritional liver disease killed by phagotherapy: a new therapeutic target].}, journal = {Medecine sciences : M/S}, volume = {36}, number = {4}, pages = {310-312}, doi = {10.1051/medsci/2020052}, pmid = {32356701}, issn = {1958-5381}, mesh = {Animals ; Bacteriophages/physiology ; Ethanol/metabolism ; Fatty Liver, Alcoholic/genetics/microbiology/pathology/therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Genetic Predisposition to Disease ; Humans ; Klebsiella pneumoniae/metabolism/virology ; Liver Diseases/genetics/*microbiology/*therapy ; Mice ; Non-alcoholic Fatty Liver Disease/genetics/microbiology/pathology/therapy ; Nutrition Disorders/complications/genetics/microbiology/prevention &amp; control ; *Phage Therapy/methods ; Saccharomyces/metabolism ; }, }
@article {pmid33081767, year = {2020}, author = {Uzan-Yulzari, A and Morr, M and Tareef-Nabwani, H and Ziv, O and Magid-Neriya, D and Armoni, R and Muller, E and Leibovici, A and Borenstein, E and Louzoun, Y and Shai, A and Koren, O}, title = {The intestinal microbiome, weight, and metabolic changes in women treated by adjuvant chemotherapy for breast and gynecological malignancies.}, journal = {BMC medicine}, volume = {18}, number = {1}, pages = {281}, doi = {10.1186/s12916-020-01751-2}, pmid = {33081767}, issn = {1741-7015}, abstract = {BACKGROUND: Adjuvant chemotherapy induces weight gain, glucose intolerance, and hypertension in about a third of women. The mechanisms underlying these events have not been defined. This study assessed the association between the microbiome and weight gain in patients treated with adjuvant chemotherapy for breast and gynecological cancers.<br><br>METHODS: Patients were recruited before starting adjuvant therapy. Weight and height were measured before treatment and 4-6 weeks after treatment completion. Weight gain was defined as an increase of 3% or more in body weight. A stool sample was collected before treatment, and 16S rRNA gene sequencing was performed. Data regarding oncological therapy, menopausal status, and antibiotic use was prospectively collected. Patients were excluded if they were treated by antibiotics during the study. Fecal transplant experiments from patients were conducted using Swiss Webster germ-free mice.<br><br>RESULTS: Thirty-three patients were recruited; of them, 9 gained 3.5-10.6% of baseline weight. The pretreatment microbiome of women who gained weight following treatment was significantly different in diversity and taxonomy from that of control women. Fecal microbiota transplantation from pretreatment samples of patients that gained weight induced metabolic changes in germ-free mice compared to mice transplanted with pretreatment fecal samples from the control women.<br><br>CONCLUSION: The microbiome composition is predictive of weight gain following adjuvant chemotherapy and induces adverse metabolic changes in germ-free mice, suggesting it contributes to adverse metabolic changes seen in patients. Confirmation of these results in a larger patient cohort is warranted.}, }
@article {pmid33077775, year = {2020}, author = {Zhang, J and Rodríguez, F and Navas, MJ and Costa-Hurtado, M and Almagro, V and Bosch-Camós, L and López, E and Cuadrado, R and Accensi, F and Pina-Pedrero, S and Martínez, J and Correa-Fiz, F}, title = {Fecal microbiota transplantation from warthog to pig confirms the influence of the gut microbiota on African swine fever susceptibility.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {17605}, doi = {10.1038/s41598-020-74651-3}, pmid = {33077775}, issn = {2045-2322}, support = {AGL2016-78160-C2-1-R//Ministry of Economy and Competitiveness (MINECO) from the Spanish Government/ ; }, abstract = {African swine fever virus (ASFV) is the causative agent of a devastating hemorrhagic disease (ASF) that affects both domestic pigs and wild boars. Conversely, ASFV circulates in a subclinical manner in African wild pigs, including warthogs, the natural reservoir for ASFV. Together with genetic differences, other factors might be involved in the differential susceptibility to ASF observed among Eurasian suids (Sus scrofa) and African warthogs (Phacochoerus africanus). Preliminary evidence obtained in our laboratory and others, seems to confirm the effect that environmental factors might have on ASF infection. Thus, domestic pigs raised in specific pathogen-free (SPF) facilities were extremely susceptible to highly attenuated ASFV strains that were innocuous to genetically identical domestic pigs grown on conventional farms. Since gut microbiota plays important roles in maintaining intestinal homeostasis, regulating immune system maturation and the functionality of the innate/adaptive immune responses, we decided to examine whether warthog fecal microbiota transplantation (FMT) to domestic pigs affects host susceptibility to ASFV. The present work demonstrates that warthog FMT is not harmful for domestic weaned piglets, while it modifies their gut microbiota; and that FMT from warthogs to pigs confers partial protection against attenuated ASFV strains. Future work is needed to elucidate the protective mechanisms exerted by warthog FMT.}, }
@article {pmid33076980, year = {2020}, author = {Hamamoto, Y and Ouhara, K and Munenaga, S and Shoji, M and Ozawa, T and Hisatsune, J and Kado, I and Kajiya, M and Matsuda, S and Kawai, T and Mizuno, N and Fujita, T and Hirata, S and Tanimoto, K and Nakayama, K and Kishi, H and Sugiyama, E and Kurihara, H}, title = {Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model.}, journal = {Arthritis research &amp; therapy}, volume = {22}, number = {1}, pages = {249}, doi = {10.1186/s13075-020-02348-z}, pmid = {33076980}, issn = {1478-6362}, support = {18K09599//a Grant-in-Aid for Scientific Research (C)/ ; 20K18537//a Grant-in-Aid for the Encouragement of Young Scientists (B)/ ; 19K18999//a Grant-in-Aid for the Encouragement of Young Scientists (B)/ ; DE027851/DE/NIDCR NIH HHS/United States ; DE029709/DE/NIDCR NIH HHS/United States ; }, abstract = {BACKGROUND: Porphyromonas gingivalis (Pg) infection causes periodontal disease and exacerbates rheumatoid arthritis (RA). It is reported that inoculation of periodontopathogenic bacteria (i.e., Pg) can alter gut microbiota composition in the animal models. Gut microbiota dysbiosis in human has shown strong associations with systemic diseases, including RA, diabetes mellitus, and inflammatory bowel disease. Therefore, this study investigated dysbiosis-mediated arthritis by Pg oral inoculation in an experimental arthritis model mouse.<br><br>METHODS: Pg inoculation in the oral cavity twice a week for 6 weeks was performed to induce periodontitis in SKG mice. Concomitantly, a single intraperitoneal (i.p.) injection of laminarin (LA) was administered to induce experimental arthritis (Pg-LA mouse). Citrullinated protein (CP) and IL-6 levels in serum as well as periodontal, intestinal, and joint tissues were measured by ELISA. Gut microbiota composition was determined by pyrosequencing the 16 s ribosomal RNA genes after DNA purification of mouse feces. Fecal microbiota transplantation (FMT) was performed by transferring Pg-LA-derived feces to normal SKG mice. The effects of Pg peptidylarginine deiminase (PgPAD) on the level of citrullinated proteins and arthritis progression were determined using a PgPAD knockout mutant.<br><br>RESULTS: Periodontal alveolar bone loss and IL-6 in gingival tissue were induced by Pg oral infection, as well as severe joint destruction, increased arthritis scores (AS), and both IL-6 and CP productions in serum, joint, and intestinal tissues. Distribution of Deferribacteres and S24-7 was decreased, while CP was significantly increased in gingiva, joint, and intestinal tissues of Pg-inoculated experimental arthritis mice compared to experimental arthritis mice without Pg inoculation. Further, FMT from Pg-inoculated experimental arthritis mice reproduced donor gut microbiota and resulted in severe joint destruction with increased IL-6 and CP production in joint and intestinal tissues. The average AS of FMT from Pg-inoculated experimental arthritis was much higher than that of donor mouse. However, inoculation of the PgPAD knockout mutant inhibited the elevation of arthritis scores and ACPA level in serum and reduced CP amount in gingival, joint, and intestinal tissues compared to Pg wild-type inoculation.<br><br>CONCLUSION: Pg oral infection affected gut microbiota dysbiosis and joint destruction via increased CP generation.}, }
@article {pmid33075447, year = {2020}, author = {Evrensel, A and Tarhan, KN}, title = {Emerging role of Gut-microbiota-brain axis in depression and therapeutic implication.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {}, number = {}, pages = {110138}, doi = {10.1016/j.pnpbp.2020.110138}, pmid = {33075447}, issn = {1878-4216}, abstract = {The human body can be considered a superorganism in which it's eukaryotic cells and prokaryotic microorganisms coexist. Almost every organ system of the body lives a symbiotic life with these commensal bacteria. Intestinal microbiota has an important role in shaping, organizing and maintaining mental functions from as early as the intrauterine period. Microbiota-based approaches are becoming more prominent in understanding and treating the etiopathogenesis of neuropsychiatric disorders, especially depression. Antidepressant drugs, which are the first-line option in the treatment of depression today, also contain antimicrobial and immunomodulatory mechanisms of action. Treatment options for directly modifying the microbiota composition include prebiotics, probiotics (psychobiotics) and fecal microbiota transplantation. There are few preclinical and clinical studies on the efficacy and reliability of these treatment options in depression. This article will review pertinent studies on the role of intestinal microbiota in depression and discuss the treatment potential of altering ones gut microbiome.}, }
@article {pmid33073887, year = {2020}, author = {Mossad, O and Erny, D}, title = {The microbiota-microglia axis in CNS disorders.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {}, number = {}, pages = {}, doi = {10.1111/bpa.12908}, pmid = {33073887}, issn = {1750-3639}, abstract = {The innate immune system in the central nervous system (CNS) is mainly represented by specialized tissue-resident macrophages, called microglia. In the past years, various species-, host- and tissue-specific as well as environmental factors were recognized that essentially affect microglial properties and functions in the healthy and diseased brain. Host microbiota are mostly residing in the gut and contribute to microglial activation states e.g. via short-chain fatty acids (SCFAs) or aryl hydrocarbon receptor (AhR) ligands. Thereby, the gut microorganisms are deemed to influence numerous CNS diseases mediated by microglia. In this review we summarize recent findings of the interaction between the host microbiota and the CNS in health and disease, where we specifically highlight the resident gut microbiota as a crucial environmental factor for microglial function as what we coin &quot;the microbiota-microglia axis&quot;.}, }
@article {pmid33066233, year = {2020}, author = {Schierová, D and Březina, J and Mrázek, J and Fliegerová, KO and Kvasnová, S and Bajer, L and Drastich, P}, title = {Gut Microbiome Changes in Patients with Active Left-Sided Ulcerative Colitis after Fecal Microbiome Transplantation and Topical 5-aminosalicylic Acid Therapy.}, journal = {Cells}, volume = {9}, number = {10}, pages = {}, doi = {10.3390/cells9102283}, pmid = {33066233}, issn = {2073-4409}, support = {16-27449A//Ministerstvo Zdravotnictví Ceské Republiky/ ; }, abstract = {Ulcerative colitis (UC) is an inflammatory bowel disease, and intestinal bacteria are implicated in the pathogenesis of this disorder. The administration of aminosalicylates (5-ASA) is a conventional treatment that targets the mucosa, while fecal microbial transplantation (FMT) is a novel treatment that directly targets the gut microbiota. The aim of this study was to identify changes in fecal bacterial composition after both types of treatments and evaluate clinical responses. Sixteen patients with active left-sided UC underwent enema treatment using 5-ASA (n = 8) or FMT (n = 8) with a stool from a single donor. Fecal microbiota were analyzed by 16S rDNA high-throughput sequencing, and clinical indices were used to assess the efficacy of treatments. 5-ASA therapy resulted in clinical remission in 50% (4/8) of patients, but no correlation with changes in fecal bacteria was observed. In FMT, remission was achieved in 37.5% (3/8) of patients and was associated with a significantly increased relative abundance of the families Lachnospiraceae, Ruminococcaceae, and Clostridiaceae of the phylum Firmicutes, and Bifidobacteriaceae and Coriobacteriaceae of the phylum Actinobacteria. At the genus level, Faecalibacterium, Blautia, Coriobacteria, Collinsela, Slackia, and Bifidobacterium were significantly more frequent in patients who reached clinical remission. However, the increased abundance of beneficial taxa was not a sufficient factor to achieve clinical improvement in all UC patients. Nevertheless, our preliminary results indicate that FMT as non-drug-using method is thought to be a promising treatment for UC patients.}, }
@article {pmid33066156, year = {2020}, author = {Suganya, K and Koo, BS}, title = {Gut-Brain Axis: Role of Gut Microbiota on Neurological Disorders and How Probiotics/Prebiotics Beneficially Modulate Microbial and Immune Pathways to Improve Brain Functions.}, journal = {International journal of molecular sciences}, volume = {21}, number = {20}, pages = {}, doi = {10.3390/ijms21207551}, pmid = {33066156}, issn = {1422-0067}, support = {2019R1F1A1060821//National Research Foundation/ ; }, abstract = {The gut microbiome acts as an integral part of the gastrointestinal tract (GIT) that has the largest and vulnerable surface with desirable features to observe foods, nutrients, and environmental factors, as well as to differentiate commensals, invading pathogens, and others. It is well-known that the gut has a strong connection with the central nervous system (CNS) in the context of health and disease. A healthy gut with diverse microbes is vital for normal brain functions and emotional behaviors. In addition, the CNS controls most aspects of the GI physiology. The molecular interaction between the gut/microbiome and CNS is complex and bidirectional, ensuring the maintenance of gut homeostasis and proper digestion. Besides this, several mechanisms have been proposed, including endocrine, neuronal, toll-like receptor, and metabolites-dependent pathways. Changes in the bidirectional relationship between the GIT and CNS are linked with the pathogenesis of gastrointestinal and neurological disorders; therefore, the microbiota/gut-and-brain axis is an emerging and widely accepted concept. In this review, we summarize the recent findings supporting the role of the gut microbiota and immune system on the maintenance of brain functions and the development of neurological disorders. In addition, we highlight the recent advances in improving of neurological diseases by probiotics/prebiotics/synbiotics and fecal microbiota transplantation via the concept of the gut-brain axis.}, }
@article {pmid33064448, year = {2020}, author = {Arulsamy, A and Tan, QY and Balasubramaniam, V and O'Brien, TJ and Shaikh, MF}, title = {Gut Microbiota and Epilepsy: A Systematic Review on Their Relationship and Possible Therapeutics.}, journal = {ACS chemical neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1021/acschemneuro.0c00431}, pmid = {33064448}, issn = {1948-7193}, abstract = {Dysbiosis of gut microbiota may lead to a range of diseases including neurological disorders. Thus, it is hypothesized that regulation of the intestinal microbiota may prevent or treat epilepsy. The purpose of this systematic review is to evaluate the evidence investigating the relationship between gut microbiota and epilepsy and possible interventions. A systematic review of the literature was done on four databases (PubMed, Scopus, EMBASE, and Web of Science). Study selection was restricted to original research articles while following the PRISMA guidelines. Six studies were selected. These studies cohesively support the interaction between gut microbiota and epileptic seizures. Gut microbiota analysis identified increases in Firmicutes, Proteobacteria, Verrucomicrobia, and Fusobacteria with decreases in Bacteroidetes and Actinobacteria in epileptic patients. Ketogenic diet, probiotics, and fecal microbiota transplantation (FMT) improved the dysbiosis of the gut microbiota and seizure activity. However, the studies either had a small sample size, lack of subject variability, or short study or follow-up period, which may question their reliability. Nevertheless, these limited studies conclusively suggest that gut microbiota diversity and dysbiosis may be involved in the pathology of epilepsy. Future studies providing more reliable and in depth insight into the gut microbial community will spark promising alternative therapies to current epilepsy treatment.}, }
@article {pmid33055258, year = {2020}, author = {Steed, DB and Wang, T and Raheja, D and Waldman, AD and Babiker, A and Dhere, T and Kraft, CS and Woodworth, MH}, title = {Gram-Negative Taxa and Antimicrobial Susceptibility after Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {mSphere}, volume = {5}, number = {5}, pages = {}, pmid = {33055258}, issn = {2379-5042}, support = {UM1 AI104681/AI/NIAID NIH HHS/United States ; K23 AI144036/AI/NIAID NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation (FMT) has promising applications in reducing multidrug-resistant organism (MDRO) colonization and antibiotic resistance (AR) gene abundance. However, data on clinical microbiology results after FMT are limited. We examined the changes in antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after treatment with FMT for recurrent Clostridioides difficile infection (RCDI). We also examined whether a history of FMT changed health care provider behavior with respect to culture ordering and antibiotic prescription. Medical records for RCDI patients who underwent FMT at Emory University between July 2012 and March 2017 were reviewed retrospectively. FMT-treated patients with Gram-negative culture data in the 1-year period preceding and the 1-year period following FMT were included. Demographic and clinical data were abstracted, including CDI history, frequency of Gram-negative cultures, microbiological results, and antibiotic prescription in response to positive cultures in the period following FMT. Twelve patients were included in this case series. We pooled data from infections at all body sites and found a decrease in the number of total and Gram-negative cultures post-FMT. We compared susceptibility profiles across taxa given the potential for horizontal transmission of AR elements and observed increased susceptibility to nitrofurantoin, trimethoprim-sulfamethoxazole, and the aminoglycosides. FMT did not drastically influence health care provider ordering of bacterial cultures or antibiotic prescribing practices. We observed a reduction in Gram-negative cultures and a trend toward increased antimicrobial susceptibility. This study supports further investigation of FMT as a means of improving antimicrobial susceptibility.IMPORTANCE Fecal microbiota transplantation (FMT), which is highly efficacious in treating recurrent C. difficile infection (RCDI), has a promising application in decolonization of multidrug-resistant organisms, reduction of antibiotic resistance gene abundance, and restoration of healthy intestinal microbiota. However, data representing clinical microbiology results after FMT are limited. We sought to characterize the differences in culture positivity and antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after FMT for RCDI. Drawing on prior studies that had demonstrated the success of FMT in eradicating extraintestinal infections and the occurrence of patient-level interspecies transfer of resistance elements, we employed an agnostic analytic approach of reviewing the data irrespective of body site or species. In a small RCDI population, we observed an improvement in the antimicrobial susceptibility profile of Gram-negative bacteria following FMT, which supports further study of FMT as a strategy to combat antibiotic resistance.}, }
@article {pmid33053936, year = {2020}, author = {Sarin, SK and Sharma, S}, title = {Predictors of steroid non-response and new approaches in severe alcoholic hepatitis.}, journal = {Clinical and molecular hepatology}, volume = {26}, number = {4}, pages = {639-651}, doi = {10.3350/cmh.2020.0196}, pmid = {33053936}, issn = {2287-285X}, abstract = {Severe alcoholic hepatitis (SAH) remains a disease with high mortality. Steroid is the main stay and has been shown to give modest 28-day survival benefit in carefully selected patients, but no 90-day survival benefit. Since non-responders have high incidence of infections and increased mortality, it would be worthwhile to identify them before starting steroid therapy. A high and rising bilirubin, urinary acetyl carnitine >2,500 ng/mL, high asiloglycoprotein positive microparticles, and specific features in liver biopsy could predict steroid non-response at baseline. There is an ever-growing need to find new and effective therapies for SAH patients. Besides aggressive nutrition, granulocyte colony stimulating factor, fecal microbiota transplantation, and plasma exchange appear promising therapies and provide a hope for steroid ineligible or steroid non-responsive patients. Suppression of hepatic inflammation, preventing new bacterial or fungal infections, and enhancing liver regeneration will remain the key targets for next generation therapies.}, }
@article {pmid33051451, year = {2020}, author = {Wang, H and Liu, L and Rao, X and Zeng, B and Yu, Y and Zhou, C and Zeng, L and Zheng, P and Pu, J and Xu, S and Cheng, K and Zhang, H and Ji, P and Wei, H and Xie, P}, title = {Integrated phosphoproteomic and metabolomic profiling reveals perturbed pathways in the hippocampus of gut microbiota dysbiosis mice.}, journal = {Translational psychiatry}, volume = {10}, number = {1}, pages = {346}, doi = {10.1038/s41398-020-01024-9}, pmid = {33051451}, issn = {2158-3188}, abstract = {The dysbiosis of gut microbiota is an important environmental factor that can induce mental disorders, such as depression, through the microbiota-gut-brain axis. However, the underlying pathogenic mechanisms are complex and not completely understood. Here we utilized mass spectrometry to identify the global phosphorylation dynamics in hippocampus tissue in germ-free mice and specific pathogen-free mice (GF vs SPF), fecal microbiota transplantation (FMT) model (&quot;depression microbiota&quot; and the &quot;healthy microbiota&quot; recipient mice). As a result, 327 phosphosites of 237 proteins in GF vs SPF, and 478 phosphosites of 334 proteins in &quot;depression microbiota&quot; vs &quot;healthy microbiota&quot; recipient mice were identified as significant. These phosphorylation dysregulations were consistently associated with glutamatergic neurotransmitter system disturbances. The FMT mice exhibited disturbances in lipid metabolism and amino acid metabolism in both the periphery and brain through integrating phosphoproteomic and metabolomic analysis. Moreover, CAMKII-CREB signaling pathway, in response to these disturbances, was the primary common perturbed cellular process. In addition, we demonstrated that the spliceosome, never directly implicated in mental disorders previously, was a substantially neuronal function disrupted by gut microbiota dysbiosis, and the NCBP1 phosphorylation was identified as a novel pathogenic target. These results present a new perspective to study the pathologic mechanisms of gut microbiota dysbiosis related depression and highlight potential gut-mediated therapies for depression.}, }
@article {pmid32243790, year = {2020}, author = {}, title = {Translating Microbiome Research into Therapies: The Path Ahead.}, journal = {Cell}, volume = {181}, number = {1}, pages = {20-21}, doi = {10.1016/j.cell.2020.03.009}, pmid = {32243790}, issn = {1097-4172}, mesh = {*Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Probiotics/*therapeutic use ; *Translational Medical Research ; }, }
@article {pmid32102925, year = {2020}, author = {Barbara, G and Ianiro, G}, title = {Faecal microbial transplantation in IBS: ready for prime time?.}, journal = {Gut}, volume = {69}, number = {5}, pages = {795-796}, doi = {10.1136/gutjnl-2019-320411}, pmid = {32102925}, issn = {1468-3288}, mesh = {Double-Blind Method ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Irritable Bowel Syndrome ; *Microbiota ; }, }
@article {pmid31751317, year = {2019}, author = {Bajaj, JS and Salzman, N and Acharya, C and Takei, H and Kakiyama, G and Fagan, A and White, MB and Gavis, EA and Holtz, ML and Hayward, M and Nittono, H and Hylemon, PB and Cox, IJ and Williams, R and Taylor-Robinson, SD and Sterling, RK and Matherly, SC and Fuchs, M and Lee, H and Puri, P and Stravitz, RT and Sanyal, AJ and Ajayi, L and Le Guennec, A and Atkinson, RA and Siddiqui, MS and Luketic, V and Pandak, WM and Sikaroodi, M and Gillevet, PM}, title = {Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis.}, journal = {JCI insight}, volume = {4}, number = {24}, pages = {}, pmid = {31751317}, issn = {2379-3708}, support = {/WT_/Wellcome Trust/United Kingdom ; I01 CX001076/CX/CSRD VA/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; /DH_/Department of Health/United Kingdom ; /BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Adult ; Aged ; Capsules ; Cognition/*physiology ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Hepatic Encephalopathy/etiology/microbiology/physiopathology/*therapy ; Humans ; Liver Cirrhosis/complications/microbiology/physiopathology/*therapy ; Male ; Middle Aged ; Placebos/administration &amp; dosage ; Treatment Outcome ; United Kingdom ; Young Adult ; }, abstract = {BACKGROUNDHepatic encephalopathy (HE) is associated with poor outcomes. A prior randomized, pilot trial demonstrated safety after oral capsular fecal microbial transplant (FMT) in HE, with favorable changes in microbial composition and cognition. However, microbial functional changes are unclear. The aim of this study was to determine the effect of FMT on the gut-brain axis compared with placebo, using microbial function based on bile acids (BAs), inflammation (serum IL-6, LPS-binding protein [LBP]), and their association with EncephalApp.METHODSTwenty cirrhotic patients were randomized 1:1 into groups that received 1-time FMT capsules from a donor enriched in Lachnospiraceae and Ruminococcaceae or placebo capsules, with 5-month follow-up for safety outcomes. Stool microbiota and BA; serum IL-6, BA, and LBP; and EncephalApp were analyzed at baseline and 4 weeks after FMT/placebo. Correlation networks among microbiota, BAs, EncephalApp, IL-6, and LBP were performed before/after FMT.RESULTSFMT-assigned participants had 1 HE recurrence and 2 unrelated infections. Six placebo-assigned participants developed negative outcomes. FMT, but not placebo, was associated with reduced serum IL-6 and LBP and improved EncephalApp. FMT-assigned participants demonstrated higher deconjugation and secondary BA formation in feces and serum compared with baseline. No change was seen in placebo. Correlation networks showed greater complexity after FMT compared with baseline. Beneficial taxa, such as Ruminococcaceae, Verrucomicrobiaceae, and Lachnospiraceae, were correlated with cognitive improvement and decrease in inflammation after FMT. Fecal/serum secondary/primary ratios and PiCRUST secondary BA pathways did not increase in participants who developed poor outcomes.CONCLUSIONGut microbial function in cirrhosis is beneficially affected by capsular FMT, with improved inflammation and cognition. Lower secondary BAs in FMT recipients could select for participants who develop negative outcomes.TRIAL REGISTRATIONClinicaltrials.gov NCT03152188.FUNDINGNational Center for Advancing Translational Sciences NIH grant R21TR002024, VA Merit Review grant 2I0CX001076, the United Kingdom National Institute for Health Research Biomedical Facility at Imperial College London, the British Heart Foundation, Wellcome Trust, and King's College London.}, }
@article {pmid33046129, year = {2020}, author = {Binyamin, D and Werbner, N and Nuriel-Ohayon, M and Uzan, A and Mor, H and Abbas, A and Ziv, O and Teperino, R and Gutman, R and Koren, O}, title = {The aging mouse microbiome has obesogenic characteristics.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {87}, doi = {10.1186/s13073-020-00784-9}, pmid = {33046129}, issn = {1756-994X}, abstract = {BACKGROUND: During aging, there is a physiological decline, an increase of morbidity and mortality, and a natural change in the gut microbiome. In this study, we investigated the influence of the gut microbiome on different metabolic parameters in adult and aged mice.<br><br>METHODS: Fecal and blood samples from adult (n = 42, 100-300 days) and aging (n = 32, 550-750 days) mice were collected. Microbiome analysis was done using QIIME2. Mouse weight and body composition were measured using NMR, and insulin and leptin levels in the blood were measured with Mouse Adipokine Magnetic Bead Panel kit. Fecal microbiota transplantation experiments from adult and aged mice into young germ-free mice were carried out in order to examine the effect of the gut microbiome of adult and aging mice on weight, body composition, insulin, and leptin.<br><br>RESULTS: We demonstrate that the microbiomes from adult and aged mice are distinguishable. We also report changes in metabolic parameters as we observed significantly higher weight and fat mass and low lean mass in aged compared to adult mice along with high insulin and leptin levels in the blood. The transplanted gut microbiome from aged mice transferred part of the phenotypes seen in aged mice. Fat body mass and insulin levels were higher in the mice who received feces from aged mice than mice receiving feces from adult mice. In addition, they consumed more food and had a higher respiratory quotient compared to mice receiving adult feces.<br><br>CONCLUSIONS: We conclude that aged mice have a gut microbiota with obesogenic characteristics. In addition, the gut bacterial population itself is sufficient to induce some of the manifestations of obesity.}, }
@article {pmid32991434, year = {2020}, author = {Zheng, YM and He, XX and Xia, HH and Yuan, Y and Xie, WR and Cai, JY and Xu, JT and Wu, LH}, title = {Multi-donor multi-course faecal microbiota transplantation relieves the symptoms of chronic hemorrhagic radiation proctitis: A case report.}, journal = {Medicine}, volume = {99}, number = {39}, pages = {e22298}, doi = {10.1097/MD.0000000000022298}, pmid = {32991434}, issn = {1536-5964}, mesh = {Aftercare ; Chronic Disease ; Colonoscopy/methods ; Diarrhea/etiology ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Hemorrhage/*therapy ; Humans ; Magnetic Resonance Imaging/methods ; Middle Aged ; Proctitis/diagnosis/*etiology/pathology ; RNA, Ribosomal, 16S/genetics ; Radiation Injuries/*complications/diagnostic imaging/pathology ; Tissue Donors ; Treatment Outcome ; }, abstract = {RATIONALE: There are many treatments for chronic hemorrhagic radiation colorectal inflammation, but only a few treatments are supported by high-quality research evidence. Studies have shown that the occurrence and development of radiation proctitis are closely associated with the intestinal flora. Animal studies have indicated that faecal microbiota transplantation (FMT) can improve radiation enteropathy in a mouse model.<br><br>PATIENT CONCERNS: A 45-year-old female patient suffered from recurrent hematochezia and diarrhea for half a year after radiotherapy and underwent recurrent transfusion treatments. Colonoscopy showed obvious congestion of the sigmoid colon and rectal mucosa, a smooth surface, and bleeding that was easily induced by touch, which are consistent with radiation proctitis. The pathological findings revealed chronic mucosal inflammation. The magnetic resonance imaging examination of the pelvic cavity with a plain scan and enhancement showed changes after radiotherapy and chemotherapy, and no obvious tumor recurrence or metastasis was found. The laboratory examinations excluded pathogen infection.<br><br>DIAGNOSES: Based on the history and examinations, the final diagnosis of this patient was chronic hemorrhagic radiation proctitis.<br><br>INTERVENTIONS: The patient was treated with a total of 4 individual courses of FMT.<br><br>OUTCOMES: After the six-month follow-up, her hematochezia, abdominal pain and diarrhea were relieved. Furthermore, 16S rRNA sequencing of the feces showed that the intestinal bacterial composition of the patient obviously changed after FMT and became similar to that of the donors.<br><br>LESSONS: This case report shows that FMT can relieve the symptoms of hematochezia and diarrhea by changing the bacterial community structure in patients with chronic hemorrhagic radiation proctitis.}, }
@article {pmid33044577, year = {2020}, author = {Gerdes, LA and Yoon, H and Peters, A}, title = {[Microbiota and multiple sclerosis].}, journal = {Der Nervenarzt}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00115-020-01012-w}, pmid = {33044577}, issn = {1433-0407}, abstract = {Multiple sclerosis (MS) is an inflammatory disease of the central nervous system driven by autoreactive lymphocytes. Due to its close contact with the gut-associated lymphoid tissue, the intestinal microbiota and/or their metabolites may be one of the factors that influence the activation of autoreactive lymphocytes. This article summarizes and discusses the current research efforts to characterize the microbiome of MS patients using human material. In addition, we present research studies that utilized classical or humanized animal models to determine the influence of certain microbiota species or compositions of microbiota on the immune system and disease progression and to define possible causal associations.}, }
@article {pmid33042284, year = {2020}, author = {Xu, Y and Wang, N and Tan, HY and Li, S and Zhang, C and Zhang, Z and Feng, Y}, title = {Panax notoginseng saponins modulate the gut microbiota to promote thermogenesis and beige adipocyte reconstruction via leptin-mediated AMPKα/STAT3 signaling in diet-induced obesity.}, journal = {Theranostics}, volume = {10}, number = {24}, pages = {11302-11323}, pmid = {33042284}, issn = {1838-7640}, abstract = {Background: Activation of the thermogenic program in white and brown adipocytes presents a promising avenue for increasing energy expenditure during the treatment of obesity. The endogenous mechanism for promoting thermogenesis in brown adipocytes or browning in white adipocytes has indicated that the gut microbiota is a crucial regulator of the host energy balance. However, whether the effects of the therapeutic intervention-induced modulation of the gut microbiota on adipocyte browning involved the regulation of leptin remains unclear. Method: The adipose features were analyzed by body composition analysis, infrared camera observations, transmission electron microscopy and H&amp;E staining. The gene and protein expression in adipose tissue were detected by qRT-PCR, immunoblotting, immunohistochemistry and immunofluorescence staining. The gut microbiome signature was identified by 16S rRNA gene amplicon sequencing, and both mice with high-fat diet-induced obesity (DIO) and mice with antibiotics-induced microbiome depletion were subjected to fecal microbiota transplantation. Results: Treatment with Panax notoginseng saponins (PNS) shaped the murine gut microbiome by increasing the abundances of Akkermansia muciniphila and Parabacteroides distasonis, and as a result, DIO mice harbored a distal gut microbiota with a significantly increased capacity to reduce host adiposity. The PNS-induced modulation of the gut microbiota in DIO mice could increase brown adipose tissue (BAT) thermogenesis and beige adipocyte reconstruction by activating the leptin-AMPK/STAT3 signaling pathway, which results in the promotion of energy expenditure. Leptin has an essential influence on the anti-obesity effects of PNS. In cases of leptin deficiency, the PNS-induced modulation of the gut microbiota exerts negative effects on thermogenesis and browning in white adipose tissue (WAT), which indicates that PNS fail to reduce obesity in leptin gene-deficient mice. The PNS-induced modulation of the gut microbiota exerted a minimal effect on DIO mice with antibiotic-induced microbiome depletion, which confirmed the correlation between altered gut microbiota and the remodeling of adipose tissues in DIO mice. The direct influence of leptin on browning via the AMPKα/STAT3 signaling pathway in C3H101/2 cells supported our in vivo results that signalling through the leptin-AMPK/STAT3 pathway induced by the PNS-modulated gut microbiota was involved in beige adipocyte reconstruction. Conclusion: Our results revealed that leptin signaling is critical for alterations in microbiota-fat crosstalk and provide promising avenues for therapeutic intervention in the treatment of obesity.}, }
@article {pmid33042155, year = {2020}, author = {Macpherson, ME and Hov, JR and Ueland, T and Dahl, TB and Kummen, M and Otterdal, K and Holm, K and Berge, RK and Mollnes, TE and Trøseid, M and Halvorsen, B and Aukrust, P and Fevang, B and Jørgensen, SF}, title = {Gut Microbiota-Dependent Trimethylamine N-Oxide Associates With Inflammation in Common Variable Immunodeficiency.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {574500}, pmid = {33042155}, issn = {1664-3224}, abstract = {A substantial proportion of patients with common variable immunodeficiency (CVID) have inflammatory and autoimmune complications of unknown etiology. We have previously shown that systemic inflammation in CVID correlates with their gut microbial dysbiosis. The gut microbiota dependent metabolite trimethylamine N-oxide (TMAO) has been linked to several metabolic and inflammatory disorders, but has hitherto not been investigated in relation to CVID. We hypothesized that TMAO is involved in systemic inflammation in CVID. To explore this, we measured plasma concentrations of TMAO, inflammatory markers, and lipopolysaccharide (LPS) in 104 CVID patients and 30 controls. Gut microbiota profiles and the bacterial genes CutC and CntA, which encode enzymes that can convert dietary metabolites to trimethylamine in the colon, were examined in fecal samples from 40 CVID patients and 86 controls. Furthermore, a food frequency questionnaire and the effect of oral antibiotic rifaximin on plasma TMAO concentrations were explored in these 40 patients. We found CVID patients to have higher plasma concentrations of TMAO than controls (TMAO 5.0 [2.9-8.6] vs. 3.2 [2.2-6.3], p = 0.022, median with IQR). The TMAO concentration correlated positively with tumor necrosis factor (p = 0.008, rho = 0.26), interleukin-12 (p = 0.012, rho = 0.25) and LPS (p = 0.034, rho = 0.21). Dietary intake of meat (p = 0.678), fish (p = 0.715), egg (p = 0.138), dairy products (p = 0.284), and fiber (p = 0.767) did not significantly impact on the TMAO concentrations in plasma, nor did a 2-week course of the oral antibiotic rifaximin (p = 0.975). However, plasma TMAO concentrations correlated positively with gut microbial abundance of Gammaproteobacteria (p = 0.021, rho = 0.36). Bacterial gene CntA was present in significantly more CVID samples (75%) than controls (53%), p = 0.020, potentially related to the increased abundance of Gammaproteobacteria in these samples. The current study demonstrates that elevated TMAO concentrations are associated with systemic inflammation and increased gut microbial abundance of Gammaproteobacteria in CVID patients, suggesting that TMAO could be a link between gut microbial dysbiosis and systemic inflammation. Gut microbiota composition could thus be a potential therapeutic target to reduce systemic inflammation in CVID.}, }
@article {pmid33041818, year = {2020}, author = {Tan, P and Li, X and Shen, J and Feng, Q}, title = {Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease: An Update.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {574533}, pmid = {33041818}, issn = {1663-9812}, abstract = {Fecal microbiota transplantation (FMT) has successfully been applied for the treatment of recurrent Clostridioides difficile infection (CDI), which has led to studies on its application to other gastrointestinal diseases and extraintestinal diseases associated with gut microbiota dysbiosis. Recently, the results of FMT for patients with inflammatory bowel disease (IBD) have been encouraging. However, studies have not fully clarified the clinical application of this emerging therapy. Here, we aimed to review the current knowledge in this fast-growing field and characterize the effectiveness, safety and mechanisms of FMT for the treatment of IBD patients.}, }
@article {pmid33039712, year = {2020}, author = {Li, X and Lin, Y and Li, X and Xu, X and Zhao, Y and Xu, L and Gao, Y and Li, Y and Tan, Y and Qian, P and Huang, H}, title = {Tyrosine supplement ameliorates murine aGVHD by modulation of gut microbiome and metabolome.}, journal = {EBioMedicine}, volume = {61}, number = {}, pages = {103048}, doi = {10.1016/j.ebiom.2020.103048}, pmid = {33039712}, issn = {2352-3964}, abstract = {BACKGROUND: Microbial communities and their metabolic components in the gut are of vital importance for immune homeostasis and have an influence on the susceptibility of the host to a number of immune-mediated diseases like acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the functional connections between microbiome and metabolome in aGVHD due to the complexity of the gastrointestinal environment.<br><br>METHOD: Initially, gut microbiota and fecal metabolic phenotype in aGVHD murine models were unleashed by performing 16S ribosomal DNA gene sequencing and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics.<br><br>FINDINGS: The group with aGVHD experienced a significant drop in Lachnospiraceae_unclassified but an increase in the relative abundance of Clostridium XI, Clostridium XIVa and Enterococcus. Meanwhile, a lower content of tyrosine was observed in the gut of aGVHD mice. The correlation analysis revealed that tyrosine-related metabolites were inversely correlated with Clostridium XIVa, besides, Blautia and Enterococcus also displayed the negative tendency in aGVHD condition. Apart from exploring the importance and function of tyrosine, different tyrosine diets were offered to mice during transplantation. Additional tyrosine supplements can improve overall survival, ameliorate symptoms at the early stage of aGVHD and change the structure and composition of gut microbiota and fecal metabolic phenotype. In addition, aGVHD mice deprived from tyrosine displayed worse manifestations than the vehicle diet group.<br><br>INTERPRETATION: The results demonstrated the roles and mechanisms of gut microbiota, indispensable metabolites and tyrosine in the progression of aGVHD, which can be an underlying biomarker for aGVHD diagnosis and treatment.<br><br>FUNDING: This research was funded by the International Cooperation and Exchange Program (81520108002), the National Key R&amp;D Program of China, Stem Cell and Translation Research (2018YFA0109300), National Natural Science Foundation of China (81670169, 81670148, 81870080 and 91949115) and Natural Science Foundation of Zhejiang Province (LQ19H080006).}, }
@article {pmid33034846, year = {2020}, author = {Brown, EG and Goldman, SM}, title = {Modulation of the Microbiome in Parkinson's Disease: Diet, Drug, Stool Transplant, and Beyond.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1007/s13311-020-00942-2}, pmid = {33034846}, issn = {1878-7479}, abstract = {The gastrointestinal microbiome is altered in Parkinson's disease and likely plays a key role in its pathophysiology, affecting symptoms and response to therapy and perhaps modifying progression or even disease initiation. Gut dysbiosis therefore has a significant potential as a therapeutic target in Parkinson's disease, a condition elusive to disease-modifying therapy thus far. The gastrointestinal environment hosts a complex ecology, and efforts to modulate the relative abundance or function of established microorganisms are still in their infancy. Still, these techniques are being rapidly developed and have important implications for our understanding of Parkinson's disease. Currently, modulation of the microbiome can be achieved through non-pharmacologic means such as diet, pharmacologically through probiotic, prebiotic, or antibiotic use and procedurally through fecal transplant. Novel techniques being explored include the use of small molecules or genetically engineered organisms, with vast potential. Here, we review how some of these approaches have been used to date, important areas of ongoing research, and how microbiome modulation may play a role in the clinical management of Parkinson's disease in the future.}, }
@article {pmid33033580, year = {2020}, author = {Nie, X and Chen, J and Ma, X and Ni, Y and Shen, Y and Yu, H and Panagiotou, G and Bao, Y}, title = {A metagenome-wide association study of gut microbiome and visceral fat accumulation.}, journal = {Computational and structural biotechnology journal}, volume = {18}, number = {}, pages = {2596-2609}, pmid = {33033580}, issn = {2001-0370}, abstract = {Purpose: Visceral fat is an independent risk factor for metabolic and cardiovascular disease. The study aimed to investigate the associations between gut microbiome and visceral fat.<br><br>Methods: We recruited 32 obese adults and 30 healthy controls at baseline. Among the obese subjects, 14 subjects underwent laparoscopic sleeve gastrectomy (LSG) and were followed 6 months after surgery. Abdominal visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by magnetic resonance imaging. Waist, hipline, waist-to-hip ratio (WHR) and body mass index (BMI) were included as simple obese parameters. Gut microbiome was analyzed by metagenomic sequencing.<br><br>Results: Among the obese parameters, VFA had the largest number of correlations with the species that were differentially enriched between obese and healthy subjects, following by waist, WHR, BMI, hipline, and SFA. Within the species negatively correlated with VFA, Eubacterium eligens had the strongest correlation, following by Clostridium citroniae, C. symbiosum, Bacteroides uniformis, E. ventriosum, Ruminococcaceae bacterium D16, C. hathewayi, etc. C. hathewayi and C. citroniae were increased after LSG. Functional analyses showed that among all the obese parameters, VFA had strongest correlation coefficients with the obesity-related microbial pathways. Microbial pathways involved in carbohydrate fermentation and biosynthesis of L-glutamate and L-glutamine might contribute to visceral fat accumulation.<br><br>Conclusions: Visceral fat was more closely correlated with gut microbiome compared with subcutaneous fat, suggesting an intrinsic connection between gut microbiome and metabolic cardiovascular diseases. Specific microbial species and pathways which were closely associated with visceral fat accumulation might contribute to new targeted therapies for metabolic disorders.}, }
@article {pmid33027674, year = {2020}, author = {Arnoriaga-Rodríguez, M and Mayneris-Perxachs, J and Burokas, A and Contreras-Rodríguez, O and Blasco, G and Coll, C and Biarnés, C and Miranda-Olivos, R and Latorre, J and Moreno-Navarrete, JM and Castells-Nobau, A and Sabater, M and Palomo-Buitrago, ME and Puig, J and Pedraza, S and Gich, J and Pérez-Brocal, V and Ricart, W and Moya, A and Fernández-Real, X and Ramió-Torrentà, L and Pamplona, R and Sol, J and Jové, M and Portero-Otin, M and Maldonado, R and Fernández-Real, JM}, title = {Obesity Impairs Short-Term and Working Memory through Gut Microbial Metabolism of Aromatic Amino Acids.}, journal = {Cell metabolism}, volume = {32}, number = {4}, pages = {548-560.e7}, doi = {10.1016/j.cmet.2020.09.002}, pmid = {33027674}, issn = {1932-7420}, abstract = {The gut microbiome has been linked to fear extinction learning in animal models. Here, we aimed to explore the gut microbiome and memory domains according to obesity status. A specific microbiome profile associated with short-term memory, working memory, and the volume of the hippocampus and frontal regions of the brain differentially in human subjects with and without obesity. Plasma and fecal levels of aromatic amino acids, their catabolites, and vegetable-derived compounds were longitudinally associated with short-term and working memory. Functionally, microbiota transplantation from human subjects with obesity led to decreased memory scores in mice, aligning this trait from humans with that of recipient mice. RNA sequencing of the medial prefrontal cortex of mice revealed that short-term memory associated with aromatic amino acid pathways, inflammatory genes, and clusters of bacterial species. These results highlight the potential therapeutic value of targeting the gut microbiota for memory impairment, specifically in subjects with obesity.}, }
@article {pmid33024394, year = {2020}, author = {Wu, YN and Zhang, L and Chen, T and Li, X and He, LH and Liu, GX}, title = {Granulocyte-macrophage colony-stimulating factor protects mice against hepatocellular carcinoma by ameliorating intestinal dysbiosis and attenuating inflammation.}, journal = {World journal of gastroenterology}, volume = {26}, number = {36}, pages = {5420-5436}, pmid = {33024394}, issn = {2219-2840}, abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. The gut microbiota can help maintain healthy metabolism and immunity. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a critical factor in promoting health and homeostasis; it promotes intestinal immunity, stimulates bone marrow precursors to generate macrophage colonies, and enhances the antibacterial and antitumor activity of circulating monocytes. As such, GM-CSF may protect against HCC development by regulating immunity as well as intestinal microecology.<br><br>AIM: To investigate the impact of GM-CSF on the gut microbiome and metabolic characteristics of HCC.<br><br>METHODS: Thirty-six male BALB/c nude mice were divided into three groups: Control (n = 10), HCC (n = 13), and HCC + GM-CSF (GM-CSF overexpression, n = 13). We utilized HCC cells to establish orthotopic transplantation tumor models of HCC with normal and over-expressing GM-CSF. Liver injury, immune inflammatory function and intestinal barrier function were evaluated. The fecal microbiome and metabolome were studied using 16S rRNA absolute quantification sequencing and gas chromatography-mass spectrometry.<br><br>RESULTS: GM-CSF overexpression significantly affected the gut microbiome of mice with HCC and resulted in a high abundance of organisms of the genera Roseburia, Blautia and Butyricimonass, along with a significant reduction in Prevotella, Parabacteroides, Anaerotruncus, Streptococcus, Clostridium, and Mucispirillum. Likewise, GM-CSF overexpression resulted in a substantial increase in fecal biotin and oleic acid levels, along with a prominent decrease in the fecal succinic acid, adenosine, fumaric acid, lipoic acid, and maleic acid levels. Correlation analysis revealed that the intestinal microbiota and fecal metabolites induced by GM-CSF were primarily involved in pathways related to reducing the inflammatory response, biotin metabolism, and intestinal barrier dysfunction.<br><br>CONCLUSION: GM-CSF can protect against HCC development by regulating immunity and modulating the abundance of specific intestinal microorganisms and their metabolites. This study provides new insights into the therapeutic approaches for HCC.}, }
@article {pmid33023268, year = {2020}, author = {Qureshi, F and Adams, J and Hanagan, K and Kang, DW and Krajmalnik-Brown, R and Hahn, J}, title = {Multivariate Analysis of Fecal Metabolites from Children with Autism Spectrum Disorder and Gastrointestinal Symptoms before and after Microbiota Transfer Therapy.}, journal = {Journal of personalized medicine}, volume = {10}, number = {4}, pages = {}, doi = {10.3390/jpm10040152}, pmid = {33023268}, issn = {2075-4426}, support = {1R01AI110642/NH/NIH HHS/United States ; }, abstract = {Fecal microbiota transplant (FMT) holds significant promise for patients with Autism Spectrum Disorder (ASD) and gastrointestinal (GI) symptoms. Prior work has demonstrated that plasma metabolite profiles of children with ASD become more similar to those of their typically developing (TD) peers following this treatment. This work measures the concentration of 669 biochemical compounds in feces of a cohort of 18 ASD and 20 TD children using ultrahigh performance liquid chromatography-tandem mass spectroscopy. Subsequent measurements were taken from the ASD cohort over the course of 10-week Microbiota Transfer Therapy (MTT) and 8 weeks after completion of this treatment. Univariate and multivariate statistical analysis techniques were used to characterize differences in metabolites before, during, and after treatment. Using Fisher Discriminant Analysis (FDA), it was possible to attain multivariate metabolite models capable of achieving a sensitivity of 94% and a specificity of 95% after cross-validation. Observations made following MTT indicate that the fecal metabolite profiles become more like those of the TD cohort. There was an 82-88% decrease in the median difference of the ASD and TD group for the panel metabolites, and among the top fifty most discriminating individual metabolites, 96% report more comparable values following treatment. Thus, these findings are similar, although less pronounced, as those determined using plasma metabolites.}, }
@article {pmid33022904, year = {2020}, author = {Jung, CY and Bae, JM}, title = {Pathophysiology and protective approaches of gut injury in critical illness.}, journal = {Yeungnam University journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.12701/yujm.2020.00703}, pmid = {33022904}, issn = {2384-0293}, abstract = {The gut is a complex organ that has played an important role in digestion, absorption, endocrine functions, and immunity. The gut mucosal barriers consist of the immunologic barrier and nonimmunologic barrier. During critical illnesses, the gut is susceptible to injury due to the induction of intestinal hyperpermeability. Gut hyperpermeability and barrier dysfunction may lead to systemic inflammatory response syndrome. Additionally, gut microbiota are altered during critical illnesses. The etiology of such microbiome alterations in critical illnesses is multifactorial. The interaction or systemic host defense modulation between distant organs and the gut microbiome is increasingly studied in disease research. No treatment modality exists to significantly enhance the gut epithelial integrity, permeability, or mucus layer in critically ill patients. However, multiple helpful approaches including clinical and preclinical strategies exist. Enteral nutrition is associated with an increased mucosal barrier in animal and human studies. The trophic effects of enteral nutrition might help to maintain the intestinal physiology, prevent atrophy of gut villi, reduce intestinal permeability, and protect against ischemia-reperfusion injury. The microbiome approach such as the use of probiotics, fecal microbial transplantation, and selective decontamination of the digestive tract has been suggested. However, its evidence does not have a high quality. To promote rapid hypertrophy of the small bowel, various factors have been reported, including the epidermal growth factor, membrane permeant inhibitor of myosin light chain kinase, mucus surrogate, pharmacologic vagus nerve agonist, immune-enhancing diet, and glucagon-like peptide-2 as preclinical strategies. However, the evidence remains unclear.}, }
@article {pmid33022571, year = {2020}, author = {Yu, X and Lv, K and Guan, S and Zhang, X and Sun, L}, title = {Long-term exposure to phenanthrene at environmental-level induces intestinal dysbiosis and disrupted hepatic lipid metabolism in mice.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {268}, number = {Pt B}, pages = {115738}, doi = {10.1016/j.envpol.2020.115738}, pmid = {33022571}, issn = {1873-6424}, abstract = {Phenanthrene (Phe), among the most ubiquitous polycyclic aromatic hydrocarbons (PAHs) existing in nature and foodstuffs, has severe effects on hepatic lipids metabolism. However, the detailed mechanism involved is still unknown. For environmental chemicals can disturb intestinal microbiota, which plays a vital role in lipids metabolism, we hypothesized that oral exposure to Phe may disrupt the intestinal microbiota, leading to the induction of an abnormal inflammatory response and lipid metabolism dysfunction. Herein, male mice were orally exposed to Phe (0.05, 0.5 and 5 mg/kg/2d) for ten weeks and the results showed that long term exposure to Phe induced significant alteration in relative Bacteroidetes, Firmicutes and Proteobacteria abundance in male mice. Histopathological anomalies, and significantly increased hepatic levels of free fatty acid, cholesterol and triglyceride were observed as well. The expression of hepatic proteins linked to lipid metabolism including peroxisome proliferator-activated receptors (PPARs), liver X receptor β (LXRβ) and retinoid X receptors (RXRs) were upregulated. The importance of the gut microbiota in Phe-altered lipid metabolism disorder was further confirmed by fecal microbiota transplantation (FMT). FMT intervention boosted microbial diversity and attenuated Phe-induced elevation in liver somatic index and hepatic total lipids levels. These results demonstrated that environmental-level Phe altered the composition of gastrointestinal bacteria and subsequently induced hepatic lipid metabolism disorder. These results would be helpful for understanding the health risk posed by Phe.}, }
@article {pmid33013647, year = {2020}, author = {Engen, PA and Zaferiou, A and Rasmussen, H and Naqib, A and Green, SJ and Fogg, LF and Forsyth, CB and Raeisi, S and Hamaker, B and Keshavarzian, A}, title = {Single-Arm, Non-randomized, Time Series, Single-Subject Study of Fecal Microbiota Transplantation in Multiple Sclerosis.}, journal = {Frontiers in neurology}, volume = {11}, number = {}, pages = {978}, pmid = {33013647}, issn = {1664-2295}, abstract = {Emerging evidence suggests intestinal microbiota as a central contributing factor to the pathogenesis of Relapsing-Remitting-Multiple-Sclerosis (RRMS). This novel RRMS study evaluated the impact of fecal-microbiota-transplantation (FMT) on a broad array of physiological/clinical outcomes using deep metagenome sequencing of fecal microbiome. FMT interventions were associated with increased abundances of putative beneficial stool bacteria and short-chain-fatty-acid metabolites, which were associated with increased/improved serum brain-derived-neurotrophic-factor levels and gait/walking metrics. This proof-of-concept single-subject longitudinal study provides evidence of potential importance of intestinal microbiota in the pathogenesis of MS, and scientific rationale to help design future randomized controlled trials assessing FMT in RRMS patients.}, }
@article {pmid33011173, year = {2020}, author = {Kelly, CR and Yen, EF and Grinspan, AM and Kahn, SA and Atreja, A and Lewis, JD and Moore, TA and Rubin, DT and Kim, AM and Serra, S and Nersesova, Y and Fredell, L and Hunsicker, D and McDonald, D and Knight, R and Allegretti, JR and Pekow, J and Absah, I and Hsu, R and Vincent, J and Khanna, S and Tangen, L and Crawford, CV and Mattar, MC and Chen, LA and Fischer, M and Arsenescu, RI and Feuerstadt, P and Goldstein, J and Kerman, D and Ehrlich, AC and Wu, GD and Laine, L}, title = {Fecal Microbiota Transplant is Highly Effective in Real-World Practice: Initial Results from the FMT National Registry.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2020.09.038}, pmid = {33011173}, issn = {1528-0012}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is commonly used for treatment of C. difficile infections (CDI), although prospective safety data are limited and real-world FMT practice and outcomes are not well described. The FMT National Registry was designed to assess FMT methods and both safety and effectiveness outcomes from North American FMT providers.<br><br>METHODS: Patients undergoing FMT in clinical practices across North America are eligible. Participating investigators enter de-identified data into an online platform including FMT protocol, baseline patient characteristics, CDI cure and recurrence, and short and long-term safety outcomes.<br><br>RESULTS: Of the first 259 participants enrolled at 20 sites, 222 have completed short-term follow-up at 1 month, and 123 have follow-up to 6 months; 171 (66%) are female. All FMTs were done for CDI, and 249 (96%) used an unknown donor (e.g., stool bank). One-month cure occurred in 200 (90%); of these, 197 (98%) received only a single FMT. Among 112 with initial cure who were followed to 6 months, 4 (4%) had CDI recurrence. Severe symptoms reported within 1-month of FMT included diarrhea (5 (2%)) and abdominal pain (4 (2%)); 3 (1%) had hospitalizations possibly related to FMT. At 6 months, new diagnoses of irritable bowel syndrome were made in 2 (1%) and inflammatory bowel disease in 2 (1%).<br><br>CONCLUSIONS: This prospective real-world study demonstrated high effectiveness of FMT for CDI with a good safety profile. Assessment of new conditions at long-term follow-up is planned as this registry grows and will be important for determining the full safety profile of FMT.}, }
@article {pmid33010597, year = {2020}, author = {Zhao, Y and Tang, Y and Chen, L and Lv, S and Liu, S and Nie, P and Aguilar, ZP and Xu, H}, title = {Restraining the TiO2 nanoparticles-induced intestinal inflammation mediated by gut microbiota in juvenile rats via ingestion of Lactobacillus rhamnosus GG.}, journal = {Ecotoxicology and environmental safety}, volume = {206}, number = {}, pages = {111393}, doi = {10.1016/j.ecoenv.2020.111393}, pmid = {33010597}, issn = {1090-2414}, abstract = {Human were given a lot of opportunities to ingest TiO2 NPs in the environment. Children have low, sensitive intestinal tolerance, and they could be exposed to higher levels of TiO2 NPs than adults. Few studies have been conducted on the interaction between TiO2 NPs and juvenile intestine phase models. Thus, in this work, weaning rats were orally exposed to TiO2 NPs for 7 and 14 days. Results indicate that Ti accumulated in the intestine, liver, and feces. Inflammatory infiltration damage was observed in the colonic epithelial tissue, and gut microbiota fluctuated with a decreased abundance of Lactobacilli in feces. Oral supplementation with Lactobacillus rhamnosus GG (LGG) lessened TiO2 NPs-induced colonic inflammatory injury, which might due to downregulation of nuclear factor kappa-B (NF-κB). Meanwhile, LGG maintained normal intestinal microbiome homeostasis, thereby improving TiO2 NPs-induced colon injury in juvenile rats. Moreover, fecal microbiota transplant (FMT) experiment indicated possible TiO2 NPs-induced intestinal microbiota disorder led to colonic inflammation. Our works suggested the urgent need for additional studies on the risk safety assessment, mechanism, and prevention of juvenile health damage from exposure to TiO2 NPs.}, }
@article {pmid33007265, year = {2020}, author = {Korpela, K and Helve, O and Kolho, KL and Saisto, T and Skogberg, K and Dikareva, E and Stefanovic, V and Salonen, A and Andersson, S and de Vos, WM}, title = {Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study.}, journal = {Cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cell.2020.08.047}, pmid = {33007265}, issn = {1097-4172}, abstract = {Infants born by vaginal delivery are colonized with maternal fecal microbes. Cesarean section (CS) birth disturbs mother-to-neonate transmission. In this study (NCT03568734), we evaluated whether disturbed intestinal microbiota development could be restored in term CS-born infants by postnatal, orally delivered fecal microbiota transplantation (FMT). We recruited 17 mothers, of whom seven were selected after careful screening. Their infants received a diluted fecal sample from their own mothers, taken 3 weeks prior to delivery. All seven infants had an uneventful clinical course during the 3-month follow-up and showed no adverse effects. The temporal development of the fecal microbiota composition of FMT-treated CS-born infants no longer resembled that of untreated CS-born infants but showed significant similarity to that of vaginally born infants. This proof-of-concept study demonstrates that the intestinal microbiota of CS-born infants can be restored postnatally by maternal FMT. However, this should only be done after careful clinical and microbiological screening.}, }
@article {pmid33006187, year = {2020}, author = {Hyde, MK and Masser, BM}, title = {Eligible blood donors' decisions about donating stool for fecal microbiota transplantation: Does ambivalence play a role?.}, journal = {Transfusion}, volume = {}, number = {}, pages = {}, doi = {10.1111/trf.16109}, pmid = {33006187}, issn = {1537-2995}, support = {//This work was supported by an award made from The University of Queensland (UQ) Vice-Chancellor's Strategic Funds (B.M.M.) and internal funds granted by the UQ School of Psychology (M.K.H.). Australian governments fund Australian Red Cross Lifeblood for the provision of blood, blood products, and services to the Australian community/ ; }, abstract = {Blood collection agencies (BCAs) are expanding core business by inviting blood donors to donate stool for fecal microbiota transplantation (FMT). However, whether blood donors also want to donate stool is unclear since, despite its benefits, stool donation is viewed by many as unpleasant. This study examined the prevalence, contributors to, and role of these mixed feelings (ambivalence) in stool donation intentions.<br><br>STUDY DESIGN AND METHODS: This cross-sectional study surveyed Australian residents aged 18 years or more who believed themselves eligible to donate blood and met broad criteria for prescreening as a stool donor (eg, healthy, not taking medication). Survey questions assessed attitude, norms, self-efficacy, motives, disgust, ambivalence, and intentions to donate stool.<br><br>RESULTS: A total of 382 eligible blood donors aged not more than 50 years (mean, 28.71 years; 48% female, 62% &quot;healthy&quot; body mass index) participated. Six percent indicated no ambivalence about donating stool. In regression, significant determinants of ambivalence were less awareness of FMT, lower self-efficacy, motivated by ensuring that stool is available for loved ones, and more disgust about stool donation. Higher ambivalence contributed to decreased donation intention. Self-efficacy and disgust differentiated participants with moderate ambivalence, a group likely responsive to intervention, from those with low or high ambivalence.<br><br>CONCLUSION: Ambivalence about donating stool was common among eligible blood donors. BCAs should raise awareness about stool donation and FMT before requesting donation. BCAs may increase cost savings and donor retention by giving clear guidance about donation requirements and implementing processes that build confidence. Early screening of potential donors for ambivalence and disgust will enable BCAs to provide decision support.}, }
@article {pmid33006061, year = {2020}, author = {Patel, SD and Hung, YC and Hashmi, ZG and Feinman, M and D'Adamo, CR and Svoboda, S and Wolf, JH}, title = {Surgical Management of Diverticulitis-Associated Clostridioides Difficile Infection.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11605-020-04812-2}, pmid = {33006061}, issn = {1873-4626}, }
@article {pmid33004295, year = {2020}, author = {Ianiro, G and Bibbò, S and Masucci, L and Quaranta, G and Porcari, S and Settanni, CR and Lopetuso, LR and Fantoni, M and Sanguinetti, M and Gasbarrini, A and Cammarota, G}, title = {Maintaining standard volumes, efficacy and safety, of fecal microbiota transplantation for C. difficile infection during the COVID-19 pandemic: A prospective cohort study.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.dld.2020.09.004}, pmid = {33004295}, issn = {1878-3562}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) can be a life-saving treatment against recurrent Clostridioides difficile infection (CDI). It is therefore necessary to maintain this procedure available for these patients during the COVID-19 pandemic while keeping high efficacy and safety standards.<br><br>AIMS: To report outcomes of a FMT service that has adapted its operational workflow during COVID-19 pandemic to continue offering FMT to patients with CDI.<br><br>METHODS: All patients with CDI referred to our center for FMT during pandemic were prospectively included. Each step of the FMT working protocol was adapted with specific security measures to prevent the transmission of SARS-CoV-2.<br><br>RESULTS: Of 26 patients evaluated for FMT, 21 were treated for recurrent or refractory CDI. Eighteen patients completed the 8-week follow-up, and no one recurred after FMT. Follow-up is ongoing in 3 patients, although in all of them diarrhea disappeared after the first procedure. No serious adverse events were reported. Two patients had also COVID-19-related pneumonia, and were cured both from CDI and COVID-19.<br><br>CONCLUSION: This is the first report to show that it is possible to maintain standard volumes, efficacy and safety of FMT for recurrent CDI during the COVID-19 pandemic, by adopting specific changes in the operational workflow.}, }
@article {pmid33003421, year = {2020}, author = {Heimesaat, MM and Genger, C and Klove, S and Weschka, D and Mousavi, S and Bereswill, S}, title = {The Host-Specific Intestinal Microbiota Composition Impacts Campylobacter coli Infection in a Clinical Mouse Model of Campylobacteriosis.}, journal = {Pathogens (Basel, Switzerland)}, volume = {9}, number = {10}, pages = {}, doi = {10.3390/pathogens9100804}, pmid = {33003421}, issn = {2076-0817}, support = {Zoonoses research consortium PAC-Campylobacter (IP7/ 01KI1725D)//Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie/ ; ZIM: ZF4117904 AJ8//Bundesministerium für Wirtschaft und Energie/ ; }, abstract = {Human Campylobacter-infections are progressively rising globally. However, the molecular mechanisms underlying C. coli-host interactions are incompletely understood. In this study, we surveyed the impact of the host-specific intestinal microbiota composition during peroral C. coli infection applying an established murine campylobacteriosis model. Therefore, microbiota-depleted IL-10-/- mice were subjected to peroral fecal microbiota transplantation from murine versus human donors and infected with C. coli one week later by gavage. Irrespective of the microbiota, C. coli stably colonized the murine gastrointestinal tract until day 21 post-infection. Throughout the survey, C. coli-infected mice with a human intestinal microbiota displayed more frequently fecal blood as their murine counterparts. Intestinal inflammatory sequelae of C. coli-infection could exclusively be observed in mice with a human intestinal microbiota, as indicated by increased colonic numbers of apoptotic epithelial cells and innate as well as adaptive immune cell subsets, which were accompanied by more pronounced pro-inflammatory cytokine secretion in the colon and mesenteric lymph nodes versus mock controls. However, in extra-intestinal, including systemic compartments, pro-inflammatory responses upon pathogen challenge could be assessed in mice with either microbiota. In conclusion, the host-specific intestinal microbiota composition has a profound effect on intestinal and systemic pro-inflammatory immune responses during C. coli infection.}, }
@article {pmid33002829, year = {2020}, author = {Fan, Q and Guan, X and Hou, Y and Liu, Y and Wei, W and Cai, X and Zhang, Y and Wang, G and Zheng, X and Hao, H}, title = {Paeoniflorin modulates gut microbial production of indole-3-lactate and epithelial autophagy to alleviate colitis in mice.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {79}, number = {}, pages = {153345}, doi = {10.1016/j.phymed.2020.153345}, pmid = {33002829}, issn = {1618-095X}, abstract = {BACKGROUND: Total glucosides of peony (TGP), extracted from the root and rhizome of Paeonia lactiflora Pall, has well-confirmed immunomodulatory efficacy in the clinic. However, the mechanism and active ingredients remain largely unclear.<br><br>HYPOTHESIS/PURPOSE: Our previous study revealed a low systemic exposure but predominant gut distribution of TGP components. The aim of this study was to investigate involvement of the gut microbiota in the immunoregulatory effects and identify the active component.<br><br>METHODS: Mice received 3% DSS to establish a model of colitis. The treatment group received TGP or single paeoniflorin (PF) or albiflorin (AF). Body weight, colon length, inflammatory and histological changes were assessed. Gut microbiota structure was profiled by 16s rRNA sequencing. Antibiotic treatment and fecal transplantation were used to explore the involvement of gut microbiota. Metabolomic assay of host and microbial metabolites in colon was performed.<br><br>RESULTS: TGP improved colonic injury and gut microbial dysbiosis in colitis mice, and PF was responsible for the protective effects. Fecal microbiota transfer from TGP-treated mice conferred resilience to colitis, while antibiotic treatment abrogated the protective effects. Both TGP and PF decreased colonic indole-3-lactate (ILA), a microbial tryptophan metabolite. ILA was further identified as an inhibitor of epithelial autophagy and ILA supplementation compromised the benefits of TGP.<br><br>CONCLUSION: Our findings suggest that TGP acts in part through a gut microbiota-ILA-epithelial autophagy axis to alleviate colitis.}, }
@article {pmid32999906, year = {2020}, author = {Ortigão, R and Pimentel-Nunes, P and Dinis-Ribeiro, M and Libânio, D}, title = {Gastrointestinal Microbiome - What We Need to Know in Clinical Practice.}, journal = {GE Portuguese journal of gastroenterology}, volume = {27}, number = {5}, pages = {336-351}, pmid = {32999906}, issn = {2341-4545}, abstract = {Human gut microbiota plays an important role in individual health. When the balance between host and gut microbiota is disrupted, changes in microbiota composition and function occur, which is referred as dysbiosis. Environmental factors as diet, proton pump inhibitors, and antibiotics can lead to a permanent dysbiotic disruption. Clarification of these imbalances was made possible by recent advances in genome sequencing methods that supported acknowledgment of the interplay between microbiome and intestinal and extraintestinal disorders. This review focuses on the microbiota impact in inflammatory bowel disease, gastric cancer, colorectal cancer, nonalcoholic fatty liver disease (NAFLD), irritable bowel syndrome (IBS), and Clostridium difficile infection (CDI). Furthermore, novel therapies are summarized. Fecal microbiota transplant (FMT) is a successful and established therapy in recurrent CDI, and its application in other dysbiosis-related diseases is attracting enormous interest. Pre- and probiotics target microbial rebalance and have positive effects mainly in NAFLD, ulcerative colitis, IBS, and CDI patients. Promising anticarcinogenic effects have also been demonstrated in animal models. The literature increasingly describes microbial changes in many dysbiotic disorders and shows what needs to be treated. However, probiotics and FMT application in clinical practice suffers from a shortage of randomized controlled trials with standardized therapy regimens to support their recommendation.}, }
@article {pmid32993381, year = {2020}, author = {Li, Q and Guo, L and Wang, L and Miao, J and Cui, H and Li, L and Geng, K and Zhao, L and Sun, X and Jia, J and Bian, Y}, title = {Composition of &quot;gold juice&quot; using an ancient method based on intestinal microecology.}, journal = {The Journal of international medical research}, volume = {48}, number = {9}, pages = {300060520931288}, doi = {10.1177/0300060520931288}, pmid = {32993381}, issn = {1473-2300}, abstract = {OBJECTIVE: To identify potentially effective bacterial components of gold juice, a traditional Chinese medicine treatment used for fecal microbiota transplantation.<br><br>METHODS: Fecal samples were collected from five healthy children (two boys and three girls; mean age, 7.52 ± 2.31 years). The children had no history of antibiotic use or intestinal microecological preparation in the preceding 3 months. Fresh fecal samples were collected from children to prepare gold juice in mid-to-late November, in accordance with traditional Chinese medicine methods, then used within 7 days. Finally, 16S rDNA sequence analysis was used to identify potentially effective bacterial components of gold juice. QIIME software was used for comparisons of microbial species among gold juice, diluent, filtrate, and loess samples.<br><br>RESULTS: Microflora of gold juice exhibited considerable changes following &quot;ancient method&quot; processing. Microbial components significantly differed between gold juice and filtrate samples. The gold juice analyzed in our study consisted of microbes that synthesize carbohydrates and amino acids by degrading substances, whereas the filtrate contained probiotic flora, Bacteroides, and Prevotella 9.<br><br>CONCLUSIONS: This study of microbial components in gold juice and filtrate provided evidence regarding effective bacterial components in gold juice, which may aid in clinical decisions concerning fecal microbiota transplantation.}, }
@article {pmid32992653, year = {2020}, author = {Quagliariello, A and Del Chierico, F and Reddel, S and Russo, A and Onetti Muda, A and D'Argenio, P and Angelino, G and Romeo, EF and Dall'Oglio, L and De Angelis, P and Putignani, L and All The Other Fmt Opbg Committee Collaborators, }, title = {Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations.}, journal = {Microorganisms}, volume = {8}, number = {10}, pages = {}, doi = {10.3390/microorganisms8101486}, pmid = {32992653}, issn = {2076-2607}, support = {201702P003961//Ministero della Salute/ ; 201802G004314//MINISTERO DELLA SALUTE/ ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts' time-point profiles, donors and control cohorts' baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient's condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.}, }
@article {pmid32991818, year = {2020}, author = {Goll, R and Johnsen, PH and Hjerde, E and Diab, J and Valle, PC and Hilpusch, F and Cavanagh, JP}, title = {Effects of fecal microbiota transplantation in subjects with irritable bowel syndrome are mirrored by changes in gut microbiome.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1794263}, doi = {10.1080/19490976.2020.1794263}, pmid = {32991818}, issn = {1949-0984}, abstract = {Irritable bowel syndrome (IBS) is a common disorder of the lower gastrointestinal tract. The pathophysiology is far from settled, but a gut microbial dysbiosis is hypothesized to be a contributing factor. We earlier published a randomized double-blind placebo-controlled clinical trial on fecal microbiota transplantation (FMT) for IBS - the REFIT trial. The present data set describes the engraftment and includes participants from the study who received active FMT; 14 participants with effect of FMT (Effect) and 8 without (No effect). Samples were collected at baseline, after 6 and 12 months. Samples from the transplants (Donor) served as a comparator. In total 66 recipient samples and 17 donor samples were subjected to deep metagenomic sequencing, and taxonomic and functional analyses were performed. Alpha diversity measures showed a significantly increased diversity and evenness in the IBS groups compared to the donors. Taxonomic profiles showed higher relative abundance of phylum Firmicutes, and lower relative abundance of phylum Bacteroidetes, compared to donors at baseline. This profile was shifted toward the donor profile following FMT. Imputed growth rates showed that the resulting growth pattern was a conglomerate of donor and recipient activity. Thirty-four functional subclasses showed distinct differences between baseline samples and donors, most of which were shifted toward a donor-like profile after FMT. All of these changes were less pronounced in the No effect group. We conclude that FMT induces long-term changes in gut microbiota, and these changes mirror the clinical effect of the treatment. The study was registered in ClinicalTrials.gov (NCT02154867).}, }
@article {pmid32991720, year = {2020}, author = {Yoshifuji, K and Inamoto, K and Kiridoshi, Y and Takeshita, K and Sasajima, S and Shiraishi, Y and Yamashita, Y and Nisaka, Y and Ogura, Y and Takeuchi, R and Toya, T and Igarashi, A and Najima, Y and Doki, N and Kobayashi, T and Ohashi, K and Suda, W and Atarashi, K and Shiota, A and Hattori, M and Honda, K and Kakihana, K}, title = {Prebiotics protect against acute graft-versus-host disease and preserve the gut microbiota in stem cell transplantation.}, journal = {Blood advances}, volume = {4}, number = {19}, pages = {4607-4617}, doi = {10.1182/bloodadvances.2020002604}, pmid = {32991720}, issn = {2473-9537}, abstract = {Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, management of aGVHD is important for successful transplantation. Mucosal damage and alteration of the gut microbiota after allo-HSCT are key factors in the development of aGVHD. We conducted a prospective study to evaluate the ability of prebiotics, which can alleviate mucosal damage and manipulate the gut microbiota, to mitigate posttransplantation complications, including aGVHD. Resistant starch (RS) and a commercially available prebiotics mixture, GFO, were administered to allo-HSCT recipients from pretransplantation conditioning to day 28 after allo-HSCT. Prebiotic intake mitigated mucosal injury and reduced the incidence of all aGVHD grades combined and of aGVHD grades 2 to 4. The cumulative incidence of skin aGVHD was markedly decreased by prebiotics intake. Furthermore, the gut microbial diversity was well maintained and butyrate-producing bacterial population were preserved by prebiotics intake. In addition, the posttransplantation fecal butyrate concentration was maintained or increased more frequently in the prebiotics group. These observations indicate that prebiotic intake may be an effective strategy for preventing aGVHD in allo-HSCT, thereby improving treatment outcomes and the clinical utility of stem cell transplantation approaches. This study was registered on the University Hospital Medical Information Network (UMIN) clinical trials registry (https://www.umin.ac.jp/ctr/index.htm) as #UMIN000027563.}, }
@article {pmid32991697, year = {2020}, author = {Khanna, S and Kraft, CS}, title = {Fecal Microbiota Transplantation: Tales of Caution.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa1492}, pmid = {32991697}, issn = {1537-6591}, }
@article {pmid32988391, year = {2020}, author = {Schwartz, DJ and Langdon, AE and Dantas, G}, title = {Understanding the impact of antibiotic perturbation on the human microbiome.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {82}, pmid = {32988391}, issn = {1756-994X}, support = {R01HD092414//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; TL1 TR002344/TR/NCATS NIH HHS/United States ; 1U1CI000033 301/CC/CDC HHS/United States ; R01 AI123394/AI/NIAID NIH HHS/United States ; R01 HD092414/HD/NICHD NIH HHS/United States ; St. Jude Children's Hospital Fellowship for Basic Research//Pediatric Infectious Diseases Society/ ; AT009741/AT/NCCIH NIH HHS/United States ; TL1 TR000449/NH/NIH HHS/United States ; }, abstract = {The human gut microbiome is a dynamic collection of bacteria, archaea, fungi, and viruses that performs essential functions for immune development, pathogen colonization resistance, and food metabolism. Perturbation of the gut microbiome's ecological balance, commonly by antibiotics, can cause and exacerbate diseases. To predict and successfully rescue such perturbations, first, we must understand the underlying taxonomic and functional dynamics of the microbiome as it changes throughout infancy, childhood, and adulthood. We offer an overview of the healthy gut bacterial architecture over these life stages and comment on vulnerability to short and long courses of antibiotics. Second, the resilience of the microbiome after antibiotic perturbation depends on key characteristics, such as the nature, timing, duration, and spectrum of a course of antibiotics, as well as microbiome modulatory factors such as age, travel, underlying illness, antibiotic resistance pattern, and diet. In this review, we discuss acute and chronic antibiotic perturbations to the microbiome and resistome in the context of microbiome stability and dynamics. We specifically discuss key taxonomic and resistance gene changes that accompany antibiotic treatment of neonates, children, and adults. Restoration of a healthy gut microbial ecosystem after routine antibiotics will require rationally managed exposure to specific antibiotics and microbes. To that end, we review the use of fecal microbiota transplantation and probiotics to direct recolonization of the gut ecosystem. We conclude with our perspectives on how best to assess, predict, and aid recovery of the microbiome after antibiotic perturbation.}, }
@article {pmid32987284, year = {2020}, author = {Proença, IM and Allegretti, JR and Bernardo, WM and de Moura, DTH and Ponte Neto, AM and Matsubayashi, CO and Flor, MM and Kotinda, APST and de Moura, EGH}, title = {Fecal microbiota transplantation improves metabolic syndrome parameters: systematic review with meta-analysis based on randomized clinical trials.}, journal = {Nutrition research (New York, N.Y.)}, volume = {83}, number = {}, pages = {1-14}, doi = {10.1016/j.nutres.2020.06.018}, pmid = {32987284}, issn = {1879-0739}, abstract = {Obesity and metabolic syndrome are important health problems that can lead to significant morbidity/mortality as well as subsequent health concerns. Alterations in the gut microbiota have been implicated in both obesity and metabolic syndrome. Fecal Microbiota Transplantation (FMT) has emerged as a new promising therapeutic approach aimed at manipulating the gut microbiota in various chronic diseases. Randomized clinical trials assessing the use of FMT in obese and metabolic syndrome patients have been reported. The purpose of this systematic review with meta-analysis using randomized clinical trials (RCT) is to evaluate the role of FMT for the treatment of obesity and metabolic syndrome and its impact on clinically relevant parameters. We searched the main databases, as well as the gray literature, to identify RCTs comparing FMT from lean donor(s) vs placebo for obese/metabolic syndrome patients. We included all studies that utilized any form of placebo (sham, saline, autologous FMT, or placebo capsules). Six studies met the inclusion criteria and were included for final analysis with a total of 154 patients. We looked for clinically significant parameters related to obesity and metabolic syndrome and organized the findings into early (2-6 weeks after intervention) and late (12 weeks after intervention) outcomes. Two to 6 weeks after intervention, mean HbA1c was lower in the FMT group (MD = -1.69 mmol/L, CI [-2.88, -0.56], P = .003) and mean HDL cholesterol was higher in the FMT group (MD = 0.09 mmol/L, CI [0.02, 0.15], P = .008). There was no difference in obesity parameters 6 to 12 weeks after intervention. No serious adverse events were reported. The findings for this meta-analysis show that FMT may have a role for the treatment of metabolic syndrome, but there is currently not enough evidence to support its use in clinical practice. High-quality well-powered RCTS with longer follow-up are necessary to clarify the role of FMT in this patient cohort.}, }
@article {pmid32987062, year = {2020}, author = {Goo, N and Bae, HJ and Park, K and Kim, J and Jeong, Y and Cai, M and Cho, K and Jung, SY and Kim, DH and Ryu, JH}, title = {The effect of fecal microbiota transplantation on autistic-like behaviors in Fmr1 KO mice.}, journal = {Life sciences}, volume = {262}, number = {}, pages = {118497}, doi = {10.1016/j.lfs.2020.118497}, pmid = {32987062}, issn = {1879-0631}, abstract = {The importance of alterations in bidirectional communication between gut and brain has become obvious in neuropsychiatric disorders. Gastrointestinal (GI) disturbances are very common in autism spectrum disorders (ASD), and the GI microbiota profiles in children with ASD are significantly different from those in the general population. Fragile X syndrome (FXS) is an inheritable developmental disability in humans, and patients with FXS exhibit autistic behaviors such as mental retardation and impaired social communication or interaction. We hypothesized that an increase in specific gut microbiota by fecal microbiota transplantation (FMT) would mitigate autistic-like behaviors. To test this hypothesis, we measured the effects of FMT from normal mice to Fmr1 KO mice on autistic-like behaviors using several behavioral tests. Because the amounts of A. muciniphila in Fmr1 KO mice was very low, we assessed A. muciniphila population, tested the expression of MUC2, and analyzed goblet cells in the gut after the FMT. We found that FMT ameliorated autistic-like behaviors, especially memory deficits and social withdrawal, and we observed that the levels of A. muciniphila were normalized to wild-type levels. In addition, FMT attenuated the increased levels of TNFα and Iba1 in the brains of Fmr1 KO mice. These results suggest that FMT could be a useful tool for the treatments of cognitive deficits and social withdrawal symptoms observed in FXS or ASD because it increases the population of A. muciniphila and decreases TNFα and Iba1 levels.}, }
@article {pmid32982371, year = {2020}, author = {Azimirad, M and Yadegar, A and Gholami, F and Shahrokh, S and Asadzadeh Aghdaei, H and Ianiro, G and Suzuki, H and Cammarota, G and Zali, MR}, title = {Treatment of Recurrent Clostridioides difficile Infection Using Fecal Microbiota Transplantation in Iranian Patients with Underlying Inflammatory Bowel Disease.}, journal = {Journal of inflammation research}, volume = {13}, number = {}, pages = {563-570}, pmid = {32982371}, issn = {1178-7031}, abstract = {Purpose: Fecal microbiota transplantation (FMT) is an effective treatment option for patients with recurrent Clostridioides difficile infection (rCDI). However, there is a paucity of evidence regarding its efficacy and safety in patients with rCDI and concurrent inflammatory bowel disease (IBD). Here, we present a single-center experience of FMT for treatment of rCDI in Iranian patients with IBD.<br><br>Patients and Methods: Eight patients with established IBD (7 with ulcerative colitis and 1 with Crohn's disease) who underwent at least one FMT via colonoscopy for treatment of rCDI were enrolled in this study. Demographics, pre-FMT and post-FMT IBD activity, efficacy for rCDI and adverse events (AEs) were assessed during a 6-month follow-up period. All patients had experienced 3 episodes of rCDI and were refractory to conventional therapies with metronidazole and vancomycin. Primary cure and secondary cure rates were assessed after FMT treatments.<br><br>Results: A total of 10 FMTs were performed via colonoscopy in 8 patients (6/8; 75% men) with a median age of 35 years (range: 22-60). Two patients received a second FMT. Overall, the primary and secondary cure rates were 75% and 100%, respectively. Two patients developed CPE-producing C. perfringens diagnoses after second FMTs. There were no other AEs, and no patient experienced IBD flare.<br><br>Conclusion: We demonstrated that FMT appears to be an effective, safe and rational therapeutic alternative for resolution of rCDI in patients with underlying IBD. Furthermore, we suggest implementing the CPE-producing C. perfringens testing in the screening of FMT donors.}, }
@article {pmid32981762, year = {2020}, author = {Martínez Pizarro, S}, title = {Transplantation of fecal microbiota in multidrug-resistant Klebsiella pneumoniae colonization and infection.}, journal = {Gastroenterologia y hepatologia}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.gastrohep.2020.06.009}, pmid = {32981762}, issn = {0210-5705}, }
@article {pmid32981509, year = {2020}, author = {Gulati, M and Singh, SK and Corrie, L and Chandwani, L and Singh, A and Kapoor, B and Kumar, R and Pandey, NK and Kumar, B and Awasthi, A and Khursheed, R}, title = {Fecal Microbiota Transplant: Latest Addition to Arsenal Against Recurrent Clostridium Difficile Infection.}, journal = {Recent patents on anti-infective drug discovery}, volume = {}, number = {}, pages = {}, doi = {10.2174/1574891X15666200925092354}, pmid = {32981509}, issn = {2212-4071}, abstract = {An infectious disease of colon, recurrent Clostridium difficile infection (RCDI) is hitherto considered insurmountable leading to significant morbidity and mortality. Gut dysbiosis, generally resulting from frequent use of antibiotics is considered to be responsible for the etiopathogenesis of rCDI. Ironically, the conventional treatment strategies for the disease also include the use of anti-infective drugs such as metronidazole, vancomycin and fidaxomycin. As a result of the efforts to overcome the limitations of these treatment options to control recurrence of disease, Fecal Microbiota Transplant (FMT) has emerged as an effective and safe alternative. It is pertinent to add here that FMT is defined as the process of engraftment of fecal suspension from the healthy person into the gastrointestinal tract of the diseased individual aiming at the restoration of gut microbiota. FMT has proved to be quite successful in the treatment of recurrent and resistant Clostridium difficile infections (RCDI). In last three decades a lot of information has been generated on the use of FMT for RCDI. A number of clinical trials have been reported with generally very high success rates. However, very small number of patents could be found in the area indicating that there still exists lacuna in the knowledge about FMT with respect to its preparation, regulation, mode of delivery and safety. The current review attempts to dive deeper to discuss the patents available in the area while supporting the information contained therein with the non-patent literature.}, }
@article {pmid32980389, year = {2020}, author = {Shaffer, SR and Witt, J and Targownik, LE and Kao, D and Lee, C and Smieliauskas, F and Rubin, DT and Singh, H and Bernstein, CN}, title = {Cost-effectiveness analysis of a fecal microbiota transplant center for treating recurrent C.difficile infection.}, journal = {The Journal of infection}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jinf.2020.09.025}, pmid = {32980389}, issn = {1532-2742}, abstract = {OBJECTIVE: We assessed the cost-effectiveness of establishing a fecal microbial transplant (FMT) unit in Canada for the treatment of recurrent CDI.<br><br>DESIGN: We performed a cost-effectiveness analysis to determine the number of patients with recurrent CDI needed to treat (NNT) annually to make establishing a FMT unit cost-effective. We compared treating patients for their second recurrence of CDI with FMT in a jurisdiction with a FMT unit, compared to being treated with antibiotics; then sent to a medical center with FMT available for the third recurrence. We used a willingness to pay threshold of $50,000 per quality-adjusted-life-year gained.<br><br>RESULTS: The minimum annual NNT was 15 for FMT via colonoscopy, 17 for FMT via capsule, and 44 for FMT via enema compared with vancomycin, and 16, 18, and 47 compared with fidaxomicin, respectively. A medical center's minimum catchment area when establishing a FMT unit would have to be 56,849 if using FMT via colonoscopy, or 64,429 if using capsules.<br><br>CONCLUSION: We report the minimum number of patients requiring treatment annually with FMT to achieve cost-effectiveness, when including start-up and ongoing costs. FMT is cost-effective in Canada in populations with a sufficient number of eligible patients, ranging from 15 to 47 depending on the FMT modality used. This is crucial for medical jurisdictions making decisions about establishing a FMT unit for the treatment of recurrent CDI. The cost-effectiveness can be generalized in other countries.}, }
@article {pmid32979504, year = {2020}, author = {Coman, V and Vodnar, DC}, title = {Gut microbiota and old age: Modulating factors and interventions for healthy longevity.}, journal = {Experimental gerontology}, volume = {141}, number = {}, pages = {111095}, doi = {10.1016/j.exger.2020.111095}, pmid = {32979504}, issn = {1873-6815}, abstract = {Our gut microbiota is a complex and dynamic ecosystem with a paramount role in shaping our metabolic and immunological functions. Recent research suggests that aging may negatively affect the composition, diversity, and function of our microbiota mainly due to alterations in diet and immunologic reactivity (i.e. immunosenescence), and increased incidence of certain diseases and, therefore, increased exposure to certain medication (e.g. antibiotics, proton pump inhibitors). In turn, this aging-related gut dysbiosis may contribute to the initiation and/or progress of other metabolic diseases, and consequently, to a decrease in healthy longevity. On the positive side, promising therapeutic interventions, such as diet supplementation with prebiotics, probiotics and synbiotics, or fecal microbiota transplantation, aimed to counteract these aging-related deleterious consequences, could improve our health, and extend our healthy lifespan. In this context, the current review aims to assess the latest progress in identifying the key elements affecting the gut microbiota of the older adults and their mechanism of action, and the effectiveness of the therapeutic interventions aimed at restoring the diversity and healthy functions of the gut microbiota in older individuals.}, }
@article {pmid32976567, year = {2020}, author = {Saha, S and Mara, K and Pardi, DS and Khanna, S}, title = {Durability Of Response To Fecal Microbiota Transplantation After Exposure to Risk Factors for Recurrence In Patients With Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa1457}, pmid = {32976567}, issn = {1537-6591}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for preventing recurrent Clostridioides difficile infection (CDI). Durability (no recurrence despite additional risk factor exposure) of FMT protection is largely unknown. We studied the durability of FMT in patients with recurrent CDI.<br><br>METHODS: A retrospective study of adults undergoing FMT for recurrent CDI was conducted. Data collected included demographics, CDI risk factors (comorbidities, healthcare exposure, systemic non-CDI antibiotic use, acid suppressant medications) and future CDI episodes. Durable response to FMT was defined as lack of CDI episodes within 1 year post-FMT despite risk factor exposure. Descriptive statistics, univariate and multivariable Cox proportional hazards regression were used as applicable. Two tailed p<0.05 was considered statistically significant.<br><br>RESULTS: Overall 460 patients were included [median age 57 (18-94) years, 65.2% female]. Comorbidities included chronic liver disease, 12.8% (n=59), cancer, 11.7% (n=54), chronic kidney disease, 3.9% (n=18) and inflammatory bowel disease, 21.9% (n=101). Overall, 31.3% (n=144) received antibiotics, 21.7% (n=100) received acid suppressants, 76.8% (n=350) had healthcare exposure after FMT. Of 374 patients with risk factor exposure, 78.1% [95% confidence interval (CI) 72.7%-84.0%] had durable response to FMT at one year. On multivariable analysis, antibiotic use was independently associated with decreased durability of FMT [hazard ratio 0.27 (95% CI, 0.15-0.49), p<0.001].<br><br>CONCLUSION: Majority of patients had a durable response to FMT despite exposure to CDI risk factors. Antibiotic exposure after FMT independently predicted loss of durability of FMT. Larger studies are needed to define predictors of durable response in patients with and without exposure to antibiotics.}, }
@article {pmid32973502, year = {2020}, author = {Cai, TT and Ye, XL and Li, RR and Chen, H and Wang, YY and Yong, HJ and Pan, ML and Lu, W and Tang, Y and Miao, H and Snijders, AM and Mao, JH and Liu, XY and Lu, YB and Ding, DF}, title = {Resveratrol Modulates the Gut Microbiota and Inflammation to Protect Against Diabetic Nephropathy in Mice.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {1249}, pmid = {32973502}, issn = {1663-9812}, abstract = {Oral administration of resveratrol is able to ameliorate the progression of diabetic nephropathy (DN); however, its mechanisms of action remain unclear. Recent evidence suggested that the gut microbiota is involved in the metabolism therapeutics. In the current study, we sought to determine whether the anti-DN effects of resveratrol are mediated through modulation of the gut microbiota using the genetic db/db mouse model of DN. We demonstrate that resveratrol treatment of db/db mice relieves a series of clinical indicators of DN. We then show that resveratrol improves intestinal barrier function and ameliorates intestinal permeability and inflammation. The composition of the gut microbiome was significantly altered in db/db mice compared to control db/m mice. Dysbiosis in db/db mice characterized by low abundance levels of Bacteroides, Alistipes, Rikenella, Odoribacter, Parabacteroides, and Alloprevotella genera were reversed by resveratrol treatment, suggesting a potential role for the microbiome in DN progression. Furthermore, fecal microbiota transplantation, derived from healthy resveratrol-treated db/m mice, was sufficient to antagonize the renal dysfunction, rebalance the gut microbiome and improve intestinal permeability and inflammation in recipient db/db mice. These results indicate that resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol, which provides supporting evidence for the gut-kidney axis in DN.}, }
@article {pmid32971101, year = {2020}, author = {Wang, L and An, J and Song, S and Mei, M and Li, W and Ding, F and Liu, S}, title = {Electroacupuncture preserves intestinal barrier integrity through modulating the gut microbiota in DSS-induced chronic colitis.}, journal = {Life sciences}, volume = {261}, number = {}, pages = {118473}, doi = {10.1016/j.lfs.2020.118473}, pmid = {32971101}, issn = {1879-0631}, abstract = {AIMS: Electroacupuncture (EA) at ST36 has been verified to ameliorate experimental acute colitis. However, the effect of EA on chronic colitis and its mechanism has not yet been explored. This study aimed to assess the protective effect of EA against chronic colitis and the related mechanisms.<br><br>MAIN METHODS: Chronic colitis was induced by dextran sulfate sodium (DSS) in C57BL/6 mice, and EA was applied throughout the entire experiment. Colonic inflammation and intestinal barrier integrity were evaluated. Alterations in the gut microbiota were analyzed by 16S rRNA gene sequencing. The fecal microbiota transplantation (FMT) experiment was used to further confirm the effect of the gut microbiota on the barrier protective effect of EA. The potential molecular mechanisms were explored by western blotting.<br><br>KEY FINDINGS: (1) EA lowered the disease activity index (DAI) and histological scores, decreased the levels of TNFα, IL1β, IL6 and iNOS, and increased the IL10 level in DSS-induced chronic colitis. (2) EA upregulated the protein expression of ZO-1, Occludin, E-Cadherin and mucin2 (MUC2), reduced the apoptosis and proliferation of intestinal epithelial cells (IECs) and intestinal permeability. (3) EA enhanced the gut microbiota diversity and restored the community structure. (4) Both the low-frequency EA (LEA) FMT and high-frequency EA (HEA) FMT maintained the intestinal barrier integrity. (5) EA promoted activation of the mitogen activated protein kinase (MAPK) signaling pathway.<br><br>SIGNIFICANCE: EA can relieve chronic experimental colitis, and this effect may depend on activation of the MAPK signaling pathway through modulation of the gut microbiota to preserve the intestinal barrier.}, }
@article {pmid32970852, year = {2020}, author = {Ross, CN and Reveles, KR}, title = {Feasibility of fecal microbiota transplantation via oral gavage to safely alter gut microbiome composition in marmosets.}, journal = {American journal of primatology}, volume = {}, number = {}, pages = {e23196}, doi = {10.1002/ajp.23196}, pmid = {32970852}, issn = {1098-2345}, support = {1P30AG044271-01A1/AG/NIA NIH HHS/United States ; }, abstract = {Disruption of microbial communities within human hosts has been associated with infection, obesity, cognitive decline, cancer risk and frailty, suggesting that microbiome-targeted therapies may be an option for improving healthspan and lifespan. The objectives of this study were to determine the feasibility of delivering fecal microbiota transplants (FMTs) to marmosets via oral gavage and to evaluate if alteration of the gut microbiome post-FMT could be achieved. This was a prospective study of marmosets housed at the Barshop Institute for Longevity and Aging Studies in San Antonio, Texas. Eligible animals included healthy young adult males (age 2-5 years) with no recent medication use. Stool from two donors was combined and administered in 0.5 ml doses to five young recipients once weekly for 3 weeks. Safety outcomes and alterations in the gut microbiome composition via 16S ribosomal RNA sequencing were compared at baseline and monthly up to 6 months post-FMT. Overall, significant differences in the percent relative abundance was seen in FMT recipients at the phylum and family levels from baseline to 1 month and baseline to 6 months post-FMT. In permutational multivariate analysis of variance analyses, treatment status (donor vs. recipient) (p = .056) and time course (p = .019) predicted β diversity (p = .056). The FMT recipients did not experience any negative health outcomes over the course of the treatment. FMT via oral gavage was safe to administer to young adult marmosets. The marmoset microbiome may be altered by FMT; however, progressive changes in the microbiome are strongly driven by the host and its baseline microbiome composition.}, }
@article {pmid32962069, year = {2020}, author = {Cold, F and Kousgaard, SJ and Halkjaer, SI and Petersen, AM and Nielsen, HL and Thorlacius-Ussing, O and Hansen, LH}, title = {Fecal Microbiota Transplantation in the Treatment of Chronic Pouchitis: A Systematic Review.}, journal = {Microorganisms}, volume = {8}, number = {9}, pages = {}, doi = {10.3390/microorganisms8091433}, pmid = {32962069}, issn = {2076-2607}, support = {7076-00129B//Danish Innovation Fund/ ; }, abstract = {The objective was to evaluate available literature on treatment of chronic pouchitis with fecal microbiota transplantation (FMT) focusing on clinical outcomes, safety, and different approaches to FMT preparation and delivery. A systematic review of electronic databases was conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials Library from inception through April 2020. Human studies of all study types reporting results of FMT to treat chronic pouchitis were included. Nine studies, reporting FMT treatment of 69 patients with chronic pouchitis were found eligible for the review. Most studies were case series and cohort studies rated as having fair to poor quality due to high risk of bias and small sample size. Only one randomized controlled trial was included, finding no beneficial effect of FMT. In total clinical response after FMT was reported in 14 (31.8%) out of 44 evaluated patients at various timepoints after FMT, and clinical remission in ten (22.7%) patients. Only minor self-limiting adverse events were reported. FMT varied greatly regarding preparation, length of treatment, and route of delivery. The effects of FMT on symptoms of chronic pouchitis are not established, though some studies show promising results. Future controlled well-designed studies are warranted.}, }
@article {pmid32957333, year = {2020}, author = {Mao, D and Jiang, Q and Sun, Y and Mao, Y and Guo, L and Zhang, Y and Man, M and Ouyang, G and Sheng, L}, title = {Treatment of intestinal graft-versus-host disease with unrelated donor fecal microbiota transplantation capsules: A case report.}, journal = {Medicine}, volume = {99}, number = {38}, pages = {e22129}, pmid = {32957333}, issn = {1536-5964}, mesh = {Adult ; Capsules ; *Fecal Microbiota Transplantation ; Graft vs Host Disease/*therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Intestinal Diseases/*therapy ; Male ; Myelodysplastic Syndromes/therapy ; Unrelated Donors ; }, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT), administering fecal suspensions via a nasoduodenal tube, has achieved a promising effect in the treatment of intestinal graft-versus-host disease (GvHD) in some pilot studies. In this study, oral FMT capsules from unrelated donor were used for the first time in the treatment of intestinal GvHD. Patient concerns: A 31-year-old male who was diagnosed as &quot;myelodysplastic syndromes with excess blasts II&quot; (intermediate risk 2 of international prognostic scoring system) received human leukocyte antigen -matched sibling donor allogeneic hematopoietic stem cell transplantation. The patient developed diarrhea, vomiting, and bloody stool on 28 days after transplantation.<br><br>DIAGNOSIS: Intestinal acute GvHD was diagnosed clinically with histological confirmation by colonoscopy and pathological biopsy.<br><br>INTERVENTIONS: This patient was treated with first cycle of oral FMT capsules after failure to initial treatment of methylprednisolone (2 mg/kg/d) combined with recombinant human tumor necrosis factor-α receptorII: IgG Fc fusion protein (25 mg, biw). The symptoms of intestinal GvHD were relieved but recurred 11 days later. Second cycle of oral FMT capsules was carried out.<br><br>OUTCOMES: After 2 cycles of fecal bacteria transplantation, intestinal GvHD was gradually controlled and did not recur again during the 2-month follow-up. The diversity and structure of the intestinal flora after FMT was closer to that of healthy donors than that before.<br><br>CONCLUSION: Our case showed oral FMT capsules could be used as a treatment option for corticosteroid refractory intestinal GvHD. Further studies are warranted to assess the clinical efficacy and safety of oral FMT capsules in the treatment of intestinal GvHD.<br><br>RATIONALE: Fecal microbiota transplantation (FMT), administering fecal suspensions via a nasoduodenal tube, has achieved a promising effect in the treatment of intestinal graft-versus-host disease (GvHD) in some pilot studies. In this study, oral FMT capsules from unrelated donor were used for the first time in the treatment of intestinal GvHD.<br><br>PATIENT CONCERNS: A 31-year-old male who was diagnosed as &quot;myelodysplastic syndromes with excess blasts II&quot; (intermediate risk 2 of international prognostic scoring system) received human leukocyte antigen -matched sibling donor allogeneic hematopoietic stem cell transplantation. The patient developed diarrhea, vomiting, and bloody stool on 28 days after transplantation.<br><br>DIAGNOSES: Intestinal acute GvHD was diagnosed clinically with histological confirmation by colonoscopy and pathological biopsy.<br><br>INTERVENTIONS: This patient was treated with first cycle of oral FMT capsules after failure to initial treatment of methylprednisolone (2 mg/kg/d) combined with recombinant human tumor necrosis factor-a receptorII: IgG Fc fusion protein (25 mg, biw). The symptoms of intestinal GvHD were relieved but recurred 11 days later. Second cycle of oral FMT capsules was carried out.<br><br>OUTCOMES: After 2 cycles of fecal bacteria transplantation, intestinal GvHD was gradually controlled and did not recur again during the 2-month follow-up. The diversity and structure of the intestinal flora after FMT was closer to that of healthy donors than that before.<br><br>CONCLUSION: Our case showed oral FMT capsules could be used as a treatment option for corticosteroid refractory intestinal GvHD. Further studies are warranted to assess the clinical efficacy and safety of oral FMT capsules in the treatment of intestinal GvHD.<br><br>LESSONS: There is still a possibility of recurrence after the treatment of GvHD with capsule fecal microbiota transplantation. How to optimize the dosage and treatment course of fecal microbiota capsule administration needs further exploration.}, }
@article {pmid32955197, year = {2020}, author = {Li, Q and Ding, X and Liu, K and Marcella, C and Liu, X and Zhang, T and Liu, Y and Li, P and Xiang, L and Cui, B and Wang, J and Bai, J and Zhang, F}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis: The Optimum Timing and Gut Microbiota as Predictors for Long-Term Clinical Outcomes.}, journal = {Clinical and translational gastroenterology}, volume = {11}, number = {8}, pages = {e00224}, pmid = {32955197}, issn = {2155-384X}, abstract = {INTRODUCTION: The previous researches aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for ulcerative colitis (UC) in a short-term observation. The present study aimed to explore the optimum timing of FMT for maintaining the long-term clinical benefits and to target the gut microbiota that may help to predict the long-term success or failure of FMT in UC.<br><br>METHODS: Two hundred two patients with UC were recruited from November 2012 to September 2018. The primary endpoint of this study was the maintaining time of the first and second courses of FMT. Relapse was defined as partial Mayo score ≥2 after achieving clinical remission and an increase of partial Mayo score ≥1 after achieving clinical response. The stool samples were analyzed by 16S rRNA gene sequencing.<br><br>RESULTS: The median maintaining time of the efficacy was 120 days (IQR, 45-180) and 182.5 days (IQR, 105-311.25) from the first course and second course of FMT, respectively. No FMT-related serious adverse events were observed. The differences of the relative abundance in Eggerthella, Lactobacillus, and Ruminococcus between pre-FMT and 5 days post-FMT were remarkably correlated with the long-term clinical remission (P < 0.05).<br><br>DISCUSSION: This study demonstrated that patients with UC should undergo the second course of FMT within 4 months after the first course of FMT for maintaining the long-term clinical benefits. The short-term alterations of microbiota after FMT may be conducive to predicting the long-term efficacy of FMT in UC (see Visual Abstract, Supplementary Digital Content, http://links.lww.com/CTG/A363).}, }
@article {pmid32954843, year = {2020}, author = {Ianiro, G and Segal, JP and Mullish, BH and Quraishi, MN and Porcari, S and Fabiani, G and Gasbarrini, A and Cammarota, G}, title = {Fecal microbiota transplantation in gastrointestinal and extraintestinal disorders.}, journal = {Future microbiology}, volume = {15}, number = {}, pages = {1173-1183}, doi = {10.2217/fmb-2020-0061}, pmid = {32954843}, issn = {1746-0921}, abstract = {Fecal microbiota transplantation (FMT) is the infusion of feces from a healthy donor into the gut of a recipient to treat a dysbiosis-related disease. FMT has been proven to be a safe and effective treatment for Clostridioides difficile infection, but increasing evidence supports the role of FMT in other gastrointestinal and extraintestinal diseases. The aim of this review is to paint the landscape of current evidence of FMT in different fields of application (including irritable bowel syndrome, inflammatory bowel disease, liver disorders, decolonization of multidrug-resistant bacteria, metabolic disorders and neurological disorders), as well as to discuss the current regulatory scenario of FMT, and hypothesize future directions of FMT.}, }
@article {pmid32953854, year = {2020}, author = {Zhong, M and Sun, Y and Wang, HG and Marcella, C and Cui, BT and Miao, YL and Zhang, FM}, title = {Awareness and attitude of fecal microbiota transplantation through transendoscopic enteral tubing among inflammatory bowel disease patients.}, journal = {World journal of clinical cases}, volume = {8}, number = {17}, pages = {3786-3796}, pmid = {32953854}, issn = {2307-8960}, abstract = {BACKGROUND: Transendoscopic enteral tubing (TET) has been used in China as a novel delivery route for fecal microbiota transplantation (FMT) into the whole colon with a high degree of patient satisfaction among adults.<br><br>AIM: To explore the recognition and attitudes of FMT through TET in patients with inflammatory bowel disease (IBD).<br><br>METHODS: An anonymous questionnaire, evaluating their awareness and attitudes toward FMT and TET was distributed among IBD patients in two provinces of Eastern and Southwestern China. Question formats included single-choice questions, multiple-choice questions and sorting questions. Patients who had not undergone FMT were mainly investigated for their cognition and acceptance of FMT and TET. Patients who had experience of FMT, the way they underwent FMT and acceptance of TET were the main interest. Then all the patients were asked whether they would recommend FMT and TET. This study also analyzed the preference of FMT delivery in IBD patients and the patient-related factors associated with it.<br><br>RESULTS: A total of 620 eligible questionnaires were included in the analysis. The survey showed that 44.6% (228/511) of patients did not know that FMT is a therapeutic option in IBD, and 80.6% (412/511) of them did not know the concept of TET. More than half (63.2%, 323/511) of the participants stated that they would agree to undergo FMT through TET. Of the patients who underwent FMT via TET [62.4% (68/109)], the majority [95.6% (65/68)] of them were satisfied with TET. Patients who had undergone FMT and TET were more likely to recommend FMT than patients who had not (94.5% vs 86.3%, P = 0.018 and 98.5% vs 87.8%, P = 0.017). Patients' choice for the delivery way of FMT would be affected by the type of disease and whether the patient had the experience of FMT. When compared to patients without experience of FMT, Crohn's disease and ulcerative colitis patients who had experience of FMT preferred mid-gut TET (P < 0.001) and colonic TET (P < 0.001), respectively.<br><br>CONCLUSION: Patients' experience of FMT through TET lead them to maintain a positive attitude towards FMT. The present findings highlighted the significance of patient education on FMT and TET.}, }
@article {pmid32946509, year = {2020}, author = {Caldeira, LF and Borba, HH and Tonin, FS and Wiens, A and Fernandez-Llimos, F and Pontarolo, R}, title = {Fecal microbiota transplantation in inflammatory bowel disease patients: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {15}, number = {9}, pages = {e0238910}, pmid = {32946509}, issn = {1932-6203}, abstract = {OBJECTIVES: Current evidence on fecal microbiota transplantation for inflammatory bowel disease is inconclusive. We conducted a systematic review to gather evidence on the efficacy and safety of fecal microbiota transplantation for inflammatory bowel disease.<br><br>METHODS: Systematic searches were conducted in PubMed, Scopus, and Web of Science. Clinical remission was considered as the primary endpoint. Pairwise meta-analyses were performed for the randomized controlled studies (Mantel Haenszel, random effects model). Proportion meta-analyses, accounting for weighted pooled rates reported in the interventional studies, were conducted using the mixed effects model. Subgroup analyses considering the type of stool, donor type, and disease subtype were also performed. Cumulative meta-analyses to assess further needs of evidence were conducted.<br><br>RESULTS: Sixty studies were included, from which 36 could be synthesized in the quantitative analyses. Pairwise meta-analyses of six controlled trials showed significant differences in favor of fecal microbiota transplantation compared with placebo (clinical remission: RR 1.70 [95% CI 1.12, 2.56]; clinical response: RR 1.68 [95% CI 1.04, 2.72]). An overall clinical remission of 37%, overall clinical response of 54%, and a prevalence of 29% of adverse events were found for the interventional studies. Frozen fecal material and universal donors were related to better efficacy outcomes. In addition, Crohn's disease patients seemed to benefit more from the procedure.<br><br>CONCLUSIONS: The comparative analyses demonstrated that frozen fecal material from universal donors may be related to a higher rate of clinical remission, especially for Crohn's disease.}, }
@article {pmid32945066, year = {2020}, author = {El-Salhy, M and Valeur, J and Hausken, T and Gunnar Hatlebakk, J}, title = {Changes in fecal short-chain fatty acids following fecal microbiota transplantation in patients with irritable bowel syndrome.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {}, number = {}, pages = {e13983}, doi = {10.1111/nmo.13983}, pmid = {32945066}, issn = {1365-2982}, support = {40415//Helse Fonna/ ; }, abstract = {BACKGROUND: Short-chain fatty acids (SCFAs) may play a role in the pathophysiology of irritable bowel syndrome (IBS). This study analyzed fecal SCFAs after performing fecal microbiota transplantation (FMT) in the IBS patients who were included in our previous study of the efficacy of FMT.<br><br>METHODS: This study included 142 of the 164 IBS patients who participated in our previous study. They were belonging to three groups: placebo (own feces), 30-g (superdonor feces), and 60-g (superdonor feces) FMT. The patients completed the IBS Severity Scoring System (IBS-SSS) Birmingham IBS Symptom, Fatigue Assessment Scale (FAS), the IBS Quality of Life (IBS-QoL) and Short-Form Nepean Dyspepsia Index (SF-NDI) questionnaires and delivered fecal samples at the baseline and 1 month after FMT. The SCFA levels were determined by vacuum distillation followed by gas chromatography.<br><br>KEY RESULTS: The fecal butyric acid level was significantly increased after FMT in both the 30-g and 60-g groups (both P ≤ 0.001). In the 60-g group, the levels of total SCFAs and isobutyric, isovaleric, and valeric acids increased after FMT. Butyric acid levels in the responders in both the 30-g and 60-g FMT groups were significantly inversely correlated with IBS-SSS and FAS scores (P = 0.001, r = -0.3 and P = 0.0001. r=- 0.3, respectively). There were no differences in the SCFA levels in the placebo group after FMT.<br><br>CONCLUSION AND INFERENCES: FMT increases the fecal SCFA levels in IBS patients. The increase in the butyric acid level is inversely correlated with symptoms in IBS patients following FMT, suggesting that SCFAs might play a role in the pathophysiology of IBS. www.clini​caltr​ials.gov (NCT03822299).}, }
@article {pmid32943612, year = {2020}, author = {Xie, Z and Jiang, H and Liu, W and Zhang, X and Chen, D and Sun, S and Zhou, C and Liu, J and Bao, S and Wang, X and Zhang, Y and Li, J and Hu, L and Li, J}, title = {The triterpenoid sapogenin (2α-OH-Protopanoxadiol) ameliorates metabolic syndrome via the intestinal FXR/GLP-1 axis through gut microbiota remodelling.}, journal = {Cell death &amp; disease}, volume = {11}, number = {9}, pages = {770}, pmid = {32943612}, issn = {2041-4889}, support = {81673493//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81803596//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81673493//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2018M632186//China Postdoctoral Science Foundation/ ; }, abstract = {Gypenosides, extracts of Gynostemma yixingense, have been traditionally prescribed to improve metabolic syndrome in Asian folk and local traditional medicine hospitals. However, the mechanism of its action remains unclarified. In this work, our results indicated that chronic administration of 2α-OH-protopanoxadiol (GP2), a metabolite of gypenosides in vivo, protected mice from high-fat diet-induced obesity and improved glucose tolerance by improving intestinal L-cell function. Mechanistically, GP2 treatment inhibited the enzymatic activity of bile salt hydrolase and modulated the proportions of the gut microbiota, which led to an increase in the accumulation of tauro-β-muricholic acid (TβMCA) in the intestine. TβMCA induced GLP-1 production and secretion by reducing the transcriptional activity of nuclear receptor farnesoid X receptor (FXR). Transplantation of GP2-remodelled fecal microbiota into antibiotic-treated mice also increased the intestinal TβMCA content and improved intestinal L-cell function. These findings demonstrate that GP2 ameliorates metabolic syndrome at least partly through the intestinal FXR/GLP-1 axis via gut microbiota remodelling and also suggest that GP2 may serve as a promising oral therapeutic agent for metabolic syndrome.}, }
@article {pmid32942889, year = {2020}, author = {Stebel, R and Vojtilová, L and Husa, P}, title = {Clostridium difficile Infection: an update on treatment and prevention.}, journal = {Vnitrni lekarstvi}, volume = {66}, number = {2}, pages = {58-62}, pmid = {32942889}, issn = {0042-773X}, abstract = {Disruption of the colonic microflora is one of the most significant adverse effects of antibiotic (ATB) therapy. Excessive multiplication of toxigenic Clostridioides difficile strains is responsible for about 20 % of cases of post-antibiotic diarrhoea. The global trend of Clostridium colitis incidence, severity, mortality and in particular therapeutic failure keeps rising. At the Department of Infectious Diseases we work on long-term monitoring of the most important colitis-associated risk factors and evaluation of individual therapeutic and preventive procedures (selective ATB therapy, faecal bacteriotherapy). A diligent analysis of risk factors and knowledge of pathogenesis are a prerequisite to practical implementation of effective and rational precautions to curb spreading of this illness. In the future, we anticipate increased use of fecal microbiota transplant, improvements in faecal transplant administration, wider use of probiotics and selective ATBs and further introduction of passive and active immunization into practice.}, }
@article {pmid32939928, year = {2020}, author = {Masetti, R and Zama, D and Leardini, D and Muratore, E and Turroni, S and Prete, A and Brigidi, P and Pession, A}, title = {The gut microbiome in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.}, journal = {Pediatric blood &amp; cancer}, volume = {}, number = {}, pages = {e28711}, doi = {10.1002/pbc.28711}, pmid = {32939928}, issn = {1545-5017}, abstract = {The gut microbiome (GM) has been associated with different clinical outcomes in the context of allogeneic hematopoietic stem cell transplantation (HSCT). Large multicenter cohort studies in adults have found significant correlations with overall survival, relapse, and incidence of complications. Moreover, GM is already a promising target for therapeutic interventions. However, few data are available in children, a population presenting unique features and challenges. During childhood, the GM evolves rapidly with large structural fluctuations, alongside with the maturation of the immune system. Furthermore, the HSCT procedure presents significant differences in children. These considerations underline the importance of a specific focus on the pediatric setting, and the role of GM and its age-dependent trajectory in influencing the immunity reconstitution and clinical outcomes. This review provides a comprehensive overview of the available evidence in the field of GM and pediatric HSCT, highlighting age-specific issues and discussing GM-based therapeutic approaches.}, }
@article {pmid32931218, year = {2020}, author = {Ebell, MH}, title = {Fecal Microbiota Transplant Effective for Irritable Bowel Syndrome.}, journal = {American family physician}, volume = {102}, number = {6}, pages = {377}, pmid = {32931218}, issn = {1532-0650}, }
@article {pmid32929373, year = {2020}, author = {Wu, J and Wei, Z and Cheng, P and Qian, C and Xu, F and Yang, Y and Wang, A and Chen, W and Sun, Z and Lu, Y}, title = {Rhein modulates host purine metabolism in intestine through gut microbiota and ameliorates experimental colitis.}, journal = {Theranostics}, volume = {10}, number = {23}, pages = {10665-10679}, pmid = {32929373}, issn = {1838-7640}, abstract = {Background: Gut microbiota, which plays a crucial role in inflammatory bowel diseases (IBD), might have therapeutic benefits for ulcerative colitis or Crohn's disease. Targeting gut microbiota represents a new treatment strategy for IBD patients. Rhein is one of the main components of rhubarb and exhibits poor oral bioavailability but still exerts anti-inflammatory effects in some diseases. Therefore, we investigated the effect of rhein on colitis and studied its possible mechanisms. Methods: The chronic mouse colitis model was induced by four rounds of 2% dextran sulfate sodium (DSS) treatment. The mice were treated with 50 mg/kg and 100 mg/kg rhein daily, body weight, colon length, histological score, inflammatory cytokines in serum or intestine, and fecal lipocalin 2 concentration were determined. Th17 cell, Th1 cell and Th2 cell infiltration in the mesenteric lymph node were analyzed by flow cytometry. Metabolic profiles were collected by non-targeted metabolomics and key metabolic pathways were identified using MetaboAnalyst 4.0. We also assessed intestinal barrier permeability and performed 16s rDNA sequencing. Lactobacillus sp. was cultured, and fecal microbiota transplantation (FMT) was employed to evaluate the contribution of gut microbiota. Results: Rhein could significantly alleviate DSS-induced chronic colitis. Uric acid was identified as a crucial modulator of colitis and rhein treatment led to decreased uric acid levels. We determined that rhein changed purine metabolism indirectly, while the probiotic Lactobacillus was involved in the regulation of host metabolism. Uric acid resulted in a worsened intestinal barrier, which could be rescued by rhein. We further confirmed that rhein-treated gut microbiota was sufficient to relieve DSS-induced colitis by FMT. Conclusion: We showed that rhein could modulate gut microbiota, which indirectly changed purine metabolism in the intestine and subsequently alleviated colitis. Our study has identified a new approach to the clinical treatment of colitis.}, }
@article {pmid32925627, year = {2020}, author = {Jeney, SES and Lane, F and Oliver, A and Whiteson, K and Dutta, S}, title = {Fecal Microbiota Transplantation for the Treatment of Refractory Recurrent Urinary Tract Infection.}, journal = {Obstetrics and gynecology}, volume = {136}, number = {4}, pages = {771-773}, doi = {10.1097/AOG.0000000000004052}, pmid = {32925627}, issn = {1873-233X}, }
@article {pmid32924908, year = {2020}, author = {Liu, Y and Qin, S and Feng, Y and Song, Y and Lv, N and Liu, F and Zhang, X and Wang, S and Wei, Y and Li, S and Su, S and Zhang, W and Xue, Y and Hao, Y and Zhu, B and Ma, J and Yang, H}, title = {Perturbations of gut microbiota in gestational diabetes mellitus patients induce hyperglycemia in germ-free mice.}, journal = {Journal of developmental origins of health and disease}, volume = {}, number = {}, pages = {1-9}, doi = {10.1017/S2040174420000768}, pmid = {32924908}, issn = {2040-1752}, abstract = {Shifts in the maternal gut microbiota have been implicated in the development of gestational diabetes mellitus (GDM). Understanding the interaction between gut microbiota and host glucose metabolism will provide a new target of prediction and treatment. In this nested case-control study, we aimed to investigate the causal effects of gut microbiota from GDM patients on the glucose metabolism of germ-free (GF) mice. Stool and peripheral blood samples, as well as clinical information, were collected from 45 GDM patients and 45 healthy controls (matched by age and prepregnancy body mass index (BMI)) in the first and second trimester. Gut microbiota profiles were explored by next-generation sequencing of the 16S rRNA gene, and inflammatory factors in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Fecal samples from GDM and non-GDM donors were transferred to GF mice. The gut microbiota of women with GDM showed reduced richness, specifically decreased Bacteroides and Akkermansia, as well as increased Faecalibacterium. The relative abundance of Akkermansia was negatively associated with blood glucose levels, and the relative abundance of Faecalibacterium was positively related to inflammatory factor concentrations. The transfer of fecal microbiota from GDM and non-GDM donors to GF mice resulted in different gut microbiota colonization patterns, and hyperglycemia was induced in mice that received GDM donor microbiota. These results suggested that the shifting pattern of gut microbiota in GDM patients contributed to disease pathogenesis.}, }
@article {pmid32923252, year = {2020}, author = {Lin, Z and Iqbal, Z and Ortiz, JF and Khan, SA and Jahan, N}, title = {Fecal Microbiota Transplantation in Recurrent Clostridium Difficile Infection: Is it Superior to Other Conventional Methods?.}, journal = {Cureus}, volume = {12}, number = {8}, pages = {e9653}, pmid = {32923252}, issn = {2168-8184}, abstract = {Clostridium difficile (C. difficile) is a gram-positive species of spore-forming bacteria. C. difficile infection (CDI) is one of the most common hospital-acquired infections in the United States, mainly caused by the use of recent antibiotics that leads to intestinal dysbiosis. Recurrent C. difficile infection (rCDI) often occurs after the successful treatment of CDI. Approximately, 30% of patients experience a clinical recurrence of prior symptoms within eight weeks of antibiotic cessation. This present literature review covers the current pathophysiology of CDI, risk factors for infection, diagnostic methods, several treatment modalities, and the potential use of fecal microbial transplant (FMT) for patients with multiple recurrent CDIs. Recent studies have focused on FMT, with an efficacy rate of nearly 90% in multiple recurrent CDI settings. Despite its efficacy, it is not commonly used as first-line treatment. More studies are needed to establish this therapy as the first option in patients with rCDI.}, }
@article {pmid32922400, year = {2020}, author = {Kreft, L and Hoffmann, C and Ohnmacht, C}, title = {Therapeutic Potential of the Intestinal Microbiota for Immunomodulation of Food Allergies.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1853}, pmid = {32922400}, issn = {1664-3224}, abstract = {Food allergy is an atopic disease that is caused by the immune system targeting harmless food antigens that can result in life-threatening anaphylaxis. As humans and microbes have co-evolved, inevitably commensal microbes have a tremendous impact on our health. As such, the gut with its enormous microbial richness reflects a highly tolerogenic environment at steady state, in which immune cells are educated to react in a well-calibrated manner to food and microbial antigens. Recent evidence indicates that the susceptibility to food allergy is critically linked to microbial dysbiosis and can be transmitted by microbial transfer from humans to mice. Experimental work and epidemiological studies further point toward a critical time window in early childhood during which the immune system is imprinted by microbial colonization. Particularly, Foxp3-expressing regulatory T cells turn out to be key players, acting as rheostats for controlling the magnitude of food allergic reactions. An increasing number of bacterial metabolites has recently been shown to regulate directly or indirectly the differentiation of peripherally induced Tregs, most of which co-express the RAR-related orphan receptor gamma t (RORγt). Genetic ablation provided additional direct evidence for the importance of RORγt+ Tregs in food allergy. Future strategies for the stratification of food allergic patients with the aim to manipulate the intestinal microbiota by means of fecal transplantation efforts, pre- or probiotic regimens or for boosting oral immunotherapy may improve diagnosis and therapy. In this review some of the key underlying mechanisms are summarized and future directions for potential microbial therapy are explored.}, }
@article {pmid32920548, year = {2020}, author = {Zhang, L and Zhou, W and Zhan, L and Hou, S and Zhao, C and Bi, T and Lu, X}, title = {Fecal microbiota transplantation alters the susceptibility of obese rats to type 2 diabetes mellitus.}, journal = {Aging}, volume = {12}, number = {17}, pages = {17480-17502}, pmid = {32920548}, issn = {1945-4589}, abstract = {Obesity is one of the susceptibility factors for type 2 diabetes (T2DM), both of which could accelerate the aging of the body and bring many hazards. A causal relationship is present between intestinal microbiota and body metabolism, but how the microbiota play a role in the progression of obesity to T2DM has not been elucidated. In this study, we transplanted healthy or obese-T2DM intestinal microbiota to ZDF and LZ rats, and used 16S rRNA and targeted metabonomics to evaluate the directional effect of the microbiota on the susceptibility of obese rats to T2DM. The glycolipid metabolism phenotype could be changed bidirectionally in obese rats instead of in lean ones. One possible mechanism is that the microbiota and metabolites alter the structure of the intestinal tract, and improve insulin and leptin resistance through JAK2 / IRS / Akt pathway. It is worth noting that 7 genera, such as Lactobacillus, Clostridium and Roche, can regulate 15 metabolites, such as 3-indolpropionic acid, acetic acid and docosahexaenoic acid, and have a significant improvement on glycolipid metabolism phenotype. Attention to intestinal homeostasis may be the key to controlling obesity and preventing T2DM.}, }
@article {pmid32920061, year = {2020}, author = {Seong, H and Lee, SK and Cheon, JH and Yong, DE and Koh, H and Kang, YK and Jeong, WY and Lee, WJ and Sohn, Y and Cho, Y and Hyun, JH and Baek, YJ and Kim, MH and Kim, JH and Ahn, JY and Ku, NS and Jeong, SJ and Yeom, JS and Cho, MS and Lee, JH and Kim, BY and Choi, JY}, title = {Fecal Microbiota Transplantation for multidrug-resistant organism: Efficacy and Response prediction.}, journal = {The Journal of infection}, volume = {}, number = {}, pages = {4834}, doi = {10.1016/j.jinf.2020.09.003}, pmid = {32920061}, issn = {1532-2742}, abstract = {OBJECTIVES: The increasing prevalence of multidrug-resistant microorganisms (MDRO) is increasing the frequency of poor clinical outcomes, prolonging hospitalizations, and raising healthcare costs. This study evaluated the eradication efficacy of fecal microbiota transplantation (FMT) and identified microbial and functional biomarkers of MDRO decolonization.<br><br>METHODS: Fecal solution obtained from healthy unrelated donors was infused in the participants' guts which had been colonized with carbapenemase-producing enterobacteriacea (CPE), vancomycin-resistant enterococci (VRE), or both CPE and VRE. Fecal samples from recipients were collected and microbiome changes before and after FMT were assessed.<br><br>RESULTS: Twenty-four (68.6%) out of 35 patients were decolonized within one year of receiving FMT. Multivariate analysis showed that FMT (FMT: hazard ratio (HR) = 5.343, 95% confidence interval (CI) = 1.877-15.212, p = 0.002) and MDRO types (CPE: HR = 11.146, 95% CI = 2.420-51.340, p = 0.002; CPE/VRE: HR = 2.948, 95% CI = 1.200-7.246, p = 0.018; VRE served as the reference) were significant independent factors associated with time to decolonization. Microbiota analysis showed higher richness and biodiversity before FMT resulted in VRE decolonization. The species Clostridium ramosum and the genuses Anaerostipes and Eisenbergiella could serve as taxonomic biomarkers and K02017 could serve as a functional biomarker for VRE clearance.<br><br>CONCLUSION: FMT is an effective way to decolonize MDRO and its effectiveness may be predicted by microbiome analysis.}, }
@article {pmid32917563, year = {2020}, author = {Apartsin, K and Smirnova, V}, title = {Convalescent fecal microbiota transplantation as a possible treatment for COVID-19.}, journal = {Clinics and research in hepatology and gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {32917563}, issn = {2210-741X}, }
@article {pmid32911536, year = {2020}, author = {Vicente Dueñas, C and Janssen, S and Oldenburg, M and Auer, F and González Herrero, I and Casado-García, A and Isidro-Hernández, M and Raboso-Gallego, J and Westhoff, P and Pandyra, AA and Hein, D and Gössling, KL and Alonso-López, D and De Las Rivas, J and Bhatia, S and Garcia-Criado, FJ and García Cenador, MB and Weber, APM and Köhrer, K and Hauer, J and Fischer, U and Sanchez-Garcia, I and Borkhardt, A}, title = {An intact gut microbiome protects genetically predisposed mice against leukemia.}, journal = {Blood}, volume = {}, number = {}, pages = {}, doi = {10.1182/blood.2019004381}, pmid = {32911536}, issn = {1528-0020}, abstract = {The majority of childhood leukemias are precursor B cell-acute lymphoblastic leukemias (pB-ALL) caused by a combination of prenatal genetic predispositions and oncogenic events occurring after birth. Although genetic predispositions are frequent in children (>1-5%), fewer than 1% of genetically predisposed carriers will develop pB-ALL. While infectious stimuli are believed to play a major role in leukemogenesis, the critical determinants are not well defined. Here, employing murine models of pB-ALL, we show that microbiome disturbances incurred by antibiotic treatment early in life were sufficient to induce leukemia in genetically predisposed mice even in the absence of infectious stimuli and independent of T-cells. Using V4 and full-length 16S rRNA sequencing of a series of fecal samples, we found that genetic predisposition to pB-ALL (Pax5 heterozygosity or ETV6-RUNX1 fusion) shaped a distinct gut microbiome. Machine learning accurately (96.8%) predicted genetic predisposition using 40 of 3,983 amplicon sequence variants (ASVs) as proxies for bacterial species. Transplantation of either wild type (WT) or Pax5+/- hematopoietic bone marrow cells into WT recipient mice revealed that the microbiome is shaped and determined in a donor-genotype-specific manner. Gas chromatography-mass spectrometric (GC-MS) analyses of sera from WT and Pax5+/- mice demonstrated the presence of a genotype-specific distinct metabolomic profile. Taken together, our data indicate that it is a lack of commensal microbiota rather than the presence of specific bacteria that promotes leukemia in genetically predisposed mice. Future large-scale longitudinal studies are required to determine whether targeted microbiome modification in children predisposed to pB-ALL could become a successful prevention strategy.}, }
@article {pmid32909356, year = {2020}, author = {Chen, M and Liu, XL and Zhang, YJ and Nie, YZ and Wu, KC and Shi, YQ}, title = {Efficacy and safety of fecal microbiota transplantation by washed preparation in patients with moderate to severely active ulcerative colitis.}, journal = {Journal of digestive diseases}, volume = {}, number = {}, pages = {}, doi = {10.1111/1751-2980.12938}, pmid = {32909356}, issn = {1751-2980}, support = {81600443//National Natural Science Foundation of China/ ; 81873554//National Natural Science Foundation of China/ ; }, abstract = {OBJECTIVE: We aimed to evaluate the short-term efficacy and safety of fecal microbiota transplantation (FMT) by washed preparation for moderate to severely active UC.<br><br>METHODS: An open-label prospective trial was conducted in an inflammatory bowel disease (IBD) tertiary referral center from April 2016 to March 2018. Patients with moderate to severely active UC were randomly assigned to undergo FMT thrice on day 1, 3 and 5 by nasojejunal tube (NJT) or transendoscopic enteral tubing (TET). The primary end-point was a clinical response at week 2 post-FMT. The secondary end-points were clinical and endoscopic remission at week 12 post-FMT, safety and disease progression.<br><br>RESULTS: Of the nine patients included, 77.8% (7/9) achieved a clinical response at week 2. And 55.6% (5/9) and 33.3% (3/9), respectively, achieved clinical remission and endoscopic remission at week 12. In two patients who had no response to FMT, one switched to anti-tumor necrosis factor-α therapy, and the other underwent a colectomy. FMT was delivered through NJT in 44.4% (4/9) of the patients, while TET was used in 55.6% (5/9). The clinical outcomes did not differ significantly based on the delivery route (P > 0.05). Adverse events, all mild and self-limiting, were observed in 33.3% (3/9) of the patients.<br><br>CONCLUSIONS: FMT by washed preparation appears to be a safe and effective adjunct therapy for moderate to severely active UC during a short-term follow-up. The efficacy did not differ significantly between the NJT or TET delivery routes. Further randomized controlled studies are needed to confirm these findings.}, }
@article {pmid32908211, year = {2020}, author = {Park, JC and Im, SH}, title = {Of men in mice: the development and application of a humanized gnotobiotic mouse model for microbiome therapeutics.}, journal = {Experimental &amp; molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/s12276-020-0473-2}, pmid = {32908211}, issn = {2092-6413}, abstract = {Considerable evidence points to the critical role of the gut microbiota in physiology and disease. The administration of live microbes as a therapeutic modality is increasingly being considered. However, key questions such as how to identify candidate microorganisms and which preclinical models are relevant to recapitulate human microbiota remain largely unanswered. The establishment of a humanized gnotobiotic mouse model through the fecal microbiota transplantation of human feces into germ-free mice provides an innovative and powerful tool to mimic the human microbial system. However, numerous considerations are required in designing such a model, as various elements, ranging from the factors pertaining to human donors to the mouse genetic background, affect how microbes colonize the gut. Thus, it is critical to match the murine context to that of human donors to provide a continuous and faithful progression of human flora in mice. This is of even greater importance when the need for accuracy and reproducibility across global research groups are taken into account. Here, we review the key factors that affect the formulation of a humanized mouse model representative of the human gut flora and propose several approaches as to how researchers can effectively design such models for clinical relevance.}, }
@article {pmid32906656, year = {2020}, author = {Roussin, L and Prince, N and Perez-Pardo, P and Kraneveld, AD and Rabot, S and Naudon, L}, title = {Role of the Gut Microbiota in the Pathophysiology of Autism Spectrum Disorder: Clinical and Preclinical Evidence.}, journal = {Microorganisms}, volume = {8}, number = {9}, pages = {}, doi = {10.3390/microorganisms8091369}, pmid = {32906656}, issn = {2076-2607}, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 160 people in the world. Although there is a strong genetic heritability to ASD, it is now accepted that environmental factors can play a role in its onset. As the prevalence of gastrointestinal (GI) symptoms is four-times higher in ASD patients, the potential implication of the gut microbiota in this disorder is being increasingly studied. A disturbed microbiota composition has been demonstrated in ASD patients, accompanied by altered production of bacterial metabolites. Clinical studies as well as preclinical studies conducted in rodents have started to investigate the physiological functions that gut microbiota might disturb and thus underlie the pathophysiology of ASD. The first data support an involvement of the immune system and tryptophan metabolism, both in the gut and central nervous system. In addition, a few clinical studies and a larger number of preclinical studies found that modulation of the microbiota through antibiotic and probiotic treatments, or fecal microbiota transplantation, could improve behavior. Although the understanding of the role of the gut microbiota in the physiopathology of ASD is only in its early stages, the data gathered in this review highlight that this role should be taken in consideration.}, }
@article {pmid32905484, year = {2020}, author = {Cheung, MK and Yue, GGL and Tsui, KY and Gomes, AJ and Kwan, HS and Chiu, PWY and Lau, CBS}, title = {Discovery of an interplay between the gut microbiota and esophageal squamous cell carcinoma in mice.}, journal = {American journal of cancer research}, volume = {10}, number = {8}, pages = {2409-2427}, pmid = {32905484}, issn = {2156-6976}, abstract = {Esophageal squamous cell carcinoma (ESCC) is the main type of esophageal cancer (EC) worldwide, causing half a million deaths each year. Recent evidence has demonstrated the role of the gut microbiota in health and disease. However, our current understanding of the gut microbiome in EC remains scarce. Here, we characterized the gut and esophageal microbiome in a metastatic mouse model of ESCC and examined the functional roles of the gut microbiota in EC development in fecal microbiota transplantation (FMT) experiments. Nude mice intraperitoneally xenografted with human EC-109 cells showed significant alterations in the overall structure, but not alpha diversity, of the gut and esophageal microbiome as compared to naïve control mice. Xenograft of EC cells depleted the order Pasteurellales in the gut microbiome, and enriched multiple predicted metabolic pathways, including those involved in carbohydrate and lipid metabolism, in the esophageal microbiome. FMT of stool from healthy mice to antibiotic-treated xenograft-bearing mice significantly attenuated liver metastasis, suggesting a protective role of the commensal gut microbiota in EC. Moreover, we showed that combination chemotherapy with cisplatin and 5-fluorouracil, and the anti-EC medicinal herb Andrographis paniculata (AP) differentially affected the gut and esophageal microbiome in EC. FMT experiment revealed a reduced anti-metastatic efficacy of AP on liver metastasis in antibiotic-treated xenograft-bearing mice, suggesting a role of the commensal gut microbiota in the anti-metastatic efficacy of the herb. In conclusion, our findings reveal for the first time an interplay between the gut microbiota and EC and provide insights into the treatment strategies for EC.}, }
@article {pmid32901505, year = {2020}, author = {Lozupone, M and D'Urso, F and Piccininni, C and Montagna, M and Sardone, R and Resta, E and Dibello, V and Daniele, A and Giannelli, G and Bellomo, A and Panza, F}, title = {The relationship between epigenetics and microbiota in neuropsychiatric diseases.}, journal = {Epigenomics}, volume = {12}, number = {17}, pages = {1559-1568}, doi = {10.2217/epi-2020-0053}, pmid = {32901505}, issn = {1750-192X}, abstract = {Microbiota might be considered as a pool for environmental epigenetic factors. Evidence is accumulating that environmental exposures - including microbes, diet, drugs - play a role in the pathogenesis of many neuropsychiatric disorders. Underlying mechanisms are complex, involving the sensitive interplay of genetics with epigenetics, neuroinflammation and the innate immune system. Modifications of microbiota affect neurogenesis and the maturation of microglia, influencing social behavior, stress-related responses and fear learning mechanisms. The excitatory neurons in the medial prefrontal cortex appear to play a key role. The mechanisms through which antibiotics administration may modulate microbiota and, therefore, behavior and neuropsychiatric disorders, may be influenced by several variables such as pre-existing gastrointestinal inflammation, the baseline microbiota composition, diet and stress perception. Probiotics, individualized diet, antibiotics and fecal transplantation could positively modulate the effects of epigenetic factors on neuropsychiatric disorders.}, }
@article {pmid32899236, year = {2020}, author = {Wang, SC and Chen, YC and Chen, SJ and Lee, CH and Cheng, CM}, title = {Alcohol Addiction, Gut Microbiota, and Alcoholism Treatment: A Review.}, journal = {International journal of molecular sciences}, volume = {21}, number = {17}, pages = {}, pmid = {32899236}, issn = {1422-0067}, support = {108-2314-B-695 -002 -//Ministry of Science and Technology, Taiwan/ ; }, abstract = {Alcohol addiction is a leading risk factor for personal death and disability. In 2016, alcohol use caused 2.2% of female deaths and 6.8% of male deaths, and disability-adjusted life years (DALYs) were 2.3% in female and 8.9% in male. Individuals with alcohol use disorder are at high risk of anxiety, depression, impaired cognition performance, and illicit drug use and are comorbid with liver disease, such as alcoholic hepatitis and liver cirrhosis, which is a major cause of personal death and disability worldwide. Psychological interventions, such as cognitive behavior therapy and motivational interviewing, as well as medical treatments, such as disulfiram, naltrexone, acamprosate, and nalmefene, are used for the treatment of alcohol addiction in Europe and the United States. However, the effect of current interventions is limited, and the need for additional interventions is substantial. Alcohol use impairs the intestinal barrier and causes changes to the intestinal permeability as well as the gut microbiota composition. Emerging studies have tried to reveal the role of the gut-brain axis among individuals with alcohol use disorder with or without alcohol liver disease. Bacterial products penetrate the impaired intestinal barrier and cause central inflammation; changes to the gut microbiota impair enterohepatic circulation of bile acids; alcohol abuse causes shortage of vital nutrients such as thiamine. Several studies have suggested that probiotics, through either oral administration or fecal microbiota transplantation, increased intestinal levels of potentially beneficial bacteria such as bifidobacteria and lactobacilli, improving the levels of liver-associated enzymes in patients with mild alcoholic hepatitis, and demonstrating beneficial psychotropic effects on anxiety and depression. In addition to medications for alcohol addiction, gene editing therapy such as clustered regularly interspaced short palindromic repeats (CRISPRs) may be another potential research target. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are associated with ADH and ALDH genes, are major enzymes involved in alcohol metabolism, and gene editing approaches may have the potential to directly modify specific genes to treat alcoholism caused by genetic defects. Further research is needed to study the effect of the combined treatment for alcohol addiction.}, }
@article {pmid32896201, year = {2020}, author = {Galan-Ros, J and Ramos-Arenas, V and Conesa-Zamora, P}, title = {Predictive values of colon microbiota in the treatment response to colorectal cancer.}, journal = {Pharmacogenomics}, volume = {21}, number = {14}, pages = {1045-1059}, doi = {10.2217/pgs-2020-0044}, pmid = {32896201}, issn = {1744-8042}, abstract = {The crosstalk between the colon mucosa and the microbiota represents a complex and delicate equilibrium. Gastrointestinal diseases such as inflammatory bowel disease and colorectal cancer (CRC) are associated with a state of altered microbiota composition known as dysbiosis, which seems to play a causative role in some of these illnesses. Recent reports have shown that the colorectal microbiome is responsible for the response and safety to treatments against CRC, especially immunotherapy, hence opening the possibility to use bacteria as a predictive marker and also as a therapeutic agent. The review objective is to summarize updated reports about the the implication of the colorectal microbiome in the development of CRC, in treatment response and its potential as a therapeutic approach.}, }
@article {pmid32893721, year = {2020}, author = {Martinez-Gili, L and McDonald, JAK and Liu, Z and Kao, D and Allegretti, JR and Monaghan, TM and Barker, GF and Miguéns Blanco, J and Williams, HRT and Holmes, E and Thursz, MR and Marchesi, JR and Mullish, BH}, title = {Understanding the mechanisms of efficacy of fecal microbiota transplant in treating recurrent Clostridioides difficile infection and beyond: the contribution of gut microbial-derived metabolites.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1810531}, pmid = {32893721}, issn = {1949-0984}, abstract = {Fecal microbiota transplant (FMT) is a highly-effective therapy for recurrent Clostridioides difficile infection (rCDI), and shows promise for certain non-CDI indications. However, at present, its mechanisms of efficacy have remained poorly understood. Recent studies by our laboratory have noted the particular key importance of restoration of gut microbe-metabolite interactions in the ability of FMT to treat rCDI, including the impact of FMT upon short chain fatty acid (SCFAs) and bile acid metabolism. This includes a significant impact of these metabolites upon the life cycle of C. difficile directly, along with potential postulated additional benefits, including effects upon host immune response. In this Addendum, we first present an overview of these recent advancements in this field, and then describe additional novel data from our laboratory on the impact of FMT for rCDI upon several gut microbial-derived metabolites which had not previously been implicated as being of relevance.}, }
@article {pmid32881759, year = {2020}, author = {Dawoodbhoy, FM and Patel, BK and Patel, K and Bhatia, M and Lee, CN and Moochhala, SM}, title = {Gut Microbiota Dysbiosis as a Target for Improved Post-Surgical Outcomes and Improved Patient Care. A Review of Current Literature.}, journal = {Shock (Augusta, Ga.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/SHK.0000000000001654}, pmid = {32881759}, issn = {1540-0514}, abstract = {Critical illness results in significant changes in the human gut microbiota, leading to the breakdown of the intestinal barrier function, which plays a role in the pathogenesis of multiple organ dysfunction. Patients with sepsis/acute respiratory distress syndrome (ARDS) have a profoundly distorted intestinal microbiota rhythm, which plays a considerable role in the development of gut-derived infections and intestinal dysbiosis. Despite recent medical developments, post-surgical complications are associated with a high morbidity and mortality rate. Bacterial translocation (BT), which is the movement of bacteria and bacterial products across the intestinal barrier, was shown to be a mechanism behind sepsis. Current research is focusing on a solution by addressing significant factors that contribute to intestinal dysbiosis, which subsequently leads to multiple organ failure and, thus, mortality. It may, however, be challenging to manipulate the microbiota in critically ill patients for enhanced therapeutic gain. Probiotic manipulation is advantageous for maintaining the gut-barrier defense and for modulating the immune response. Based on available published research, this review aims to address the application of potential strategies in the intensive care unit (ICU), supplemented with current therapeutics by the administration of probiotics, prebiotics, and fecal microbiota transplant, to reduce post-surgical complications of sepsis/ARDS in critically ill patients.}, }
@article {pmid32880314, year = {2020}, author = {Labuschaigne, M and Slabbert, M and Budree, S and Hoosien, E and Brink, A and Blockman, M}, title = {The ethicolegal framework relevant to human faecal microbiota transplants in South Africa: Part 3. Stool as a 'drug' or medicine.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {110}, number = {8}, pages = {819-821}, doi = {10.7196/SAMJ.2020.v110i8.15070}, pmid = {32880314}, issn = {2078-5135}, mesh = {Biological Specimen Banks/legislation &amp; jurisprudence ; *Fecal Microbiota Transplantation ; Feces ; Humans ; South Africa ; *Therapeutic Human Experimentation/ethics/legislation &amp; jurisprudence ; Tissue and Organ Procurement/*legislation &amp; jurisprudence ; }, abstract = {The purpose of this article, the last in a series of three exploring the legal framework for the regulation of faecal microbiota transplantation (FMT) in South Africa (SA), is to determine the regulatory framework that applies to microbial-based treatments involving a level of manipulation that exceeds that of basic stool transplantation, e.g. processed FMT-derived products in capsule form. The article highlights the legal requirements for the registration of these products as biological medicines in SA law. Although human stool banks are not regulated in terms of the National Health Act 61 of 2003 (NHA) and regulations, the earlier articles point out that human stool fits the definition of human tissue and human biological material as defined by the NHA. For this reason, stool banks should be considered tissue banks in terms of the NHA and regulations. Healthcare practitioners and researchers involved in FMT banking and transplantation should strive to comply with these regulations in the absence of clear legal direction at present.}, }
@article {pmid32880313, year = {2020}, author = {Labuschaigne, M and Slabbert, M and Budree, S and Hoosien, E and Brink, A and Blockman, M}, title = {The ethicolegal framework relevant to human faecal microbiota transplants in South Africa: Part 2. Human stool as tissue?.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {110}, number = {8}, pages = {816-818}, doi = {10.7196/SAMJ.2020.v110i8.15069}, pmid = {32880313}, issn = {2078-5135}, mesh = {Biological Specimen Banks/legislation &amp; jurisprudence ; *Fecal Microbiota Transplantation ; Feces ; Humans ; South Africa ; Therapeutic Human Experimentation/ethics/legislation &amp; jurisprudence ; Tissue and Organ Procurement/ethics/*legislation &amp; jurisprudence ; }, abstract = {Faecal microbiota transplantation (FMT) has been shown to be an effective treatment for recurrent Clostridioides difficile infection. The purpose of this article, the second of a series of three articles, is to explore the legal framework governing human FMT in South Africa (SA). FMT involves different modes of administration that require different regulatory considerations. The focus of this article is to explore the legal classification of human stool as tissue in terms of the National Health Act 61 of 2003, as well as the regulation of human stool banks as tissue banks. The article concludes with specific recommendations aimed at improving the current regulatory vacuum relating to the regulation of FMT in SA.}, }
@article {pmid32880312, year = {2020}, author = {Labuschaigne, M and Slabbert, M and Budree, S and Hoosien, E and Brink, A and Blockman, M}, title = {The ethicolegal framework relevant to human faecal microbiota transplants in South Africa: Part 1. A legal vacuum.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {110}, number = {8}, pages = {812-815}, doi = {10.7196/SAMJ.2020.v110i8.14563}, pmid = {32880312}, issn = {2078-5135}, mesh = {Biological Specimen Banks/legislation &amp; jurisprudence ; *Fecal Microbiota Transplantation ; Feces ; Gastrointestinal Microbiome ; Humans ; *Legislation, Medical ; South Africa ; }, abstract = {The legal regulation of faecal microbiota transplantation (FMT) in South Africa (SA) is currently unclear. The purpose of this article, the first of three in a series, is to explore the nature, role and clinical application of FMT in SA in order to determine, from a legal perspective, the appropriate regulatory pathways governing FMT as a procedure that may combine approaches for the treatment of drugs, human tissue for transplantation, or clinical treatment as part of the practice of medicine. FMT has been shown to be a novel, safe and effective treatment for recurrent Clostridioides difficile infection (CDI). Stool banks are instrumental in enabling access to FMT for patients and clinicians and help to catalyse research in the microbiome. However, the regulatory landscape in SA remains unclear. Microbial therapies such as FMT are necessary, especially in a time of rising microbiome-associated inflammatory diseases and increasing resistance to traditional antibiotics. FMT is now considered as part of the standard of care for recurrent CDI overseas, but is currently only being used for research purposes in a minority of clinical cases of CDI in SA. This article, which lays the foundation for consideration of this question in three parts, suggests that the relevant regulatory system would depend on the categorisation of human stool as tissue, the exact composition of the FMT, how it is administered to patients, and the relevant levels of manipulation of the stool for FMT-derived products.}, }
@article {pmid32874052, year = {2020}, author = {Yue, B and Yu, ZL and Lv, C and Geng, XL and Wang, ZT and Dou, W}, title = {Regulation of the intestinal microbiota: An emerging therapeutic strategy for inflammatory bowel disease.}, journal = {World journal of gastroenterology}, volume = {26}, number = {30}, pages = {4378-4393}, pmid = {32874052}, issn = {2219-2840}, abstract = {The rapid development of metagenomics, metabolomics, and metatranscriptomics provides novel insights into the intestinal microbiota factors linked to inflammatory bowel disease (IBD). Multiple microorganisms play a role in intestinal health; these include bacteria, fungi, and viruses that exist in a dynamic balance to maintain mucosal homeostasis. Perturbations in the intestinal microbiota disrupt mucosal homeostasis and are closely related to IBD in humans and colitis in mice. Therefore, preventing or correcting the imbalance of microbiota may serve as a novel prevention or treatment strategy for IBD. We review the most recent evidence for direct or indirect interventions targeting intestinal microbiota for treatment of IBD in order to overcome the current limitations of IBD therapies and shed light on personalized treatment options.}, }
@article {pmid32871960, year = {2020}, author = {Xue, LJ and Yang, XZ and Tong, Q and Shen, P and Ma, SJ and Wu, SN and Zheng, JL and Wang, HG}, title = {Fecal microbiota transplantation therapy for Parkinson's disease: A preliminary study.}, journal = {Medicine}, volume = {99}, number = {35}, pages = {e22035}, pmid = {32871960}, issn = {1536-5964}, mesh = {Aged ; Colonoscopy ; Fecal Microbiota Transplantation/adverse effects/methods/*statistics &amp; numerical data ; Female ; Humans ; Intubation, Gastrointestinal ; Male ; Middle Aged ; Parkinson Disease/*therapy ; Patient Satisfaction ; Pilot Projects ; Young Adult ; }, abstract = {Imbalances in the gut microbiota mediate the progression of neurodegenerative diseases such as Parkinson's disease (PD). Fecal microbiota transplantation (FMT) is currently being explored as a potential therapy for PD. The objective of this study was to assess the efficacy and safety of FMT on PD. Fifteen PD patients were included, 10 of them received FMT via colonoscopy (colonic FMT group) and 5 received FMT via nasal-jejunal tube (nasointestinal FMT group). The score of PSQI, HAMD, HAMA, PDQ-39, NMSQ and UPDRS-III significantly decreased after FMT treatment (all P < .05). Colonic FMT group showed significant improvement and longer maintenance of efficacy compared with nasointestinal FMT (P = .002). Two patients achieved self-satisfying outcomes that last for more than 24 months. However, nasointestinal FMT group had no significant therapeutic effect, although UPDRS-III score slightly reduced. There were no patients were satisfied with nasointestinal FMT for more than 3 months. Among 15 PD patients, there were 5 cases had adverse events (AEs), including diarrhea (2 cases), abdominal pain (2 cases) and flatulence (1 case). These AEs were mild and self-limiting. We conclude that FMT can relieve the motor and non-motor symptoms with acceptable safety in PD. Compared with nasointestinal FMT, colonic FMT seems better and preferable.}, }
@article {pmid32866799, year = {2020}, author = {Marcondes Ávila, PR and Fiorot, M and Michels, M and Dominguini, D and Abatti, M and Vieira, A and de Moura, AB and Behenck, JP and Borba, LA and Botelho, MEM and Réus, GZ and Dal-Pizzol, F and Ritter, C}, title = {Effects of microbiota transplantation and the role of the vagus nerve in gut-brain axis in animals subjected to chronic mild stress.}, journal = {Journal of affective disorders}, volume = {277}, number = {}, pages = {410-416}, doi = {10.1016/j.jad.2020.08.013}, pmid = {32866799}, issn = {1573-2517}, abstract = {INTRODUCTION: Currently, there is a growing emphasis on the study of intestinal signaling as an influencer in the pathophysiology of neuropsychiatric diseases, and the gut-brain axis is recognized as a communication route through endocrine, immune, and neural pathways (vagus nerve). Studies have shown that diets that modify the microbiota can reduce stress-related behavior and hypothalamic-pituitary-adrenal axis activation. Investigators have used fecal microbiota transplantation (FMT) approaches to demonstrate that stress-related microbiota composition plays a causal role in behavioral changes.<br><br>AIM: We hypothesized that FMT may present immunomodulatory, biochemical, endocrine, cognitive, and behavioral benefits in stress situations and that these changes can be mediated via the vagus nerve.<br><br>METHODS: Animals were subjected to a chronic mild stress (CMS) protocol. In one experiment, animals were divided into five groups: control, control + FMT, control + FMT + CMS, CMS + saline, and CMS + FMT. The animals received FMT, and behavioral tests were performed; cytokine and carbonyl levels were measured. In a second experiment, animals were submitted to vagotomy and divided into two groups: CMS + FMT and CMS + vagotomy + FMT.<br><br>RESULTS: Animals submitted to the CMS protocol or that received FMT from stressed animals showed behavioral changes and changes in neuroactive substances (increased IL-6 and TNF-α levels and carbonyl proteins). The FMT of healthy donors improved the analyzed parameters. In addition, vagotomy influenced beneficial FMT results, confirmed by behavioral testing and protein carbonyl in the hippocampus.<br><br>CONCLUSION: Manipulation of the microbiota reversed the behavioral and biochemical changes induced by the CMS protocol, and the vagus nerve influenced the gut-brain axis response.}, }
@article {pmid32865119, year = {2020}, author = {Magruder, M and Edusei, E and Zhang, L and Albakry, S and Satlin, MJ and Westblade, LF and Malha, L and Sze, C and Lubetzky, M and Dadhania, DM and Lee, JR}, title = {Gut commensal microbiota and decreased risk for Enterobacteriaceae bacteriuria and urinary tract infection.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1805281}, pmid = {32865119}, issn = {1949-0984}, abstract = {Urinary tract infection (UTI) is a common complication in kidney transplant recipients and can lead to significant morbidity and mortality. Recent evidence supports a role for the gut as a source for UTIs but little is known about the relationship between gut commensal bacteria and UTI development. We hypothesized that the abundance of gut commensal bacteria is associated with a lower risk of developing bacteriuria and UTIs. We performed gut microbiome profiling using 16S rRNA gene sequencing of the V4-V5 hypervariable region on 510 fecal specimens in 168 kidney transplant recipients. Fifty-one kidney transplant recipients (30%) developed Enterobacteriaceae bacteriuria within the first 6 months after transplantation (Enterobacteriaceae Bacteriuria Group) and 117 did not (No Enterobacteriaceae Bacteriuria Group). The relative abundances of Faecalibacterium and Romboutsia were significantly higher in the fecal specimens from the No Enterobacteriaceae Bacteriuria Group than those from the Enterobacteriaceae Bacteriuria Group (Adjusted P value<.01). The combined relative abundance of Faecalibacterium and Romboutsia was inversely correlated with the relative abundance of Enterobacteriaceae (r = -0.13, P = .003). In a multivariable Cox Regression, a top tercile cutoff of the combined relative abundance of Faecalibacterium and Romboutsia of ≥13.7% was independently associated with a decreased risk for Enterobacteriaceae bacteriuria (hazard ratio 0.3, P = .02) and Enterobacteriaceae UTI (hazard ratio 0.4, P = .09). In conclusion, we identify bacterial taxa associated with decreased risk for Enterobacteriaceae bacteriuria and Enterobacteriaceae UTI in kidney transplant recipients, which supports future studies on modulating the gut microbiota as a novel treatment for preventing UTIs.}, }
@article {pmid32864024, year = {2020}, author = {Raghu Subramanian, C and Talluri, S and Khan, SU and Katz, JA and Georgetson, M and Sinh, P}, title = {Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in Patients With Multiple Comorbidities: Long-Term Safety and Efficacy Results From a Tertiary Care Community Hospital.}, journal = {Gastroenterology research}, volume = {13}, number = {4}, pages = {138-145}, pmid = {32864024}, issn = {1918-2805}, abstract = {Background: Cure rates of Clostridium difficile infection (CDI) with fecal microbiota transplant (FMT) have been promising. However, there is debate regarding success of FMT in patients with comorbidities.<br><br>Methods: Electronic chart review was done to collect data on patients who underwent FMT from January 2015 to August 2017. Charts were analyzed in November 2018 with a median follow-up of 25.4 months (interquartile range 20 - 31 months).<br><br>Results: Twenty patients underwent FMT. The primary success rate at our institution was 90% and overall success rate was 100%. Six patients (43%) had FMT failure (two early and four late).<br><br>Conclusions: This case series is a description of our center's initial experience with FMT for treatment of recurrent CDI. Our high success rate reiterates the efficacy and safety of FMT in this population including patients with comorbidities.}, }
@article {pmid32862830, year = {2020}, author = {Kwak, S and Choi, J and Hink, T and Reske, KA and Blount, K and Jones, C and Bost, MH and Sun, X and Burnham, CD and Dubberke, ER and Dantas, G and , }, title = {Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {125}, pmid = {32862830}, issn = {2049-2618}, support = {5U54CK000162/CC/CDC HHS/United States ; }, abstract = {BACKGROUND: Intestinal microbiota restoration can be achieved by complementing a subject's perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another emerging application of interest is reducing antibiotic-resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome.<br><br>RESULTS: All patients exhibited significant recovery of gut microbiome diversity and a decrease of ARG relative abundance during the first 7 days post-treatment. However, the microbiome and resistome shifts toward average configurations from unperturbed individuals were more significant and longer-lasting in RBX2660 recipients compared to placebo. We quantified microbiome and resistome modification by RBX2660 using a novel &quot;transplantation index&quot; metric. We identified taxonomic and metabolic features distinguishing the baseline microbiome of non-transplanted patients and taxa specifically enriched during the process of transplantation. We elucidated the correlation between resistome and taxonomic transplantations and post-treatment dynamics of patient-specific and RBX2660-specific ARGs. Whole genome sequencing of AROs cultured from RBX2660 product and patient samples indicate ARO eradication in patients via RBX2660 administration, but also, to a lesser extent, introduction of RBX2660-derived AROs.<br><br>CONCLUSIONS: Through shotgun metagenomic sequencing, we elucidated the effects of RBX2660 in the microbiome and resistome. Antibiotic discontinuation alone resulted in significant recovery of gut microbial diversity and reduced ARG relative abundance, but RBX2660 administration more rapidly and completely changed the composition of patients' microbiome, resistome, and ARO colonization by transplanting RBX2660 microbiota into the recipients. Although ARGs and AROs were transmitted through RBX2660, the resistome post-RBX2660 more closely resembled that of the administered product-a proxy for the donor-than an antibiotic perturbed state.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299570 . Registered 19 November 2014 Video Abstract.}, }
@article {pmid32861068, year = {2020}, author = {Zhang, F and Zhang, X and Yu, J and Tan, Y and Guo, P and Wu, C}, title = {The gut microbiota confers the lipid-lowering effect of bitter melon (Momordica charantia L.) In high-fat diet (HFD)-Induced hyperlipidemic mice.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {131}, number = {}, pages = {110667}, doi = {10.1016/j.biopha.2020.110667}, pmid = {32861068}, issn = {1950-6007}, abstract = {The bitter melon (Momordica charantia) is a medical food with well-documented hypoglycemic and anti-hyperlipidemic activities. Previous studies showed that the M. charantia fruit (MC) could modulate the gut microbiota, but whether this modulation is essential for MC's pharmacological effects is largely unknown. Here, we assessed the causality of gut microbes in MC-elicited anti-hyperlipidemic effects for the first time. Oral administration of MC significantly prevented hyperlipidemia, but this amelioration substantially diminished when co-treated with antibiotics. Transplantation of gut flora from MC-treated donor mice also significantly decreased serum lipids. The microbiological analysis revealed that MC moderately increased diversity and shifted the overall structure of gut microbiota. It selectively enhanced the relative abundance of short-chain fatty acid (SCFAs)-producing genera and increased fecal SCFAs content. These results demonstrate that M. charantia fruit (MC) may exert an anti-hyperlipidemic effect through modulating gut microbes and increasing SCFAs production.}, }
@article {pmid32860791, year = {2020}, author = {Rinott, E and Youngster, I and Meir, AY and Tsaban, G and Zelicha, H and Kaplan, A and Knights, D and Tuohy, K and Fava, F and Scholz, MU and Ziv, O and Reuven, E and Tirosh, A and Rudich, A and Blüher, M and Stumvoll, M and Ceglarek, U and Clement, K and Koren, O and Wang, DD and Hu, FB and Stampfer, MJ and Shai, I}, title = {Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2020.08.041}, pmid = {32860791}, issn = {1528-0012}, abstract = {BACKGROUND &amp; AIMS: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight loss phase.<br><br>METHODS: In the DIRECT-PLUS weight loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to (1)healthy dietary guidelines, (2)Mediterranean diet, and (3)green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both iso-caloric Mediterranean groups consumed 28g/day walnuts (+440mg/d polyphenols provided). The green-Mediterranean dieters further consumed green tea (3-4 cups/day) and a Wolffia-globosa (Mankai strain;100g/day) green shake (+800mg/day polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight regain phase (months 6-14). Secondary outcomes were gastrointestinal symptoms, waist-circumference, glycemic status and changes in the gut microbiome, as measured by metagenomic sequencing and 16s-rRNA. We validated the results in a parallel in-vivo study of mice specifically fed with Mankai, as compared to control chow diet.<br><br>RESULTS: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules over the transplantation period. No aFMT-related adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6-14 (aFMT, 30.4% vs. placebo, 40.6%;P=.28), aFMT significantly attenuated weight regain in the green-Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P=.02), but not in the dietary guidelines (P=.57) or Mediterranean diet (P=.64) groups (P for the interaction=.03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89cm vs placebo, 5.05cm;P=.01) and insulin rebound (aFMT, 1.46±3.6μIU/ml vs placebo, 1.64±4.7μIU/ml;P=.04) in the green Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction=.04 and .03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight loss phase, and to prompt preservation of weight loss-associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) following the aFMT. In mice, Mankai-modulated aFMT in the weight loss phase, compared with control diet aFMT, significantly prevented weight regain, and resulted in better glucose tolerance, during a high-fat-diet induced regain phase (P<.05 for all).<br><br>CONCLUSIONS: Autologous FMT, collected during the weight loss phase and administrated in the regain phase, might preserve weight loss and glycemic control and is associated with specific microbiome signatures. High-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure. (ClinicalTrials.gov number, NCT03020186).}, }
@article {pmid32860788, year = {2020}, author = {Kong, L and Lloyd-Price, J and Vatanen, T and Seksik, P and Beaugerie, L and Simon, T and Vlamakis, H and Sokol, H and Xavier, RJ}, title = {Linking strain engraftment in fecal microbiota transplantation with maintenance of remission in Crohn's disease.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2020.08.045}, pmid = {32860788}, issn = {1528-0012}, support = {R01 AT009708/AT/NCCIH NIH HHS/United States ; }, abstract = {BACKGROUND AND AIMS: Crohn's Disease (CD) is a chronic gastrointestinal disease resulting from the dysfunctional interplay between genetic susceptibility, the immune system and commensal intestinal microbiota. Emerging evidence suggests that treatment by suppression of the immune response and replacement of the microbiota through Fecal Microbiota Transplantation (FMT) is a promising approach for the treatment of CD.<br><br>METHODS: We obtained stool metagenomes from CD patients in remission and assessed gut microbiome composition before and after FMT at the species and strain levels. Longitudinal follow-up evaluation allowed us to identify the gain, loss, and strain replacement of specific species, and link these events to the maintenance of remission in CD.<br><br>RESULTS: We find that FMT had a significant long-term effect on patient microbial compositions, though this was primarily driven by the engraftment of donor species which remained at low abundance. 38% of FMT-driven changes were strain replacements, emphasizing the importance of detailed profiling methods such as metagenomics. Several instances of long-term coexistence between donor and patient strains were also observed. Engraftment of some Actinobacteria, and engraftment or loss of Proteobacteria, were related to better disease outcomes in CD patients who received FMT, while transmission of Bacteroidetes was deleterious.<br><br>CONCLUSION: Our results suggest clades that may be beneficial to transmit/eliminate through FMT, and thus provide criteria that may help identify personalized FMT donors to more effectively maintain remission in CD patients. The framework established here creates a foundation for future studies centered around the application of FMT and defined microbial communities as a therapeutic approach for treating CD.}, }
@article {pmid32859933, year = {2020}, author = {Ianiro, G and Rossi, E and Thomas, AM and Schinzari, G and Masucci, L and Quaranta, G and Settanni, CR and Lopetuso, LR and Armanini, F and Blanco-Miguez, A and Asnicar, F and Consolandi, C and Iacovelli, R and Sanguinetti, M and Tortora, G and Gasbarrini, A and Segata, N and Cammarota, G}, title = {Faecal microbiota transplantation for the treatment of diarrhoea induced by tyrosine-kinase inhibitors in patients with metastatic renal cell carcinoma.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4333}, pmid = {32859933}, issn = {2041-1723}, mesh = {Aged ; Carcinoma, Renal Cell/*complications ; Diarrhea/*therapy ; Double-Blind Method ; Drug Therapy ; Dysbiosis ; Enzyme Inhibitors/*metabolism ; Fecal Microbiota Transplantation/*methods ; Feces ; Female ; Gastrointestinal Microbiome ; Humans ; Kidney Neoplasms/*complications ; Male ; Middle Aged ; Tissue Donors ; Tyrosine/*metabolism ; }, abstract = {Diarrhoea is one of the most burdensome and common adverse events of chemotherapeutics, and has no standardised therapy to date. Increasing evidence suggests that the gut microbiome can influence the development of chemotherapy-induced diarrhoea. Here we report findings from a randomised clinical trial of faecal microbiota transplantation (FMT) to treat diarrhoea induced by tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (ClinicalTrials.gov number: NCT04040712). The primary outcome is the resolution of diarrhoea four weeks after the end of treatments. Twenty patients are randomised to receive FMT from healthy donors or placebo FMT (vehicle only). Donor FMT is more effective than placebo FMT in treating TKI-induced diarrhoea, and a successful engraftment is observed in subjects receiving donor faeces. No serious adverse events are observed in both treatment arms. The trial meets pre-specified endpoints. Our findings suggest that the therapeutic manipulation of gut microbiota may become a promising treatment option to manage TKI-dependent diarrhoea.}, }
@article {pmid32857289, year = {2020}, author = {Wang, Y and Liu, F and Zhang, G and Su, Y and Sun, X and Chen, Q and Wang, C and Fu, H and He, Y and Zhu, X and Liu, X and Lv, M and Zhao, X and Zhao, X and Li, Y and Wang, Q and Huang, X and Zhang, X}, title = {Gut microbiome alterations and its link to corticosteroid resistance in immune thrombocytopenia.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11427-020-1788-2}, pmid = {32857289}, issn = {1869-1889}, abstract = {Quantitative metagenomic studies have linked the gut microbiota to autoimmune disorders. Here, we performed deep shotgun metagenomic sequencing of fecal samples from 99 immune thrombocytopenia (ITP) patients and 52 healthy controls. Dysbiosis in the gut microbiome of ITP was detected phylogenetically and functionally, and classifier based on species markers distinguished individuals with ITP from healthy controls. In particular, the abundance of Ruminococcus gnavus, Bifidobacterium longum and Akkermansia muciniphila was markedly increased in treatment-naïve ITP patients, and the alterations of microbial species were correlated with clinical indices. Functionally, the secondary bile acid biosynthesis and flagellar assembly were depleted in the gut microbiota of ITP, which may contribute to the onset of ITP by affecting the immune system. Furthermore, we found that corticosteroid treatment affected the gut microbiome of ITP. Compared with corticosteroid-sensitive ITP patients, we identified that the corticosteroid-resistant ITP patients displayed a distinct gut microbiome, which was different from that of the treatment-naïve ITP patients. Together, we provided support for the critical role of gut microbiota in the development of ITP and established a foundation for further research characterizing gut microbiota in relation to corticosteroid resistance of ITP.}, }
@article {pmid32850913, year = {2020}, author = {Ouyang, J and Isnard, S and Lin, J and Fombuena, B and Peng, X and Nair Parvathy, S and Chen, Y and Silverman, MS and Routy, JP}, title = {Treating From the Inside Out: Relevance of Fecal Microbiota Transplantation to Counteract Gut Damage in GVHD and HIV Infection.}, journal = {Frontiers in medicine}, volume = {7}, number = {}, pages = {421}, pmid = {32850913}, issn = {2296-858X}, abstract = {The gastrointestinal (GI) tract is a complex and well-balanced milieu of anatomic and immunological barriers. The epithelial surface of the GI tract is colonized by trillions of microorganisms, known as the gut microbiota, which is considered an &quot;organ&quot; with distinctive endocrine and immunoregulatory functions. Dysregulation of the gut microbiota composition, termed dysbiosis, has been associated with epithelial damage and translocation of microbial products into the circulating blood. Dysbiosis, increased gut permeability and chronic inflammation play a major role on the clinical outcome of inflammatory bowel diseases, graft-vs.-host disease (GVHD) and HIV infection. In this review, we focus on GVHD and HIV infection, conditions sharing gut immune damage leading to dysbiosis. The degree of dysbiosis and level of epithelial gut damage predict poor clinical outcome in both conditions. Emerging interventions are therefore warranted to promote gut microbiota homeostasis and improve intestinal barrier function. Interventions such as anti-inflammatory medications, and probiotics have toxicity and/or limited transitory effects, justifying innovative approaches. Fecal microbiota transplantation (FMT) is one such approach where fecal microorganisms are transferred from healthy donors into the GI tract of the recipient to restore microbiota composition in patients with Clostridium difficile-induced colitis or inflammatory bowel diseases. Preliminary findings point toward a beneficial effect of FMT to improve GVHD and HIV-related outcomes through the engraftment of beneficial donor bacteria, notably those producing anti-inflammatory metabolites. Herein, we critically review the potential for FMT in alleviating dysbiosis and gut damage in patients with GVHD or HIV-infection. Understanding the underlying mechanism by which FMT restores gut function will pave the way toward novel scalable and targeted interventions.}, }
@article {pmid32850467, year = {2020}, author = {Sehgal, R and Bedi, O and Trehanpati, N}, title = {Role of Microbiota in Pathogenesis and Management of Viral Hepatitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {341}, pmid = {32850467}, issn = {2235-2988}, abstract = {Hepatitis is a condition that can be self-limiting or can progress to fibrosis (scarring), cirrhosis, or liver cancer. These days, gut microbiota becomes an important part of our immune system, which is important for disease progression or recovery. Translocation of gut microbial and metabolic products causes intestinal inflammation by modulating immune cells leading to impairment of the primary barrier. But there are limited studies discussing pathogenesis and management of hepatitis with gut microbiota. In this review, we have discussed the role of gut microbiota in pathogenesis and management of various hepatitis, especially hepatitis B and C. We have discussed the role of bacterial products, LPS-TLR4 pathway, and unmethylated CpG DNA, which ultimately affects downstream NF-kB signaling in hepatitis. Finally, we have discussed the role of fecal microbiota transplantation in the management of hepatitis.}, }
@article {pmid32849912, year = {2020}, author = {Barberio, B and Massimi, D and Bonfante, L and Facchin, S and Calò, L and Trevenzoli, M and Savarino, EV and Cattelan, AM}, title = {Fecal microbiota transplantation for norovirus infection: a clinical and microbiological success.}, journal = {Therapeutic advances in gastroenterology}, volume = {13}, number = {}, pages = {1756284820934589}, pmid = {32849912}, issn = {1756-283X}, }
@article {pmid32849279, year = {2020}, author = {Sfera, A and Osorio, C and Diaz, EL and Maguire, G and Cummings, M}, title = {The Other Obesity Epidemic-Of Drugs and Bugs.}, journal = {Frontiers in endocrinology}, volume = {11}, number = {}, pages = {488}, pmid = {32849279}, issn = {1664-2392}, abstract = {Chronic psychiatric patients with schizophrenia and related disorders are frequently treatment-resistant and may require higher doses of psychotropic drugs to remain stable. Prolonged exposure to these agents increases the risk of weight gain and cardiometabolic disorders, leading to poorer outcomes and higher medical cost. It is well-established that obesity has reached epidemic proportions throughout the world, however it is less known that its rates are two to three times higher in mentally ill patients compared to the general population. Psychotropic drugs have emerged as a major cause of weight gain, pointing to an urgent need for novel interventions to attenuate this unintended consequence. Recently, the gut microbial community has been linked to psychotropic drugs-induced obesity as these agents were found to possess antimicrobial properties and trigger intestinal dysbiosis, depleting Bacteroidetes phylum. Since germ-free animals exposed to psychotropics have not demonstrated weight gain, altered commensal flora composition is believed to be necessary and sufficient to induce dysmetabolism. Conversely, not only do psychotropics disrupt the composition of gut microbiota but the later alter the metabolism of the former. Here we review the role of gut bacterial community in psychotropic drugs metabolism and dysbiosis. We discuss potential biomarkers reflecting the status of Bacteroidetes phylum and take a closer look at nutritional interventions, fecal microbiota transplantation, and transcranial magnetic stimulation, strategies that may lower obesity rates in chronic psychiatric patients.}, }
@article {pmid32846251, year = {2020}, author = {Li, L and Wang, Q and Gao, Y and Liu, L and Duan, Y and Mao, D and Luo, Y}, title = {Colistin and amoxicillin combinatorial exposure alters the human intestinal microbiota and antibiotic resistome in the simulated human intestinal microbiota.}, journal = {The Science of the total environment}, volume = {750}, number = {}, pages = {141415}, doi = {10.1016/j.scitotenv.2020.141415}, pmid = {32846251}, issn = {1879-1026}, abstract = {Antibiotics treatment could cause the dysbiosis of human intestinal microbiota and antibiotic resistome. Fecal microbiota transplantation (FMT) has been an efficacious treatment to restore the dysbiosis of intestinal microbiota in a variety of intestinal diseases. However, to data, the effect of the combinatorial antibiotic treatment on microbiota, antibiotic resistome and the FMT for restoration affected by combinatorial antibiotic exposure in the human intestinal microbiota remain unclear. In this study, we systematically investigated the effect of the colistin and amoxicillin combinatorial exposure in the simulator of the human intestinal microbial ecosystem (SHIME) and found that this combinatorial exposure significantly altered (p < 0.05) the human intestinal microbiota and antibiotic resistome. The shift of bacterial community and antibiotic resistome could incompletely recovery to baseline by FMT treatment after combinatorial antibiotic exposure. Additionally, the variance of antibiotic resistome was dominantly driven by the bacterial community (41.18%-68.03%) after the combinatorial antibiotic exposure. Overall, this study first to investigate the influence of the colistin and amoxicillin combinatorial exposure on the intestinal microbiota and antibiotic resistome, and assess the FMT recovery in the simulated human intestinal microbiota, which may potentially provide a correct administration of antibiotics and application of FMT in the clinic.}, }
@article {pmid32842435, year = {2020}, author = {Zhang, W and Jiang, KW}, title = {[Role of gut microbiota in carcinogenesis and treatment for colorectal cancer].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {5}, pages = {516-520}, doi = {10.3760/cma.j.cn.441530-20190820-00314}, pmid = {32842435}, issn = {1671-0274}, support = {2016YFC0106000//National Key Research and Development Plan/ ; }, abstract = {Colorectal cancer is one of the most common malignant tumors of digestive tract. There are a large number of microorganisms in the digestive tract. Under normal physiological conditions, intestinal microorganisms can help with digestion and absorption, resist pathogen invasion and regulate the proliferation of intestinal mucosal cells. However, intestinal microflora imbalance will affect the intestinal microenvironment and intestinal cell function, and is closely related to the incidence and progression of colorectal cancer. Firstly, this paper introduces the changes of intestinal flora in patients with colorectal cancer, and then summarizes the mode of intestinal flora participating in the occurrence of colorectal cancer from the macro level. Then, we elaborate the involvement of intestinal flora in colorectal cancer from the aspects of cytokine-dependent chronic inflammation, DNA damage of intestinal epithelial cells, carcinogenic metabolites of intestinal flora and cellular enzymes, and changes of intestinal immune system. The pathogenesis of colorectal cancer provides a reference for further study of the pathogenesis of colorectal cancer. Finally, from the perspective of intestinal flora and colorectal cancer treatment, we analyze the significance of probiotics and bacterial flora transplantation for the treatment of colorectal cancer, and provide some new treatment ideas and methods that may be useful for the treatment of colorectal cancer.}, }
@article {pmid32842434, year = {2020}, author = {Zhang, XY and Chen, QY and Li, N and Qin, HL}, title = {[Indication selection and clinical application strategies of fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {5}, pages = {509-515}, doi = {10.3760/cma.j.cn.441530-20200110-00015}, pmid = {32842434}, issn = {1671-0274}, support = {SHDC12017112, SHDC12019114//Emerging Cutting-Edge Technology Joint Research Projects of Shanghai/ ; }, abstract = {Fecal microbiota transplant (FMT) has become an effective method for the treatment of recurrent C. difficile infection. In addition, it has shown certain effects in other diseases inside and outside the intestine. A large number of clinical trials have been carried out. However, there is still lack of uniform standard for strategies of FMT. In this paper, we discussed the current hot and controversial issues of FMT from the aspects of indication, donor screening, fecal suspension quality control, methodology, follow-up and efficacy judgment, treatment of adverse reaction and ethical supervision based on our team's clinical experience.}, }
@article {pmid32841976, year = {2020}, author = {Collins, M and DeWitt, M}, title = {Fecal microbiota transplantation in the treatment of Crohn disease.}, journal = {JAAPA : official journal of the American Academy of Physician Assistants}, volume = {33}, number = {9}, pages = {34-37}, doi = {10.1097/01.JAA.0000694964.31958.b9}, pmid = {32841976}, issn = {1547-1896}, abstract = {Fecal microbiota transplantation (FMT) is an alternative treatment option with minimal risk for patients with Crohn disease. This article explains FMT and how it effectively targets the gut microbiota changes associated with the pathogenesis of Crohn disease.}, }
@article {pmid32841646, year = {2020}, author = {Kelly, CR and Laine, LA and Wu, GD}, title = {MONITORING FECAL MICROBIOTA TRANSPLANTATION PRACTICE IN A RAPIDLY EVOLVING HEALTH AND REGULATORY ENVIRONMENT.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2020.08.039}, pmid = {32841646}, issn = {1528-0012}, }
@article {pmid32839368, year = {2020}, author = {Song, DS}, title = {[Medical Treatment of Alcoholic Liver Disease].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {76}, number = {2}, pages = {65-70}, doi = {10.4166/kjg.2020.76.2.65}, pmid = {32839368}, issn = {2233-6869}, abstract = {Alcoholic liver disease is a major cause of liver disease that results in significant morbidity and mortality in Korea. Abstinence is the most important strategy to prevent disease progression. Corticosteroids improve the one-month survival in patients with severe alcoholic hepatitis, but it was not effective on long-term survival. An N-acetylcysteine treatment combined with corticosteroids may provide a short-term survival benefit than corticosteroids alone. Pentoxifylline is unlikely to affect short-term survival. Hence, studies on new therapies, such as granulocyte colony-stimulating factor and fecal microbiota transplantation, are ongoing. This paper briefly reviews the current knowledge of the medical treatment of alcoholic liver disease.}, }
@article {pmid32839363, year = {2020}, author = {Yoon, H and Shim, HI and Seol, M and Shin, CM and Park, YS and Kim, N and Lee, DH}, title = {Factors Related to Outcomes of Fecal Microbiota Transplantation in Patients with Clostridioides difficile Infection.}, journal = {Gut and liver}, volume = {}, number = {}, pages = {}, doi = {10.5009/gnl20135}, pmid = {32839363}, issn = {2005-1212}, abstract = {Background/Aims: The aim of this study was to evaluate factors related to outcomes of fecal microbiota transplantation (FMT) in patients with Clostridioides difficile infection (CDI) and viability of frozen stock for FMT.<br><br>Methods: Clinical data of patients who had received FMT for CDI were prospectively collected. Next-generation 16S rRNA gene sequencing of bacteria was performed from donors' and recipients' stool. Colony-forming units (CFUs) of cultures from frozen stock solutions for FMT were measured at 0, 4, 8, 12, 24, 48 weeks after preparation of the solutions.<br><br>Results: In total, 25 FMT procedures were performed in 20 cases (14 fresh and 11 frozen FMT). Forty-five percent of cases involved fulminant CDI. The overall success rate was 55% after the 1st FMT and 75% after the 2nd FMT. The success rate was significantly higher in partially treated CDI than in refractory CDI (100% vs 71.4%; p=0.001). In successful cases only, the decrease in alpha-diversity in the recipient stool microbiomes was recovered after FMT to a level similar to that in donor stools. There was a significant difference in the microbiome composition in pre-FMT recipients' stool between successful and failed cases (p=0.001). The CFUs of frozen solution for FMT did not decrease for 48 weeks in both aerobic and anaerobic cultures.<br><br>Conclusions: FMT is highly effective in partially treated CDI but not in refractory CDI. The microbiome differs between failed and successful cases. Frozen stock for FMT is viable up to 48 weeks.}, }
@article {pmid32835916, year = {2020}, author = {Zhan, J and Ma, X and Liu, D and Liang, Y and Li, P and Cui, J and Zhou, Z and Wang, P}, title = {Gut microbiome alterations induced by tributyltin exposure are associated with increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {266}, number = {Pt 3}, pages = {115276}, doi = {10.1016/j.envpol.2020.115276}, pmid = {32835916}, issn = {1873-6424}, mesh = {Animals ; Body Weight ; *Gastrointestinal Microbiome ; Glucose ; Homeostasis ; Insulin ; Mice ; Mice, Inbred ICR ; Trialkyltin Compounds ; }, abstract = {Tributyltin (TBT), an organotin compound once widely used in agriculture and industry, has been reported to induce obesity and endocrine disruption. Gut microbiota has a strong connection with the host's physiology. Nevertheless, the influences of TBT exposure on gut microbiota and whether TBT-influenced gut microbiota is related to TBT-induced toxicity remain unclear. To fill these gaps, ICR (CD-1) mice were respectively exposed to TBT at NOEL (L-TBT) and tenfold NOEL (H-TBT) daily by gavage for 8 weeks in the current study. The results showed that TBT exposure significantly increased body weight as well as epididymal fat, and led to adipocyte hypertrophy, dyslipidemia and impaired glucose and insulin homeostasis in mice. Additionally, TBT exposure significantly decreased the levels of T4, T3 and testosterone in serum. Also of note, TBT exposure changed gut microbiota composition mainly by decreasing Bacteroidetes and increasing Firmicutes proportions. To confirm the role of gut microbiota in TBT-induced overweight and hormonal disorders, fecal microbiota transplantation was performed and the mice receiving gut microbiota from H-TBT mice had similar phenotypes with their donor mice including significant body weight and epididymal fat gain, glucose and insulin dysbiosis and hormonal disorders. These results suggested that gut microbiome altered by TBT exposure was involved in the TBT-induced increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice, providing significant evidence and a novel perspective for better understanding the mechanism by which TBT induces toxicity.}, }
@article {pmid32835671, year = {2020}, author = {Badran, M and Khalyfa, A and Ericsson, A and Gozal, D}, title = {Fecal microbiota transplantation from mice exposed to chronic intermittent hypoxia elicits sleep disturbances in naïve mice.}, journal = {Experimental neurology}, volume = {334}, number = {}, pages = {113439}, doi = {10.1016/j.expneurol.2020.113439}, pmid = {32835671}, issn = {1090-2430}, support = {RF1 AG061824/AG/NIA NIH HHS/United States ; }, abstract = {Obstructive sleep apnea (OSA) is a chronic prevalent condition characterized by intermittent hypoxia (IH) and sleep fragmentation (SF). Evidence suggests that OSA can alter the gut microbiome (GM) diversity and composition that may then promote the occurrence of some of the OSA-associated morbidities. However, it is unclear whether perturbations in the GM caused by IH can elicit sleep disturbances that underlie the increased sleep propensity that occurs in IH-exposed mice. To evaluate this issue, we exposed C57Bl/6 J mice to IH or room air (RA) for 6 weeks, and fecal matter was collected and frozen. C57Bl/6 J naïve mice were then randomly assigned to a fecal microbiota transfer (FMT) protocol for 3 weeks with either IH or RA fecal slur, and their GM was then analyzed using 16 s rRNA sequencing. In addition, FMT recipients underwent sleep recordings using piezoelectric approaches for 3 consecutive days. As anticipated, FMT-IH and FMT-RA mice showed different taxonomic profiles that corresponded to previous effects of IH on GM. Furthermore, FMT-IH mice exhibited increased sleep duration and the frequency of longer sleep bouts during the dark cycle, suggesting increased sleepiness (p < 0.0001 vs. FMT-RA mice). Thus, alterations of GM diversity induced by IH exposures can elicit sleep disturbances in the absence of concurrent IH, suggesting that sleep disturbances can be mediated, at least in part, by IH-induced alterations in GM.}, }
@article {pmid32831634, year = {2020}, author = {Li, K and Wei, S and Hu, L and Yin, X and Mai, Y and Jiang, C and Peng, X and Cao, X and Huang, Z and Zhou, H and Ma, G and Liu, Z and Li, H and Zhao, B}, title = {Protection of Fecal Microbiota Transplantation in a Mouse Model of Multiple Sclerosis.}, journal = {Mediators of inflammation}, volume = {2020}, number = {}, pages = {2058272}, pmid = {32831634}, issn = {1466-1861}, abstract = {Given the growing evidence of a link between gut microbiota (GM) dysbiosis and multiple sclerosis (MS), fecal microbiota transplantation (FMT), aimed at rebuilding GM, has been proposed as a new therapeutic approach to MS treatment. To evaluate the viability of FMT for MS treatment and its impact on MS pathology, we tested FMT in mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We provide evidence that FMT can rectify altered GM to some extent with a therapeutic effect on EAE. We also found that FMT led to reduced activation of microglia and astrocytes and conferred protection on the blood-brain barrier (BBB), myelin, and axons in EAE. Taken together, our data suggest that FMT, as a GM-based therapy, has the potential to be an effective treatment for MS.}, }
@article {pmid32830227, year = {2020}, author = {Zou, J and Zhao, X and Shi, Z and Zhang, Z and Vijay-Kumar, M and Chassaing, B and Gewirtz, AT}, title = {Critical role of innate immunity to flagellin in absence of adaptive immunity.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiaa521}, pmid = {32830227}, issn = {1537-6613}, abstract = {BACKGROUND: Bacterial flagellin is a major target of innate and adaptive immunity, both of which can promote and/or compensate for deficiencies in each other's function.<br><br>AIM/METHODS: To investigate the role of innate immune detection of flagellin irrespective of adaptive immunity, we examined the consequences of loss of toll-like receptor 5 (T5) and/or Nod-like receptor 4 (N4) upon a Rag1-deficient background.<br><br>RESULTS: Mice lacking TLR5 and Rag1 (T5/Rag-DKO) exhibited frequent lethal Pasteurellaceae-containing abscesses that prevented breeding of these mice. Mice lacking TLR5, NLRC4, and Rag1 (T5/N4/Rag-TKO) also resulted in sporadic lethal abdominal abscesses caused by similar Pasteurellaceae. In the absence of such infections, relative to Rag1-KO, T5/N4/Rag-TKO mice exhibited microbiota encroachment, low-grade inflammation, microbiota dysbiosis, and, moreover were highly prone to Citrobacter infection and developed severe colitis when adoptively transferred with colitogenic T-cells. Relative proneness of T5/N4/Rag-TKO mice to T-cell colitis was ablated by antibiotics while fecal microbiota transplant from T5/N4/Rag-TKO mice to WT mice transferred proneness to Citrobacter infection, indicating that dysbiosis in T5/N4/Rag-TKO mice contributed to these phenotypes.<br><br>CONCLUSIONS: These results demonstrate a critical role for innate immune detection of flagellin, especially in the intestinal tract and particularly in hosts deficient in adaptive immunity.}, }
@article {pmid32821439, year = {2020}, author = {Chen, H and Chen, Z and Shen, L and Wu, X and Ma, X and Lin, D and Zhang, M and Ma, X and Liu, Y and Wang, Z and Zhang, Y and Kuang, Z and Lu, Z and Li, X and Ma, L and Lin, X and Si, L and Chen, X}, title = {Fecal microbiota transplantation from patients with autoimmune encephalitis modulates Th17 response and relevant behaviors in mice.}, journal = {Cell death discovery}, volume = {6}, number = {}, pages = {75}, pmid = {32821439}, issn = {2058-7716}, abstract = {The significance of the microbiota-gut-brain axis has been increasingly recognized as a major modulator of autoimmunity. Here, we aim to characterize the gut microbiota of a large cohort of treatment-naïve anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis patients relative to that of healthy controls (HCs). Relative to HCs, anti-NMDAR encephalitis patients had a decreased microbiome alpha-diversity index, marked disturbances of gut microbial composition and intestinal permeability damage. Disturbed microbiota in anti-NMDAR encephalitis patients might be linked with different clinical characteristics. Imputed KEGG analysis revealed perturbations of functional modules in the gut microbiomes of anti-NMDAR encephalitis. Compared to HCs, microbiota-depleted mice receiving fecal microbiota transplantation (FMT) from anti-NMDAR encephalitis patients had hypersensitivity and cognitive impairment. Furthermore, anti-NMDAR encephalitis FMT mice showed altered T cells in the spleen and small intestine lamina propria with an increased Th17 cells. Overall, this study first suggests that the anti-NMDAR encephalitis microbiome itself can influence neurologic, Th17 response and behavioral function. The gut microbiota is a potential therapeutic target for anti-NMDAR encephalitis.}, }
@article {pmid32821067, year = {2020}, author = {Ghouri, YA and Tahan, V and Shen, B}, title = {Secondary causes of inflammatory bowel diseases.}, journal = {World journal of gastroenterology}, volume = {26}, number = {28}, pages = {3998-4017}, pmid = {32821067}, issn = {2219-2840}, abstract = {Inflammatory bowel diseases (IBD), conventionally consist of Crohn's disease (CD) and ulcerative colitis. They occur in individuals with high risk genotype for the disease in the setting of appropriate environmental factors. The pathogenesis of IBD involves a dysregulated autoimmune response to gut dysbiosis, which in turn is triggered due to exposure to various inciting environmental factors. But there is no clearly defined etiology of IBD and this type of disease is termed as &quot;idiopathic IBD&quot;, &quot;classic IBD&quot;, or &quot;primary IBD&quot;. We reviewed the current medical literature and found that certain etiological factors may be responsible for the development of IBD or IBD-like conditions, and we consider this form of de novo IBD as &quot;secondary IBD&quot;. Currently known factors that are potentially responsible for giving rise to secondary IBD are medications; bowel altering surgeries and transplantation of organs, stem cells or fecal microbiome. Medications associated with the development of secondary IBD include; immunomodulators, anti-tumor necrosis factor alpha agents, anti-interleukin agents, interferons, immune stimulating agents and checkpoint inhibitors. Colectomy can in some cases give rise to de novo CD, pouchitis of the ileal pouch, or postcolectomy enteritis syndrome. After solid organ transplantation or hematopoietic stem cell transplantation, the recipient may develop de novo IBD or IBD flare. Fecal microbiota transplantation has been widely used to treat patients suffering from recurrent Clostridium difficile infection but can also causes IBD flares.}, }
@article {pmid32819434, year = {2020}, author = {Li, Y and Luo, ZY and Hu, YY and Bi, YW and Yang, JM and Zou, WJ and Song, YL and Li, S and Shen, T and Li, SJ and Huang, L and Zhou, AJ and Gao, TM and Li, JM}, title = {The gut microbiota regulates autism-like behavior by mediating vitamin B6 homeostasis in EphB6-deficient mice.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {120}, pmid = {32819434}, issn = {2049-2618}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a developmental disorder, and the effective pharmacological treatments for the core autistic symptoms are currently limited. Increasing evidence, particularly that from clinical studies on ASD patients, suggests a functional link between the gut microbiota and the development of ASD. However, the mechanisms linking the gut microbiota with brain dysfunctions (gut-brain axis) in ASD have not yet been full elucidated. Due to its genetic mutations and downregulated expression in patients with ASD, EPHB6, which also plays important roles in gut homeostasis, is generally considered a candidate gene for ASD. Nonetheless, the role and mechanism of EPHB6 in regulating the gut microbiota and the development of ASD are unclear.<br><br>RESULTS: Here, we found that the deletion of EphB6 induced autism-like behavior and disturbed the gut microbiota in mice. More importantly, transplantation of the fecal microbiota from EphB6-deficient mice resulted in autism-like behavior in antibiotic-treated C57BL/6J mice, and transplantation of the fecal microbiota from wild-type mice ameliorated the autism-like behavior in EphB6-deficient mice. At the metabolic level, the disturbed gut microbiota in EphB6-deficient mice led to vitamin B6 and dopamine defects. At the cellular level, the excitation/inhibition (E/I) balance in the medial prefrontal cortex was regulated by gut microbiota-mediated vitamin B6 in EphB6-deficient mice.<br><br>CONCLUSIONS: Our study uncovers a key role for the gut microbiota in the regulation of autism-like social behavior by vitamin B6, dopamine, and the E/I balance in EphB6-deficient mice, and these findings suggest new strategies for understanding and treating ASD. Video abstract.}, }
@article {pmid32817490, year = {2020}, author = {Britton, GJ and Contijoch, EJ and Spindler, MP and Aggarwala, V and Dogan, B and Bongers, G and San Mateo, L and Baltus, A and Das, A and Gevers, D and Borody, TJ and Kaakoush, NO and Kamm, MA and Mitchell, H and Paramsothy, S and Clemente, JC and Colombel, JF and Simpson, KW and Dubinsky, MC and Grinspan, A and Faith, JJ}, title = {Defined microbiota transplant restores Th17/RORγt+ regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {35}, pages = {21536-21545}, pmid = {32817490}, issn = {1091-6490}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; R01 GM108505/GM/NIGMS NIH HHS/United States ; F31 DK112679/DK/NIDDK NIH HHS/United States ; T32 AI078892/AI/NIAID NIH HHS/United States ; }, abstract = {The building evidence for the contribution of microbiota to human disease has spurred an effort to develop therapies that target the gut microbiota. This is particularly evident in inflammatory bowel diseases (IBDs), where clinical trials of fecal microbiota transplantation have shown some efficacy. To aid the development of novel microbiota-targeted therapies and to better understand the biology underpinning such treatments, we have used gnotobiotic mice to model microbiota manipulations in the context of microbiotas from humans with inflammatory bowel disease. Mice colonized with IBD donor-derived microbiotas exhibit a stereotypical set of phenotypes, characterized by abundant mucosal Th17 cells, a deficit in the tolerogenic RORγt+ regulatory T (Treg) cell subset, and susceptibility to disease in colitis models. Transplanting healthy donor-derived microbiotas into mice colonized with human IBD microbiotas led to induction of RORγt+ Treg cells, which was associated with an increase in the density of the microbiotas following transplant. Microbiota transplant reduced gut Th17 cells in mice colonized with a microbiota from a donor with Crohn's disease. By culturing strains from this microbiota and screening them in vivo, we identified a specific strain that potently induces Th17 cells. Microbiota transplants reduced the relative abundance of this strain in the gut microbiota, which was correlated with a reduction in Th17 cells and protection from colitis.}, }
@article {pmid32816876, year = {2020}, author = {Zhang, L and Roy, S}, title = {Opioid Modulation of the Gut-Brain Axis in Opioid-Associated Comorbidities.}, journal = {Cold Spring Harbor perspectives in medicine}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a040485}, pmid = {32816876}, issn = {2157-1422}, abstract = {Growing evidence from animal and human studies show that opioids have a major impact on the composition and function of gut microbiota. This leads to disruption in gut permeability and altered microbial metabolites, driving both systemic and neuroinflammation, which in turn impacts central nervous system (CNS) homeostasis. Tolerance and dependence are the major comorbidities associated with prolonged opioid use. Inflammatory mediators and signaling pathways have been implicated in both opioid tolerance and dependence. We provide evidence that targeting the gut microbiome during opioid use through prebiotics, probiotics, antibiotics, and fecal microbial transplantation holds the greatest promise for novel treatments for opioid abuse. Basic research and clinical trials are required to examine what is more efficacious to yield new insights into the role of the gut-brain axis in opioid abuse.}, }
@article {pmid32814133, year = {2020}, author = {Yu, Z and Shi, Z and Zheng, Z and Han, J and Yang, W and Lu, R and Lin, W and Zheng, Y and Nie, D and Chen, G}, title = {DEHP induce cholesterol imbalance via disturbing bile acid metabolism by altering the composition of gut microbiota in rats.}, journal = {Chemosphere}, volume = {263}, number = {}, pages = {127959}, doi = {10.1016/j.chemosphere.2020.127959}, pmid = {32814133}, issn = {1879-1298}, abstract = {Di(2-ethylhexyl) phthalate (DEHP) is one of the most widespread environmental contaminants worldwide because of its massive production, extensive use in common products, and liability to leach from products. This study investigated the mechanisms of DEHP mediated alteration of lipid metabolism. Rats were treated with 0.5 mg kg-1 d-1 of DEHP for 23 weeks. Results showed that the treatment induced cholesterol imbalance. Further fecal transplantation experiments corroborated the involvement of gut microbiota in DEHP-induced cholesterol imbalance. In addition, 16S rRNA gene sequencing analysis of cecal contents showed that DEHP disrupted the gut microbiota diversity in rats and increased the ratio of Firmicutes to Bacteroidetes. Further cecal metabolomic analyses, bile salt hydrolase enzyme activity, and gene expression examination revealed that chronic DEHP exposure generated a bile acid profile in the gut that is a more potent activator of farnesoid X receptor (FXR). The activation of FXR in the gut induced the expression of fibroblast growth factor 15, which subsequently suppressed cytochrome P450 family 7 subfamily A member 1 in the liver and bile acid synthesis. These results suggest that DEHP might induce cholesterol imbalance by regulating bile acid metabolism via the remodeling of the gut microbiota.}, }
@article {pmid32814026, year = {2020}, author = {Stephen-Victor, E and Crestani, E and Chatila, TA}, title = {Dietary and Microbial Determinants in Food Allergy.}, journal = {Immunity}, volume = {53}, number = {2}, pages = {277-289}, pmid = {32814026}, issn = {1097-4180}, support = {R01 AI126915/AI/NIAID NIH HHS/United States ; R21 AI132843/AI/NIAID NIH HHS/United States ; }, abstract = {The steep rise in food allergy (FA) has evoked environmental factors involved in disease pathogenesis, including the gut microbiota, diet, and their metabolites. Early introduction of solid foods synchronizes with the &quot;weaning reaction,&quot; a time during which the microbiota imprints durable oral tolerance. Recent work has shown that children with FA manifest an early onset dysbiosis with the loss of Clostridiales species, which promotes the differentiation of ROR-γt+ regulatory T cells to suppress FA. This process can be reversed in pre-clinical mouse models by targeted bacteriotherapy. Here, we review the dominant tolerance mechanisms enforced by the microbiota to suppress FA and discuss therapeutic intervention strategies that act to recapitulate the early life window of opportunity in stemming the FA epidemic.}, }
@article {pmid32808030, year = {2020}, author = {Olesen, SW and Gerardin, Y}, title = {Re-evaluating the evidence for fecal microbiota transplantation &quot;super-donors&quot; in inflammatory bowel disease.}, journal = {Journal of Crohn's &amp; colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjaa170}, pmid = {32808030}, issn = {1876-4479}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a recommended treatment for recurrent Clostridioides difficile infection, and there is promise that FMT may be effective for conditions like inflammatory bowel disease (IBD). Previous FMT clinical trials have considered the possibility of a &quot;donor effect&quot;, that is, that FMT material from different donors has different clinical efficacies.<br><br>AIM &amp; METHODS: Here we re-evaluate evidence for donor effects in published FMT clinical trials for IBD.<br><br>RESULTS: In 10 of 12 published studies, no statistically significant donor effect was detected when rigorously re-evaluating the original analyses. One study had statistically significant separation of microbiota composition of pools of donor stool when stratified by patient outcome. One study reported a significant effect but did not have underlying data available for re-evaluation. When quantifying the uncertainty on the magnitude of the donor effect, confidence intervals were large, including both zero donor effect and very substantial donor effects.<br><br>CONCLUSION: Although we found very little evidence for donor effects, the existing data also cannot rule out the possibility that donor effects are clinically important. Large clinical trials prospectively designed to detect donor effects are likely necessary to determine if donor effects are clinically relevant for IBD.}, }
@article {pmid32805128, year = {2020}, author = {Vandekerckhove, E and Janssens, F and Tate, D and De Looze, D}, title = {Treatment of Gut Fermentation Syndrome With Fecal Microbiota Transplantation.}, journal = {Annals of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.7326/L20-0341}, pmid = {32805128}, issn = {1539-3704}, }
@article {pmid32801142, year = {2020}, author = {van Lier, YF and Davids, M and Haverkate, NJE and de Groot, PF and Donker, ML and Meijer, E and Heubel-Moenen, FCJI and Nur, E and Zeerleder, SS and Nieuwdorp, M and Blom, B and Hazenberg, MD}, title = {Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients.}, journal = {Science translational medicine}, volume = {12}, number = {556}, pages = {}, doi = {10.1126/scitranslmed.aaz8926}, pmid = {32801142}, issn = {1946-6242}, abstract = {Disruption of the intestinal microbiota occurs frequently in allogeneic hematopoietic cell transplantation (allo-HCT) recipients and predisposes them to development of graft-versus-host disease (GvHD). In a prospective, single-center, single-arm study, we investigated the effect of donor fecal microbiota transplantation (FMT) on symptoms of steroid-refractory or steroid-dependent, acute or late-onset acute intestinal GvHD in 15 individuals who had undergone allo-HCT. Study participants received a fecal suspension from an unrelated healthy donor via nasoduodenal infusion. Donor FMT was well tolerated, and infection-related adverse events did not seem to be related to the FMT procedure. In 10 of 15 study participants, a complete clinical response was observed within 1 month after FMT, without additional interventions to alleviate GvHD symptoms. This response was accompanied by an increase in gut microbial α-diversity, a partial engraftment of donor bacterial species, and increased abundance of butyrate-producing bacteria, including Clostridiales and Blautia species. In 6 of the 10 responding donor FMT recipients, immunosuppressant drug therapy was successfully tapered. Durable remission of steroid-refractory or steroid-dependent GvHD after donor FMT was associated with improved survival at 24 weeks after donor FMT. This study highlights the potential of donor FMT as a treatment for steroid-refractory or steroid-dependent GvHD, but larger clinical trials are needed to confirm the safety and efficacy of this procedure.}, }
@article {pmid32799901, year = {2020}, author = {Wang, S and Ishima, T and Zhang, J and Qu, Y and Chang, L and Pu, Y and Fujita, Y and Tan, Y and Wang, X and Hashimoto, K}, title = {Ingestion of Lactobacillus intestinalis and Lactobacillus reuteri causes depression- and anhedonia-like phenotypes in antibiotic-treated mice via the vagus nerve.}, journal = {Journal of neuroinflammation}, volume = {17}, number = {1}, pages = {241}, pmid = {32799901}, issn = {1742-2094}, support = {none//Smoking Research Foundation/ ; JP19dm0107119//Japan Agency for Medical Research and Development/ ; }, abstract = {BACKGROUND: The brain-gut-microbiota axis plays a role in the pathogenesis of stress-related disorders such as depression. In this study, we examined the effects of fecal microbiota transplantation (FMT) in mice with antibiotic-treated microbiota depletion.<br><br>METHODS: The fecal microbiota was obtained from mice subjected to chronic social defeat stress (CSDS) and control (no CSDS) mice. FMT from these two groups was performed to antibiotic-treated mice. 16S rRNA analysis was performed to examine the composition of gut microbiota. Furthermore, the effects of subdiaphragmatic vagotomy in depression-like phenotypes after ingestion of microbes were examined.<br><br>RESULTS: The ingestion of fecal microbiota from CSDS-susceptible mice resulted in an anhedonia-like phenotype, higher plasma levels of interleukin-6 (IL-6), and decreased expression of synaptic proteins in the prefrontal cortex (PFC) in antibiotic-treated mice but not in water-treated mice. 16S rRNA analysis suggested that two microbes (Lactobacillus intestinalis and Lactobacillus reuteri) may be responsible for the anhedonia-like phenotype in antibiotic-treated mice after FMT. Ingestion of these two microbes for 14 days led to depression- and anhedonia-like phenotypes, higher plasma IL-6 levels, and decreased expression of synaptic proteins in the PFC of antibiotic-treated mice. Interestingly, subdiaphragmatic vagotomy significantly blocked the development of behavioral abnormalities, elevation of plasma IL-6 levels, and downregulation of synaptic proteins in the PFC after ingestion of these two microbes.<br><br>CONCLUSIONS: These findings suggest that microbiota depletion using an antibiotic cocktail is essential for the development of FMT-induced behavioral changes and that the vagus nerve plays a key role in behavioral abnormalities in antibiotic-treated mice after the ingestion of L. intestinalis and L. reuteri. Therefore, it is likely that the brain-gut-microbiota axis participates in the pathogenesis of depression via the vagus nerve.}, }
@article {pmid32785703, year = {2020}, author = {Su, X and Yin, X and Liu, Y and Yan, X and Zhang, S and Wang, X and Lin, Z and Zhou, X and Gao, J and Wang, Z and Zhang, Q}, title = {Gut Dysbiosis Contributes to the Imbalance of Treg and Th17 Cells in Graves' Disease Patients by Propionic Acid.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {105}, number = {11}, pages = {}, doi = {10.1210/clinem/dgaa511}, pmid = {32785703}, issn = {1945-7197}, abstract = {BACKGROUND: Graves' disease (GD) is a typical organ-specific autoimmune disease. Intestinal flora plays a pivotal role in immune homeostasis and autoimmune disease development. However, the association and mechanism between intestinal flora and GD remain elusive.<br><br>OBJECTIVE: To investigate the association and mechanism between intestinal flora and GD.<br><br>METHODS: We recruited 58 initially untreated GD patients and 63 healthy individuals in the study. The composition and metabolic characteristics of the intestinal flora in GD patients and the causal relationship between intestinal flora and GD pathogenesis were assessed using 16S rRNA gene sequencing, targeted/untargeted metabolomics, and fecal microbiota transplantation.<br><br>RESULTS: The composition, metabolism, and inter-relationships of the intestinal flora were also changed, particularly the significantly reduced short-chain fatty acid (SCFA)-producing bacteria and SCFAs. The YCH46 strain of Bacteroides fragilis could produce propionic acid and increase Treg cell numbers while decreasing Th17 cell numbers. Transplanting the intestinal flora of GD patients significantly increased GD incidence in the GD mouse model. Additionally, there were 3 intestinal bacteria genera (Bacteroides, Alistipes, Prevotella) could distinguish GD patients from healthy individuals with 85% accuracy.<br><br>CONCLUSIONS: Gut dysbiosis contributes to a Treg/Th17 imbalance through the pathway regulated by propionic acid and promotes the occurrence of GD, together with other pathogenic factors. Bacteroides, Alistipes, and Prevotella have great potential to serve as adjunct markers for GD diagnosis. This study provided valuable clues for improving immune dysfunction of GD patients using B. fragilis and illuminated the prospects of microecological therapy for GD as an adjunct treatment.}, }
@article {pmid32773765, year = {2020}, author = {Zhang, Q and Lu, Q and Luo, Y}, title = {Fecal Microbiota Transplantation and Detection of Prevalence of IgA-Coated Bacteria in the Gut.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {161}, pages = {}, doi = {10.3791/60772}, pmid = {32773765}, issn = {1940-087X}, abstract = {Gut microbiota exert pleiotropic roles in human health and disease. Fecal microbiota transplantation (FMT) is an effective method to investigate the biological function of intestinal bacteria as a whole or at the species level. Several different FMT methods have been published. Here, we present an FMT protocol that successfully depletes gut microbiota in a matter of days, followed by transplantation of fecal microbiota from fresh or frozen donor intestinal contents to conventional mice. Real time-PCR is applied to test the efficacy of bacterial depletion. Sequencing of the 16S ribosomal RNA (rRNA) is then applied to test the relative abundance and identity of gut microbiota in recipient mice. We also present a flow cytometry-based detection method of immunoglobulin A (IgA)-coated bacteria in the gut.}, }
@article {pmid32772093, year = {2020}, author = {Sood, A and Singh, A and Mahajan, R and Midha, V and Kaur, K and Singh, D and Bansal, N and Dharni, K}, title = {Clinical Predictors of response to Faecal Microbiota Transplantation in patients with active ulcerative colitis.}, journal = {Journal of Crohn's &amp; colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjaa163}, pmid = {32772093}, issn = {1876-4479}, abstract = {BACKGROUND: Fecal Microbiota Transplantation (FMT) has been shown to be effective for induction of remission in patients with active ulcerative colitis (UC). At present, clinical factors impacting the response to FMT in UC remain unclear.<br><br>METHODS: Patients with active UC treated with multisession FMT via colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22, were analysed. Response to FMT was defined as achievement of corticosteroid free clinical remission at week 30. Patient and disease characteristics were evaluated to determine the predictors of response to FMT.<br><br>RESULTS: Out of 140 patients with active UC treated with FMT, 93 patients [mean age 34.96±11.27 years, 62.36% males (n=58), mean Mayo clinic score 8.07±2.00] who completed the multi-session FMT protocol were analysed. Fifty-seven (61.29%) patients achieved clinical remission. Younger age (OR for age 0.93, 95% CI 0.89-0.97, p=0.001), moderate (Mayo clinic score 6-9) disease severity (OR 3.01, 95% CI 1.12 to 8.06, p=0.025) and endoscopic Mayo score 2 (OR 5.55, 95% CI 2.18-14.06, p<0.001) were significant predictors of remission on univariate analysis. Younger age, disease extent E2 and endoscopic mayo score 2 (OR 0.925, 95% CI 0.88-0.97, p=0.002; OR 2.89, 95% CI 1.01-8.25, p=0.04 and OR 8.43, 95% CI 2.38-29.84, p=0.001, respectively) were associated with clinical remission on multivariate logistic regression. A mathematical model (nomogram) was developed for estimating the probability of remission with FMT protocol.<br><br>CONCLUSION: Younger age, disease extent E2, and endoscopic mayo score 2 significantly predict achievement of clinical remission with FMT in active UC. The prediction model can help in selecting individuals for FMT. Validation in larger cohorts is needed.}, }
@article {pmid32769886, year = {2020}, author = {He, Y and Xu, R and Wang, W and Zhang, J and Hu, X}, title = {Probiotics, prebiotics, antibiotic, Chinese herbal medicine, and fecal microbiota transplantation in irritable bowel syndrome: Protocol for a systematic review and network meta-analysis.}, journal = {Medicine}, volume = {99}, number = {32}, pages = {e21502}, doi = {10.1097/MD.0000000000021502}, pmid = {32769886}, issn = {1536-5964}, mesh = {Adolescent ; Adult ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Bayes Theorem ; Drugs, Chinese Herbal/*therapeutic use ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/microbiology/*therapy ; Male ; Middle Aged ; Network Meta-Analysis ; Prebiotics/*administration &amp; dosage ; Probiotics/*therapeutic use ; Randomized Controlled Trials as Topic ; Research Design ; Systematic Reviews as Topic ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disease, with a high global incidence, which seriously influences the quality of life and work efficiency of patients. Extensive research showed that IBS is related to changes in the intestinal microenvironment. The novel treatment strategy targeting the gut microbiota is being actively implemented. Probiotics, antibiotics, prebiotics, fecal microbiota transplantation, and Chinese Herbal Medicine have been proven to be effective in the treatment of IBS, and all have an impact on the intestinal flora of patients. However, these 5 treatments have their own pros and cons and have not been systematically evaluated and compared. Therefore, this study will indirectly compare the safety and effectiveness of these 5 methods in the treatment of IBS through network meta-analysis.<br><br>METHODS: The following databases including Embase, Pubmed, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, WHO International Clinical Trials Registry Platform and ClinicalTrials.gov will be retrieved from inception to June 2020 without language restrictions. Literature selection, data extraction, and bias analysis will be done by 2 researchers. The primary outcome is global symptoms improvement. The secondary outcomes will include individual IBS symptom scores, emotional response, and adverse events. The conventional pair-wise meta-analysis will be performed using Stata V.14.0 and be pooled using a random-effects model. We will use WinBUGS V.1.4.3 (Cambridge, United Kingdom) with a Bayesian hierarchical random-effects model to conduct the network meta-analysis.<br><br>RESULTS: This study will provide systematic reviews and indirect network comparison results about treatments of IBS.<br><br>CONCLUSIONS: This study will systematically evaluate and compare 5 intestinal flora-related therapies for IBS and to provide an evidence-based medical decision-making basis for clinicians.<br><br>TRIAL REGISTRATION NUMBER: INPLASY202050047.}, }
@article {pmid32767183, year = {2020}, author = {Tan, GSE and Tay, HL and Tan, SH and Lee, TH and Ng, TM and Lye, DC}, title = {Gut Microbiota Modulation: Implications for Infection Control and Antimicrobial Stewardship.}, journal = {Advances in therapy}, volume = {37}, number = {10}, pages = {4054-4067}, doi = {10.1007/s12325-020-01458-z}, pmid = {32767183}, issn = {1865-8652}, abstract = {The human microbiome comprises a complex ecosystem of microbial communities that exist within the human body, the largest and most diverse of which are found within the human intestine. It has been increasingly implicated in human health and diseases, demonstrably playing a critical role in influencing host immune response, protection against pathogen overgrowth, biosynthesis, and metabolism. As our understanding of the links between the gut microbiota with host immunity and infectious diseases deepens, there is a greater need to incorporate methods of modulating it as a means of therapy or infection prevention in daily clinical practice. Traditional antimicrobial stewardship principles have been evaluated to assess their impact on the gut microbiota diversity and the consequent repercussions, taking into consideration antibiotic pharmacokinetic and pharmacodynamic properties. Novel strategies of selective digestive decontamination and fecal microbiota transplantation to regulate the gut microbiota have also been tested in different conditions with variable results. This review seeks to provide an overview of the available literature on the modulation of the gut microbiota and its implications for infection control and antimicrobial stewardship. With increased understanding, gut microbiota profiling through metataxonomic analysis may provide further insight into modulating microbial communities in the context of infection prevention and control.}, }
@article {pmid32765600, year = {2020}, author = {Yang, CQ and Guo, XS and Ji-Li,  and Wei, ZB and Zhao, L and Zhao, GT and Sheng, ST}, title = {Rifaximin Improves Visceral Hyperalgesia via TRPV1 by Modulating Intestinal Flora in the Water Avoidance Stressed Rat.}, journal = {Gastroenterology research and practice}, volume = {2020}, number = {}, pages = {4078681}, pmid = {32765600}, issn = {1687-6121}, abstract = {Background: Rifaximin is effective in relieving pain symptoms with IBS patients, although the mechanisms were not clear. The aims of the research were to investigate whether the visceral hyperalgesia was alleviated by rifaximin via TRPV1 channel in rats.<br><br>Methods: Rats were subjected to water avoidance stress (WAS) and were pretreated with rifaximin by oral gavage. The visceromotor response to colorectal distension was measured. The changes of TRPV1 in peripheral and central neurons of rats were detected by immunofluorescence, western blot method, and RT-PCR. Bacterial 16S ribosomal DNA in ileal contents was assessed using the Illumina MiSeq platform. The effect of intestinal flora on TRPV1 channel was observed by fecal microbiota transplantation (FMT) methods.<br><br>Results: Rifaximin could relieve the visceral hyperalgesia and reduce the TRPV1 expression of neurons and ileum mucosa in rats induced by WAS. The reduced relative abundance of intestinal flora induced by WAS could be partly prevented by rifaximin. The electromyographical activities and immunoreactivity of TRPV1 in rats could be changed after FMT.<br><br>Conclusions: Rifaximin could improve visceral hyperalgesia via TRPV1 channels of peripheral and central neurons by modulating intestinal flora in rats.}, }
@article {pmid32764526, year = {2020}, author = {Alagna, L and Palomba, E and Mangioni, D and Bozzi, G and Lombardi, A and Ungaro, R and Castelli, V and Prati, D and Vecchi, M and Muscatello, A and Bandera, A and Gori, A}, title = {Multidrug-Resistant Gram-Negative Bacteria Decolonization in Immunocompromised Patients: A Focus on Fecal Microbiota Transplantation.}, journal = {International journal of molecular sciences}, volume = {21}, number = {16}, pages = {}, pmid = {32764526}, issn = {1422-0067}, abstract = {Antimicrobial resistance is an important issue for global health; in immunocompromised patients, such as solid organ and hematological transplant recipients, it poses an even bigger threat. Colonization by multidrug-resistant (MDR) bacteria was acknowledged as a strong risk factor to subsequent infections, especially in individuals with a compromised immune system. A growing pile of studies has linked the imbalance caused by the dominance of certain taxa populating the gut, also known as intestinal microbiota dysbiosis, to an increased risk of MDR bacteria colonization. Several attempts were proposed to modulate the gut microbiota. Particularly, fecal microbiota transplantation (FMT) was successfully applied to treat conditions like Clostridioides difficile infection and other diseases linked to gut microbiota dysbiosis. In this review we aimed to provide a look at the data gathered so far on FMT, focusing on its possible role in treating MDR colonization in the setting of immunocompromised patients and analyzing its efficacy and safety.}, }
@article {pmid32764281, year = {2020}, author = {Arias, N and Arboleya, S and Allison, J and Kaliszewska, A and Higarza, SG and Gueimonde, M and Arias, JL}, title = {The Relationship between Choline Bioavailability from Diet, Intestinal Microbiota Composition, and Its Modulation of Human Diseases.}, journal = {Nutrients}, volume = {12}, number = {8}, pages = {}, pmid = {32764281}, issn = {2072-6643}, support = {PSI2017-83893-R//Ministerio de Ciencia e Innovación/ ; PSI2015-73111-EXP//Ministerio de Economía y Competitividad/ ; PSI2017-90806-REDT//Ministerio de Economía y Competitividad/ ; AGL2017-83653R//Ministerio de Economía y Competitividad/ ; IJCI-2017-32156//Ministerio de Ciencia e Innovación/ ; }, abstract = {Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which, upon absorption by the host is converted into trimethylamine-N-oxide (TMAO) in the liver. A high accumulation of both components is related to cardiovascular disease, inflammatory bowel disease, non-alcoholic fatty liver disease, and chronic kidney disease. However, the relationship between the microbiota production of these components and its impact on these diseases still remains unknown. In this review, we will address which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., the genotype) and diet affect TMA production, and the colonization of these microbes and the reversal of dysbiosis as a therapy for these diseases.}, }
@article {pmid32762536, year = {2020}, author = {Witkowski, M and Weeks, TL and Hazen, SL}, title = {Gut Microbiota and Cardiovascular Disease.}, journal = {Circulation research}, volume = {127}, number = {4}, pages = {553-570}, pmid = {32762536}, issn = {1524-4571}, support = {P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; }, abstract = {Fecal microbial community changes are associated with numerous disease states, including cardiovascular disease (CVD). However, such data are merely associative. A causal contribution for gut microbiota in CVD has been further supported by a multitude of more direct experimental evidence. Indeed, gut microbiota transplantation studies, specific gut microbiota-dependent pathways, and downstream metabolites have all been shown to influence host metabolism and CVD, sometimes through specific identified host receptors. Multiple metaorganismal pathways (involving both microbe and host) both impact CVD in animal models and show striking clinical associations in human studies. For example, trimethylamine N-oxide and, more recently, phenylacetylglutamine are gut microbiota-dependent metabolites whose blood levels are associated with incident CVD risks in large-scale clinical studies. Importantly, a causal link to CVD for these and other specific gut microbial metabolites/pathways has been shown through numerous mechanistic animal model studies. Phenylacetylglutamine, for example, was recently shown to promote adverse cardiovascular phenotypes in the host via interaction with multiple ARs (adrenergic receptors)-a class of key receptors that regulate cardiovascular homeostasis. In this review, we summarize recent advances of microbiome research in CVD and related cardiometabolic phenotypes that have helped to move the field forward from associative to causative results. We focus on microbiota and metaorganismal compounds/pathways, with specific attention paid to short-chain fatty acids, secondary bile acids, trimethylamine N-oxide, and phenylacetylglutamine. We also discuss novel therapeutic strategies for directly targeting the gut microbiome to improve cardiovascular outcomes.}, }
@article {pmid32760391, year = {2020}, author = {Jouhten, H and Ronkainen, A and Aakko, J and Salminen, S and Mattila, E and Arkkila, P and Satokari, R}, title = {Cultivation and Genomics Prove Long-Term Colonization of Donor's Bifidobacteria in Recurrent Clostridioides difficile Patients Treated With Fecal Microbiota Transplantation.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1663}, pmid = {32760391}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) and it's also considered for treating other indications. Metagenomic studies have indicated that commensal donor bacteria may colonize FMT recipients, but cultivation has not been employed to verify strain-level colonization. We combined molecular profiling of Bifidobacterium populations with cultivation, molecular typing, and whole genome sequencing (WGS) to isolate and identify strains that were transferred from donors to recipients. Several Bifidobacterium strains from two donors were recovered from 13 recipients during the 1-year follow-up period after FMT. The strain identities were confirmed by WGS and comparative genomics. Our results show that specific donor-derived bifidobacteria can colonize rCDI patients for at least 1 year, and thus FMT may have long-term consequences for the recipient's microbiota and health. Conceptually, we demonstrate that FMT trials combined with microbial profiling can be used as a platform for discovering and isolating commensal strains with proven colonization capacity for potential therapeutic use.}, }
@article {pmid32756350, year = {2020}, author = {Mańkowska-Wierzbicka, D and Stelmach-Mardas, M and Gabryel, M and Tomczak, H and Skrzypczak-Zielińska, M and Zakerska-Banaszak, O and Sowińska, A and Mahadea, D and Baturo, A and Wolko, Ł and Słomski, R and Dobrowolska, A}, title = {The Effectiveness of Multi-Session FMT Treatment in Active Ulcerative Colitis Patients: A Pilot Study.}, journal = {Biomedicines}, volume = {8}, number = {8}, pages = {}, pmid = {32756350}, issn = {2227-9059}, support = {502-01-222-38-000//grant for young scientists from Poznan University of Medical Sciences, Poznan, Poland/ ; }, abstract = {The modification of the microbiome through fecal microbiota transplantation (FMT) is becoming a very promising therapeutic option for inflammatory bowel disease (IBD) patients. Our pilot study aimed to assess the effectiveness of multi-session FMT treatment in active ulcerative colitis (UC) patients. Ten patients with UC were treated with multi-session FMT (200 mL) from healthy donors, via colonoscopy/gastroscopy. Patients were evaluated as follows: at baseline, at week 7, and after 6 months, routine blood tests (including C reactive protein (CRP) and calprotectin) were performed. 16S rRNA gene (V3V4) sequencing was used for metagenomic analysis. The severity of UC was classified based on the Truelove-Witts index. The assessment of microbial diversity showed significant differences between recipients and healthy donors. FMT contributed to long-term, significant clinical and biochemical improvement. Metagenomic analysis revealed an increase in the amount of Lactobacillaceaea, Micrococcaceae, Prevotellaceae, and TM7 phylumsp.oral clone EW055 during FMT, whereas Staphylococcaceae and Bacillaceae declined significantly. A positive increase in the proportion of the genera Bifidobacterium, Lactobacillus, Rothia, Streptococcus, and Veillonella and a decrease in Bacillus, Bacteroides, and Staphylococcus were observed based on the correlation between calprotectin and Bacillus and Staphylococcus; ferritin and Lactobacillus, Veillonella, and Bifidobacterium abundance was indicated. A positive change in the abundance of Firmicutes was observed during FMT and after 6 months. The application of multi-session FMT led to the restoration of recipients' microbiota and resulted in the remission of patients with active UC.}, }
@article {pmid32755639, year = {2020}, author = {Holmes, A and Finger, C and Morales-Scheihing, D and Lee, J and McCullough, LD}, title = {Gut dysbiosis and age-related neurological diseases; an innovative approach for therapeutic interventions.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.trsl.2020.07.012}, pmid = {32755639}, issn = {1878-1810}, support = {R01 NS103592/NS/NINDS NIH HHS/United States ; RF1 AG058463/AG/NIA NIH HHS/United States ; }, abstract = {The gut microbiota is a complex ecosystem of bacteria, fungi, and viruses that acts as a critical regulator in microbial, metabolic, and immune responses in the host organism. Imbalances in the gut microbiota, termed &quot;dysbiosis,&quot; often induce aberrant immune responses, which in turn disrupt the local and systemic homeostasis of the host. Emerging evidence has highlighted the importance of gut microbiota in intestinal diseases, and more recently, in age-related central nervous systems diseases, for example, stroke and Alzheimer's disease. It is now generally recognized that gut microbiota significantly influences host behaviors and modulates the interaction between microbiota, gut, and brain, via the &quot;microbiota-gut-brain axis.&quot; Several approaches have been utilized to reduce age-related dysbiosis in experimental models and in clinical studies. These include strategies to manipulate the microbiome via fecal microbiota transplantation, administration of prebiotics and probiotics, and dietary interventions. In this review, we explore both clinical and preclinical therapies for treating age-related dysbiosis.}, }
@article {pmid32755385, year = {2020}, author = {Bernardazzi, C and Xu, H and Tong, H and Laubitz, D and Figliuolo da Paz, V and Curiel, L and Ghishan, FK}, title = {An indisputable role of NHE8 in mucosal protection.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {319}, number = {4}, pages = {G421-G431}, doi = {10.1152/ajpgi.00246.2020}, pmid = {32755385}, issn = {1522-1547}, support = {R01DK3023890/GF/NIH HHS/United States ; }, abstract = {The loss of the intestinal Na+/H+ exchanger isoform 8 (NHE8) results in an ulcerative colitis-like condition with reduction of mucin production and dysbiosis, indicating that NHE8 plays an important role in intestinal mucosal protection. The aim of this study was to investigate the potential rebalance of the altered microbiota community of NHE8-deficient mice via fecal microbiota transplantation (FMT) and feeding probiotic VSL#3. We also aimed to stimulate mucin production by sodium butyrate administration via enema. Data from 16S rRNA sequencing showed that loss of NHE8 contributes to colonic microbial dysbiosis with reduction of butyrate-producing bacteria. FMT increased bacterial adhesion in the colon in NHE8 knockout (NHE8KO) mice. Periodic-acid Schiff reagent (PAS) stain and quantitative PCR showed no changes in mucin production during FMT. In mice treated with the probiotic VSL#3, a reduction of Lactobacillus and segmented filamentous bacteria (SFB) in NHE8KO mouse colon was detected and an increase in goblet cell theca was observed. In NHE8KO mice receiving sodium butyrate (NaB), 1 mM NaB stimulated Muc2 expression without changing goblet cell theca, but 10 mM NaB induced a significant reduction of goblet cell theca without altering Muc2 expression. Furthermore, 5 mM and 10 mM NaB-treated HT29-MTX cells displayed increased apoptosis, while 0.5 mM NaB stimulated Muc2 gene expression. These data showed that loss of NHE8 leads to dysbiosis with reduction of butyrate-producing bacteria and FMT and VSL#3 failed to rebalance the microbiota in NHE8KO mice. Therefore, FMT, VSL#3, and NaB are not able to restore mucin production in the absence of NHE8 in the intestine.NEW &amp; NOTEWORTHY Loss of Na+/H+ exchanger isoform 8 (NHE8), a Slc9 family of exchanger that contributes to sodium uptake, cell volume regulation, and intracellular pH homeostasis, resulted in dysbiosis with reduction of butyrate-producing bacteria and decrease of Muc2 production in the intestine in mice. Introducing fecal microbiota transplantation (FMT) and VSL#3 in NHE8 knockout (NHE8KO) mice failed to rebalance the microbiota in these mice. Furthermore, administration of FMT, VSL#3, and sodium butyrate was unable to restore mucin production in the absence of NHE8 in the intestine.}, }
@article {pmid32751239, year = {2020}, author = {Perillo, F and Amoroso, C and Strati, F and Giuffrè, MR and Díaz-Basabe, A and Lattanzi, G and Facciotti, F}, title = {Gut Microbiota Manipulation as a Tool for Colorectal Cancer Management: Recent Advances in Its Use for Therapeutic Purposes.}, journal = {International journal of molecular sciences}, volume = {21}, number = {15}, pages = {}, pmid = {32751239}, issn = {1422-0067}, support = {IG-2019 22923//Associazione Italiana per la Ricerca sul Cancro/ ; }, abstract = {Colorectal cancer (CRC) is a multifaceted disease influenced by both environmental and genetic factors. A large body of literature has demonstrated the role of gut microbes in promoting inflammatory responses, creating a suitable microenvironment for the development of skewed interactions between the host and the gut microbiota and cancer initiation. Even if surgery is the primary therapeutic strategy, patients with advanced disease or cancer recurrence after surgery remain difficult to cure. Therefore, the gut microbiota has been proposed as a novel therapeutic target in light of recent promising data in which it seems to modulate the response to cancer immunotherapy. The use of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics, and fecal microbiota transplantation, is therefore considered to support current therapies in CRC management. In this review, we will discuss the importance of host-microbe interactions in CRC and how promoting homeostatic immune responses through microbe-targeted therapies may be useful in preventing/treating CRC development.}, }
@article {pmid32750174, year = {2020}, author = {Bajaj, JS and Gavis, EA and Fagan, A and Wade, JB and Thacker, LR and Fuchs, M and Patel, S and Davis, B and Meador, J and Puri, P and Sikaroodi, M and Gillevet, PM}, title = {A Randomized Clinical Trial of Fecal Microbiota Transplant for Alcohol Use Disorder.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep.31496}, pmid = {32750174}, issn = {1527-3350}, abstract = {BACKGROUND &amp; AIMS: Alcohol use disorder (AUD) is associated with microbial alterations that worsen with cirrhosis. Fecal microbiota transplant (FMT) could be a promising approach.<br><br>APPROACH &amp; RESULTS: In this phase 1, double-blind, randomized clinical trial, AUD-related cirrhosis patients with problem drinking (AUDIT-10>8) were randomized 1:1 into receiving one placebo or FMT enema from a donor enriched in Lachnospiraceae and Ruminococcaceae. 6-month safety was the primary outcome. Alcohol craving questionnaire, alcohol consumption (urinary ethylglucuronide/creatinine, Etg), quality of life (QOL), cognition, serum IL-6 and lipopolysaccharide-binding protein (LBP), plasma/stool short-chain fatty acids (SCFA) and stool microbiota were tested at baseline and day 15. A 6-month follow-up with serious adverse events (SAE) analysis was performed. 20 patients with AUD-related cirrhosis [65±6.4 years, all men, MELD 8.9±2.7] with similar demographics, cirrhosis and AUD severity were included. Craving reduced significantly in 90% of FMT versus 30% in placebo at day15(p=0.02) with lower urinary Etg (p=0.03), improved cognition and psychosocial QOL. There was reduction in serum IL-6 and LBP and increased butyrate/isobutyrate compared to baseline in FMT but not placebo. Microbial diversity increased with higher Ruminococcaceae and other SCFA producing taxa post-FMT but not placebo, which were linked with SCFA levels. At 6 months, patients with any SAEs (8 vs 2, p=0.02), AUD-related SAEs (7 vs 1, p=0.02) and SAEs/patient [median(IQR),1.5(1.25) vs 0(0.25) in FMT,p=0.02] were higher in placebo versus FMT.<br><br>CONCLUSIONS: This phase 1 trial shows that FMT is safe and associated with short-term reduction in alcohol craving and consumption with favorable microbial changes versus placebo in patients with alcohol-related cirrhosis with alcohol misuse. There was also a reduction in AUD-related events over 6 months in patients assigned to FMT.}, }
@article {pmid32742991, year = {2020}, author = {Yue, YY and Fan, XY and Zhang, Q and Lu, YP and Wu, S and Wang, S and Yu, M and Cui, CW and Sun, ZR}, title = {Bibliometric analysis of subject trends and knowledge structures of gut microbiota.}, journal = {World journal of clinical cases}, volume = {8}, number = {13}, pages = {2817-2832}, pmid = {32742991}, issn = {2307-8960}, abstract = {BACKGROUND: Gut microbiota is an emerging field of research, with related research having breakthrough development in the past 15 years. Bibliometric analysis can be applied to analyze the evolutionary trends and emerging hotspots in this field.<br><br>AIM: To study the subject trends and knowledge structures of gut microbiota related research fields from 2004 to 2018.<br><br>METHODS: The literature data on gut microbiota were identified and downloaded from the PubMed database. Through biclustering analysis, strategic diagrams, and social network analysis diagrams, the main trend and knowledge structure of research fields concerning gut microbiota were analyzed to obtain and compare the research hotspots in each period.<br><br>RESULTS: According to the strategic coordinates and social relationship network map, Clostridium Infections/microbiology, Clostridium Infections/therapy, RNA, Ribosomal, 16S/genetics, Microbiota/genetics, Microbiota/immunology, Dysbiosis/immunology, Infla-mmation/immunology, Fecal Microbiota Transplantation/methods, Fecal Microbiota Transplantation can be used as an emerging research hotspot in the past 5 years (2014-2018).<br><br>CONCLUSION: Some subjects were not yet fully studied according to the strategic coordinates; and the emerging hotspots in the social network map can be considered as directions of future research.}, }
@article {pmid32742177, year = {2020}, author = {Abhyankar, D and McKee, KT and Vukojevic, P}, title = {Gut Microbiota and Response to Immunotherapeutic Drugs in Oncology: More Questions Than Answers.}, journal = {Clinical Medicine Insights. Oncology}, volume = {14}, number = {}, pages = {1179554920933868}, pmid = {32742177}, issn = {1179-5549}, abstract = {Immuno-oncology drugs (IODs) have revolutionized the treatment of some cancers. Although IODs are enabling some patients with cancer to become long-time survivors, only 30% to 40% respond to these drugs. There is experimental and clinical evidence that the gut microbiome may play a role in IOD response, leading to speculation that manipulation of the gut microenvironment might improve the response rate to IODs. We review the evidence relating to how gut microorganisms may affect response to IODs and discuss the implications of targeting the microbiome to improve IOD response, including the challenges to refine and translate the findings to practical clinical use.}, }
@article {pmid32739967, year = {2020}, author = {Guery, B and Barbut, F and Tschudin-Sutter, S}, title = {Diagnostic and therapy of severe Clostridioides difficile infections in the ICU.}, journal = {Current opinion in critical care}, volume = {26}, number = {5}, pages = {450-458}, doi = {10.1097/MCC.0000000000000753}, pmid = {32739967}, issn = {1531-7072}, abstract = {PURPOSE OF REVIEW: The purpose of the review is to provide all the recent data focusing on the diagnostic and treatment of Clostridioides difficile infection in patients admitted in the ICU.<br><br>RECENT FINDINGS: In the ICU, diagnosis remains complicated with a large number of alternative diagnosis. The treatment classically relies on vancomycin but fidaxomicin and fecal microbiota transplantation are now potential solutions in selected indications.<br><br>SUMMARY: Data on ICU-related CDI remain limited and conflicting. To date, there is no unique and simple way to obtain a diagnosis for CDI, the combination of clinical signs and a two-step testing algorithm remains the recommended gold-standard. Two molecules can be proposed for first line treatment: vancomycin and fidaxomicin. Although metronidazole may still be discussed as a treatment option for mild CDI in low-risk patients, its use for ICU-patients does not seem reasonable. Several reports suggest that fecal microbiota transplantation could be discussed, as it is well tolerated and associated with a high rate of clinical cure. CDI is a dynamic and active area of research with new diagnostic techniques, molecules, and management concepts likely changing our approach to this old disease in the near future.}, }
@article {pmid32738249, year = {2020}, author = {Allegretti, JR and Kelly, CR and Grinspan, A and Mullish, BH and Kassam, Z and Fischer, M}, title = {Outcomes of Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Diseases and Recurrent Clostridioides difficile Infection.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2020.07.045}, pmid = {32738249}, issn = {1528-0012}, }
@article {pmid32737354, year = {2020}, author = {Wasinger, VC and Lu, K and Yau, YY and Nash, J and Lee, J and Chang, J and Paramsothy, S and Kaakoush, NO and Mitchell, HM and Leong, RWL}, title = {Spp24 is associated with endocytic signalling, lipid metabolism, and discrimination of tissue integrity for 'leaky-gut' in inflammatory bowel disease.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {12932}, pmid = {32737354}, issn = {2045-2322}, support = {sponsored research//Takeda Science Foundation/ ; IBD-0391R//Crohn's and Colitis Foundation of America/ ; }, abstract = {Epithelial barrier injury allows contaminants to cross-over into the blood stream and trigger an inflammatory response, contributing to inflammatory bowel disease (IBD). Currently there is no single test that can reliably diagnose intestinal mucosal barrier function or measure impaired epithelial cell integrity associated with increasing permeability. Here, we assess the association between serum proteins and small intestinal permeability as detected by confocal laser endomicroscopy (CLE); in particular the known IBD marker-secreted phosphoprotein 24 (SPP24) and its binding partners; and use developed monoclonal antibodies to assess the role of SPP24 in mucosal healing. Sera were obtained from 28 IBD patients and non-IBD controls undergoing CLE with scores ranging from low to high permeability, as well as active ulcerative colitis from 53 patients undergoing fecal microbiota transplant therapy (FMT). Higher permeability associated with altered lipid metabolism, heightened innate immune response and junctional protein signalling in UC patients. A correlation between increasing leak and SPP24 peptide was observed. There is a strong indication of the novel role of SPP24 in gut barrier dysfunction particularly in ulcerative colitis. Its correlation to the established CLE for monitoring permeability has the potential to provide a blood based parallel to monitor and guide therapy more readily across a broad spectrum of illnesses for which 'leak' dominates the pathology.}, }
@article {pmid32729978, year = {2020}, author = {Lu, JF and Zhu, MQ and Zhang, H and Liu, H and Xia, B and Wang, YL and Shi, X and Peng, L and Wu, JW}, title = {Neohesperidin attenuates obesity by altering the composition of the gut microbiota in high-fat diet-fed mice.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {}, number = {}, pages = {}, doi = {10.1096/fj.201903102RR}, pmid = {32729978}, issn = {1530-6860}, support = {81670758//National Natural Science Foundation of China (NSFC)/ ; 81970713//National Natural Science Foundation of China (NSFC)/ ; 7182147//Beijing Municipal Natural Science Foundation/ ; 2018-2-4062//Capital's Funds for Health Improvement and Research/ ; 2018RC310023//Fundamental Research Funds of the Chinese Academy of Medical Science/ ; //Programs for Shaanxi Science &amp; Technology: 2020NY-01/ ; //Special Talent Recruitment Fund of China to JWW/ ; }, abstract = {Obesity and related metabolic disorders are associated with intestinal microbiota dysbiosis, disrupted intestinal barrier, and chronic inflammation. Neohesperidin (Neo), a natural polyphenol abundant in citrus fruits, is known for its preventative and therapeutic effects on numerous diseases. Here, we report that Neo administration attenuates weight gain, low-grade inflammation, and insulin resistance in mice fed high-fat diet (HFD). Also, Neo administration substantially restores gut barrier damage, metabolic endotoxemia, and systemic inflammation. Sequencing of 16S rRNA genes in fecal samples revealed that Neo administration reverses HFD-induced intestinal microbiota dysbiosis: an increase in the diversity of gut microbiota and alteration in the composition of intestinal microbiota (particularly in the relative abundances of Bacteroidetes and Firmicutes). Furthermore, systemic antibiotic treatment abolishes the beneficial effects of Neo in body weight control, suggesting that the effect of Neo on obesity attenuation largely depends on the gut microbiota. More importantly, we demonstrate that the impact of Neo on the regulation of obesity could be transferred from Neo-treated mice to HFD-fed mice via fecal microbiota transplantation. Collectively, our data highlight the efficacy of Neo as a prebiotic agent for attenuating obesity, implying a potential mechanism for gut microbiota mediated the beneficial effect of Neo.}, }
@article {pmid32727864, year = {2020}, author = {Bhattacharjee, D and Seekatz, AM}, title = {Dilution as a Solution: Targeting Microbial Populations with a Simplified Dilution Strategy.}, journal = {mSphere}, volume = {5}, number = {4}, pages = {}, pmid = {32727864}, issn = {2379-5042}, mesh = {*Clostridium Infections ; *Clostridium difficile ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {The gut microbiota is an integral part of maintaining resistance against infection by Clostridioides (Clostridium) difficile, a pathogen of increasing concern in both health care and community settings. The recent article by J. M. Auchtung, E. C. Preisner, J. Collins, A. I. Lerma, and R. A. Britton (mSphere 5:e00387-20, 2020, https://doi.org/10.1128/mSphere.00387-20) demonstrates an innovative approach to identify microbes that inhibit C. difficile by employing a dilution scheme to test different microbial mixtures in vitro and in vivo This type of approach can advance the identification and validation of specific microbes that elicit functions of interest for many conditions involving the microbiota, of which the complexity and variability can often complicate causality.}, }
@article {pmid32727857, year = {2020}, author = {Auchtung, JM and Preisner, EC and Collins, J and Lerma, AI and Britton, RA}, title = {Identification of Simplified Microbial Communities That Inhibit Clostridioides difficile Infection through Dilution/Extinction.}, journal = {mSphere}, volume = {5}, number = {4}, pages = {}, pmid = {32727857}, issn = {2379-5042}, support = {R01 AI123278/AI/NIAID NIH HHS/United States ; U01 AI124290/AI/NIAID NIH HHS/United States ; }, abstract = {The gastrointestinal microbiome plays an important role in limiting susceptibility to infection with Clostridioides difficile To better understand the ecology of bacteria important for C. difficile colonization resistance, we developed an experimental platform to simplify complex communities of fecal bacteria through dilution and rapidly screen for their ability to resist C. difficile colonization after challenge, as measured by >100-fold reduction in levels of C. difficile in challenged communities. We screened 76 simplified communities diluted from cultures of six fecal donors and identified 24 simplified communities that inhibited C. difficile colonization in vitro Sequencing revealed that simplified communities were composed of 19 to 67 operational taxonomic units (OTUs) and could be partitioned into four distinct community types. One simplified community could be further simplified from 56 to 28 OTUs through dilution and retain the ability to inhibit C. difficile We tested the efficacy of seven simplified communities in a humanized microbiota mouse model. We found that four communities were able to significantly reduce the severity of the initial C. difficile infection and limit susceptibility to disease relapse. Analysis of fecal microbiomes from treated mice demonstrated that simplified communities accelerated recovery of indigenous bacteria and led to stable engraftment of 19 to 22 OTUs from simplified communities. Overall, the insights gained through the identification and characterization of these simplified communities increase our understanding of the microbial dynamics of C. difficile infection and recovery.IMPORTANCEClostridioides difficile is the leading cause of antibiotic-associated diarrhea and a significant health care burden. Fecal microbiota transplantation is highly effective at treating recurrent C. difficile disease; however, uncertainties about the undefined composition of fecal material and potential long-term unintended health consequences remain. These concerns have motivated studies to identify new communities of microbes with a simpler composition that will be effective at treating disease. This work describes a platform for rapidly identifying and screening new simplified communities for efficacy in treating C. difficile infection. Four new simplified communities of microbes with potential for development of new therapies to treat C. difficile disease are identified. While this platform was developed and validated to model infection with C. difficile, the underlying principles described in the paper could be easily modified to develop therapeutics to treat other gastrointestinal diseases.}, }
@article {pmid32724908, year = {2020}, author = {Zukauckas, K and Vandiver, J and Biehle, L}, title = {It's time to rethink your approach to C diff infection.}, journal = {The Journal of family practice}, volume = {69}, number = {6}, pages = {293-300}, pmid = {32724908}, issn = {1533-7294}, abstract = {Metronidazole is no longer the drug of choice for first-line therapy. And fecal microbiota transplantation has proven effective for certain patients.}, }
@article {pmid32718072, year = {2020}, author = {Wagner-Skacel, J and Dalkner, N and Moerkl, S and Kreuzer, K and Farzi, A and Lackner, S and Painold, A and Reininghaus, EZ and Butler, MI and Bengesser, S}, title = {Sleep and Microbiome in Psychiatric Diseases.}, journal = {Nutrients}, volume = {12}, number = {8}, pages = {}, pmid = {32718072}, issn = {2072-6643}, abstract = {OBJECTIVES: Disturbances in the gut-brain barrier play an essential role in the development of mental disorders. There is considerable evidence showing that the gut microbiome not only affects digestive, metabolic and immune functions of the host but also regulates host sleep and mental states through the microbiota-gut-brain axis. The present review summarizes the role of the gut microbiome in the context of circadian rhythms, nutrition and sleep in psychiatric disorders.<br><br>METHODS: A PubMed search (studies published between April 2015-April 2020) was conducted with the keywords: &quot;sleep, microbiome and psychiatry&quot;; &quot;sleep, microbiome and depression&quot;; &quot;sleep, microbiome and bipolar disorder&quot;, &quot;sleep, microbiome and schizophrenia&quot;, &quot;sleep, microbiome and anorexia nervosa&quot;, &quot;sleep, microbiome and substance use disorder&quot;, &quot;sleep, microbiome and anxiety&quot;; &quot;clock gene expression and microbiome&quot;, &quot;clock gene expression and nutrition&quot;. Only studies investigating the relationship between sleep and microbiome in psychiatric patients were included in the review.<br><br>RESULTS: Search results yielded two cross-sectional studies analyzing sleep and gut microbiome in 154 individuals with bipolar disorder and one interventional study analyzing the effect of fecal microbiota transplantation in 17 individuals with irritable bowel syndrome on sleep. In patients with bipolar disorder, Faecalibacterium was significantly associated with improved sleep quality scores and a significant correlation between Lactobacillus counts and sleep.<br><br>CONCLUSION: Translational research on this important field is limited and further investigation of the bidirectional pathways on sleep and the gut microbiome in mood disorders is warranted.}, }
@article {pmid32717434, year = {2020}, author = {Murthy, HS and Gharaibeh, RZ and Al-Mansour, Z and Kozlov, A and Trikha, G and Newsome, RC and Gauthier, J and Farhadfar, N and Wang, Y and Kelly, DL and Lybarger, J and Jobin, C and Wang, GP and Wingard, JR}, title = {Baseline Gut Microbiota Composition Is Associated with Major Infections Early after Hematopoietic Cell Transplantation.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbmt.2020.07.023}, pmid = {32717434}, issn = {1523-6536}, abstract = {Infection is a major cause of morbidity and mortality after hematopoietic cell transplantation (HCT). Gut microbiota (GM) composition and metabolites provide colonization resistance against dominance of potential pathogens, and GM dysbiosis following HCT can be deleterious to immune reconstitution. Little is known about the composition, diversity, and evolution of GM communities in HCT patients and their association with subsequent febrile neutropenia (FN) and infection. Identification of markers before HCT that predict subsequent infection could be useful in developing individualized antimicrobial strategies. Fecal samples were collected prospectively from 33 HCT recipients at serial time points: baseline, post-conditioning regimen, neutropenia onset, FN onset (if present), and hematologic recovery. GM was assessed by 16S rRNA sequencing. FN and major infections (ie, bloodstream infection, typhlitis, invasive fungal infection, pneumonia, and Clostridium difficile enterocolitis) were identified. Significant shifts in GM composition and diversity were observed during HCT, with the largest alterations occurring after initiation of antibiotics. Loss of diversity persisted without a return to baseline at hematologic recovery. GM in patients with FN was enriched in Mogibacterium, Bacteroides fragilis, and Parabacteroides distasonis, whereas increased abundance of Prevotella, Ruminococcus, Dorea, Blautia, and Collinsella was observed in patients without fever. A baseline protective GM profile (BPGMP) was predictive of protection from major infection. The BPGMP was associated with subsequent major infections with 77% accuracy and an area under the curve of 79%, with sensitivity, specificity, and positive and negative predictive values of 0.71, 0.91, 0.77, and 0.87, respectively. Our data show that large shifts in GM composition occur early after HCT, and differences in baseline GM composition are associated with the development of subsequent major infections.}, }
@article {pmid32713786, year = {2020}, author = {Chiu, CH and Tsai, MC and Cheng, HT and Le, PH and Kuo, CJ and Chiu, CT}, title = {Fecal microbiota transplantation and donor screening for Clostridioides difficile infection during COVID-19 pandemic.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {}, number = {}, pages = {}, pmid = {32713786}, issn = {0929-6646}, }
@article {pmid32712721, year = {2020}, author = {Reyes-Castillo, Z and Valdés-Miramontes, E and Llamas-Covarrubias, M and Muñoz-Valle, JF}, title = {Troublesome friends within us: the role of gut microbiota on rheumatoid arthritis etiopathogenesis and its clinical and therapeutic relevance.}, journal = {Clinical and experimental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10238-020-00647-y}, pmid = {32712721}, issn = {1591-9528}, abstract = {The role of gut microbiota on immune regulation and the development of autoimmune diseases such as rheumatoid arthritis (RA) is an emerging research topic. Multiple studies have demonstrated alterations on gut microbiota composition and/or function (referred to as dysbiosis) both in early and established RA patients. Still, research delineating the molecular mechanisms by which gut microorganisms induce the loss of immune tolerance or contribute to disease progression is scarce. Available data indicate that gut microbiota alterations are involved in RA autoimmune response by several mechanisms including the post-translational modification of host proteins, molecular mimicry between bacterial and host epitopes, activation of immune system and polarization toward inflammatory phenotypes, as well as induction of intestinal permeability. Therefore, in this review we analyze recent clinical and molecular evidence linking gut microbiota with the etiopathogenesis of RA. The potential of the gut microbiota as a diagnostic or severity biomarker is discussed, as well as the opportunity areas for the development of complementary therapeutic strategies based on the modulation of gut microbiota in the rheumatic patient.}, }
@article {pmid32711581, year = {2020}, author = {Zhang, P and Liu, J and Xiong, B and Zhang, C and Kang, B and Gao, Y and Li, Z and Ge, W and Cheng, S and Hao, Y and Shen, W and Yu, S and Chen, L and Tang, X and Zhao, Y and Zhang, H}, title = {Microbiota from alginate oligosaccharide-dosed mice successfully mitigated small intestinal mucositis.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {112}, pmid = {32711581}, issn = {2049-2618}, support = {31772408//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: The increasing incidence of cancer and intestinal mucositis induced by chemotherapeutics are causing worldwide concern. Many approaches such as fecal microbiota transplantation (FMT) have been used to minimize mucositis. However, it is still unknown whether FMT from a donor with beneficial gut microbiota results in more effective intestinal function in the recipient. Recently, we found that alginate oligosaccharides (AOS) benefit murine gut microbiota through increasing &quot;beneficial&quot; microbes to rescue busulfan induced mucositis.<br><br>RESULTS: In the current investigation, FMT from AOS-dosed mice improved small intestine function over FMT from control mice through the recovery of gene expression and an increase in the levels of cell junction proteins. FMT from AOS-dosed mice showed superior benefits over FMT from control mice on recipient gut microbiotas through an increase in &quot;beneficial&quot; microbes such as Leuconostocaceae and recovery in blood metabolome. Furthermore, the correlation of gut microbiota and blood metabolites suggested that the &quot;beneficial&quot; microbe Lactobacillales helped with the recovery of blood metabolites, while the &quot;harmful&quot; microbe Mycoplasmatales did not.<br><br>CONCLUSION: The data confirm our hypothesis that FMT from a donor with superior microbes leads to a more profound recovery of small intestinal function. We propose that gut microbiota from naturally produced AOS-treated donor may be used to prevent small intestinal mucositis induced by chemotherapeutics or other factors in recipients. Video Abstract.}, }
@article {pmid32702186, year = {2020}, author = {Zhao, D and Dai, W and Tao, H and Zhuang, W and Qu, M and Chang, YN}, title = {Polysaccharide isolated from Auricularia auricular-judae (Bull.) prevents dextran sulfate sodium-induced colitis in mice through modulating the composition of the gut microbiota.}, journal = {Journal of food science}, volume = {85}, number = {9}, pages = {2943-2951}, doi = {10.1111/1750-3841.15319}, pmid = {32702186}, issn = {1750-3841}, abstract = {Inflammatory bowel disease (IBD) is a chronic intestinal disease, which was commonly found in westerners whereas is increasingly prevalent in Asia because of the changing eating habits. In previous research, we found that a water-soluble polysaccharide isolated from Auricularia auricular-judae (Bull.)-a kind of edible mushroom (Aap)-is composed of β-1,3 glycosidic bonds, which is regarded as therapeutic or protective substance in enteritis. We therefore aimed to find the preventing effect of Aap on IBD. Here, we reported that pre-administration of Aap not only ameliorated weight loss, colon damage, and mucosal inflammation in colitis mice, but also prevented the damage of intestinal barrier by reducing the D-lactic acid and diamine oxidase level in plasma. Through high-throughput sequencing, we found that Aap changed gut microbiota composition. Furthermore, the preventing effect was transmissible via horizontal feces transfer from Aap-treated mice to normal mice. Our results indicated that oral administration of Aap is a promising protective substance of IBD. PRACTICAL APPLICATION: Our study proved that Auricularia auricula polysaccharide had substantial preventing effect on DSS-induced colitis in mice. This research might lay the theoretical foundation and technical support for the development of related functional foods. People could also enhance their gut immunity by eating Auricularia auricular in their daily life. Auricularia auricular as a highly nutritious agricultural product showed the broad significance in nutrition and food function.}, }
@article {pmid32701590, year = {2020}, author = {, }, title = {Nanjing consensus on methodology of washed microbiota transplantation.}, journal = {Chinese medical journal}, volume = {133}, number = {19}, pages = {2330-2332}, doi = {10.1097/CM9.0000000000000954}, pmid = {32701590}, issn = {2542-5641}, }
@article {pmid32701563, year = {2020}, author = {Tariq, R and Saha, S and Solanky, D and Pardi, DS and Khanna, S}, title = {Predictors and Management of Failed Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001398}, pmid = {32701563}, issn = {1539-2031}, abstract = {BACKGROUND AND GOALS: Clostridioides difficile infection (CDI) recurs in 10% to 15% after fecal microbiota transplantation (FMT). We identify predictors, and describe management and outcome of patients with recurrent CDI after FMT in a predominantly outpatient cohort.<br><br>METHODS: A nested case-control study of patients undergoing FMT for recurrent CDI from August 2012 to January 2017 was performed. FMT failure was defined as recurrent diarrhea with positive C. difficile stool test during follow-up (≥2 mo). Controls (patients without FMT failures) were matched to cases 1:1 for sex and timing of FMT±1 month.<br><br>RESULTS: Overall, 522 patients underwent FMT; 70 [13.4%; median age 53.8 years (range, 18 to 89 y), 54.3% females] recurred within a median 5.6 months (range, 0.2 to 34.9 mo). Number of prior CDI episodes, prior CDI treatment, and prior CDI-related hospitalizations were similar in cases and controls. Systemic antibiotics after FMT (54.3% vs. 21.4%, P<0.0001), inflammatory bowel disease (IBD) (34.3% vs. 15.7%, P=0.01), pseudomembranes at FMT (4.3% vs. 0%, P=0.03), and poor bowel preparation (68.5% vs. 31.4%, P=0.01) were associated with FMT failure. On multivariate analysis, IBD [odds ratio (OR) 4.34; 95% confidence interval (CI), 1.24-15.15], systemic antibiotics (OR 7.39; 95% CI, 3.02-18.07), and poor bowel preparation (OR 3.84; 95% CI, 1.59-9.28) predicted FMT failure with an area under the curve of 0.78. Among FMT failures, 37 (52.8%) were managed with antibiotics, 32 (45.7%) with repeat FMT after antibiotics and 1 with colectomy.<br><br>CONCLUSIONS: Use of systemic antibiotics, IBD, and poor bowel preparation predict FMT failure. Patients with FMT failure can be managed with antibiotics and/or repeat FMT.}, }
@article {pmid32697259, year = {2020}, author = {Jing, N and Liu, X and Jin, M and Yang, X and Hu, X and Li, C and Zhao, K}, title = {Fubrick tea attenuates high-fat diet induced fat deposition and metabolic disorder by regulating gut microbiota and caffeine metabolism.}, journal = {Food &amp; function}, volume = {11}, number = {8}, pages = {6971-6986}, doi = {10.1039/d0fo01282c}, pmid = {32697259}, issn = {2042-650X}, abstract = {Fubrick tea aqueous extract (FTEs) has been reported to improve lipid metabolism and gut microbiota communities in mice and humans. However, it is still unclear how FTEs prevents obesity through gut microbiota, and whether some other regulatory mechanisms are involved in the process. Here, we found that FTEs supplementation effectively alleviated the body weight gain, visceral fat accumulation, dyslipidemia, and impaired glucose tolerance induced by a high-fat diet (HFD), and fecal microbiota transplantation (FMT) from FTEs-treated mice showed similar protective effects as FTEs supplementation in mice fed with a HFD. The results confirmed that gut microbiota played key roles in attenuating HFD-induced fat deposition and metabolic disorder. In particular, FTEs reversed HFD-induced gut microbiota dysbiosis via increasing the relative abundances of Bacteroides, Adlercreutzia, Alistipes, Parabacteroides, and norank_f_Lachnospiraceae, and reducing that of Staphylococcus. Interestingly, FTEs could still alleviate HFD-induced lipid accumulation in mice treated with antibiotics, which had increased relative abundances of Bacteroidetes, Bacteroides, and Bacteroides_uniformis sp. In addition, supplementation with FTEs also modified the serum metabolome, especially the &quot;caffeine metabolism&quot; pathway. Furthermore, FTEs supplementation increased the concentrations of caffeine, theophylline, and theobromine in serum, which were positively correlated with an abundance of norank_f_Lachnospiraceae. Overall, FTEs exerts beneficial effects against obesity induced by HFD, and the underlying mechanism is partially related to the reprogramming of intestinal microbiota, while the metabolism of caffeine in FTEs also played an important role in the process. This study provides a theoretical basis for the further study of the anti-obesity effects of FTEs and the consideration of gut microbiota as a potential target for the treatment of obesity induced by a HFD.}, }
@article {pmid32690139, year = {2020}, author = {Halsey, T and Ologun, G and Wargo, J and Jenq, RR}, title = {Uncovering the role of the gut microbiota in immune checkpoint blockade therapy: A mini-review.}, journal = {Seminars in hematology}, volume = {57}, number = {1}, pages = {13-18}, pmid = {32690139}, issn = {1532-8686}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; T32 CA009599/CA/NCI NIH HHS/United States ; }, abstract = {In recent years, the microbiota has been implicated as a key factor associated with both response and toxicity from immune checkpoint blockade therapy. Numerous studies have been published that specifically highlight the importance of the microbiome as a distinct influencer of anti-PD-1/PD-L1 and anti-CTLA-4 activity in cancer patients, but a full understanding of mechanisms behind these interactions has yet to be achieved. With greater insight into how the microbiome can modulate immune checkpoint blockade comes the potential to target the microbiome to improve response rates and minimize toxicities. This mini-review looks at noteworthy studies that have explored the relationship between the microbiome and immune checkpoint blockade response and toxicity in both preclinical and clinical studies, with an emphasis on current hypotheses regarding mechanisms of action and potential microbiome-targeted therapeutic strategies under development.}, }
@article {pmid32686598, year = {2020}, author = {Zhu, Z and Huang, J and Li, X and Xing, J and Chen, Q and Liu, R and Hua, F and Qiu, Z and Song, Y and Bai, C and Mo, YY and Zhang, Z}, title = {Gut microbiota regulate tumor metastasis via circRNA/miRNA networks.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1788891}, pmid = {32686598}, issn = {1949-0984}, abstract = {BACKGROUND: Increasing evidence indicates that gut microbiota plays an important role in cancer progression. However, the underlying mechanism remains largely unknown. Here, we report that broad-spectrum antibiotics (ABX) treatment leads to enhanced metastasis by the alteration of gut microbiome composition.<br><br>METHODS: Cancer LLC and B16-F10 cell metastasis mouse models, and microarray/RNA sequencing analysis were used to reveal the regulatory functions of microbiota-mediated circular RNA (circRNA)/microRNA (miRNA) networks that may contribute to cancer metastasis.<br><br>RESULTS: The specific pathogen-free (SPF) mice with ABX treatment demonstrated enhanced lung metastasis. Fecal microbiota transplantation (FMT) from SPF mice or Bifidobacterium into germ-free mice significantly suppressed lung metastasis. Mechanistically, gut microbiota impacts circRNA expression to regulate levels of corresponding miRNAs. Specifically, such modulations of gut microbiota inhibit mmu_circ_0000730 expression in an IL-11-dependent manner. Bioinformatics analysis combined with luciferase reporter assays revealed reciprocal repression between mmu_circ_0000730 and mmu-miR-466i-3p. We further showed that both mmu-miR-466i-3p and mmu-miR-466 f-3p suppresses a number of genes involved in epithelial-mesenchymal transition (EMT) and stemness of cancer stem cells such as SOX9.<br><br>CONCLUSIONS: These results provide evidence of a previously unrecognized regulatory role of non-coding RNAs in microbiota-mediated cancer metastasis, and thus, the microbiome may serve as a therapeutic target.}, }
@article {pmid32685087, year = {2020}, author = {Wei, Z and Shen, P and Cheng, P and Lu, Y and Wang, A and Sun, Z}, title = {Gut Bacteria Selectively Altered by Sennoside A Alleviate Type 2 Diabetes and Obesity Traits.}, journal = {Oxidative medicine and cellular longevity}, volume = {2020}, number = {}, pages = {2375676}, pmid = {32685087}, issn = {1942-0994}, abstract = {Accumulating evidences implicate that gut microbiota play an important role in the onset and prolongation of fat inflammation and diabetes. Sennoside A, the main active ingredient of Rhizoma Rhei (rhubarb), is widely used for constipation as a kind of anthranoid laxative (e.g., senna). Here, we put forward the hypothesis that the structural alteration of gut microbiota in obesity mice may be involved in the pathogenesis of type 2 diabetes (T2D) which may be ameliorated by Sennoside A. We investigated the appearance of obesity, insulin resistance, host inflammation, and leaky gut phenotype with or without Sennoside A in db/db mice. Horizontal fecal microbiota transplantation (FMT) was used to confirm the critical roles of gut microbiota in the amelioration of the indices in T2D mice after Sennoside A treatment. As a result, we found that Sennoside A administration markedly improved the indices in T2D mice and obesity-related traits including blood glucose level, body weight, lipid metabolism disorder, and insulin resistance. The gut microbiota changed quickly during the onset of T2D in db/db mice, which confirmed the hypothesis that gut microbiota was involved in the pathogenesis of T2D. Sennoside A altered gut microbial composition which might mediate the antiobesogenic effects in T2D remission. Sennoside A also reduced inflammation and increased tight junction proteins in the ileum in gene-deficient mice via gut microbiota alteration. FMT lowered the blood glucose level and improved insulin resistance, corroborating that Sennoside A perhaps exerted its antiobesogenic effects through gut microbiota alteration. Chemical Compounds Studied in This Article. Compounds studied in this article include Sennoside A (PubChem CID: 73111) and metformin hydrochloride (PubChem CID: 14219).}, }
@article {pmid32684346, year = {2020}, author = {Martínez-González, AE and Andreo-Martínez, P}, title = {Prebiotics, probiotics and fecal microbiota transplantation in autism: A systematic review.}, journal = {Revista de psiquiatria y salud mental}, volume = {13}, number = {3}, pages = {150-164}, doi = {10.1016/j.rpsm.2020.06.002}, pmid = {32684346}, issn = {1989-4600}, abstract = {In recent years, there has been an increase in studies of the implications of the gut microbiota (GM) in children with autism spectrum disorder (ASD). There is a hypothesis which propose a relationship between the emotional state and the abundance of intestinal microbes through the so-called microbiota-intestine-brain axis. In this sense, dysbiotic GM could be a contributing factor to the appearance of ASD. This systematic review article analyzes the results of the intervention using prebiotics (carrot powder, vitamin A, partially hydrolyzed guar gum, galactooligosaccharides, etc.), probiotics (mainly: Lactobacillus, Bifidobacterium, etc.) and transplantation of fecal microbiota in ASD children. In conclusion, the results of the initial studies suggest changes in ASD symptoms, gastro-intestinal symptoms and GM composition after the interventions. However, the results should be taken with caution because there are very few studies that analyze the efficacy of long-term treatments and the different combinations of them.}, }
@article {pmid32681922, year = {2020}, author = {Holvoet, T and Joossens, M and Vázquez-Castellanos, JF and Christiaens, E and Heyerick, L and Boelens, J and Verhasselt, B and van Vlierberghe, H and De Vos, M and Raes, J and De Looze, D}, title = {Fecal Microbiota Transplantation Reduces Symptoms in Some Patients With Irritable Bowel Syndrome with Predominant Abdominal Bloating: Short- and Long-Term Results from a Placebo-Controlled Randomized Trial.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2020.07.013}, pmid = {32681922}, issn = {1528-0012}, abstract = {BACKGROUND &amp; AIMS: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with intestinal dysbiosis. Given reported promising results of open-label fecal microbiota transplantation (FMT) therapy in patients with predominant abdominal bloating, we studied efficacy of this treatment in a randomized, placebo-controlled trial.<br><br>METHODS: Patients with refractory IBS, defined as failure of ≥ 3 conventional therapies, were randomly assigned to single-dose nasojejunal administration of donor stools (n=43) or autologous stools (n=19) in a double-blind study, performed from December 2015 through October 2017, and followed for 1 year. IBS-related symptoms were assessed using a daily symptom diary to determine general abdominal discomfort, abdominal bloating, abdominal pain and flatulence on a scale of 1-6. Number of daily bowel movements, consistency of the stools, and the abdominal circumference were also recorded. Patients completed the IBS-specific quality of life questionnaire. Primary endpoints were improvement of IBS symptoms and bloating at 12 weeks (response). Secondary endpoints were changes in IBS-symptom-scores and quality of life. Stool samples were collected for microbiota amplicon sequencing. Open-label re-transplantation was offered after the trial.<br><br>RESULTS: At week 12, 56% of patients given donor stool reported improvement in both primary endpoints compared with 26% of patients given placebo (P=.03). Patients given donor stool had significant improvements in level of discomfort (mean reduction of 19%; median score preFMT, 3.98; range, 2.13-6.00; median score post-FMT, 3.1; range, 951.29-5.90), stool frequency (mean reduction of 13%, median score preFMT, 2.10; range, 0.57-14.29; median score postFMT 1.7; range, 0.71-4.29), urgency (mean reduction of 38%; median score preFMT, 0.61; range, 0.00-1.00; median score postFMT, 0.37; range, 0.00-1.00), abdominal pain (mean reduction of 26%; median score preFMT, 3.88; range, 1.57-5.17; median score postFMT, 2.80; range, 1.14-4.94), flatulence (mean reduction of 10%; median score preFMT, 3.42; range, 0.71-6.00; median score postFMT, 3.07; range, 0.79-4.23), and quality of life (mean increase of 16%; median score preFMT 32.6; range, 11-119; median score postFMT, 43.1; range, 32.25-99). A significantly higher proportion of women given donor stool (69%) had a response than men (29%) (P=.01). Fecal samples from responders had higher diversity of microbiomes before administration of donor material than fecal samples from non-responders (P=.04) and distinct baseline composition (P= .04), but no specific marker taxa were associated with response. After single FMT, 21% of patients given donor stool reported effects that lasted for more than 1 year, compared with 5% of patients given placebo stool. A second FMT reduced symptoms in 67% of patients with an initial response to donor stool, but not in patients with a prior non-response.<br><br>CONCLUSIONS: In a randomized trial of patients with treatment-refractory IBS with predominant bloating, FMT relieved symptoms compared with placebo (autologous transplant), although effects decreased over 1 year. A second FMT restored the response patients with a prior response. Response associated with composition of the fecal microbiomes before FMT; this might be used to as a biomarker to select patients for this treatment. ClinicalTrials.gov no: NCT02299973.}, }
@article {pmid32681643, year = {2020}, author = {Ghani, R and Mullish, BH and McDonald, JAK and Ghazy, A and Williams, HRT and Brannigan, ET and Mookerjee, S and Satta, G and Gilchrist, M and Duncan, N and Corbett, R and Innes, AJ and Pavlů, J and Thursz, MR and Davies, F and Marchesi, JR}, title = {Disease prevention not decolonization - a model for fecal microbiota transplantation in patients colonized with multidrug-resistant organisms.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa948}, pmid = {32681643}, issn = {1537-6591}, abstract = {Fecal microbiota transplantation (FMT) yields variable intestinal decolonization results for multidrug-resistant organisms (MDROs). This study showed significant reductions in antibiotic duration, bacteremia and length of stay in 20 patients colonized/ infected with MDRO receiving FMT (compared to pre-FMT history, and a matched group not receiving FMT), despite modest decolonization rates.}, }
@article {pmid32681029, year = {2020}, author = {Jang, YO and Lee, SH and Choi, JJ and Kim, DH and Choi, JM and Kang, MJ and Oh, YM and Park, YJ and Shin, Y and Lee, SW}, title = {Fecal microbial transplantation and a high fiber diet attenuates emphysema development by suppressing inflammation and apoptosis.}, journal = {Experimental &amp; molecular medicine}, volume = {52}, number = {7}, pages = {1128-1139}, doi = {10.1038/s12276-020-0469-y}, pmid = {32681029}, issn = {2092-6413}, support = {2019R1F1A1057875//National Research Foundation of Korea (NRF)/ ; 2016R1A6A3A11932575//National Research Foundation of Korea (NRF)/ ; }, abstract = {Recent work has suggested a microbial dysbiosis association between the lung and gut in respiratory diseases. Here, we demonstrated that gut microbiome modulation attenuated emphysema development. To modulate the gut microbiome, fecal microbiota transplantation (FMT) and diet modification were adopted in mice exposed to smoking and poly I:C for the emphysema model. We analyzed the severity of emphysema by the mean linear intercept (MLI) and apoptosis by the fluorescent TUNEL assay. Microbiome analysis was also performed in feces and fecal extracellular vesicles (EVs). The MLI was significantly increased with smoking exposure. FMT or a high-fiber diet (HFD) attenuated the increase. Weight loss, combined with smoking exposure, was not noted in mice with FMT. HFD significantly decreased macrophages and lymphocytes in bronchoalveolar lavage fluid. Furthermore, IL-6 and IFN-γ were decreased in the bronchoalveolar lavage fluid and serum. The TUNEL score was significantly lower in mice with FMT or HFD, suggesting decreased cell apoptosis. In the microbiome analysis, Bacteroidaceae and Lachnospiraceae, which are alleged to metabolize fiber into short-chain fatty acids (SCFAs), increased at the family level with FMT and HFD. FMT and HFD attenuated emphysema development via local and systemic inhibition of inflammation and changes in gut microbiota composition, which could provide a new paradigm in COPD treatment.}, }
@article {pmid32677955, year = {2020}, author = {Sui, H and Zhang, L and Gu, K and Chai, N and Ji, Q and Zhou, L and Wang, Y and Ren, J and Yang, L and Zhang, B and Hu, J and Li, Q}, title = {YYFZBJS ameliorates colorectal cancer progression in ApcMin/+ mice by remodeling gut microbiota and inhibiting regulatory T-cell generation.}, journal = {Cell communication and signaling : CCS}, volume = {18}, number = {1}, pages = {113}, pmid = {32677955}, issn = {1478-811X}, support = {81830120, 81573805, 81573749, 81874399//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Progression of Colorectal cancer (CRC) is influenced by single or compounded environmental factors. Accumulating evidence shows that microbiota can influence the outcome of cancer immunotherapy. T cell, one of the main populations of effector immune cells in antitumor immunity, has been considered as a double-edged sword during the progression of CRC. Our previous studies indicate that traditional Chinese herbs (TCM) have potential anticancer effects in improving quality of life and therapeutic effect. However, little is known about the mechanism of TCM formula in cancer prevention.<br><br>METHODS: Here, we used C57BL/6 J ApcMin/+ mice, an animal model of human intestinal tumorigenesis, to investigate the gut bacterial diversity and their mechanisms of action in gastrointestinal adenomas, and to evaluate the effects of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) on of colon carcinogenesis in vivo and in vitro. Through human-into-mice fecal microbiota transplantation (FMT) experiments from YYFZBJS volunteers or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration.<br><br>RESULTS: We report herein, YYFZBJS treatment blocked tumor initiation and progression in ApcMin/+ mice with less change of body weight and increased immune function. Moreover, diversity analysis of fecal samples demonstrated that YYFZBJS regulated animal's natural gut flora, including Bacteroides fragilis, Lachnospiraceae and so on. Intestinal tumors from conventional and germ-free mice fed with stool from YYFZBJS volunteers had been decreased. Some inflammation' expression also have been regulated by the gut microbiota mediated immune cells. Intestinal lymphatic, and mesenteric lymph nodes (MLN), accumulated CD4+ CD25+ Foxp3 positive Treg cells were reduced by YYFZBJS treatment in ApcMin/+ mice. Although YYFZBJS had no inhibition on CRC cell proliferation by itself, the altered Tregs mediated by YYFZBJS repressed CRC cancer cell growth, along with reduction of the phosphorylation of β-catenin.<br><br>CONCLUSIONS: In conclusion, we demonstrated that gut microbiota and Treg were involved in CRC development and progression, and we propose YYFZBJS as a new potential drug option for the treatment of CRC. Video abstract.}, }
@article {pmid32677453, year = {2020}, author = {Khanna, S}, title = {Fecal transplant clinical trials for Clostridioides difficile: an interview with Sahil Khanna.}, journal = {Future microbiology}, volume = {15}, number = {}, pages = {709-712}, doi = {10.2217/fmb-2020-0102}, pmid = {32677453}, issn = {1746-0921}, abstract = {This interview was conducted by Atiya Henry, Commissioning Editor of Future Microbiology. Sahil Khanna is an Associate Professor of Medicine in the Division of Gastroenterology and Hepatology at Mayo Clinic, Rochester (MN, USA). He currently directs the Comprehensive Gastroenterology Interest group, Clostridioides difficile clinic, Fecal Microbiota Transplantation program and C. difficile related clinical trials at Mayo Clinic. He completed Medical School at the All India Institute of Medical Sciences, New Delhi; followed by Post Doctoral Research at University of California, San Diego (CA, USA); residency in Internal Medicine and Fellowship in Gastroenterology and Hepatology at Mayo Clinic, before joining the Faculty. He also completed Masters in Clinical and Translational Sciences during his fellowship. His research and clinical interests include epidemiology, outcomes and emerging therapeutics for C. difficile infection, an arena in which he has had numerous publications and presentations. He has over 100 peer-reviewed publications, serves as reviewer, is on the editorial board of several journals and has won numerous awards.}, }
@article {pmid32677450, year = {2020}, author = {Dubois, NE and Read, CY and O'Brien, K and Ling, K}, title = {Challenges of Screening Prospective Stool Donors for Fecal Microbiota Transplantation.}, journal = {Biological research for nursing}, volume = {}, number = {}, pages = {1099800420941185}, doi = {10.1177/1099800420941185}, pmid = {32677450}, issn = {1552-4175}, abstract = {Despite high efficacy rates, significant costs and logistical challenges associated with procuring stool from healthy donors for fecal microbiota transplantation (FMT) have presented barriers to broader institutional adoption and limited the availability of this life-saving treatment. Published outcomes for donor screening programs report donor deferral rates between 90% and 96%. Due to the paucity of FMT donor screening data, a secondary analysis on a cohort of previously screened donors (n = 7,968) was conducted to provide a synopsis of the observed trends and rationales for prospective stool donor deferrals. Upon completion of the evaluation, 1.7% of prospective donors (n = 134) qualified for stool donation. Over 50% of donors who completed the online pre-screen were deferred, primarily for a body mass index of 30 kg/m2 or greater (n = 1,516, 37.0%), logistics (n = 841, 20.5%), and travel history (n = 638, 15.5%). Despite pre-screening, 569 donors (72.8%) who completed the in-person clinical assessment were ultimately deferred due primarily to potentially microbiome-mediated diseases (n = 187, 32.9%). A notably small portion of donors (n = 46, 25.6%) were deferred during the laboratory assessment process suggesting the clinical assessment was effective at deferring donors at higher risk for transmissible diseases. Donors lost to follow-up throughout the screening process presented a significant challenge and contributed to a notable (n = 3,117; 39.1%) portion of donor attrition. Findings were used to support recommendations for improving prospective stool donor screening programs and to provide suggestions for future research.}, }
@article {pmid32675857, year = {2020}, author = {Dupont, HL and Jiang, ZD and Dupont, AW and Utay, NS}, title = {THE INTESTINAL MICROBIOME IN HUMAN HEALTH AND DISEASE.}, journal = {Transactions of the American Clinical and Climatological Association}, volume = {131}, number = {}, pages = {178-197}, pmid = {32675857}, issn = {0065-7778}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; }, abstract = {The Human Microbiome Initiative of NIH, begun in 2007, has opened the door to the power of the intestinal microbiome in health and disease. The 100 trillion gut microbes influence body function through three pathways: (1) via the neural route where 500 million neurons of the enteric nervous system (the body's second brain) connect to the brain and spinal cord, (2) via the immune route where the gut-immune capacity prevents infection and elicits immune response to vaccines, and (3) by the hormonal route wherein biologically active chemicals are released from enteroendocrine cells to control mood and body functions. Through research, the identification of diseases and disorders associated with abnormal microbiome (&quot;dysbiosis&quot;) has increased in number with potential for reversibility. Our team has developed an orally administered fecal microbiota transplantation product that is effective in reversing dysbiosis in recurrent Clostridioides difficile (C. difficile) and is being used to reverse abnormal microbiomes in chronic dysbiotic disorders.}, }
@article {pmid32675782, year = {2020}, author = {Touchefeu, Y and Duchalais, E and Bruley des Varannes, S and Alameddine, J and Mirallie, E and Matysiak-Budnik, T and Le Bastard, Q and Javaudin, F and Rimbert, M and Jotereau, F and Montassier, E}, title = {Concomitant decrease of double-positive lymphocyte population CD4CD8αα and Faecalibacterium prausnitzii in patients with colorectal cancer.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MEG.0000000000001842}, pmid = {32675782}, issn = {1473-5687}, abstract = {INTRODUCTION AND AIMS: Changes in the composition of the gut microbiota in patients with colorectal cancer (CRC) compatible with a contribution of the gut microbiota in carcinogenesis have been reported. In particular, a decrease Faecalibacterium prausnitzii has been identified. A CD4CD8αα, double-positive lymphocyte population (DP8α) has recently been demonstrated in the human colon and blood with regulatory functions and specificity for F. prausnitzii. Here, we aimed to detect dysbiosis in the fecal microbiome of patients with CRC by metagenomic analysis, and to look for changes in the levels of DP8α circulating T cells specific for F. prausnitzii in these patients.<br><br>PATIENTS AND METHODS: Patients with CRC and control subjects were prospectively included. None had received antibiotics in the previous month or any anti-tumor treatment. A stool sample was collected for each participant, and analyzed by shotgun sequencing. The DP8α T cell population was identified and quantified on fresh whole blood by flow cytometry with anti-CD45, anti-CD3, anti-CD4 and anti-CD8α co-labeling.<br><br>RESULTS: Twenty-one patients with CRC and 20 controls subjects were included. We found that mean relative abundance of five species was significantly decreased in CRC patients compared with controls, including F. prausnitzii, Barnesiella intestinihominis, Alistipes finegoldii, Bacteroides eggerthii and Eubacterium siraeum. We also found that the DP8α T cell population was significantly decreased in the blood of CRC patients compared with controls.<br><br>CONCLUSION: In our work, we showed that a reduced abundance of F. prausnitzii in CRC patients was associated to a significant decrease in the circulating DP8α Treg population, suggesting a potential involvement of reduced activity of DP8α T cells in colonic carcinogenesis. These findings open new diagnostic and therapeutic strategies for CRC.}, }
@article {pmid32671773, year = {2020}, author = {Wang, T and Liu, K and Wen, L and Yang, Y and Yin, X and Liu, K and Chen, Y and He, Y and Yang, M and Wei, Y and Wang, B and Chen, D}, title = {Autophagy and Gastrointestinal Diseases.}, journal = {Advances in experimental medicine and biology}, volume = {1207}, number = {}, pages = {529-556}, doi = {10.1007/978-981-15-4272-5_38}, pmid = {32671773}, issn = {0065-2598}, mesh = {*Autophagy/drug effects ; Cholera ; Crohn Disease ; Gastritis, Atrophic ; *Gastrointestinal Diseases/drug therapy ; Gastrointestinal Neoplasms ; Helicobacter Infections ; Humans ; }, abstract = {Normal gastrointestinal physiology is fundamental for all the living beings. Gastrointestinal diseases mainly include gastrointestinal motility disorders, infectious inflammation (such as Helicobacter pylori infection, cholera, and intestinal parasites), non-infectious inflammation (such as chronic gastritis and Crohn's disease), and gastrointestinal cancers. In addition, intestinal microbial disorder is also an important cause of intestinal diseases, so intestinal microecological treatment (fecal microbiota transplantation) is an important mean of treating gastrointestinal diseases. In recent years, the role of autophagy in gastrointestinal diseases has been studied extensively. Autophagy is observed under various pathological processes of the gastrointestinal tract. For example, it has been demonstrated that autophagy plays an important role in maintaining the homeostasis and integrity of intestinal epithelium. Additionally, autophagy regulates host response to H. pylori infection and development of gastrointestinal cancers. Therefore, we will discuss pivotal roles of autophagy in various gastrointestinal diseases and analyze the underlying molecular mechanisms, which may provide new therapeutic targets applicable for the treatment of gastrointestinal diseases.}, }
@article {pmid32670347, year = {2020}, author = {Qi, X and Zhong, X and Xu, S and Zeng, B and Chen, J and Zang, G and Zeng, L and Bai, S and Zhou, C and Wei, H and Xie, P}, title = {Extracellular Matrix and Oxidative Phosphorylation: Important Role in the Regulation of Hypothalamic Function by Gut Microbiota.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {520}, pmid = {32670347}, issn = {1664-8021}, abstract = {Background: In previous studies, our team examined the gut microbiota of healthy individuals and depressed patients using fecal microbiota transplantation of germ-free (GF) mice. Our results showed that depression-like and anxiety-like behavioral phenotypes of host mice were increased, but the molecular mechanism by which gut microbiota regulate host behavioral phenotypes is still unclear.<br><br>Methods: To investigate the molecular mechanism by which gut microbiota regulate host brain function, adult GF mice were colonized with fecal samples derived from healthy control (HC) individuals or patients with major depressive disorder (MDD). Transcriptomic profiling of hypothalamus samples was performed to detect differentially expressed genes (DEGs). qRT-PCR was used for validation experiments.<br><br>Results: Colonization germ-free (CGF) mice had 243 DEGs compared with GF mice. The most enriched KEGG pathways associated with upregulated genes were &quot;protein digestion and absorption,&quot; &quot;extracellular matrix (ECM)-receptor interaction,&quot; and &quot;focal adhesion.&quot; MDD mice had 642 DEGs compared with HC mice. The most enriched KEGG pathways associated with upregulated genes in MDD mice were also &quot;protein digestion and absorption,&quot; &quot;ECM-receptor interaction,&quot; and &quot;focal adhesion.&quot; Meanwhile, the most enriched KEGG pathway associated with downregulated genes in these mice was &quot;oxidative phosphorylation,&quot; and genes related to this pathway were found to be highly correlated in PPI network analysis.<br><br>Conclusion: In summary, our findings suggested that regulation of ECM is a key mechanism shared by different gut microbiota and that inhibition of energy metabolism in the hypothalamus by gut microbiota derived from MDD patients is a potential mechanism of behavioral regulation and depression.}, }
@article {pmid32667590, year = {2020}, author = {Generoso, JS and Giridharan, VV and Lee, J and Macedo, D and Barichello, T}, title = {The role of the microbiota-gut-brain axis in neuropsychiatric disorders.}, journal = {Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)}, volume = {}, number = {}, pages = {}, doi = {10.1590/1516-4446-2020-0987}, pmid = {32667590}, issn = {1809-452X}, abstract = {The microbiota-gut-brain axis is a bidirectional signaling mechanism between the gastrointestinal tract and the central nervous system. The complexity of the intestinal ecosystem is extraordinary; it comprises more than 100 trillion microbial cells that inhabit the small and large intestine, and this interaction between microbiota and intestinal epithelium can cause physiological changes in the brain and influence mood and behavior. Currently, there has been an emphasis on how such interactions affect mental health. Evidence indicates that intestinal microbiota are involved in neurological and psychiatric disorders. This review covers evidence for the influence of gut microbiota on the brain and behavior in Alzheimer disease, dementia, anxiety, autism spectrum disorder, bipolar disorder, major depressive disorder, Parkinson's disease, and schizophrenia. The primary focus is on the pathways involved in intestinal metabolites of microbial origin, including short-chain fatty acids, tryptophan metabolites, and bacterial components that can activate the host's immune system. We also list clinical evidence regarding prebiotics, probiotics, and fecal microbiota transplantation as adjuvant therapies for neuropsychiatric disorders.}, }
@article {pmid32664182, year = {2020}, author = {Zhang, S and Lv, J and Ren, X and Hao, X and Zhou, P and Wang, Y}, title = {The efficacy and safety of fecal microbiota transplantation in the treatment of systemic sclerosis: A protocol for systematic review and meta analysis.}, journal = {Medicine}, volume = {99}, number = {28}, pages = {e21267}, pmid = {32664182}, issn = {1536-5964}, mesh = {Adolescent ; Adult ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Male ; Meta-Analysis as Topic ; Middle Aged ; Research Design ; Scleroderma, Systemic/microbiology/*therapy ; Systematic Reviews as Topic ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Systemic sclerosis (SSc) is 1 of the most complex systemic autoimmune diseases.Accumulating evidence suggests that gut microbiota affect the development and function of the immune system and may play a role in the pathogenesis of autoimmune diseases. This new paradigm raises the possibility that many diseases result, at least partially, from microbiota-related dysfunction. This understanding invites the investigation of fecal microbiota transplantation (FMT) in the treatment of SSc. However, no study has specifically and systematically investigated the efficacy and safety of FMT in the treatment of SSc. Thus, this study will systematically and comprehensively appraise the efficacy and safety of FMT in the treatment of SSc.<br><br>METHODS: We will search the following sources without restrictions for date, language, or publication status: PubMed, Web of Science,Cochrane Central Register of Controlled Trials (CENTRAL) Cochrane Library, EMBASE and China National Knowledge Infrastructure. We will apply a combination of Medical Subject Heading (MeSH) and free-text terms incorporating database-specific controlled vocabularies and text words to implement search strategies. We will also search the ongoing trials registered in the World Health Organization's International Clinical Trials Registry Platform. Besides, the previous relevant reviews conducted on FMT for SSc and reference lists of included studies will also be searched.<br><br>RESULTS: This study will provide a reliable basis for the treatment of SSc with FMT.<br><br>CONCLUSIONS: The findings will be an available reference to evaluate the efficacy and safety of FMT in the treatment of SSc.<br><br>REGISTRATION NUMBER: INPLASY202060019.}, }
@article {pmid32663372, year = {2020}, author = {Lim, YY and Lee, YS and Ooi, DSQ}, title = {Engineering the Gut Microbiome for Treatment of Obesity: A Review of Current Understanding and Progress.}, journal = {Biotechnology journal}, volume = {}, number = {}, pages = {e2000013}, doi = {10.1002/biot.202000013}, pmid = {32663372}, issn = {1860-7314}, abstract = {Obesity is a complex, multifactorial disease that is increasing in prevalence despite extensive research and efforts to curb it. Over the last decade, gut microbiome has emerged as an important contributor to the pathogenesis of obesity. Microbiome profile is altered in obese phenotype and the causative role of microbiome in obesity is demonstrated in fecal microbiota transplantation studies. Herein, recent evidences supporting the role of gut microbiome in obesity and the current therapies designed to engineer gut microbiome for treatment of obesity will be reviewed. The microbial enterotypes associated with obesity is outlined, and the gut microbiota-driven metabolism and low-grade inflammation linking gut microbiome and obesity is examined. How the different intrinsic and extrinsic factors such as host genetics, mode of childbirth delivery, diet, lifestyle habits and use of antibiotics influence the composition of the gut microbiome in the development of obesity is evaluated. Also, the efficacy of current microbiome-based therapies in the forms of prebiotics, probiotics and engineered microbes that are used to manipulate gut microbiome in treating obesity is discussed.}, }
@article {pmid32663072, year = {2020}, author = {Matsuoka, K}, title = {Fecal microbiota transplantation for ulcerative colitis.}, journal = {Immunological medicine}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/25785826.2020.1792040}, pmid = {32663072}, issn = {2578-5826}, abstract = {Altered abundance and composition of the gut microbiota, i.e., dysbiosis, is reported to be involved in the pathogenesis of various diseases including not only gastrointestinal diseases but also metabolic, neurological, and autoimmune disorders. Fecal microbiota transplantation (FMT) aims to correct dysbiosis by administrating feces collected from donors and thus treat the underlying disease. Ulcerative colitis (UC) is a disease characterized by chronic inflammation in the large intestine. Patients with UC have been reported to have dysbiosis, and more specifically, reduced diversity and abundance of the gut microbiota. FMT has been tried as a treatment for UC. Favorable effects of FMT on UC had been reported in case reports or case series. Recently, four randomized controlled trials of FMT for UC were published. Three of the four studies reported that FMT was more effective than control treatment. Thus, FMT is considered as a promising treatment for UC; however, there are many issues to solve before FMT can become a standard therapy for UC including donor selection, administration routes, frequencies, easy-to-administer formulation development, and optimal patient population.}, }
@article {pmid32658171, year = {2020}, author = {Blanco, C}, title = {The influence of the gut microbiome on obesity.}, journal = {Journal of the American Association of Nurse Practitioners}, volume = {32}, number = {7}, pages = {504-510}, doi = {10.1097/JXX.0000000000000480}, pmid = {32658171}, issn = {2327-6924}, abstract = {Obesity is a disease with multiple environmental and genetic factors, which when combined contribute to the maintenance of an elevated body weight, thereby reducing long-term success of weight loss. The human gut microbiome is becoming a new potential contributor to obesity. Specifically, gut bacteria and their metabolites are known to affect dysbiosis, metabolism, endotoxemia, and inflammation. Many environmental and lifestyle factors can alter the gut microbiota affecting obesity. Potential therapies to alter the gut microbiota include supplementation with probiotic organisms and the use of fecal microbiota transplantation. This review will examine the growing evidence supporting the mechanisms with which the human gut microbiota may influence obesity, various influences on the microbiota, and potential therapies.}, }
@article {pmid32657282, year = {2020}, author = {Huang, GQ and Bai, Y and Sun, ZQ and Liu, J}, title = {Successful Treatment of Pseudomembranous Colitis with Fecal Microbiota Transplantation - A Case Study on A Patient Rescued by Extracorporeal Cardiopulmonary Resuscitation After Cardiac Arrest.}, journal = {Annals of transplantation}, volume = {25}, number = {}, pages = {e923283}, pmid = {32657282}, issn = {2329-0358}, abstract = {BACKGROUND Pseudomembranous colitis (PMC) is an opportunistic, nosocomial infection caused by Clostridium difficile. CASE REPORT Here we described a patient who developed PMC during her recovery from cardiac arrest. A 16-year-old female high school student experienced sudden cardiac arrest. Spontaneous circulation was not returned by standard cardiopulmonary resuscitation. After her admission to the emergency unit, her cardiac function and neurologic function were finally resumed by extracorporeal cardiopulmonary resuscitation (ECPR); however, after 14 days, her recovery was complicated with excessive diarrhea and shock. Colonoscopy confirmed the diagnosis of PMC. Metronidazole and vancomycin were immediately administered; however, the treatment did not result in any improvement. Fecal microbiota transplantation was then performed, and after 4 transplantations, her diarrhea was significantly ameliorated. After hospital stay for 135 days, the patient was finally discharged with grade II brain function. She later recovered self-care ability in follow-up. CONCLUSIONS The patient suffered from a long-term gastrointestinal ischemia-hypoxia resulting from cardiac arrest. The use of broad-spectrum antibiotics in the later treatment led to refractory PMC, which was successfully managed by multiple fecal microbiota transplantation.}, }
@article {pmid32656839, year = {2020}, author = {Lahtinen, P and Jalanka, J and Hartikainen, A and Mattila, E and Hillilä, M and Punkkinen, J and Koskenpato, J and Anttila, VJ and Tillonen, J and Satokari, R and Arkkila, P}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome. Authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {52}, number = {3}, pages = {557-558}, doi = {10.1111/apt.15875}, pmid = {32656839}, issn = {1365-2036}, mesh = {*Anemia ; Azathioprine ; Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome ; *Leukopenia ; }, }
@article {pmid32656836, year = {2020}, author = {Segal, JP and Mullish, BH and Quraishi, MN and Iqbal, TH}, title = {Letter: faecal microbiota transplantation for IBS.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {52}, number = {3}, pages = {556-557}, doi = {10.1111/apt.15824}, pmid = {32656836}, issn = {1365-2036}, mesh = {Azathioprine ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome ; }, }
@article {pmid32656604, year = {2020}, author = {Agarwal, A and Maheshwari, A and Verma, S and Arrup, D and Phillips, L and Vinayek, R and Nair, P and Hagan, M and Dutta, S}, title = {Superiority of Higher-Volume Fresh Feces Compared to Lower-Volume Frozen Feces in Fecal Microbiota Transplantation for Recurrent Clostridioides Difficile Colitis.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-020-06459-0}, pmid = {32656604}, issn = {1573-2568}, abstract = {GOALS: To compare the clinical outcomes of different protocols for fecal microbiota transplantation (FMT) in two community hospitals with similar patient demographics.<br><br>BACKGROUND: FMT is commonly performed for recurrent or refractory Clostridioides difficile infection (rCDI). The clinical efficacy of FMT for this indication has been well established. However, there has been no standardization or optimization of the amount of fecal material, method of feces preparation, or route of delivery for FMT.<br><br>STUDY: In this retrospective study, patients with rCDI received FMT using commercially available frozen fecal preparation (22.7 g) at Center A and locally prepared fresh fecal filtrate (30-50 g) at Center B. The primary outcome was defined as complete resolution of clinical symptoms related to rCDI after at least 8 weeks of follow-up.<br><br>RESULTS: Fifty patients from each center were included in the study. Clinical success after initial FMT with lower-volume frozen fecal preparation at Center A was 32/50 (64.0%) compared to 49/50 (98.0%) with higher-volume fresh fecal filtrate at Center B (p < 0.0001). Seventeen patients in Center A and 1 patient in Center B underwent at least one repeat FMT. Overall clinical success was achieved in 43/50 (86%) of patients in Center A and 50/50 (100%) in Center B (p = 0.012).<br><br>CONCLUSIONS: Our results suggest superior clinical efficacy of a larger amount of fresh fecal filtrate over a smaller amount of commercially available frozen fecal preparation. Further studies are needed to examine the effect of varying amounts of feces and the optimal protocol for FMT in patients with rCDI.}, }
@article {pmid32655675, year = {2020}, author = {Zhu, Y and Zhang, JY and Wei, YL and Hao, JY and Lei, YQ and Zhao, WB and Xiao, YH and Sun, AD}, title = {The polyphenol-rich extract from chokeberry (Aronia melanocarpa L.) modulates gut microbiota and improves lipid metabolism in diet-induced obese rats.}, journal = {Nutrition &amp; metabolism}, volume = {17}, number = {}, pages = {54}, pmid = {32655675}, issn = {1743-7075}, abstract = {The gut microbiota plays a critical role in obesity and lipid metabolism disorder. Chokeberry (Aronia melanocarpa L.) are rich in polyphenols with various physiological and pharmacological activities. We determined serum physiological parameters and fecal microbial components by using related kits, liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA gene sequencing every 10 days. Real-time PCR analysis was used to measure gene expression of bile acids (BAs) and lipid metabolism in liver and adipose tissues. We analyzed the effects of different Chokeberry polyphenol (CBPs) treatment time on obesity and lipid metabolism in high fat diet (HFD)-fed rats. The results indicated that CBPs treatment prevents obesity, liver steatosis and improves dyslipidemia in HFD-fed rats. CBPs modulated the composition of the gut microbiota with the extended treatment time, reducing the Firmicutes/Bacteroidetes ratio (F/B ratio) and increasing the relative abundance of Bacteroides, Prevotella, Akkermansia and other bacterial species associated with anti-obesity properties. We found that CBPs treatment gradually decreased the total BAs pool and particularly reduced the relative content of cholic acid (CA), deoxycholic acid (DCA) and enhanced the relative content of chenodeoxycholic acid (CDCA). These changes were positively correlated Bacteroides, Prevotella and negatively correlated with Clostridium, Eubacterium, Ruminococcaceae. In liver and white adipose tissues, the gene expression of lipogenesis, lipolysis and BAs metabolism were regulated after CBPs treatment in HFD-fed rats, which was most likely mediated through FXR and TGR-5 signaling pathway to improve lipid metabolism. In addition, the mRNA expression of PPARγ, UCP1 and PGC-1α were upregulated markedly in interscapular brown adipose tissue (iBAT) after CBPs treatment. We confirmed that CBPs could reduce the body weight of HFD-fed rats by accelerating energy homeostasis and thermogenesis in iBAT. Finally, the fecal microbiota transplantation (FMT) experiment results demonstrated that FMT from CBPs-treated rats failed to reduce the weight of HFD-fed rats. However, FMT from CBPs-treated rats improved dyslipidemia and reshaped gut microbiota in HFD-fed rats. In conclusion, CBPs treatment improved obesity and complications by regulating gut microbiota in HFD-fed rats. The gut microbiota plays an important role in BAs metabolism after CBPs treatment, and BAs have therefore emerged as major effectors in microbe-host signaling events that influence host lipid metabolism, energy metabolism and thermogenesis.}, }
@article {pmid32655239, year = {2020}, author = {Ryu, AJ and Rahimi, RS and Leise, MD}, title = {The Current Hepatic Encephalopathy Pipeline.}, journal = {Journal of clinical and experimental hepatology}, volume = {10}, number = {4}, pages = {377-385}, pmid = {32655239}, issn = {0973-6883}, abstract = {Hepatic encephalopathy (HE) is a complication of acute or chronic liver failure; its mechanism is complex, involving multiple organ systems, and is still being elucidated. The standard of care, lactulose, has remained generally unchanged for decades. However, in recent years, better understanding of the pathophysiology has yielded new therapeutic targets for this reversible condition. These novel treatments act both on traditional pathways established in the ammonia hypothesis and through more recently discovered mechanisms. Here, we review contemporary investigational therapies for HE. We used narrative reviews and searched ClinicalTrials.gov database for the condition &quot;hepatic encephalopathy&quot; through August 29, 2019. Our review yielded six key areas of therapeutic focus: (1) antibiotics against urease-producing gut bacteria, (2) intravenous ammonia scavengers, (3) modified synthetic probiotics, (4) fecal microbiota transplant, (5) brain steroid-modulating agents, and 6) nonlactulose laxatives. Active trials are ongoing in each of these therapeutic areas.}, }
@article {pmid32649987, year = {2020}, author = {Keskey, R and Cone, JT and DeFazio, JR and Alverdy, JC}, title = {The use of fecal microbiota transplant in sepsis.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.trsl.2020.07.002}, pmid = {32649987}, issn = {1878-1810}, abstract = {Sepsis is defined as a dysregulated inflammatory response, which ultimately results from a perturbed interaction of both an altered immune system and the biomass and virulence of involved pathogens. This response has been tied to the intestinal microbiota, as the microbiota and its associated metabolites play an essential role in regulating the host immune response to infection. In turn, critical illness as well as necessary health care treatments result in a collapse of the intestinal microbiota diversity and a subsequent loss of health-promoting short chain fatty acids, such as butyrate, leading to the development of a maladaptive pathobiome. These perturbations of the microbiota contribute to the dysregulated immune response and organ failure associated with sepsis. Several case series have reported the ability of fecal microbiota transplant (FMT) to restore the host immune response and aid in recovery of septic patients. Additionally, animal studies have revealed the mechanism of FMT rescue in sepsis is likely related to the ability of FMT to restore butyrate producing bacteria and alter the innate immune response aiding in pathogen clearance. However, several studies have reported lethal complications associated with FMT, including bacteremia. Therefore, FMT in the treatment of sepsis is and should remain investigational until a more detailed mechanism of how FMT restores the host immune response in sepsis is determined, allowing for the development of more fine-tuned microbiota therapies.}, }
@article {pmid32645991, year = {2020}, author = {Shin, YC and Shin, W and Koh, D and Wu, A and Ambrosini, YM and Min, S and Eckhardt, SG and Fleming, RYD and Kim, S and Park, S and Koh, H and Yoo, TK and Kim, HJ}, title = {Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip.}, journal = {Micromachines}, volume = {11}, number = {7}, pages = {}, pmid = {32645991}, issn = {2072-666X}, support = {F99CA245801//National Cancer Institute of the National Institutes of Health (NIH/NCI)/ ; BWF 1019990.01//Burroughs Wellcome Fund Collaborative Research Travel Grant/ ; 771066//American College of Veterinary Internal Medicine Advance Research Fellowships/ ; 2018M3A9H3025030//Ministry of Science and ICT, South Korea/ ; UTA18-000889/CRI/Cancer Research Institute/United States ; R21CA236690//National Cancer Institute of the National Institutes of Health/ ; 1912-03604//Leona M. and Harry B. Helmsley Charitable Trust/ ; RR160093//Cancer Prevention and Research Institute of Texas/ ; }, abstract = {The regeneration of the mucosal interface of the human intestine is critical in the host-gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn's disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic-oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host-microbiome crosstalk to target a patient-specific disease modeling.}, }
@article {pmid32645451, year = {2020}, author = {Cheng, YW and Alhaffar, D and Saha, S and Khanna, S and Bohm, M and Phelps, E and Ghabril, M and Orman, E and Sashidhar, S and Rogers, N and Xu, H and Khoruts, A and Vaughn, B and Kao, D and Wong, K and Cammarota, G and Ianiro, G and Dhere, T and Kraft, CS and Mehta, N and Woodworth, MH and Allegretti, JR and Nativ, L and Marcus, J and El-Nachef, N and Fischer, M}, title = {Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2020.06.051}, pmid = {32645451}, issn = {1542-7714}, abstract = {BACKGROUND &amp; AIMS: Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter observational study to evaluate the efficacy and safety of FMT for CDI in patients with cirrhosis.<br><br>METHODS: We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at the 8-week follow-up evaluation. We also obtained data on adverse events (AEs) and severe AEs within 12 weeks of FMT.<br><br>RESULTS: Patients underwent FMT for recurrent CDI (55 of 63; 87.3%), severe CDI (6 of 63; 9.5%), or fulminant CDI (2 of 63; 3.2%) primarily via colonoscopy (59 of 63; 93.7%) as outpatients (47 of 63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at the time of FMT (44.4% vs 5.6%; P < .001), had Child-Pugh scores of B or C (100% vs 37.7%; P < .001), used probiotics (77.8% vs 24.1%; P = .003), had pseudomembranes (22.2% vs 0; P = .018), and underwent FMT as inpatients (45.5% vs 19%; P = .039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at the time of FMT (odds ratio, 17.43; 95% CI, 2.00-152.03; P = .01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81-78.3; P = .01) were associated with a greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21 of 63)-most were self-limited abdominal cramps or diarrhea. There were only 5 severe AEs that possibly were related to FMT; none involved infection or death.<br><br>CONCLUSIONS: In a retrospective study, we found FMT to be safe and effective for the treatment of CDI in patients with cirrhosis.}, }
@article {pmid32641428, year = {2020}, author = {Seekatz, AM}, title = {mSphere of Influence: Translating Gut Microbiome Studies To Benefit Human Health.}, journal = {mSphere}, volume = {5}, number = {4}, pages = {}, pmid = {32641428}, issn = {2379-5042}, abstract = {Anna M. Seekatz works in the field of the gut microbiome as it related to infectious diseases. In this &quot;mSphere of Influence&quot; article, she reflects on how two studies, &quot;The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins&quot; (N. P. McNulty, T. Yatsunenko, A. Hsiao, et al., Sci Transl Med 3:106ra106, 2011) and &quot;High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria&quot; (M. J. Hamilton, A. R. Weingarden, T. Unno, A. Khoruts, and M. J. Sadowsky, Gut Microbes 4:125-135, 2013), shaped how she approaches interpreting microbiome studies.}, }
@article {pmid32639360, year = {2020}, author = {Van den Houte, K and Colomier, E and Schol, J and Carbone, F and Tack, J}, title = {Recent advances in diagnosis and management of irritable bowel syndrome.}, journal = {Current opinion in psychiatry}, volume = {33}, number = {5}, pages = {460-466}, doi = {10.1097/YCO.0000000000000628}, pmid = {32639360}, issn = {1473-6578}, abstract = {PURPOSE OF REVIEW: This review summarizes recent progress in the diagnosis and management of irritable bowel syndrome, with a focus on dietary and microbiota aspects.<br><br>RECENT FINDINGS: From a pathophysiological point of view, IBS is a multifactorial condition with both peripheral (transit) as central (visceral hypersensitivity, anxiety, depression) contribution in a cumulative fashion to the symptom pattern and severity. More recently, the focus has shifted to diet and microbiota. The number of dietary options that can be used for IBS and the understanding of determinants of their efficacy is rapidly increasing. Several studies have confirmed the efficacy of the low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet. Sucrose-isomaltase deficiency has emerged as pathogenetic mechanisms in a subset of patients, who do not respond to low FODMAP diet but may respond to starch and sucrose elimination. Herbal remedies, probiotics and secretagogues have been the topic of additional treatment trials. The efficacy of fecal microbiota transplantation in IBS is variable across studies, but donor selection is emerging as a critical factor.<br><br>SUMMARY: Irritable bowel syndrome has evolved into a disorder of interaction between dietary factors and gut microbiota, with impact on bowel symptoms as well as extra-intestinal, central, symptoms. Dietary adjustments and treatments targeting the gut microbiota are areas of active research and clinical progress.}, }
@article {pmid32636823, year = {2020}, author = {Moreno-Indias, I and Lundberg, R and Krych, L and Metzdorff, SB and Kot, W and Sørensen, DB and Nielsen, DS and Hansen, CHF and Hansen, AK}, title = {A Humanized Diet Profile May Facilitate Colonization and Immune Stimulation in Human Microbiota-Colonized Mice.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1336}, pmid = {32636823}, issn = {1664-302X}, abstract = {Background: In spite of the importance of the use of gnotobiotic mice for human fecal transfer, colonization efficiency and immune stimulation after human microbiota inoculation in mice are poorly studied compared to mouse microbiota inoculation. We tested the colonization efficiency and immune responses in mice bred for one additional generation after inoculating the parent generation with either a human (HM) or a mouse microbiota (MM). Furthermore, we tested if colonization efficiency and immune stimulation could be improved in HM-colonized mice by dietary approaches: if these were fed a diet closer to the human diet either in its sources of animal fat and protein [the &quot;animal source&quot; (AS) diet] or in its proportions of macronutrients from the normal sources of a mouse diet [the &quot;human profile&quot; (HP) diet].<br><br>Results: Although significantly lower in mice with a human microbiota (30-40% vs. 61-70%) the colonization efficiency was significantly higher in HM mice fed the HP diet (40%), and in MM mice fed AS (70%). The microbiota of mice fed HP was comparable to the microbiota of mice fed a standard rodent chow, while the microbiota of mice fed the animal source diet (AS) clustered separately. Mice inoculated with mouse fecal matter had significantly more CD4+ T cells and Cd4 expression and significantly fewer regulatory T cells (Tregs) and FoxP3 expression than human microbiota inoculated mice, but cell proportions differences were mostly apparent between mice fed the AS diet. Mice fed the HP diet had significantly higher expression of Cd8a.<br><br>Conclusion: It is concluded that a diet with a humanized profile could support the establishment of a human microbiota in mice, which will, however, still elicit a lower colonization efficiency compared to mice inoculated with a mouse microbiota.}, }
@article {pmid32629118, year = {2020}, author = {Su, CW and Chen, CY and Jiao, L and Long, SR and Mao, T and Ji, Q and O'Donnell, S and Stanton, C and Zheng, S and Walker, WA and Cherayil, BJ and Shi, HN}, title = {Helminth-Induced and Th2-Dependent Alterations of the Gut Microbiota Attenuate Obesity Caused by High-Fat Diet.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {10}, number = {4}, pages = {763-778}, pmid = {32629118}, issn = {2352-345X}, abstract = {BACKGROUND &amp; AIMS: Epidemiological and animal studies have indicated an inverse correlation between the rising prevalence of obesity and metabolic syndrome and exposure to helminths. Whether helminth-induced immune response contributes to microbiota remodeling in obesity remains unknown. The aim of this study is to explore the immune-regulatory role of helminth in the prevention of HFD-induced obesity through remodeling gut microbiome.<br><br>METHODS: C57BL/6J WT and STAT6-/- mice were infected with Heligmosomoides polygyrus and followed by high fat diet (HFD) feeding for 6 weeks. The host immune response, body weight, and fecal microbiota composition were analyzed. We used adoptive transfer of M2 macrophages and microbiota transplantation approaches to determine the impact of these factors on HFD-obesity. We also examined stool microbiota composition and short chain fatty acids (SCFAs) concentration and determined the expression of SCFA-relevant receptors in the recipient mice.<br><br>RESULTS: Helminth infection of STAT6-/- (Th2-deficient) mice and adoptive transfer of helminth-induced alternatively activated (M2) macrophages demonstrated that the helminth-associated Th2 immune response plays an important role in the protection against obesity and induces changes in microbiota composition. Microbiota transplantation showed that helminth-induced, Th2-dependent alterations of the gut microbiota are sufficient to confer protection against obesity. Collectively, these results indicate that helminth infection protects against HFD-induced obesity by Th2-dependent, M2 macrophage-mediated alterations of the intestinal microbiota.<br><br>CONCLUSION: Our findings provide new mechanistic insights into the complex interplay between helminth infection, the immune system and the gut microbiota in a HFD-induced obesity model and holds promise for gut microbiome-targeted immunotherapy in obesity prevention.}, }
@article {pmid32620839, year = {2020}, author = {Xiao, Y and Angulo, MT and Lao, S and Weiss, ST and Liu, YY}, title = {An ecological framework to understand the efficacy of fecal microbiota transplantation.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {3329}, pmid = {32620839}, issn = {2041-1723}, support = {R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; U19 AI095219/AI/NIAID NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; Clostridium Infections/microbiology/*therapy ; Clostridium difficile/physiology ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Mice ; Models, Theoretical ; Recurrence ; Treatment Outcome ; }, abstract = {Human gut microbiota plays critical roles in physiology and disease. Our understanding of ecological principles that govern the dynamics and resilience of this highly complex ecosystem remains rudimentary. This knowledge gap becomes more problematic as new approaches to modifying this ecosystem, such as fecal microbiota transplantation (FMT), are being developed as therapeutic interventions. Here we present an ecological framework to understand the efficacy of FMT in treating conditions associated with a disrupted gut microbiota, using the recurrent Clostridioides difficile infection as a prototype disease. This framework predicts several key factors that determine the efficacy of FMT. Moreover, it offers an efficient algorithm for the rational design of personalized probiotic cocktails to decolonize pathogens. We analyze data from both preclinical mouse experiments and a clinical trial of FMT to validate our theoretical framework. The presented results significantly improve our understanding of the ecological principles of FMT and have a positive translational impact on the rational design of general microbiota-based therapeutics.}, }
@article {pmid32620549, year = {2020}, author = {Ianiro, G and Mullish, BH and Kelly, CR and Kassam, Z and Kuijper, EJ and Ng, SC and Iqbal, TH and Allegretti, JR and Bibbò, S and Sokol, H and Zhang, F and Fischer, M and Costello, SP and Keller, JJ and Masucci, L and van Prehn, J and Quaranta, G and Quraishi, MN and Segal, J and Kao, D and Satokari, R and Sanguinetti, M and Tilg, H and Gasbarrini, A and Cammarota, G}, title = {Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic.}, journal = {Gut}, volume = {69}, number = {9}, pages = {1555-1563}, pmid = {32620549}, issn = {1468-3288}, mesh = {Betacoronavirus ; Change Management ; Clostridium Infections/microbiology/*therapy ; *Coronavirus Infections/epidemiology/prevention &amp; control ; *Donor Selection ; Fecal Microbiota Transplantation/*methods ; *Gastroenterology/organization &amp; administration/trends ; Gastrointestinal Microbiome ; Humans ; Infection Control/methods/standards ; *Pandemics/prevention &amp; control ; *Patient Selection ; *Pneumonia, Viral/epidemiology/prevention &amp; control ; Risk Adjustment/methods/standards ; }, abstract = {The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.}, }
@article {pmid32618725, year = {2020}, author = {Claytor, JD and El-Nachef, N}, title = {Fecal microbial transplant for inflammatory bowel disease.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {23}, number = {5}, pages = {355-360}, doi = {10.1097/MCO.0000000000000676}, pmid = {32618725}, issn = {1473-6519}, abstract = {PURPOSE OF REVIEW: The purpose of this brief review is to investigate the current utility of fecal microbial transplantation (FMT) to ameliorate dysbiosis contributing to inflammatory bowel disease pathogenesis.<br><br>RECENT FINDINGS: Increasing data from randomized, controlled trials support a role for multiple FMT administrations in the induction of remission and even as a maintenance therapy in mild-to-moderate Ulcerative Colitis. Small series and one small randomized controlled trial among patients with Crohn's Disease and with pouchitis continue to produce conflicting clinical results and microbial profile data on the host and donor levels. It is not clear whether patients with Crohn's disease are more susceptible to disease flare after FMT. Novel FMT delivery systems, including oral, and early-intensity colonoscopic devices, are under investigation.<br><br>SUMMARY: The allure of minimizing the risks and cost of long-term immunosuppression via modulation of patient microbiota remains enticing, and the most recent randomized controlled data in ulcerative colitis reveals acceptable clinical remission rates. However, prior to wide adoption of FMT within the inflammatory bowel disease treatment armamentarium, large clinical trials identifying biomarkers of treatment success, ensuring safety across all indications, and cultivating optimized donor and host selection are needed.}, }
@article {pmid32618656, year = {2020}, author = {Craven, L and Rahman, A and Nair Parvathy, S and Beaton, M and Silverman, J and Qumosani, K and Hramiak, I and Hegele, R and Joy, T and Meddings, J and Urquhart, B and Harvie, R and McKenzie, C and Summers, K and Reid, G and Burton, JP and Silverman, M}, title = {Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {7}, pages = {1055-1065}, doi = {10.14309/ajg.0000000000000661}, pmid = {32618656}, issn = {1572-0241}, mesh = {Double-Blind Method ; Duodenoscopy ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; *Intestine, Small ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*therapy ; Permeability ; }, abstract = {INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability.<br><br>METHODS: Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT.<br><br>RESULTS: There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT.<br><br>DISCUSSION: FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.}, }
@article {pmid32618640, year = {2020}, author = {Khanna, S and Pardi, D}, title = {Fecal Microbiota Transplantation for Recurrent Clostridioides difficile infection: The COVID-19 Era.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {7}, pages = {971-974}, pmid = {32618640}, issn = {1572-0241}, mesh = {Anti-Bacterial Agents/therapeutic use ; Biological Specimen Banks/standards ; Clostridium Infections/diagnosis/microbiology/*therapy ; Clostridium difficile/isolation &amp; purification ; *Coronavirus Infections/diagnosis ; Donor Selection ; *Fecal Microbiota Transplantation ; Humans ; Mass Screening ; *Pandemics ; *Pneumonia, Viral/diagnosis ; Recurrence ; }, }
@article {pmid32617914, year = {2020}, author = {Floyd, JL and Grant, MB}, title = {The Gut-Eye Axis: Lessons Learned from Murine Models.}, journal = {Ophthalmology and therapy}, volume = {9}, number = {3}, pages = {499-513}, pmid = {32617914}, issn = {2193-8245}, support = {R01EY028858/NH/NIH HHS/United States ; R01 EY012601/EY/NEI NIH HHS/United States ; T32 HL105349/HL/NHLBI NIH HHS/United States ; R01 EY025383/EY/NEI NIH HHS/United States ; R01EY028037/NH/NIH HHS/United States ; R01EY025383/NH/NIH HHS/United States ; R01EY012601/NH/NIH HHS/United States ; R01 EY028037/EY/NEI NIH HHS/United States ; R01 EY028858/EY/NEI NIH HHS/United States ; }, abstract = {A healthy gut microbiota is essential in maintaining the human body in a homeostatic state by its functions in digestion and immune tolerance. Under states of aberrant microbial composition or function (dysbiosis), the gut microbiota induces systemic inflammation that can lead to the onset of many diseases. In this review, we describe some evidence, largely from rodent studies, that supports the possible role of a dysbiotic gut microbiota in the onset and exacerbation of ocular diseases, primarily diabetic retinopathy, age-related macular degeneration, choroidal neovascularization, and uveitis. Furthermore, we examine several potential therapeutic measures that show promise in restoring the gut microbiota to a eubiotic state, preventing the aforementioned disease pathologies.}, }
@article {pmid32611702, year = {2020}, author = {Woodworth, MH}, title = {mSphere of Influence: Microbiome-Associated Phenotypes Are Modifiable.}, journal = {mSphere}, volume = {5}, number = {4}, pages = {}, pmid = {32611702}, issn = {2379-5042}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; }, abstract = {Michael Woodworth focuses on translational microbiome therapeutic research. In this mSphere of Influence article, he reflects on how &quot;Gut microbiomes of Malawian twin pairs discordant for kwashiorkor&quot; by Michelle Smith et al. (M. I. Smith, T. Yatsunenko, M. J. Manary, I. Trehan, et al., Science 339:548-554, 2013, https://doi.org/10.1126/science.1229000) made an impact on him by revealing the causal influence of microbial communities in the development of severe malnutrition.}, }
@article {pmid32610522, year = {2020}, author = {Bilinski, J and Dziurzynski, M and Grzesiowski, P and Podsiadly, E and Stelmaszczyk-Emmel, A and Dzieciatkowski, T and Dziewit, L and Basak, GW}, title = {Multimodal Approach to Assessment of Fecal Microbiota Donors based on Three Complementary Methods.}, journal = {Journal of clinical medicine}, volume = {9}, number = {7}, pages = {}, pmid = {32610522}, issn = {2077-0383}, support = {1WP/FS200/ZW2/17//Ministerstwo Nauki i Szkolnictwa Wyższego/ ; }, abstract = {Methods of stool assessment are mostly focused on next-generation sequencing (NGS) or classical culturing, but only rarely both. We conducted a series of experiments using a multi-method approach to trace the stability of gut microbiota in various donors over time, to find the best method for the proper selection of fecal donors and to find &quot;super-donor&quot; indicators. Ten consecutive stools donated by each of three donors were used for the experiments (30 stools in total). The experiments assessed bacterial viability measured by flow cytometry, stool culturing on different media and in various conditions, and NGS (90 samples in total). There were no statistically significant differences between live and dead cell numbers; however, we found a group of cells classified as not-dead-not-alive, which may be possibly important in selection of &quot;good&quot; donors. Donor C, being a regular stool donor, was characterized by the largest number of cultivable species (64). Cultivable core microbiota (shared by all donors) was composed of only 16 species. ANCOM analysis of NGS data highlighted particular genera to be more abundant in one donor vs. the others. There was a correlation between the not-dead-not-alive group found in flow cytometry and Anaeroplasma found by NGS, and we could distinguish a regular stool donor from the others. In this work, we showed that combining various methods of microbiota assessment gives more information than each method separately.}, }
@article {pmid32607098, year = {2020}, author = {Park, R and Umar, S and Kasi, A}, title = {Immunotherapy in Colorectal Cancer: Potential of Fecal Transplant and Microbiota-augmented Clinical Trials.}, journal = {Current colorectal cancer reports}, volume = {16}, number = {4}, pages = {81-88}, pmid = {32607098}, issn = {1556-3790}, support = {R01 CA185322/CA/NCI NIH HHS/United States ; }, abstract = {Purpose of review: This review summarizes the role of the microbiome in colorectal cancer (CRC) in the setting of immunotherapy and emphasizes the potential of microbiota-influencing strategies with a focus on the use of fecal microbiota transplant (FMT).<br><br>Recent findings: Observations from preclinical and clinical studies suggest that the human gut microbiome is implicated in the CRC carcinogenesis and is integral in determining the clinical response and toxicity to immunotherapy. Among the therapeutic methods devised to exploit the microbiome, FMT is the most direct method and is backed by the highest level of evidence of efficacy in nonneoplastic disease settings. Furthermore, a favorable microbiome has the potential to overcome immunotherapy resistance and ameliorate immune-related adverse events (irAEs). To this end, clinical trials are underway to evaluate the potential of FMT and microbiota-augmented methods in the setting of immunotherapy in CRC.<br><br>Summary: Evidence from animal studies, retrospective studies, and smaller-scale prospective human studies have led to initiation of a number of microbiota-augmented clinical trials in CRC. Given the intimate relationship between the gut microbiota and the immune system as well as antitumor immune responses, potentiating immunotherapy and managing its toxicity are major areas of research in microbiota-augmented therapies in cancer. Therefore, evaluation of the patient microbiome as a routine part of clinical outcome analysis is warranted in future clinical trials.}, }
@article {pmid32605650, year = {2020}, author = {Benech, N and Sokol, H}, title = {Fecal microbiota transplantation in gastrointestinal disorders: time for precision medicine.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {58}, doi = {10.1186/s13073-020-00757-y}, pmid = {32605650}, issn = {1756-994X}, abstract = {Fecal microbiota transplantation (FMT) has demonstrated efficacy in treating inflammatory bowel diseases and irritable bowel syndrome in an increasing number of randomized controlled trials. Recently published data gives striking insights into the factors associated with FMT success paving the road for the use of precision medicine in gastrointestinal disorders.}, }
@article {pmid32601752, year = {2020}, author = {Meyer, DC and Hill, SS and Bebinger, DM and McDade, JA and Davids, JS and Alavi, K and Maykel, JA}, title = {Resolution of multiply recurrent and multifocal diverticulitis after fecal microbiota transplantation.}, journal = {Techniques in coloproctology}, volume = {24}, number = {9}, pages = {971-975}, doi = {10.1007/s10151-020-02275-w}, pmid = {32601752}, issn = {1128-045X}, abstract = {BACKGROUND: The exact pathophysiology of diverticulitis is not well understood and may be multifactorial. Recent studies highlight dysbiosis as a plausible mechanism. FMT is a safe strategy to restore commensal colon microbiota and has proven to be an effective treatment for gastrointestinal dysbiosis such as Clostridium difficile infection (CDI). There have been no studies reporting the treatment of diverticulitis with FMT. Our aim was to describe the novel application of fecal microbiota transplantation (FMT) for the treatment of recurrent diverticulitis.<br><br>CASE: We report a case of a 63-year-old woman who had a 13-year history of multiply recurrent and multifocal diverticulitis previously treated with numerous short courses of intravenous and oral antibiotics for acute flares, two segmental colon resections, and suppressive antibiotic therapy for recurrent disease. Secondary to multiple courses of antibiotics , the patient developed CDI. She was treated with a single round of FMT and subsequently stopped all antibiotics at the time of FMT.<br><br>RESULTS: In 20 months of follow-up, the patient has had no further recurrence of diverticulitis or CDI.<br><br>CONCLUSIONS: FMT could prove to be a novel therapy for refractory diverticulitis but requires further investigation.}, }
@article {pmid32601270, year = {2020}, author = {Fremin, BJ and Sberro, H and Bhatt, AS}, title = {MetaRibo-Seq measures translation in microbiomes.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {3268}, pmid = {32601270}, issn = {2041-1723}, support = {P50 AG047366/AG/NIA NIH HHS/United States ; }, mesh = {Metagenomics ; Microbiota/*genetics ; Protein Biosynthesis/genetics ; RNA-Seq/*methods ; }, abstract = {No method exists to measure large-scale translation of genes in uncultured organisms in microbiomes. To overcome this limitation, we develop MetaRibo-Seq, a method for simultaneous ribosome profiling of tens to hundreds of organisms in microbiome samples. MetaRibo-Seq was benchmarked against gold-standard Ribo-Seq in a mock microbial community and applied to five different human fecal samples. Unlike RNA-Seq, Ribo-Seq signal of a predicted gene suggests it encodes a translated protein. We demonstrate two applications of this technique: First, MetaRibo-Seq identifies small genes, whose identification until now has been challenging. For example, MetaRibo-Seq identifies 2,091 translated, previously unannotated small protein families from five fecal samples, more than doubling the number of small proteins predicted to exist in this niche. Second, the combined application of RNA-Seq and MetaRibo-Seq identifies differences in the translation of transcripts. In summary, MetaRibo-Seq enables comprehensive translational profiling in microbiomes and identifies previously unannotated small proteins.}, }
@article {pmid32600151, year = {2020}, author = {Hazan, S}, title = {Rapid improvement in Alzheimer's disease symptoms following fecal microbiota transplantation: a case report.}, journal = {The Journal of international medical research}, volume = {48}, number = {6}, pages = {300060520925930}, pmid = {32600151}, issn = {1473-2300}, abstract = {Alzheimer's disease (AD), the most common form of dementia, is a leading cause of death and a major cause of morbidity in older people. The disease is characterized by progressive memory loss, cognitive impairment, and the cerebral accumulation of amyloid-β peptide. Given the health and economic impacts of AD, treatments that target the underlying etiology of AD or modify the course of the disease are of significant interest. The gut microbiome has been increasingly implicated in the pathogenesis of several neurological diseases, including multiple sclerosis and Parkinson's disease. Furthermore, emerging evidence has demonstrated that there are alterations in gut microbiome composition in patients with AD, suggesting involvement of the microbiome-gut-brain axis. We present symptom improvement in a patient with AD following fecal microbiota transplantation for a Clostridioides difficile infection.}, }
@article {pmid32594732, year = {2020}, author = {Chen, QY and Tian, HL and Yang, B and Qin, HL and Li, N}, title = {[A case report of refractory methemoglobinemia after nitrite poisoning treated by fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {90-92}, doi = {10.3760/cma.j.cn.441530-20200416-00218}, pmid = {32594732}, issn = {1671-0274}, mesh = {Fecal Microbiota Transplantation/*methods ; Humans ; Methemoglobinemia/*chemically induced/*therapy ; Nitrites/*poisoning ; }, }
@article {pmid32594731, year = {2020}, author = {Yang, B and Chen, QY and Tian, HL and Lin, ZL and Zhao, D and Ye, C and Zhang, XY and Qin, HL and Li, N}, title = {[Application of modified blind nasojejunal tube technique in fecal microbiota transplantation - report of 2267 cases].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {86-89}, doi = {10.3760/cma.j.cn.441530-20200414-00209}, pmid = {32594731}, issn = {1671-0274}, mesh = {Enteral Nutrition ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Humans ; Intubation, Gastrointestinal/*methods ; Jejunum ; Treatment Outcome ; }, }
@article {pmid32594729, year = {2020}, author = {Chen, QY and Yang, B and Tian, HL and Lin, ZL and Zhao, D and Ye, C and Zhang, XY and Qin, HL and Li, N}, title = {[Association between the clinical efficacy of fecal microbiota transplantation in recipients and the choice of donor].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {69-76}, doi = {10.3760/cma.j.cn.441530-20200417-00222}, pmid = {32594729}, issn = {1671-0274}, support = {81670493//National Natural Science Fundation of China/ ; }, mesh = {Autistic Disorder/*therapy ; Butyrates/analysis ; Case-Control Studies ; *Donor Selection ; Fatty Acids, Volatile/analysis ; Fecal Microbiota Transplantation/*methods ; Feces/chemistry/microbiology ; Humans ; Intestinal Diseases/*therapy ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Objective: To examine the association between the clinical efficacy of fecal microbiota transplantation (FMT) in recipients and the choice of donor, and to observe the characteristics of intestinal flora and metabolites among different donors. Methods: A retrospective case-control study was conducted. Donor whose feces was administrated for more than 30 recipients was enrolled. Data of 20 FMT donors and corresponding recipients at Intestinal Microecology Diagnosis and Treatment Center of the Tenth People's Hospital from October 2018 to December 2019 were collected retrospectively. During follow-up, the efficacy of each recipient 8-week after FMT treatment was recorded and analyzed. Based on the efficacy of each donor, the donors were divided into three groups: high efficacy group (effective rate >60%, 10 donors), moderate efficacy group (effective rate 30%-60%, 6 donors) and low efficacy group (effective rate <30%, 4 donors). The structure of the bacterial flora and the content of fecal short-chain fatty acids in each group of donors were detected and compared among groups. Association of the efficacy of each donor group with the morbidity of complications, and association of efficacy of recipients with donors were analyzed. The evaluation indicators of FMT efficacy included objective clinical effectiveness and/or subjective effectiveness. Objective effectiveness indicated clinical cure plus clinical improvement, and subjective effectiveness indicated marked effectiveness plus medium effectiveness through questionnaire during follow-up. Results: A total of 1387 recipients were treated by 20 donors, including 749 cases of chronic constipation, 141 cases of chronic diarrhea, 107 cases of inflammatory bowel disease (IBD), 121 cases of irritable bowel syndrome (IBS), 83 cases of autism, and 186 cases of other diseases, such as radiation bowel injury, intestinal pseudo-obstruction, paralytic intestinal obstruction, functional bloating and allergic diseases. There were 829 cases, 403 cases, and 155 cases in high efficacy group, moderate efficacy group and low efficacy group respectively. Baseline data among 3 groups were not significantly different (all P> 0.05). In comparison of bacterial abundance (operational taxonomic unit, OTU) among different effective donor groups, the high efficacy group was the highest (330.68±57.28), the moderate efficacy group was the second (237.79±41.89), and the low efficacy group was the lowest (160.60±49.61), whose difference was statistically significant (F=16.910, P<0.001). In comparison of bacterial diversity (Shannon index), the high efficacy group and the moderate efficacy group were higher (2.96±0.36 and 2.67±0.54, respectively), and the low efficacy group was lower (2.09±0.55), whose difference was statistically significant (F=5.255, P=0.017). In comparison of butyric acid content among three groups, the high efficacy group had the highest [(59.20±9.00) μmol/g], followed by middle efficacy group [(46.92±9.48) μmol/g], and the low efficacy group had the lowest [(37.23±5.03) μmol/g], whose difference was statistically significant (F=10.383, P=0.001). The differences of acetic acid and propionic acid among three groups were not statistically significant (all P>0.05). A total of 418 cases developed complications (30.1%). Morbidity of complication in low efficacy group, moderate efficacy group and high efficacy group was 40.6% (63/155), 30.0% (121/403) and 28.2% (243/829) respectively, and the difference was statistically significant (χ(2)=9.568, P=0.008). The incidence of diarrhea in low efficacy group, moderate efficacy group and high efficacy group was 7.1% (11/155), 4.0% (16/403) and 2.8% (23/829) respectively, and the difference was statistically significant (χ(2)=7.239, P=0.027). Comparing the incidences of other types of complications, no statistically significant differences were found (all P>0.05). Follow up began 8 weeks after the FMT treatment. The total follow-up rate was 83.6% (1160/1387). The overall effective rate 58.3% (676/1160). Effective rates of various diseases were as follows: chronic constipation 54.3% (328/604), chronic diarrhea 88.5% (115/130), IBD 56.1% (55/98), IBS 55.1% (59/107), autism 61.6% (45/73), and other diseases 50.0% (74/148). Comparing the effective rate of three groups of donors for different diseases, there was no statistically significant difference in chronic diarrhea (P>0.05); there was a positive correlation trend in IBD, IBS and autism, but the differences were not statistically significant (all P>0.05). For chronic constipation and other diseases, high efficacy group had the highest effective rate [65.0% (243/374) and 63.2% (55/87)], followed by moderate efficacy group [49.4% (86/174) and 38.1% (16/42)], and low efficacy group had the lowest [16.1% (9/56) and 15.8% (3/19)], whose differences were significant (all P<0.05). Conclusions: Different donors have different efficacy in different diseases. Chronic constipation, radiation bowel injury, etc. need to choose donors with high efficacy. IBD, IBS and autism may also be related to the effectiveness of donors, while chronic diarrhea is not associated to the donor. The efficiency of the donor is negatively correlated to the morbidity of complications. The abundance and diversity of intestinal flora and the content of butyric acid may affect the efficacy of the donor.}, }
@article {pmid32594728, year = {2020}, author = {Tian, HL and Chen, QY and Yang, B and Ma, CL and Lin, ZL and Zhang, XY and Zhou, SL and Qin, HL and Li, N}, title = {[Effects of fecal microbiota transplantation in different routes on the clinical efficacy of slow transit constipation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {63-68}, doi = {10.3760/cma.j.cn.441530-20200415-00212}, pmid = {32594728}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; 04.99.18001//Special fund for the construction of the clinical center of Tenth People's Hospital of Tongji University/ ; }, mesh = {Adult ; Constipation/physiopathology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Transit/*physiology ; Humans ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Objective: To evaluate the efficacy and safety of the fecal microbiota transplantation (FMT) in the different route administration for slow transit constipation (STC). Methods: A retrospective cohort study was conducted. The clinical data of 270 STC patients who voluntarily received FMT treatment in the Tenth People's Hospital of Tongji University from May 2018 to May 2019 were collected. Non-relative healthy adult standard donors were applied. The treatment routes of bacterial flora transplantation included nasojejunal tube (nasal enteral tube group, 120 cases), oral enterobacterial capsule treatment (oral capsule group, 120 cases), and colonoscopy infusion (colonoscopy group, 30 cases). The efficacy and safety of treatment among the three groups were compared. Results: Transplanted bacteria of three groups were extracted from 100 g of fresh feces. All the patients successfully completed the transplantation. The waiting time for the nasal enteral tube group, oral capsule group and colonoscopy group was (1.5±0.5) d, (0.4±0.3) d and (3.6±0.8) d respectively; the cost of establishing the transplantation path was (495±20) yuan, (25±10) yuan and (1420±45) yuan respectively, whose differences were statistically significant (F=9.210, P=0.03; F=10.600,P=0.01). The clinical improvement rates at 1 month after FMT treatment in the nasojejunal tube group, oral capsule group and colonoscopy group were 74.2% (89/120), 60.0% (72/120) and 53.3% (16/30) respectively, whose difference was statistically significant (χ(2)=5.990, P<0.05). The clinical improvement rates at 3 months after treatment were 71.1% (69/97), 53.6% (45/84), and 44.0% (11/25) respectively, whose difference was statistically significant (χ(2)=7.620, P<0.05). The incidence of adverse reactions in the colonoscopy group was 76.7% (23/30), which was higher than that in the nasal nasojejunal group (39.2%, 47/120) and oral capsule group (21.7%, 26/120). The most common adverse reactions in the nasojejunal tube group, oral capsule group and colonoscopy group were respiratory discomfort (17.5%, 21/120), nausea and vomiting (10.0%, 12/120), and diarrhea (36.7%, 11/30). During the 3-month follow-up after treatment, no FMT-related adverse reactions were reported. Conclusions: The nasojejunal tube route has stable clinical efficacy and operability, while the oral capsule route has shorter waiting time and less cost. However, the adverse reactions caused by different transplantation methods are different, thus personalized transplantation method should be recommended.}, }
@article {pmid32594727, year = {2020}, author = {Lin, ZL and Chen, QY and Tian, HL and Yang, B and Zhao, D and Ye, C and Zhang, XY and Ma, CL and Qin, HL and Li, N}, title = {[Effect of fecal bacterial preservation time on the outcomes of fecal microbiota transplantation for slow transit constipation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {56-62}, doi = {10.3760/cma.j.cn.441530-20200414-00207}, pmid = {32594727}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; 04.99.18001//Special Fund for the Construction of the Clinical Center of Tenth People's Hospital of Tongji University/ ; }, mesh = {Constipation/physiopathology/*therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Transit/*physiology ; Humans ; Quality of Life ; Retrospective Studies ; Time Factors ; Treatment Outcome ; }, abstract = {Objective: To investigate the effect of different fecal bacterial preservation time on the efficacy and complications of FMT. Methods: A retrospective cohort study was carried out. Clinical data of 483 patients with slow transit constipation undergoing voluntary FMT at Intestinal Microecology Diagnosis and Treatment Center from August 2017 to October 2019 were retrospectively collected. According to the storage time of fecal bacterial samples used in FMT treatment, the cases were divided into fresh bacterial solution (n=29), bacterial solution stored at -80℃ for 1 week (n=187), 1 month (n=121), 3 months (n=89), 6 months (n=38), and 12 months (n=19). The total number of complete bowel movement, Wexner constipation score, gastrointestinal quality of life index (GIQLI), FMT satisfaction score and related adverse reactions were summarized and compared among groups 1 week and 1 month after FMT treatment. Results: There were no statistically significant differences in the baseline data of patients among different bacterial solution storage time (all P>0.05). After 1 month of treatment, the overall frequency of defecation of all the patients was (3.83 ± 1.22) times/week, Wexner constipation score was (6.74 ± 3.56) points, GIQLI score was (108.76 ± 15.38) points, clinical cure rate was 57.8% (279/483). The improvement rate was 66.3% (320/483), and the treatment satisfaction was (3.85 ± 0.93) points. No severe FMT-associated complication and death were observed during treatment and follow-up period. FMT-related adverse events occurred in 115 cases (23.8%), including nausea in 25 cases (5.2%), vomiting in 13 (2.7%), diarrhea in 21 (4.3%), abdominal pain in 16 (3.3%), abdominal distension in 33 (6.8%), sore throat in 56 (11.6%) and fever in 16(3.3%), all of which relieved after symptomatic treatment. There were no statistically significant differences in the number of defecations, Wexner constipation scores, and GIQLI scores before FMT, 1 week and 1 month after FMT treatment among different bacterial solution storage groups (all P>0.05). Differences of clinical cure rate, clinical improvement rate, and treatment satisfaction of patients 1 week and 1 month after treatment were not statistically significant (all P>0.05). Among the groups, differences in the overall complications and types of complications after FMT treatment were not statistically significant (all P>0.05). Conclusions: FMT is safe and effective in the treatment of slow transit constipation. Fresh fecal bacterial samples or fecal bacterial samples frozen at -80℃ for 1 year can be safely applied to FMT for the treatment of slow transit constipation, with stable short-term efficacy and without serious adverse reactions.}, }
@article {pmid32594726, year = {2020}, author = {Chen, QY and Tian, HL and Yang, B and Lin, ZL and Zhao, D and Ye, C and Zhang, XY and Qin, HL and Li, N}, title = {[Effect of intestinal preparation on the efficacy and safety of fecal microbiota transplantation treatment].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {48-55}, doi = {10.3760/cma.j.cn.441530-20200418-00225}, pmid = {32594726}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; }, mesh = {Adult ; Anti-Bacterial Agents/administration &amp; dosage ; Autistic Disorder/*therapy ; Cathartics/administration &amp; dosage ; Enema ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Humans ; Intestinal Diseases/*therapy ; Male ; Middle Aged ; Preoperative Care/methods ; Recurrence ; Retrospective Studies ; Time Factors ; Treatment Outcome ; }, abstract = {Objective: To investigate the effect of intestinal preparation on the efficacy and complications of fecal microbiota transplantation (FMT). Methods: A retrospective cohort study was performed. Clinical and follow-up data of 1501 patients who received FMT in the department of Colorectal Disease Specialty, Intestinal Microecology Diagnosis and Treatment Center, the Tenth People's Hospital, Tongji University from February 2018 to June 2019 were collected retrospectively. According to the intestinal preparation before FMT treatment, patients were divided into non-intestinal preparation group (n=216), antibiotic pretreatment group (n=383), intestinal cleansing group (n=267), and antibiotic combined with intestinal cleansing group (n=635). The adverse reactions after FMT treatment and the effective rates at 4-week and 8-week after treatment among the groups were compared. Patients, who repeated FMT treatment in the 3rd month and the 6th month due to reduced efficacy or ineffectiveness were divided into two subgroups: without intestinal preparation group and with intestinal preparation group. The effective rates of the two subgroups were compared. Results: Of the 1501 cases, 588 were male and 913 were female with mean age of (43.3±13.7) years and body mass index of (20.2±2.1) kg/m(2). Transplantation course was (3.3±1.7) weeks. The underlying diseases mainly included constipation (n=564), Crohn's disease (n=157), ulcerative colitis (n=142), irritable bowel syndrome (n=158), recurrent C. difficile infection (CDI) (n=106), autism (n=84), radiation intestinal injury (n=133), radiation enteritis (n=133), and non-CDI chronic diarrhea (n=60); the remaining cases (n=155). Baseline data among the 4 groups were not significantly different (all P>0.05). The overall morbidity of complication was 31.1% (467/1501), including 41 cases of vomiting (2.7%), 91 of nausea (6.1%), 49 of diarrhea (3.3%), 41 of abdominal pain (2.7%), 79 of bloating (5.3%), 72 of throat pain (4.8%), 38 of dizziness (2.5%), 51 of fever (3.4%), 3 of pulmonary infection (0.2%) and 2 of intestinal infection (0.1%). The above symptoms disappeared after symptomatic treatment. There was no statistically significant difference in the incidence of adverse reactions among the 4 groups (P>0.05). After 4-week of FMT treatment, the overall effective rate was 63.5% (902/1420); the effective rate of non-intestinal preparation group, antibiotic pretreatment group, intestinal cleaning group, and antibiotic combined with intestinal cleansing groupwas 57.6% (114/198), 64.2% (231/360), 60.2% (154/265) and 66.5% (403/606), respectively, with no statistically significant difference (χ(2)=6.659, P=0.084). After 8-week of FMT treatment, the overall effective rate was 61.3% (729/1293); the effective rate of non-intestinal preparation group, antibiotic pretreatment group, intestinal cleaning group, and antibiotic combined with intestinal cleansing group was 54.0% (88/163), 62.2% (202/325), 57.4% (132/230) and 64.4% (370/575), respectively, with no statistically significant difference (χ(2)=13.620, P=0.003). The effective rates of antibiotic combined with intestinal cleansing group and antibiotic pretreatment group were obviously higher than that of non-intestinal preparation group (χ(2)=5.789, P=0.016; χ(2)=10.117, P=0.001). Subgroup analysis showed that in the third month, the effective rate at 4-week after treatment was 60.1% (184/306) in the without intestinal preparation group and 61.5% (115/187) in the with intestinal preparation group, whose difference was not significant (χ(2)=0.091, P=0.763); however, in the sixth month, the effective rate at 4-week after treatment was 51.4% (89/173) in the without intestinal preparation group and 61.2% (161/263) in the with intestinal preparationgroup, whose difference was significant (χ(2)=4.229, P=0.040). Conclusions: FMT treatment is safe and effective. The combination of antibiotics and intestinal cleaning can improve overall efficacy of FMT. For patients who need repeated FMT treatment, the combination of antibiotics and intestinal cleaning program within 3 months has no significant effect on the effective rate, but in the sixth month, combinedpreparation is necessary.}, }
@article {pmid32594725, year = {2020}, author = {Zhang, FM and Liu, YF}, title = {[Evidence and decision of the choice of delivery way in washed microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {45-47}, doi = {10.3760/cma.j.cn.441530-20200507-00259}, pmid = {32594725}, issn = {1671-0274}, mesh = {Enema ; Enteral Nutrition ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Humans ; Intubation, Gastrointestinal ; }, abstract = {Washed microbiota transplantation (WMT) is a new concept and technique of fecal microbiota transplantation. The delivery routes of WMT include oral capsule, nasogastric tube, nasojejunal tube, gastroscopy, colonic transendoscopic enteral tubing, and anal enema. The research results among different indications or different designs based on the same indication are quite different, partially because of the influence of WMT delivery route. In the process of clinical research design and clinical practice, there are four aspects that affect the decision-making of WMT delivery route: safety, efficacy, cost-effectiveness, and patients' willingness. This article focuses on how to integrate the four aspects mentioned above in the decision-making process of choosing proper delivery of WMT for the final goal of mutual satisfaction between doctors and patients.}, }
@article {pmid32594720, year = {2020}, author = {,  and ,  and ,  and , }, title = {[Chinese experts consensus on clinical practice of the selection and establishment of fecal microbiota transplantation delivery routes].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {14-20}, doi = {10.3760/cma.j.cn.441530-20200420-00228}, pmid = {32594720}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; }, mesh = {China ; Consensus ; Fecal Microbiota Transplantation/adverse effects/*methods/*standards ; Humans ; }, abstract = {Fecal microbiota transplantation (FMT) has gradually shown application prospects in the treatment of intestinal and extraintestinal diseases. In order to standardized FMT operation, based on the clinical experience of the Tenth People's Hospital Affiliated to Tongji University, combined with domestic and foreign literature, Parenteral and Enteral Nutrition Branch of Chinese Medical Association, Enhanced Recovery after Surgery Branch of China International Health Care Promotion Exchange Association, China Microecological Treatment Innovation Alliance, and Microecology Committee of Shanghai Preventive Medicine Association to formulated the&quot; Chinese experts consensus on clinical practice of the selection and establishment of fecal microbiota transplantation delivery routes&quot;. It includes four parts: the selection of delivery route, the methodology of transplantation path establishment, the clinical application, and the monitoring of adverse events.}, }
@article {pmid32594719, year = {2020}, author = {,  and ,  and ,  and , }, title = {[Chinese experts consensus on standardized methodology and clinical application of fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {5-13}, doi = {10.3760/cma.j.cn.441530-20200420-00231}, pmid = {32594719}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; }, mesh = {China ; Consensus ; Fecal Microbiota Transplantation/adverse effects/*methods/*standards ; Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is to transplant the functional bacteria in the feces of healthy people into the patients' intestines, rebuild the new balance of intestinal flora, and achieve the treatment goals of intestinal and extraintestinal diseases. In the past 10 years, FMT has made a breakthrough in the treatment of intestinal and extraintestinal diseases, which is highly expected to treat difficult diseases. However, due to the complexity of FMT methodology and the lack of a unified standard, there is a high heterogeneity in FMT efficacy among various researches, greatly affected its clinical application. Under the initiative of Parenteral and Enteral Nutrition Branch of Chinese Medical Association, Enhanced Recovery after Surgery Branch of China International Health Care Promotion Exchange Association, China Microecological Treatment Innovation Alliance, and Microecology Committee of Shanghai Preventive Medicine Association, the first expert consensus on standardized methodology and clinical application of FMT was established in China, with a view to improving the efficacy of FMT, reducing the incidence of adverse reactions and promoting the clinical application of FMT.}, }
@article {pmid32594718, year = {2020}, author = {Li, N}, title = {[Practice and consideration of fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {1-4}, doi = {10.3760/cma.j.cn.441530-20200420-00230}, pmid = {32594718}, issn = {1671-0274}, mesh = {China ; Clostridium Infections/*therapy ; Clostridium difficile/*isolation &amp; purification ; Fecal Microbiota Transplantation/methods/*standards ; Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestines/*microbiology/physiology/physiopathology ; Recurrence ; Treatment Outcome ; }, abstract = {As an innovative therapy, FMT has made a breakthrough in the treatment of recurrent Clostridium difficile infection (CDI). With the rapid development of biotechnology, the relationship between intestinal microflora and diseases has been gradually eluciated. Great hope has also been given to FMT in other intestinal and extraintestinal diseases with ineffective traditional treatment. However, as a new therapy method, FMT still has many unknown fields, such as the selection of clinical donors, the preparation of standardized bacterial solution and capsule, the selection of indications, the matching of donor and receptor, and the prevention and treatment of complications. Since 2012, our center has carried out treatment research and practice of FMT, so far with more than 60 000 FMTs for more than 3500 cases. Based on large sample data and experience, this special issue reports and discusses the above topics, and focuses on the establishment and clinical application of standardized methodology of FMT, which will undoubtedly play a positive role in promoting the healthy development of FMT treatment in China.}, }
@article {pmid32592577, year = {2020}, author = {Jiang, S and Wang, B and Sha, T and Li, X}, title = {Changes in the Intestinal Microbiota in Patients with Stage 5 Chronic Kidney Disease on a Low-Protein Diet and the Effects of Human to Rat Fecal Microbiota Transplantation.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {26}, number = {}, pages = {e921557}, pmid = {32592577}, issn = {1643-3750}, abstract = {BACKGROUND Dietary protein restriction is recommended for patients with stage 5 chronic kidney disease (CKD), or end-stage renal disease (ESRD). This study aimed to investigate the changes in the intestinal microbiota due to different dietary regimens in patients with stage 5 CKD and the effects of human to rat fecal microbiota transplantation. MATERIAL AND METHODS Second-generation high-throughput sequencing was used to analyze the amplifiers in the 16S rRNA V4 region in the intestinal microbiota of patients with stage 5 CKD and healthy individuals. The intestinal microbiota of patients with stage 5 CKD in the low-protein group and the healthy individual group was transferred by human to rat fecal microbiota transplantation using Sprague-Dawley rats. Data underwent meta-analysis using Meta-Stat. RESULTS Patients with CKD on a very low-protein diet showed an increase in intestinal Escherichia, Shigella, and Klebsiella, a decrease in Blautia, heat map analysis showed that Christensenellaceae R-7 group rs1 were significantly increased, and MetaStat analysis showed that Bacteroides, Prevotella, and Mitsuokella were significantly increased. Following human to rat fecal microbiota transplantation from patients with stage 5 CKD, the profile of the rat intestinal microbiota became similar to the human donors. The weight of the rats fed a very low-protein diet after fecal microbiota transplantation significantly decreased after six weeks compared with normal rats and rats that received normal fecal microbiota transplantation. CONCLUSIONS Patients with stage 5 CKD on a very low-protein diet showed changes in the intestinal microbiota that could be transferred from humans to rats by fecal microbiota transplantation.}, }
@article {pmid32588829, year = {2020}, author = {Zhgun, ES and Kislun, YV and Kalachniuk, TN and Veselovsky, VA and Urban, AS and Tikhonova, PO and Pavlenko, AV and Ilchenko, GN and Ilina, EN}, title = {[Evaluation of metabolites levels in feces of patients with inflammatory bowel diseases].}, journal = {Biomeditsinskaia khimiia}, volume = {66}, number = {3}, pages = {233-240}, doi = {10.18097/PBMC20206603233}, pmid = {32588829}, issn = {2310-6972}, abstract = {Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn's disease (CD), are chronic intestinal inflammatory disorders with an unknown etiology. They are characterized by chronic recurrent inflammation of the intestinal mucosa and lead to a significant decrease in the quality of life and death of patients. IBD are associated with suppression of normal intestinal microflora, including a decrease in bacteria, producers of short chain fatty acids (SCFAs), exhibiting anti-inflammatory and protective properties. Among the various methods of intestinal microflora correction, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, is of a particular interest. As a result, a positive therapeutic effect is observed, accompanied by the restoration of the normal intestinal microflora of the patient. A significant drawback of the method is the lack of standardization. Metabolites produced by intestinal microflora, namely SCFAs, allow objective assessment of the functional state of the intestinal microbiota and, consequently, the success of the FMT procedure. Using gas chromatography and nuclear magnetic resonance spectroscopy techniques, we have analyzed concentrations and molar ratios of SCFAs in fecal samples of 60 healthy donors. Results were in good accord when comparing two methods as well as with published data. Analysis of SCFAs in feces of patients with UC (19 patients) and CD (17 patients) revealed a general decrease in the concentration of fatty acids in the experimental groups with significant fluctuations in the values in experimental groups compared to control group of healthy donors. On the limited group of IBD patients (6 patients with UC and 5 patients with CD) concentration of SCFAs before and within 30 days of observation after FMT was determined. It was shown that FMT had a significant impact on the SCFAs levels within 1 month term; tendency to reach characteristics of healthy donors is unambiguously traced for both diseases.}, }
@article {pmid32587239, year = {2020}, author = {Li, H and Xu, H and Li, Y and Jiang, Y and Hu, Y and Liu, T and Tian, X and Zhao, X and Zhu, Y and Wang, S and Zhang, C and Ge, J and Wang, X and Wen, H and Bai, C and Sun, Y and Song, L and Zhang, Y and Hui, R and Cai, J and Chen, J}, title = {Alterations of gut microbiota contribute to the progression of unruptured intracranial aneurysms.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {3218}, pmid = {32587239}, issn = {2041-1723}, mesh = {Animals ; Case-Control Studies ; Clostridiaceae/*metabolism ; Cohort Studies ; Disease Progression ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; *Intracranial Aneurysm/microbiology/pathology ; Male ; Mice ; Prognosis ; Risk Factors ; Taurine/*metabolism ; }, abstract = {Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Whether changes in gut microbial composition participate in the development of UIAs remains largely unknown. We perform a case-control metagenome-wide association study in two cohorts of Chinese UIA patients and control individuals and mice that receive fecal transplants from human donors. After fecal transplantation, the UIA microbiota is sufficient to induce UIAs in mice. We identify UIA-associated gut microbial species link to changes in circulating taurine. Specifically, the abundance of Hungatella hathewayi is markedly decreased and positively correlated with the circulating taurine concentration in both humans and mice. Consistently, gavage with H. hathewayi normalizes the taurine levels in serum and protects mice against the formation and rupture of intracranial aneurysms. Taurine supplementation also reverses the progression of intracranial aneurysms. Our findings provide insights into a potential role of H. hathewayi-associated taurine depletion as a key factor in the pathogenesis of UIAs.}, }
@article {pmid32585945, year = {2020}, author = {Leo, S and Lazarevic, V and Girard, M and Gaïa, N and Schrenzel, J and de Lastours, V and Fantin, B and Bonten, M and Carmeli, Y and Rondinaud, E and Harbarth, S and Huttner, BD}, title = {Metagenomic Characterization of Gut Microbiota of Carriers of Extended-Spectrum Beta-Lactamase or Carbapenemase-Producing Enterobacteriaceae Following Treatment with Oral Antibiotics and Fecal Microbiota Transplantation: Results from a Multicenter Randomized Trial.}, journal = {Microorganisms}, volume = {8}, number = {6}, pages = {}, pmid = {32585945}, issn = {2076-2607}, support = {282512//European Commission under the Seventh Framework Programme (FP7/2007) for Research and technology/ ; }, abstract = {Background: The R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) WP3 study was the first multicenter randomized clinical trial systematically investigating fecal microbiota transplantation (FMT) for intestinal decolonization of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Here, we characterized the temporal dynamics of fecal microbiota changes in a sub-cohort of the R-GNOSIS WP3 participants before and after antibiotics/FMT using whole metagenome shotgun sequencing. Methods: We sequenced fecal DNA obtained from 16 ESBL-E/CPE carriers having received oral colistin/neomycin followed by FMT and their corresponding seven donors. Ten treatment-naïve controls from the same trial were included. Fecal samples were collected at baseline (V0), after antibiotics but before FMT (V2) and three times after FMT (V3, V4 and V5). Results: Antibiotic treatment transiently decreased species richness and diversity and increased the abundance of antibiotic resistance determinants (ARDs). Bifidobacterium species, together with butyrate- and propionate-producing species from Lachnospiraceae and Ruminococcaceae families were significantly enriched in post-FMT microbiota of treated carriers. After FMT, the proportion of Enterobacteriaceae was lower compared to baseline but without statistical significance. Conclusions: Combined antibiotic and FMT treatment resulted in enrichment of species that are likely to limit the gut colonization by ESBL-E/CPE.}, }
@article {pmid32585148, year = {2020}, author = {Basson, AR and Zhou, Y and Seo, B and Rodriguez-Palacios, A and Cominelli, F}, title = {Autologous fecal microbiota transplantation for the treatment of inflammatory bowel disease.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {}, number = {}, pages = {}, pmid = {32585148}, issn = {1878-1810}, support = {R01 DK055812/DK/NIDDK NIH HHS/United States ; }, abstract = {The term autologous fecal microbiota transplantation (a-FMT) refers herein to the use of one's feces during a healthy state for later use to restore gut microbial communities after perturbations. Generally, heterologous fecal microbiota transplantation (h-FMT), where feces from a ``healthy&quot; donor is transplanted into a person with illness, has been used to treat infectious diseases such as recurrent Clostridioides difficile infection (CDI), with cure rates of up to 90%. In humans, due to limited response to medicines, h-FMT has become a hallmark intervention to treat CDI. Extrapolating the benefits from CDI, h-FMT has been attempted in various diseases, including inflammatory bowel disease (IBD), but clinical response has been variable and less effective (ranging between 24% and 50%). Differences in h-FMT clinical response could be because CDI is caused by a Clostridial infection, whereas IBD is a complex, microbiome-driven immunological inflammatory disorder that presents predominantly within the gut wall of genetically-susceptible hosts. FMT response variability could also be due to differences in microbiome composition between donors, recipients, and within individuals, which vary with diet, and environments, across regions. While donor selection has emerged as a key factor in FMT success, the use of heterologous donor stool still places the recipient at risk of exposure to infectious/pathogenic microorganisms. As an implementable solution, herein we review the available literature on a-FMT, and list some considerations on the benefits of a-FMT for IBD.}, }
@article {pmid32584703, year = {2020}, author = {Gong, Z and Wang, Y}, title = {Immune Checkpoint Inhibitor-Mediated Diarrhea and Colitis: A Clinical Review.}, journal = {JCO oncology practice}, volume = {16}, number = {8}, pages = {453-461}, doi = {10.1200/OP.20.00002}, pmid = {32584703}, issn = {2688-1535}, abstract = {Immune-mediated diarrhea and colitis (IMDC) is among the most common immune-related adverse events in patients with cancer treated with immune checkpoint inhibitors (ICIs). Many factors will affect the risk of IMDC, including the type of ICI used, the type of underlying cancer, and patient characteristics. A recent study showed that preexisting inflammatory bowel disease significantly increases the risk of diarrhea and colitis with ICI treatment. In terms of management, early endoscopic evaluation improves clinical outcome by identifying high-risk patients who will benefit from early add-on immunosuppressants. Inflammatory markers, including fecal lactoferrin and calprotectin, are good screening tools to predict which patients are at risk for colitis. Calprotectin especially is associated with colitis outcome and can be used as a surrogate marker to follow treatment response. Corticosteroids remain the first-line medical treatment of IMDC management, and add-on therapy with vedolizumab or infliximab should be considered in selected patients. Fecal microbiota transplantation may be considered in refractory cases. The decision to resume ICI should be decided by balancing the risk of recurrent IMDC and the likelihood of benefiting from further ICI treatment. There is no clear evidence about whether the use of immunosuppressants will result in a worse cancer outcome. With emerging evidence, our understanding and management strategies are likely to evolve in the future.}, }
@article {pmid32582202, year = {2020}, author = {Yan, Y and Zhou, X and Guo, K and Zhou, F and Yang, H}, title = {Chlorogenic Acid Protects Against Indomethacin-Induced Inflammation and Mucosa Damage by Decreasing Bacteroides-Derived LPS.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1125}, pmid = {32582202}, issn = {1664-3224}, abstract = {Background: Chlorogenic acid (CGA), a natural bioactive polyphenol, exerts anti-inflammatory, antioxidant, and antibacterial effects that support the maintenance of intestinal health. However, the influence of CGA on gut microbiota and their metabolites, as well as its potential effects and mechanism of action in inflammatory bowel disease, remain to be elucidated. Methods: First, an oral gavage was used to administer CGA to indomethacin-treated mice. Then, fecal microbiota transplantation was performed to explore the role of intestinal microbiota in indomethacin-induced inflammation. Results: CGA treatment protected against body weight loss, damage to intestinal morphology and integrity, inflammation, and alteration of microbiota composition in indomethacin-treated mice. Interestingly, CGA failed to inhibit inflammation or protect intestine integrity in mice treated with antibiotics. Notably, mice who had been colonized with intestinal microbiota from CGA-treated or CGA-and-indomethacin-treated mice, through the fecal microbiota transplantation program, were protected from indomethacin-induced inflammation, growth of Bacteroides, and the accumulation of Bacteroides-derived LPS, in congruence with those who had been treated with CGA. Conclusion: The results suggest that CGA may protect intestine integrity and alleviate inflammatory responses, primarily by inhibiting the growth of Bacteroides and the accumulation of Bacteroides-derived LPS, in indomethacin-induced colitis. This newly identified mechanism broadens our knowledge of how CGA exerts protective effects on intestinal inflammation and provides strategies for the prevention of gastrointestinal mucosal damage in patients treated with indomethacin.}, }
@article {pmid32582121, year = {2020}, author = {Liang, W and Zhao, L and Zhang, J and Fang, X and Zhong, Q and Liao, Z and Wang, J and Guo, Y and Liang, H and Wang, L}, title = {Colonization Potential to Reconstitute a Microbe Community in Pseudo Germ-Free Mice After Fecal Microbe Transplant From Equol Producer.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1221}, pmid = {32582121}, issn = {1664-302X}, abstract = {Human intestinal microbiota plays a crucial role in the conversion of isoflavones into equol. Usually, human microbiota-associated (HMA) animal models are used, since it is difficult to establish the mechanism and causal relationship between equol and microbiota in human studies. Currently, several groups have successfully established HMA animal models that produce equol through germ-free mice or rats; however, the HMA model of producing equol through pseudo germ-free mice has not been established. The objective of this study is to establish an HMA mice model for equol production through pseudo germ-free mice, mimicking the gut microbiota of an adult human equol producer. First, a higher female equol producer was screened as a donor from 15 volunteers. Then, mice were exposed to vancomycin, neomycin sulfate, metronidazole, and ampicillin for 3 weeks to obtain pseudo germ-free mice. Finally, pseudo germ-free mice were inoculated with fecal microbiota of the equol producer for 3 weeks to establish HMA mice of producing equol. The results showed that (i) the ability to produce equol was partially transferred from the donor to the HMA mice. (ii) Most of the original intestinal microbiota of mice were eliminated after broad-spectrum antibiotic administration. (iii) The taxonomy data from HMA mice revealed similar taxa to the donor sample, and the species richness returned to the level close to the donor. (iv) The family Coriobacteriaceae and genera Collinsella were successfully transferred from the donor to HMA mice. In conclusion, the HMA mice model for equol production, based on pseudo germ-free mice, can replace the model established by germ-free mice. The model also provides a basis for studying microbiota during the conversion from isoflavones into equol.}, }
@article {pmid32580023, year = {2020}, author = {Inamura, K}, title = {Gut microbiota contributes towards immunomodulation against cancer: New frontiers in precision cancer therapeutics.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2020.06.006}, pmid = {32580023}, issn = {1096-3650}, abstract = {The microbiota influences human health and the development of diverse diseases, including cancer. Microbes can influence tumor initiation and development in either a positive or negative manner. In addition, the composition of the gut microbiota affects the efficacy and toxicity of cancer therapeutics as well as therapeutic resistance. The striking impact of microbiota on oncogenesis and cancer therapy provides compelling evidence to support the notion that manipulating microbial networks represents a promising strategy for treating and preventing cancer. Specific microbes or the microbial ecosystem can be modified via a multiplicity of processes, and therapeutic methods and approaches have been evolving. Microbial manipulation can be applied as an adjunct to traditional cancer therapies such as chemotherapy and immunotherapy. Furthermore, this approach displays great promise as a stand-alone therapy following the failure of standard therapy. Moreover, such strategies may also benefit patients by avoiding the emergence of toxic side effects that result in treatment discontinuation. A better understanding of the host-microbial ecosystem in patients with cancer, together with the development of methodologies for manipulating the microbiome, will help expand the frontiers of precision cancer therapeutics, thereby improving patient care. This review discusses the roles of the microbiota in oncogenesis and cancer therapy, with a focus on efforts to harness the microbiota to fight cancer.}, }
@article {pmid32577835, year = {2020}, author = {McQuade, JL and Ologun, GO and Arora, R and Wargo, JA}, title = {Gut Microbiome Modulation Via Fecal Microbiota Transplant to Augment Immunotherapy in Patients with Melanoma or Other Cancers.}, journal = {Current oncology reports}, volume = {22}, number = {7}, pages = {74}, doi = {10.1007/s11912-020-00913-y}, pmid = {32577835}, issn = {1534-6269}, abstract = {PURPOSE OF REVIEW: We review emerging evidence regarding the impact of gut microbes on antitumor immunity, and ongoing efforts to translate this in clinical trials.<br><br>RECENT FINDINGS: Pre-clinical models and human cohort studies support a role for gut microbes in modulating overall immunity and immunotherapy response, and numerous trials are now underway exploring strategies to modulate gut microbes to enhance responses to cancer therapy. This includes the use of fecal microbiota transplant (FMT), which is being used to treat patients with Clostridium difficile infection among other non-cancer indications. The use of FMT is now being extended to modulate gut microbes in patients being treated with cancer immunotherapy, with the goal of enhancing responses and/or to ameliorate toxicity. However, significant complexities exist with such an approach and will be discussed herein. Data from ongoing studies of FMT in cancer will provide critical insights for optimization of this approach.}, }
@article {pmid32575899, year = {2020}, author = {Giannone, G and Ghisoni, E and Genta, S and Scotto, G and Tuninetti, V and Turinetto, M and Valabrega, G}, title = {Immuno-Metabolism and Microenvironment in Cancer: Key Players for Immunotherapy.}, journal = {International journal of molecular sciences}, volume = {21}, number = {12}, pages = {}, pmid = {32575899}, issn = {1422-0067}, abstract = {Immune checkpoint inhibitors (ICIs) have changed therapeutic algorithms in several malignancies, although intrinsic and secondary resistance is still an issue. In this context, the dysregulation of immuno-metabolism plays a leading role both in the tumor microenvironment (TME) and at the host level. In this review, we summarize the most important immune-metabolic factors and how they could be exploited therapeutically. At the cellular level, an increased concentration of extracellular adenosine as well as the depletion of tryptophan and uncontrolled activation of the PI3K/AKT pathway induces an immune-tolerant TME, reducing the response to ICIs. Moreover, aberrant angiogenesis induces a hypoxic environment by recruiting VEGF, Treg cells and immune-suppressive tumor associated macrophages (TAMs). On the other hand, factors such as gender and body mass index seem to affect the response to ICIs, while the microbiome composition (and its alterations) modulates both the response and the development of immune-related adverse events. Exploiting these complex mechanisms is the next goal in immunotherapy. The most successful strategy to date has been the combination of antiangiogenic drugs and ICIs, which prolonged the survival of patients with non-small-cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC), while results from tryptophan pathway inhibition studies are inconclusive. New exciting strategies include targeting the adenosine pathway, TAMs and the microbiota with fecal microbiome transplantation.}, }
@article {pmid32574836, year = {2020}, author = {Zhang, F and Chen, H and Zhang, R and Liu, Y and Kong, N and Guo, Y and Xu, M}, title = {5-Fluorouracil induced dysregulation of the microbiome-gut-brain axis manifesting as depressive like behaviors in rats.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1866}, number = {10}, pages = {165884}, doi = {10.1016/j.bbadis.2020.165884}, pmid = {32574836}, issn = {1879-260X}, abstract = {Disturbances of the gut microbiome have been widely suggested to be associated with 5-fluorouracil (5-Fu) induced digestive pathologies. Furthermore, it has been elucidated that the gut microbiome may play a key role in the pathogenesis of depressive disorders via the microbiota-gut-brain axis. Despite the speculation, there exists no direct evidence proving the causality between disturbances in the gut microbiome induced by 5-Fu and depressive mood dysregulation. Herein, behavioral testing was used to evaluate depressive-like behaviors in 5-Fu treated rats. Subsequently, the gut microbiota and prefrontal cortex (PFC) metabolic were analyzed by 16S rRNA sequencing and 1H nuclear magnetic resonance (1H NMR). To clarify the association between the gut microbiota and their role on depressive-like behaviors caused by 5-Fu, a fecal microbiota transplantation (FMT) experiment was carried out. The results suggested that 5-Fu could significantly alter the diversity and abundance of the gut microbiome, and induce PFC metabolic disorders, as well as depressive behaviors in rats. Transplantation of fecal microbiota from healthy control into 5-Fu treated rats significantly alleviated the PFC metabolic disorder and depressive-like behaviors. In conclusion, this study demonstrated that the gut microbiome was actively involved in the occurrence of 5-Fu induced depressive-like behaviors, and manipulation of specific gut microbiome parameters may serve as a promising novel target for side effects of 5-Fu treatment.}, }
@article {pmid32574415, year = {2020}, author = {Bilinski, J and Lis, K and Tomaszewska, A and Pechcinska, A and Grzesiowski, P and Dzieciatkowski, T and Walesiak, A and Gierej, B and Ziarkiewicz-Wróblewska, B and Tyszka, M and Kacprzyk, P and Chmielewska, L and Waszczuk-Gajda, A and Wiktor-Jedrzejczak, W and Basak, GW}, title = {Eosinophilic gastroenteritis and graft-versus-host disease induced by transmission of Norovirus with fecal microbiota transplant.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {}, number = {}, pages = {e13386}, doi = {10.1111/tid.13386}, pmid = {32574415}, issn = {1399-3062}, abstract = {Fecal microbiota transplantation (FMT) was performed to decolonize gastrointestinal tract from antibiotic-resistant bacteria before allogeneic hematopoietic cells transplantation (alloHCT). AlloHCT was complicated by Norovirus gastroenteritis, acute graft-versus-host-disease and eosinophilic pancolitis. Norovirus was identified in samples from FMT material. Symptoms resolved after steroids course and second norovirus-free FMT from another donor.}, }
@article {pmid32572461, year = {2020}, author = {Mangioni, D and Alagna, L and Gori, A and Bandera, A}, title = {Fecal Microbiota Transplant: keep calm and carry on, learning from experience.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa846}, pmid = {32572461}, issn = {1537-6591}, }
@article {pmid32570299, year = {2020}, author = {Shasthry, SM}, title = {Fecal microbiota transplantation in alcohol related liver diseases.}, journal = {Clinical and molecular hepatology}, volume = {26}, number = {3}, pages = {294-301}, pmid = {32570299}, issn = {2287-285X}, abstract = {The current standard of care for severe alcoholic hepatitis (SAH) has several limitations in that only up to one-third of patients are eligible for steroid therapy. Additionally, steroids have their own issues: a portion of patients do not respond, while there is doubtful long-term benefit in those who do and a large proportion are ineligible to receive steroids entirely and hence have no definitive options for treatment. As such, there is a large gap between the problem and the available solutions. Alcohol causes dysbiosis and also disrupts gut barrier function, consequently promoting the translocation of microbial lipopolysaccharide into the portal circulation and liver. Therefore, probiotics, prebiotics, antibiotics, or transplantation of gut microbiota are likely to attenuate the dysbiosis-related liver insult. Fecal microbiota transplantation (FMT) is expected to have a role in managing alcoholic liver disease in general and SAH in particular by correcting dysbiosis, the primary insult. Results from mouse studies have suggested beyond doubt that alcohol-related liver injury is transferrable and also treatable by adopting FMT from suitable donors. Initial human trials from our center have affirmed benefits in human subjects with SAH as well, with both improvements in disease severity and as well as the rate of survival. Further studies addressing the head-to-head comparison of steroids and FMT are ongoing. Available preliminary data are promising and FMT and/or gut microbial modulation might become the standard of care in the near future for managing alcohol-related liver diseases, especially alcoholic hepatitis, with greater applicability, improved acceptability, and minimal side effects.}, }
@article {pmid32564632, year = {2020}, author = {Suraya, R and Nagano, T and Kobayashi, K and Nishimura, Y}, title = {Microbiome as a Target for Cancer Therapy.}, journal = {Integrative cancer therapies}, volume = {19}, number = {}, pages = {1534735420920721}, pmid = {32564632}, issn = {1552-695X}, abstract = {Recently, the microbiome has been gaining traction as a major player regulating various functions that correlate with many pathological conditions, including cancer. The central gut microbiota population has the capability to regulate normal inflammatory, immune, and metabolic functions, and disturbance in the balance of the normal microbiota population can subsequently induce pathological responses that closely relate with the mechanistic development and progression of cancer in various forms and sites. As a disease with major socioeconomic burden partly due to its current therapeutic options, modulating the imbalanced gut microbiota represents a novel option not only as an adjuvant therapy to relieve cancer treatment-related symptoms but also to influence cancer progression itself. In this review, we will discuss how the microbiome, specifically the gut microbiota, could affect cancer pathogenesis and what the effect of gut microbiota-targeting treatment options have on the many aspects of cancer pathologies based on the knowledge of recent years.}, }
@article {pmid32563025, year = {2020}, author = {Wang, Y and Ren, R and Sun, G and Peng, L and Tian, Y and Yang, Y}, title = {Pilot study of cytokine changes evaluation after fecal microbiota transplantation in patients with ulcerative colitis.}, journal = {International immunopharmacology}, volume = {85}, number = {}, pages = {106661}, doi = {10.1016/j.intimp.2020.106661}, pmid = {32563025}, issn = {1878-1705}, abstract = {AIMS: To evaluate the changes of serum cytokines levels after fecal microbiota transplantation (FMT) in patients with active ulcerative colitis (UC) and the correlation with UC disease activity.<br><br>METHODS: Patients with active UC who meet the inclusion and exclusion criteria were recruited, and received FMT from a single donor for three times with an interval of 2-3 months. Serum samples were collected before every FMT. Clinical responses to FMT were assessed according to the criteria of Mayo score. 41 serum cytokines, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were quantitatively detected. Changes in serum cytokines levels after FMT and their correlation with CRP, ESR and Mayo scores were investigated.<br><br>RESULTS: 16 active UC patients were enrolled, and 14(87.5%) patients achieved clinical response to FMT. Compared with those before FMT, serum concentrations of IL-1Ra, IL-6, IP-10 and ENA-78 decreased significantly after the second FMT (P < 0.05), and serum concentrations of MEC, VCAM-1 and G-CSF decreased significantly after both the first and second FMT (P < 0.05). Serum levels of IL-6, IL-1Ra and VCAM-1 were all significantly positively correlated with CRP and ESR. Serum level of IP-10 was significantly positively correlated with CRP, ESR and Mayo score. Serum level of G-CSF was significantly positively correlated with Mayo score.<br><br>CONCLUSIONS: FMT may play a therapeutic role partly through modulating the host immune response. IL-6, IL-1Ra, IP-10, VCAM-1 and G-CSF may be biomarkers to evaluate the effect of FMT on UC.}, }
@article {pmid32553109, year = {2020}, author = {Watterson, WJ and Tanyeri, M and Watson, AR and Cham, CM and Shan, Y and Chang, EB and Eren, AM and Tay, S}, title = {Droplet-based high-throughput cultivation for accurate screening of antibiotic resistant gut microbes.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32553109}, issn = {2050-084X}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; RC2 DK122394/DK/NIDDK NIH HHS/United States ; T32 DK007074/DK/NIDDK NIH HHS/United States ; 2018-2019//Samuel and Emma Winters Foundation/International ; }, abstract = {Traditional cultivation approaches in microbiology are labor-intensive, low-throughput, and yield biased sampling of environmental microbes due to ecological and evolutionary factors. New strategies are needed for ample representation of rare taxa and slow-growers that are often outcompeted by fast-growers in cultivation experiments. Here we describe a microfluidic platform that anaerobically isolates and cultivates microbial cells in millions of picoliter droplets and automatically sorts them based on colony density to enhance slow-growing organisms. We applied our strategy to a fecal microbiota transplant (FMT) donor stool using multiple growth media, and found significant increase in taxonomic richness and larger representation of rare and clinically relevant taxa among droplet-grown cells compared to conventional plates. Furthermore, screening the FMT donor stool for antibiotic resistance revealed 21 populations that evaded detection in plate-based assessment of antibiotic resistance. Our method improves cultivation-based surveys of diverse microbiomes to gain deeper insights into microbial functioning and lifestyles.}, }
@article {pmid32552337, year = {2020}, author = {Allegretti, JR and Elliott, RJ and Ladha, A and Njenga, M and Warren, K and O'Brien, K and Budree, S and Osman, M and Fischer, M and Kelly, CR and Kassam, Z}, title = {Stool processing speed and storage duration do not impact the clinical effectiveness of fecal microbiota transplantation.}, journal = {Gut microbes}, volume = {11}, number = {6}, pages = {1806-1808}, pmid = {32552337}, issn = {1949-0984}, }
@article {pmid32550753, year = {2020}, author = {Little, R and Wine, E and Kamath, BM and Griffiths, AM and Ricciuto, A}, title = {Gut microbiome in primary sclerosing cholangitis: A review.}, journal = {World journal of gastroenterology}, volume = {26}, number = {21}, pages = {2768-2780}, pmid = {32550753}, issn = {2219-2840}, abstract = {Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by biliary inflammation and stricturing. Exploration of the pathogenesis of PSC in light of its association with inflammatory bowel disease (IBD) and the &quot;gut-liver&quot; axis is an emerging area of interest. A growing number of studies have begun to elucidate the role of the gut microbiota, its metabolites and its influence on host immune responses in the development of PSC and PSC-IBD. Studies of the fecal microbiota have highlighted enriched levels of certain species, including Veillonella, Streptococcus and Enterococcus, among others. A heightened immune response to enteric dysbiosis and bacterial translocation have also been implicated. For example, Klebsiella pneumoniae strains derived from gnotobiotic mice transplanted with PSC-IBD microbiota were found to induce pore formation in human intestinal epithelial cells and enhanced Th17 responses. Gut microbes have additionally been hypothesized to be implicated in PSC pathogenesis through their role in the synthesis of various metabolites, including bile acids (BAs), which function as signaling molecules with important gut and hepatic effects. An expanded knowledge of the gut microbiome as it relates to PSC offers critical insight into the development of microbe-altering therapeutic interventions, such as antibiotics, nutritional interventions and fecal microbial transplantation. Some of these have already shown some preliminary evidence of benefit. Despite exciting progress in the field, much work remains to be done; areas that are particularly lacking include functional characterization of the microbiome and examination of pediatric populations. In this review, we summarize studies that have investigated the microbiome in PSC and PSC-IBD as well as putative mechanisms, including the potential role of metabolites, such as BAs. We then briefly review the evidence for interventions with microbe-altering properties for treating PSC.}, }
@article {pmid32548192, year = {2020}, author = {Massaro, M and Vansia, J and McGill, S}, title = {Ulcerative Proctitis in a Patient With a History of Fecal Microbiota Transplant for Clostridioides difficile Infection.}, journal = {ACG case reports journal}, volume = {7}, number = {4}, pages = {e00364}, pmid = {32548192}, issn = {2326-3253}, abstract = {Fecal microbiota transplantation (FMT) effectively treats Clostridioides difficile infection and alters the gut microbiota in the long term, but potential adverse effects are poorly understood. We report a man with a family history of ulcerative colitis who developed ulcerative proctitis within a year of FMT.}, }
@article {pmid32548190, year = {2020}, author = {Fasanello, MK and Robillard, KT and Boland, PM and Bain, AJ and Kanehira, K}, title = {Use of Fecal Microbial Transplantation for Immune Checkpoint Inhibitor Colitis.}, journal = {ACG case reports journal}, volume = {7}, number = {4}, pages = {e00360}, pmid = {32548190}, issn = {2326-3253}, abstract = {Immune checkpoint inhibitors (ICIs) can result in immune-related adverse events which require rapid identification and treatment. Gastrointestinal immune-related adverse events are among the most frequent and severe of these events. ICI colitis can be refractory to current therapies such as corticosteroids and biologic therapy. Fecal microbiota transplantation (FMT) is currently used in cases of recurrent Clostridioides difficile colitis. Many investigations are underway to test the utility of FMT for additional indications, including inflammatory bowel disease (IBD). We present a 71-year-old man with ICI colitis that was nonresponsive to currently defined management options and treated with benefit from FMT.}, }
@article {pmid32539741, year = {2020}, author = {Chinna Meyyappan, A and Forth, E and Wallace, CJK and Milev, R}, title = {Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review.}, journal = {BMC psychiatry}, volume = {20}, number = {1}, pages = {299}, pmid = {32539741}, issn = {1471-244X}, abstract = {BACKGROUND: The Gut-Brain-Axis is a bidirectional signaling pathway between the gastrointestinal (GI) tract and the brain. The hundreds of trillions of microorganisms populating the gastrointestinal tract are thought to modulate this connection, and have far reaching effects on the immune system, central and autonomic nervous systems, and GI functioning. These interactions Diagnostic and statistical manual of mental disorders have also been linked to various psychiatric illnesses such as depression, anxiety, substance abuse, autism spectrum disorder, and eating disorders. It is hypothesized that techniques aimed at strengthening and repopulating the gut microbiome, such as Fecal Microbiota Transplant (FMT), may be useful in the prevention and treatment of psychiatric illnesses.<br><br>METHODS: A systematic search of five databases was conducted using key terms related to FMT and psychiatric illnesses. All results were then evaluated based on specific eligibility criteria.<br><br>RESULTS: Twenty-one studies met the eligibility criteria and were analysed for reported changes in mood and behavioural measures indicative of psychiatric wellbeing. The studies included were either entirely clinical (n = 8), preclinical with human donors (n = 9), or entirely preclinical (n = 11). All studies found a decrease in depressive and anxiety-like symptoms and behaviours resulting from the transplantation of healthy microbiota. The inverse was also found, with the transmission of depressive and anxiety-like symptoms and behaviours resulting from the transplantation of microbiota from psychiatrically ill donors to healthy recipients.<br><br>CONCLUSION: There appears to be strong evidence for the treatment and transmission of psychiatric illnesses through FMT. Further research with larger sample sizes and stronger scientific design is warranted in order to fully determine the efficacy and safety of this potential treatment. Registered on PROSPERO, IRD: CRD42019126795.}, }
@article {pmid32537754, year = {2020}, author = {Wong, SH and Yu, J}, title = {Proton-pump inhibitor use before fecal microbiota transplant: A wonder drug, a necessary evil, or a needless prescription?.}, journal = {Journal of gastroenterology and hepatology}, volume = {35}, number = {6}, pages = {913-914}, doi = {10.1111/jgh.15103}, pmid = {32537754}, issn = {1440-1746}, }
@article {pmid32535631, year = {2020}, author = {Uchiyama, K and Wakino, S and Irie, J and Miyamoto, J and Matsui, A and Tajima, T and Itoh, T and Oshima, Y and Yoshifuji, A and Kimura, I and Itoh, H}, title = {Contribution of uremic dysbiosis to insulin resistance and sarcopenia.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {35}, number = {9}, pages = {1501-1517}, doi = {10.1093/ndt/gfaa076}, pmid = {32535631}, issn = {1460-2385}, abstract = {BACKGROUND: Chronic kidney disease (CKD) leads to insulin resistance (IR) and sarcopenia, which are associated with a high mortality risk in CKD patients; however, their pathophysiologies remain unclear. Recently, alterations in gut microbiota have been reported to be associated with CKD. We aimed to determine whether uremic dysbiosis contributes to CKD-associated IR and sarcopenia.<br><br>METHODS: CKD was induced in specific pathogen-free mice via an adenine-containing diet; control animals were fed a normal diet. Fecal microbiota transplantation (FMT) was performed by oral gavage in healthy germ-free mice using cecal bacterial samples obtained from either control mice (control-FMT) or CKD mice (CKD-FMT). Vehicle mice were gavaged with sterile phosphate-buffered saline. Two weeks after inoculation, mice phenotypes, including IR and sarcopenia, were evaluated.<br><br>RESULTS: IR and sarcopenia were evident in CKD mice compared with control mice. These features were reproduced in CKD-FMT mice compared with control-FMT and vehicle mice with attenuated insulin-induced signal transduction and mitochondrial dysfunction in skeletal muscles. Intestinal tight junction protein expression and adipocyte sizes were lower in CKD-FMT mice than in control-FMT mice. Furthermore, CKD-FMT mice showed systemic microinflammation, increased concentrations of serum uremic solutes, fecal bacterial fermentation products and elevated lipid content in skeletal muscle. The differences in gut microbiota between CKD and control mice were mostly consistent between CKD-FMT and control-FMT mice.<br><br>CONCLUSIONS: Uremic dysbiosis induces IR and sarcopenia, leaky gut and lipodystrophy.}, }
@article {pmid32535405, year = {2020}, author = {Liu, L and Wang, Q and Wu, X and Qi, H and Das, R and Lin, H and Shi, J and Wang, S and Yang, J and Xue, Y and Mao, D and Luo, Y}, title = {Vancomycin exposure caused opportunistic pathogens bloom in intestinal microbiome by simulator of the human intestinal microbial ecosystem (SHIME).}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {265}, number = {Pt B}, pages = {114399}, doi = {10.1016/j.envpol.2020.114399}, pmid = {32535405}, issn = {1873-6424}, mesh = {Dysbiosis ; Ecosystem ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Vancomycin ; }, abstract = {Antibiotics are emerging organic pollutants posing high health risks to humans by causing human intestinal microbial disorders with increasing abundances of opportunistic pathogens, and fecal microbiota transplantation (FMT) has been confirmed to restore the dysbiosis of gut flora in many kinds of intestinal disease. However, to date, few studies have focused on the bloomed opportunistic pathogens associated human disease-related pathways as well as antibiotic resistance genes (ARGs) after vancomycin exposure, and there is limited information on using FMT for restoration of intestinal microbiome affected by antibiotics. Therefore, this study investigated effects of vancomycin on the opportunistic pathogens, human disease-related pathways as well as ARGs in human gut, and the restoration of intestinal microbiome by FMT. Results indicated that vancomycin treatment substantially increased human disease-related pathways and decreased abundances of ARGs. Besides, the bloomed opportunistic pathogens including Achromobacter, Klebsiella, and Pseudomonas, caused by vancomycin exposure, were positively correlated with human disease-related pathways. The microbiota abundance and genes of human disease-related pathways and antibiotic resistance showed a remarkable return towards baseline after FMT, but not for natural recovery. These findings suggest that impacts of vancomycin on human gut are profound and FMT will be a promising strategy in clinical application that can restore the dysbiosis of gut microbiota, which may be valuable for directing future work.}, }
@article {pmid32529941, year = {2020}, author = {Li, X and He, C and Li, N and Ding, L and Chen, H and Wan, J and Yang, X and Xia, L and He, W and Xiong, H and Shu, X and Zhu, Y and Lu, N}, title = {The interplay between the gut microbiota and NLRP3 activation affects the severity of acute pancreatitis in mice.}, journal = {Gut microbes}, volume = {11}, number = {6}, pages = {1774-1789}, pmid = {32529941}, issn = {1949-0984}, abstract = {Early dysbiosis of the gut microbiota is associated with the severity of acute pancreatitis (AP), although the underlying mechanism is unclear. Here, we investigated the role of crosstalk between NLRP3 and the gut microbiota in the development of AP utilizing gut microbiota deficient mice, as well as NLRP3 knockout (KO) mouse models. Pancreatic damage and systemic inflammation were improved in antibiotic-treated (Abx) and germ-free (GF) mice, accompanied by weakened activity of the intestinal NLRP3 inflammasome. Interestingly, fecal microbiota transplantation (FMT) reactivated the intestinal NLRP3 inflammasome and exacerbated the disease in Abx and GF mice. Although the gut barrier in GF and Abx mice was disrupted, gut microbiota deficiency ameliorated the severity of AP, probably due to the reduction in bacterial translocation from the gut to the pancreas. The composition of the gut microbiota was significantly different between NLRP3 KO mice and wild-type (WT) mice at baseline, and there were alterations in response to the induction of AP. While a dramatic shift in the gut microbiota with overgrowth of Escherichia-Shigella was observed in WT mice suffering from AP, there was no significant change in NLRP3 KO mice with or without AP, suggesting that NLRP3 deficiency counteracts AP-induced microbial disturbance. With a strengthened gut barrier and decreased systemic inflammation, NLRP3 KO mice showed less severe AP, as revealed by reduced pancreatic neutrophilic infiltration and necrosis. Taken together, these results identified the bidirectional modulation between the gut microbiota and NLRP3 in the progression of AP, which suggests the interplay of the host and microbiome during AP.}, }
@article {pmid32527171, year = {2020}, author = {Biernat, MM and Urbaniak-Kujda, D and Dybko, J and Kapelko-Słowik, K and Prajs, I and Wróbel, T}, title = {Fecal microbiota transplantation in the treatment of intestinal steroid-resistant graft-versus-host disease: two case reports and a review of the literature.}, journal = {The Journal of international medical research}, volume = {48}, number = {6}, pages = {300060520925693}, pmid = {32527171}, issn = {1473-2300}, abstract = {Acute graft-versus-host disease (aGvHD) reduces the efficiency and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, attempts have been made to transplant fecal microbiota from healthy donors to treat intestinal GvHD. This study presented two cases of patients undergoing allo-HSCT who were later selected for fecal microbiota transplantation (FMT). In the first patient, FMT resulted in the complete resolution of symptoms, whereas therapeutic efficacy was not achieved in the second patient. FMT eliminated drug-resistant pathogens, namely very drug-resistant Enterococcus spp., but not multidrug-resistant Acinetobacter baumannii or Candida spp. Further research is needed, particularly on the safety of FMT in patients with intestinal steroid-resistant GvHD and on the distant impact of transplanted microflora on the outcomes of allo-HSCT. FMT appears promising for the treatment of patients with steroid-resistant GvHD.}, }
@article {pmid32523094, year = {2020}, author = {Pérez-Matute, P and Íñiguez, M and de Toro, M and Recio-Fernández, E and Oteo, JA}, title = {Autologous fecal transplantation from a lean state potentiates caloric restriction effects on body weight and adiposity in obese mice.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9388}, doi = {10.1038/s41598-020-64961-x}, pmid = {32523094}, issn = {2045-2322}, abstract = {Autologous fecal transplantation (FT-A) emerges as a promising strategy to modulate gut microbiota with minimal side effects since individual´s own feces are transplanted. With the premise of improving obesity and its associated disorders, we investigated if fecal microbiota transplantation (FMT), heterologous and autologous, potentiates the effects of a moderate caloric restriction (CR) in high-fat diet (HFD)-induced obese mice. Mice were randomized into control, HFD, CR (12 weeks on HFD and 6 weeks under CR), FT-H (similar to CR and FMT carried out with feces from controls, weeks 17 &amp; 18), and FT-A (administration of their own feces before developing obesity at weeks 17 &amp; 18). Our study demonstrated that FMT, and, especially, FT-A potentiates the effects of a moderate CR on weight loss and adiposity in the short term, by decreasing feed efficiency and increasing adipose tissue lipolysis. Although FT-A produced a significant increase in bacterial richness/diversity, FMT did not significantly modify gut microbiota composition compared to the CR at phyla and bacteria genera levels, and only significant increases in Bifidobacterium and Blautia genera were observed. These results could suggest that other mechanisms different from bacterial microbiota engraftment participates in these beneficial effects. Thus, FT-A represents a very positive synergetic approach for obese patients that do not respond well to moderate restrictive diets.}, }
@article {pmid32519746, year = {2020}, author = {Su, X and Zhao, Y and Li, Y and Ma, S and Wang, Z}, title = {Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis.}, journal = {Clinical science (London, England : 1979)}, volume = {134}, number = {12}, pages = {1521-1535}, doi = {10.1042/CS20200475}, pmid = {32519746}, issn = {1470-8736}, mesh = {Adult ; Animals ; Case-Control Studies ; Dysbiosis/*complications ; Fatty Acids/metabolism ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*pathology ; Humans ; Hypothyroidism/*complications ; Male ; Metagenomics ; Mice, Inbred BALB C ; Phylogeny ; ROC Curve ; Thyroid Gland/*pathology ; }, abstract = {Background Previous studies have shown that the gut microbiome is associated with thyroid diseases, including Graves' disease, Hashimoto's disease, thyroid nodules, and thyroid cancer. However, the association between intestinal flora and primary hypothyroidism remains elusive. We aimed to characterize gut microbiome in primary hypothyroidism patients. Methods Fifty-two primary hypothyroidism patients and 40 healthy controls were recruited. The differences in gut microbiota between the two groups were analyzed by 16S rRNA sequencing technology. Fecal microbiota transplantation (FMT) was performed in mice using flora from both groups; changes in thyroid function were then assessed in the mice. Results There were significant differences in α and β diversities of gut microbiota between primary hypothyroidism patients and healthy individuals. The random forest analysis indicated that four intestinal bacteria (Veillonella, Paraprevotella, Neisseria, and Rheinheimera) could distinguish untreated primary hypothyroidism patients from healthy individuals with the highest accuracy; this was confirmed by receiver operator characteristic curve analysis. The short chain fatty acid producing ability of the primary hypothyroidism patients' gut was significantly decreased, which resulted in the increased serum lipopolysaccharide (LPS) levels. The FMT showed that mice receiving the transplant from primary hypothyroidism patients displayed decreased total thyroxine levels. Conclusions Our study suggests that primary hypothyroidism causes changes in gut microbiome. In turn, an altered flora can affect thyroid function in mice. These findings could help understand the development of primary hypothyroidism and might be further used to develop potential probiotics to facilitate the adjuvant treatment of this disease.}, }
@article {pmid32518854, year = {2020}, author = {Kates, AE and Gaulke, I and De Wolfe, T and Zimbric, M and Haight, K and Watson, L and Suen, G and Kim, K and Safdar, N}, title = {Fecal microbiota transplantation for patients on antibiotic treatment with C. difficile infection history (GRAFT): Study protocol for a phase II, randomized, double-blind, placebo-controlled trial to prevent recurrent C. difficile infections.}, journal = {Contemporary clinical trials communications}, volume = {18}, number = {}, pages = {100576}, pmid = {32518854}, issn = {2451-8654}, support = {R03 HS025257/HS/AHRQ HHS/United States ; }, abstract = {Recurrent Clostridiodes difficile infections (rCDIs) are a burdensome problem. Patients with a history of CDI that are prescribed antibiotics are at a high risk for recurrence. Fecal microbiota transplantation (FMT) has been shown to be an effective treatment for rCDI, though there is little information on the impact of FMT with antibiotics on the gut microbiome. We are conducting a clinical trial of FMT to prevent rCDI in patients with a history of CDI currently taking antibiotics. Our primary objective is to determine the effect of FMT on the gut microbiome during antibiotic exposure. Our secondary aim is to assess safety and feasibility of using FMT as a prophylaxis for CDI. We plan to enroll 30 patients into a phase II randomized, double-blind, placebo-controlled trial with three arms: (1) 5 FMT capsules per day during antibiotic treatment and for 7 days post antibiotic cessation, (2) a one-time dose of 30 FMT capsules 48-72 h post cessation of antibiotic treatment, or (3) 5 placebo capsules per day during antibiotic treatment and for 7 days post antibiotic treatment. Patients provide stool samples throughout the duration of the study and are cultured C. difficile. Sequencing of the V4 region of the 16S rRNA gene will be carried out to assess the gut microbiota. Results of this study will provide information on the impact of FMT on the gut microbiome as well as the necessary data to examine whether or not prophylactic FMT should be explored further as a way to prevent CDI recurrence.}, }
@article {pmid32517023, year = {2020}, author = {Bibbò, S and Settanni, CR and Porcari, S and Bocchino, E and Ianiro, G and Cammarota, G and Gasbarrini, A}, title = {Fecal Microbiota Transplantation: Screening and Selection to Choose the Optimal Donor.}, journal = {Journal of clinical medicine}, volume = {9}, number = {6}, pages = {}, pmid = {32517023}, issn = {2077-0383}, abstract = {In the past decade, fecal microbiota transplantation (FMT) has rapidly spread worldwide in clinical practice as a highly effective treatment option against recurrent Clostridioides difficile infection. Moreover, new evidence also supports a role for FMT in other conditions, such as inflammatory bowel disease, functional gastrointestinal disorders, or metabolic disorders. Recently, some studies have identified specific microbial characteristics associated with clinical improvement after FMT, in different disorders, paving the way for a microbiota-based precision medicine approach. Moreover, donor screening has become increasingly more complex over years, along with standardization of FMT and the increasing number of stool banks. In this narrative review, we discuss most recent evidence on the screening and selection of the stool donor, with reference to recent studies that have identified specific microbiological features for clinical conditions such as Clostridioides difficile infection, irritable bowel syndrome, inflammatory bowel disease, and metabolic disorders.}, }
@article {pmid32516027, year = {2020}, author = {Zoll, J and Read, MN and Heywood, SE and Estevez, E and Marshall, JPS and Kammoun, HL and Allen, TL and Holmes, AJ and Febbraio, MA and Henstridge, DC}, title = {Fecal microbiota transplantation from high caloric-fed donors alters glucose metabolism in recipient mice, independently of adiposity or exercise status.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {319}, number = {1}, pages = {E203-E216}, doi = {10.1152/ajpendo.00037.2020}, pmid = {32516027}, issn = {1522-1555}, abstract = {Studies suggest the gut microbiota contributes to the development of obesity and metabolic syndrome. Exercise alters microbiota composition and diversity and is protective of these maladies. We tested whether the protective metabolic effects of exercise are mediated through fecal components through assessment of body composition and metabolism in recipients of fecal microbiota transplantation (FMT) from exercise-trained (ET) mice fed normal or high-energy diets. Donor C57BL/6J mice were fed a chow or high-fat, high-sucrose diet (HFHS) for 4 wk to induce obesity and glucose intolerance. Mice were divided into sedentary (Sed) or ET groups (6 wk treadmill-based ET) while maintaining their diets, resulting in four donor groups: chow sedentary (NC-Sed) or ET (NC-ET) and HFHS sedentary (HFHS-Sed) or ET (HFHS-ET). Chow-fed recipient mice were gavaged with feces from the respective donor groups weekly, creating four groups (NC-Sed-R, NC-ET-R, HFHS-Sed-R, HFHS-ET-R), and body composition and metabolism were assessed. The HFHS diet led to glucose intolerance and obesity in the donors, whereas exercise training (ET) restrained adiposity and improved glucose tolerance. No donor group FMT altered recipient body composition. Despite unaltered adiposity, glucose levels were disrupted when challenged in mice receiving feces from HFHS-fed donors, irrespective of donor-ET status, with a decrease in insulin-stimulated glucose clearance into white adipose tissue and large intestine and specific changes in the recipient's microbiota composition observed. FMT can transmit HFHS-induced disrupted glucose metabolism to recipient mice independently of any change in adiposity. However, the protective metabolic effect of ET on glucose metabolism is not mediated through fecal factors.}, }
@article {pmid32514151, year = {2020}, author = {Fong, W and Li, Q and Yu, J}, title = {Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer.}, journal = {Oncogene}, volume = {39}, number = {26}, pages = {4925-4943}, pmid = {32514151}, issn = {1476-5594}, support = {81972576//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Research about the role of gut microbiome in colorectal cancer (CRC) is a newly emerging field of study. Gut microbiota modulation, with the aim to reverse established microbial dysbiosis, is a novel strategy for prevention and treatment of CRC. Different strategies including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT) have been employed. Although these strategies show promising results, mechanistically by correcting microbiota composition, modulating innate immune system, enhancing gut barrier function, preventing pathogen colonization and exerting selective cytotoxicity against tumor cells, it should be noted that they are accompanied by risks and controversies that can potentially introduce clinical complications. During bench-to-bedside translation, evaluation of risk-and-benefit ratio, as well as patient selection, should be carefully performed. In view of the individualized host response to gut microbiome intervention, developing personalized microbiome therapy may be the key to successful clinical treatment.}, }
@article {pmid32511695, year = {2020}, author = {Bar-Yoseph, H and Carasso, S and Shklar, S and Korytny, A and Even Dar, R and Daoud, H and Nassar, R and Maharshak, N and Hussein, K and Geffen, Y and Chowers, Y and Geva-Zatorsky, N and Paul, M}, title = {Oral capsulized Fecal microbiota transplantation for eradication of carbapenemase-producing Enterobacteriaceae colonization with a metagenomic perspective.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa737}, pmid = {32511695}, issn = {1537-6591}, abstract = {BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) infections lead to considerable morbidity and mortality. We assessed the potential of fecal microbiota transplantation (FMT) to eradicate CPE carriage and aimed to explain failure or success through microbiome analyses.<br><br>METHODS: In this prospective cohort study, all consenting eligible CPE carriers were treated with oral capsulized FMT for 2 days. The primary outcome was CPE eradication at 1 month, defined by 3 consecutive negative rectal swabs, the last also negative for carbapenemase gene by PCR. Comprehensive metagenomics analysis of the intestinal microbiome of donors and recipients before and after FMT was performed.<br><br>RESULTS: Fifteen CPE carriers received FMT, 13 of which completed 2 days of treatment. CPE eradication at 1 month was successful in 9/15 and 9/13, respectively. Bacterial communities showed significant changes in both beta and alpha diversity metrics among participants achieving CPE eradication that were not observed among failures. Post-FMT samples' beta-diversity clustered according to the treatment outcome, both in taxonomy and in function. We observed a significant decrease in beta diversity in participants who received post-FMT antibiotics. Enterobacteriaceae abundance decreased in post-FMT samples of the responders, but increased among failures. Functionally, a clear demarcation between responders (who were similar to the donors) and failures was shown, driven by antimicrobial resistance genes.<br><br>CONCLUSION: Our study provides the biological explanation for the effect of FMT against CPE carriage. Decolonization of CPE by FMT is likely mediated by compositional and functional shifts in the microbiome. Thus, FMT might be an efficient strategy for sustained CPE eradication.}, }
@article {pmid32509162, year = {2020}, author = {Wang, H and Zhou, C and Huang, J and Kuai, X and Shao, X}, title = {The potential therapeutic role of Lactobacillus reuteri for treatment of inflammatory bowel disease.}, journal = {American journal of translational research}, volume = {12}, number = {5}, pages = {1569-1583}, pmid = {32509162}, issn = {1943-8141}, abstract = {Inflammatory bowel disease (IBD) is a chronic intestinal disease of unknown etiology. However, recent studies have established a pathological role of disordered intestinal microbiota and immune dysregulation. Clinical studies have suggested that the reconstruction of the normal intestinal flora in patients with IBD can reverse the dysbiosis caused by genetic, environmental, dietary, or antibiotic factors to ameliorate the symptoms of IBD. Lactobacillus reuteri is widely present in the intestines of healthy individuals and regulates the intestinal immune system, reducing inflammation through multiple mechanisms. This review summarizes the current knowledge of the role of L. reuteri in maintaining intestinal homeostasis and considers its possible value as a new therapeutic agent for patients with IBD.}, }
@article {pmid32508773, year = {2020}, author = {Liu, H and Wang, HH}, title = {Impact of Microbiota Transplant on Resistome of Gut Microbiota in Gnotobiotic Piglets and Human Subjects.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {932}, pmid = {32508773}, issn = {1664-302X}, abstract = {Microbiota transplant is becoming a popular process to restore or initiate &quot;healthy&quot; gut microbiota and immunity. But, the potential risks of the related practices need to be carefully evaluated. This study retrospectively examined the resistomes of donated fecal microbiota for treating intestinal disorders, vaginal microbiota of pregnant women, and infant fecal microbiota from rural and urban communities, as well as the impact of transplants on the fecal resistome of human and animal recipients. Antibiotic resistance (AR) genes were found to be abundant in all donor microbiota. An overall surge of resistomes with higher prevalence and abundance of AR genes was observed in the feces of all transplanted gnotobiotic pigs as well as in the feces of infant subjects, compared to those in donor fecal and maternal vaginal microbiota. Surprisingly, transplants using rural Amish microbiota led to more instead of less AR genes in the fecal microbiota of gnotobiotic pigs than did transplants using urban microbiota. New AR gene subtypes undetected originally also appeared in gnotobiotic pigs, in Crohn's Disease (CD) patients after transplant, and in feces of infant subjects. The data illustrated the key role of the host gastrointestinal tract system in amplifying the ever-increasing AR gene pool, even without antibiotic exposure. The data further suggest that the current approaches of microbiota transplant can introduce significant health risk factor(s) to the recipients, and newborn human and animal hosts with naïve gut microbiota were especially susceptible. Given the illustrated public health risks of microbiota transplant, minimizing massive and unnecessary damages to gut microbiota by oral antibiotics and other gut impacting drugs becomes important. Since eliminating risk factors including AR bacteria and opportunistic pathogens directly from donor microbiota is still difficult to achieve, developing microbial cocktails with defined organisms and functions has further become an urgent need, should microbiota transplantation become necessary.}, }
@article {pmid32501140, year = {2020}, author = {Reygner, J and Charrueau, C and Delannoy, J and Mayeur, C and Robert, V and Cuinat, C and Meylheuc, T and Mauras, A and Augustin, J and Nicolis, I and Modoux, M and Joly, F and Waligora-Dupriet, AJ and Thomas, M and Kapel, N}, title = {Freeze-dried fecal samples are biologically active after long-lasting storage and suited to fecal microbiota transplantation in a preclinical murine model of Clostridioides difficile infection.}, journal = {Gut microbes}, volume = {11}, number = {5}, pages = {1405-1422}, pmid = {32501140}, issn = {1949-0984}, abstract = {Fecal microbiota transplantation is now recommended for treating recurrent forms of Clostridioides difficile infection. Recent studies have reported protocols using capsules of either frozen or freeze-dried stool allowing oral administration in in- and out-patient settings. However, a central question remains the viability, engraftment, and efficacy of the microbiome over time during storage life. This study shows that both the freeze-drying and freezing procedures for fecal samples allowed preserving viability, short-chain fatty acids concentration, and anti-Clostridioides difficile properties of microbiota without significant alteration after storage for 12 months. Fecal transplantation with freeze-dried microbiota allowed engraftment of microbiota leading to clearance of Clostridioides difficile infection in a preclinical murine model with a survival rate of 70% versus 53-60% in mice treated with frozen inocula, and 20% in the untreated group. Moreover, the freeze-dried powder can be used to fill oral hard capsules using a very low amount (0.5%) of glidant excipient, allowing oral formulation. Altogether, this study showed that freeze-dried inocula can be used for the treatment of Clostridioides difficile infection with long-lasting stability of the fecal microbiota. This formulation facilitates biobanking and allows the use of hard capsules, an essential step to simplify patient access to treatment.}, }
@article {pmid32500988, year = {2020}, author = {Piekarska, A and Panasiuk, A and Stępień, PM}, title = {Clinical practice guidelines for Clostridioides (Clostridium) difficile infection and fecal microbiota transplant protocol - recommendations of the Polish Society od Epidemiology and Infectious Diseases.}, journal = {Przeglad epidemiologiczny}, volume = {74}, number = {1}, pages = {69-87}, doi = {10.32394/pe.74.06}, pmid = {32500988}, issn = {0033-2100}, abstract = {Symptomatic Clostridium difficile infection (CDI) is an acute inflammatory disease of the gastrointestinal tract, manifesting in at least 3 unformed stools within 24 hours. Predicting factors for CDI include contact with medical care (mainly hospitalization), antibiotic therapy in the last 12 weeks, use of proton pump inhibitors (PPI), H2 blockers, cancer chemotherapy, especially in the neutropenia stage, gastrointestinal surgery, advanced age and concomitant chronic diseases (renal failure, liver failure, chronic inflammatory bowel disease - especially ulcerative bowel disease, cancer, HIV infection, cachexia and hypoalbuminaemia) and vitamin D deficiency. Clinical classification distinguishes three types of CDI - mild / moderate, severe, and fulminant. The principles of treatment of the first and subsequent CDI incidents depending on the clinical course are based on oral vancomycin. CDI is recurrent. The basis for treating CDI relapses is vancomycin administered orally at a dose of 4x125 mg for 10 days followed by concomitant vancomycin dose reduction therapy. The use of fecal microbiota transfer (FMT) in the treatment of CDI relapses is considered to be the most effective therapy for recurrent CDI. An indication for FMT is antibiotic-resistant C. difficile infection, regardless of the number of incidents CDI. The panel of tests recommended for a bacterial flora donor is presented in the recommendations.}, }
@article {pmid32499711, year = {2020}, author = {Cheung, MK and Yue, GGL and Chiu, PWY and Lau, CBS}, title = {A Review of the Effects of Natural Compounds, Medicinal Plants, and Mushrooms on the Gut Microbiota in Colitis and Cancer.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {744}, pmid = {32499711}, issn = {1663-9812}, abstract = {The human gastrointestinal tract harbors a diverse array of microorganisms that play fundamental roles in health and disease. Imbalance in the gut microbiota, namely dysbiosis, can lead to various diseases, including cancer and gastrointestinal tract disorders. Approaches to improve gut dysbiosis, such as dietary intervention, intake of probiotics, and fecal microbiota transplantation are emerging strategies to treat these diseases. Various medicinal botanicals have reported anti-cancer and/or anti-inflammatory properties. Preclinical studies have illustrated that some of these natural products are also capable to modulate the gut microbiota, suggesting their use as possible alternative approach to improve gut dysbiosis and thereby assist diseases treatment. In this review article, we have summarized the current knowledge on the effects of natural compounds, medicinal plants, and mushrooms on the gut microbiota in various cancers and colitis in preclinical animal models. Challenges towards the clinical use of these medicinal botanicals as modulators of the gut microbiota in cancer and colitis treatment are also discussed.}, }
@article {pmid32499362, year = {2020}, author = {Simpson, E and Sanjar, F and Wylie, D and Park, S and Koh, H and Bae, J and Kook, SY and Kim, S and Kim, HJ}, title = {Draft Genome Sequences of Two Strains of Bifidobacterium dentium Isolated from a Crude Fecal Extract Used for Fecal Microbiota Transplantation in the Republic of Korea.}, journal = {Microbiology resource announcements}, volume = {9}, number = {23}, pages = {}, pmid = {32499362}, issn = {2576-098X}, abstract = {We present the draft genome sequences of two Bifidobacterium dentium strains isolated from a fecal extract for fecal microbiota transplantation at a hospital in the Republic of Korea. Phylogenetic and functional analyses were performed to understand the physiological characteristics and functions of Bifidobacterium spp. in the human intestine.}, }
@article {pmid32496421, year = {2020}, author = {Assimakopoulos, SF and Papadopoulou, I and Bantouna, D and de Lastic, AL and Rodi, M and Mouzaki, A and Gogos, CA and Zolota, V and Maroulis, I}, title = {Fecal Microbiota Transplantation and Hydrocortisone Ameliorate Intestinal Barrier Dysfunction and Improve Survival in a Rat Model of Cecal Ligation and Puncture-Induced Sepsis.}, journal = {Shock (Augusta, Ga.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/SHK.0000000000001566}, pmid = {32496421}, issn = {1540-0514}, abstract = {INTRODUCTION: Sepsis is a life-threatening syndrome which can progress to multiple organ dysfunction with high mortality. Intestinal barrier failure exerts a central role in the pathophysiological sequence of events that lead from sepsis to multiple organ dysfunction. The present study investigated the role of hydrocortisone (HC) administration and fecal microbiota transplantation (FMT) in several parameters of the gut barrier integrity, immune activation and survival, in a model of polymicrobial sepsis in rats.<br><br>METHODS: Forty adults male Wistar rats were randomly divided into four groups: sham (group I), cecal ligation and puncture (CLP) (group II), CLP + HC (2.8 mg/kg, intraperitoneally single dose at 6 hours) (group III) and CLP + FMT at 6 hours (group IV). At 24 h post-CLP, ileal tissues were harvested for histological and immunohistochemical analyses while endotoxin, IL-6 and IL-10 levels in systemic circulation were determined. In a second experiment the same groups were observed for seven days for mortality, with daily administration of hydrocortisone (group III) and FMT (group IV) in surviving rats.<br><br>RESULTS: HC administration and FMT significantly reduced mortality of septic rats by 50%. These interventions totally reversed intestinal mucosal atrophy by increasing villous density and mucosal thickness (μm, mean ± SD: Group I: 620 ± 35, Group II: 411 ± 52, Group III: 622 ± 19, Group IV:617 ± 44). HC and FMT reduced the apoptotic body count in intestinal crypts whereas increased the mitotic/apoptotic index. Activated caspase-3 expression in intestinal crypts was significantly reduced by HC or FMT (activated caspase-3 (+) enterocytes/10 crypts, mean ± SD: Group I: 1,6 ± 0,5, Group II: 5,8 ± 2,4, Group III: 3,6 ± 0,9, Group IV:2,3 ± 0,6). Both treatments increased Paneth cell count and decreased intraepithelial CD3(+) T lymphocytes and inflammatory infiltration of lamina propria to control levels. In the sham group almost the total of intestinal epithelial cells expressed occludin (92 ± 8%) and claudin-1 (98 ± 4%) and CLP reduced this expression to 34 ± 12% for occludin and 35 ± 7% for claudin-1. Administration of HC significantly increased occludin (51 ± 17%) and claudin-1 (77 ± 9%) expression. FMT exerted also a significant restoring effect in TJ by increasing occludin (56 ± 15%) and claudin-1 (84 ± 7%) expression. The beneficial effects of these treatments on gut barrier function led to significant reduction of systemic endotoxemia (EU/ml, mean ± SD: Group I: 0,93 ± 0,36, Group II: 2,14 ± 1,74, Group III: 1,48 ± 0,53, Group IV: 1,61 ± 0,58,), while FMT additionally decreased IL-6 and IL-10 levels.<br><br>CONCLUSION: Fecal microbiota transplantation and stress dose hydrocortisone administration in septic rats induce a multifactorial improvement of the gut mechanical and immunological barriers, preventing endotoxemia and leading to improved survival.}, }
@article {pmid32495834, year = {2020}, author = {Rasmussen, TS and Koefoed, AK and Jakobsen, RR and Deng, L and Castro-Mejía, JL and Brunse, A and Neve, H and Vogensen, FK and Nielsen, DS}, title = {Bacteriophage-mediated manipulation of the gut microbiome - promises and presents limitations.}, journal = {FEMS microbiology reviews}, volume = {44}, number = {4}, pages = {507-521}, doi = {10.1093/femsre/fuaa020}, pmid = {32495834}, issn = {1574-6976}, abstract = {Gut microbiome (GM) composition and function are linked to human health and disease, and routes for manipulating the GM have become an area of intense research. Due to its high treatment efficacy, the use of fecal microbiota transplantation (FMT) is generally accepted as a promising experimental treatment for patients suffering from GM imbalances (dysbiosis), e.g. caused by recurrent Clostridioides difficile infections (rCDI). Mounting evidence suggests that bacteriophages (phages) play a key role in successful FMT treatment by restoring the dysbiotic bacterial GM. As a refinement to FMT, removing the bacterial component of donor feces by sterile filtration, also referred to as fecal virome transplantation (FVT), decreases the risk of invasive infections caused by bacteria. However, eukaryotic viruses and prophage-encoded virulence factors remain a safety issue. Recent in vivo studies show how cascading effects are initiated when phage communities are transferred to the gut by e.g. FVT, which leads to changes in the GM composition, host metabolome, and improve host health such as alleviating symptoms of obesity and type-2-diabetes (T2D). In this review, we discuss the promises and limitations of FVT along with the perspectives of using FVT to treat various diseases associated with GM dysbiosis.}, }
@article {pmid32495743, year = {2020}, author = {Chinna Meyyappan, A and Milev, R}, title = {The Safety, Efficacy, and Tolerability of Microbial Ecosystem Therapeutic-2 in People With Major Depression and/or Generalized Anxiety Disorder: Protocol for a Phase 1, Open-Label Study.}, journal = {JMIR research protocols}, volume = {9}, number = {6}, pages = {e17223}, pmid = {32495743}, issn = {1929-0748}, abstract = {BACKGROUND: The bidirectional signaling between the gut microbiota and the brain, known as the gut-brain axis, is being heavily explored in current neuropsychiatric research. Analyses of the human gut microbiota have shown considerable individual variability in bacterial content, which is hypothesized to influence brain function, and potentially mood and anxiety symptoms, through gut-brain axis communication. Preclinical and clinical research examining these effects suggests that fecal microbiota transplant (FMT) may aid in improving the severity of depression and anxiety symptoms by recolonizing the gastrointestinal (GI) tract with healthy bacteria. The microbial ecosystem therapeutic (ie, microbial ecosystem therapeutic-2 [MET-2]) used in this study is an alternative treatment to FMT, which comprises 40 different strains of gut bacteria from a healthy donor.<br><br>OBJECTIVE: The primary objective of this study is to assess subjective changes in mood and anxiety symptoms before, during, and after administration of MET-2. The secondary objectives of this study are to assess the changes in metabolic functioning and the level of repopulation of healthy gut bacteria, the safety and tolerability of MET-2, and the effects of early stress on biomarkers of depression/anxiety and the response to treatment.<br><br>METHODS: Adults experiencing depressive or anxiety symptoms will be recruited from the Kingston area. These participants will orally consume an encapsulated MET-2 once daily-containing 40 strains of purified and laboratory-grown bacteria from a single healthy donor-for 8 weeks, followed by a 2-week treatment-free follow-up period. Participants will undergo a series of clinical assessments measuring mood, anxiety, and GI symptoms using validated clinical scales and questionnaires. Molecular data will be collected from blood and fecal samples to assess metabolic changes, neurotransmitter levels, inflammatory markers, and the level of engraftment of the fecal samples that may predict outcomes in depression or anxiety.<br><br>RESULTS: Given the association between the gut bacteria and the risk factors of depression, we expect to observe an improvement in the severity of depressive and anxiety symptoms following treatment, and we expect that this improvement is mediated by the recolonization of the GI tract with healthy bacteria. The recruitment for this study has been completed, and the data obtained are currently being analyzed.<br><br>CONCLUSIONS: This is the first time MET-2 is being tested in psychiatric indications, specifically depression and anxiety. As such, this may be the first study to show the potential effects of microbial therapy in alleviating psychiatric symptoms as well as its safety and tolerability.<br><br>DERR1-10.2196/17223.}, }
@article {pmid32493442, year = {2020}, author = {Trang-Poisson, C and Kerdreux, E and Poinas, A and Planche, L and Sokol, H and Bemer, P and Cabanas, K and Hivernaud, E and Biron, L and Flet, L and Montassier, E and Le Garcasson, G and Chiffoleau, A and Jobert, A and Lepelletier, D and Caillon, J and Le Pape, P and Imbert, BM and Bourreille, A}, title = {Impact of fecal microbiota transplantation on chronic recurrent pouchitis in ulcerative colitis with ileo-anal anastomosis: study protocol for a prospective, multicenter, double-blind, randomized, controlled trial.}, journal = {Trials}, volume = {21}, number = {1}, pages = {455}, pmid = {32493442}, issn = {1745-6215}, support = {16-267//Ministère des Affaires Sociales, de la Santé et des Droits des Femmes/ ; }, abstract = {BACKGROUND: Almost 15% of patients with ulcerative colitis (UC) will require a proctocolectomy with ileal pouch-anal anastomosis (IPAA) as a result of fulminant colitis, dysplasia, cancer, or medical refractory diseases. Around 50% will experience pouchitis, an idiopathic inflammatory condition involving the ileal reservoir, responsible for digestive symptoms, deterioration in quality of life, and disability. Though the majority of initial cases of pouchitis are easily managed with a short course of antibiotics, in about 10% of cases, inflammation of the pouch becomes chronic with very few treatments available. Previous studies have suggested that manipulating the composition of intestinal flora through antibiotics, probiotics, and prebiotics achieved significant results for treating acute episodes of UC-associated pouchitis. However, there is currently no established effective treatment for chronic antibiotic-dependent pouchitis. Fecal microbiota transplantation (FMT) is a novel therapy involving the transfer of normal intestinal flora from a healthy donor to a patient with a medical condition potentially caused by the disrupted homeostasis of intestinal microbiota or dysbiosis.<br><br>METHODS: Our project aims to compare the delay of relapse of chronic recurrent pouchitis after FMT versus sham transplantation. Forty-two patients with active recurrent pouchitis after having undergone an IPAA for UC will be enrolled at 12 French centers. The patients who respond to antibiotherapy will be randomized at a ratio of 1:1 to receive either FMT or sham transplantation.<br><br>DISCUSSION: On April 30, 2014, the World Health Organization published an alarming report on antibiotic resistance. Finding an alternative medical treatment to antibiotics in order to prevent relapses of pouchitis is therefore becoming increasingly important given the risk posed by multiresistant bacteria. Moreover, if the results of this study are conclusive, FMT, which is less expensive than biologics, could become a routine treatment in the future.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT03524352. Registered on 14 May 2018.}, }
@article {pmid32492490, year = {2020}, author = {Gulati, M and Singh, SK and Corrie, L and Kaur, IP and Chandwani, L}, title = {Delivery routes for faecal microbiota transplants: Available, anticipated and aspired.}, journal = {Pharmacological research}, volume = {159}, number = {}, pages = {104954}, doi = {10.1016/j.phrs.2020.104954}, pmid = {32492490}, issn = {1096-1186}, abstract = {Fecal microbiota transplant (FMT) has seen a historic emergence in last decade with its sojourn recently entering into a chequered path, due to a few reports of infection and subsequent mortality. Though FMT has been extensively reported, there is no comprehensive report on the delivery routes available for this non-pharmacological treatment option. Safety, efficacy and cost of FMT not only depend on the quality of contents but also on the delivery route employed. A number of delivery routes are in use for conducting FMT, which include upper gastrointestinal routes (UGI) i.e. nasogastric/nasojejunal tube, endoscopy, oral capsules and lower gastrointestinal routes (LGI) like retention enema, sigmoidoscopy or colonoscopy. Capsules, both conventional as well as colon targeted have been the most commonly used formulations. Surprisingly, the success rates with conventional gastric delivery capsules and colon targeted capsules were found to be quite similar indicating the sufficiency of the inoculum size to withstand the microbial loss in the gastric milieu. Patient compliance, cost effectiveness, comfort of administration, level of invasiveness, patient's hospital admission, risk of aspiration and infections, multiplicity of administration required, recurrence rate are the main factors that seem to influence the choice for route of administration of physicians. The best route for FMT has not been established yet. Extensive studies are required to understand the interplay of route adopted, type of donor, physical nature of sample (fresh or frozen), patient compliance and cost effectiveness to design an approach for the risk free, convenient and cost-effective administration route for FMT.}, }
@article {pmid32487252, year = {2020}, author = {Adelman, MW and Woodworth, MH and Langelier, C and Busch, LM and Kempker, JA and Kraft, CS and Martin, GS}, title = {The gut microbiome's role in the development, maintenance, and outcomes of sepsis.}, journal = {Critical care (London, England)}, volume = {24}, number = {1}, pages = {278}, pmid = {32487252}, issn = {1466-609X}, support = {K23AI144036//National Institute of Allergy and Infectious Diseases/International ; K08 HS-025240//Agency for Healthcare Research and Quality (US)/International ; K23HL138461-01A1/HL/NHLBI NIH HHS/United States ; UL1 TR-002378/TR/NCATS NIH HHS/United States ; }, abstract = {The gut microbiome regulates a number of homeostatic mechanisms in the healthy host including immune function and gut barrier protection. Loss of normal gut microbial structure and function has been associated with diseases as diverse as Clostridioides difficile infection, asthma, and epilepsy. Recent evidence has also demonstrated a link between the gut microbiome and sepsis. In this review, we focus on three key areas of the interaction between the gut microbiome and sepsis. First, prior to sepsis onset, gut microbiome alteration increases sepsis susceptibility through several mechanisms, including (a) allowing for expansion of pathogenic intestinal bacteria, (b) priming the immune system for a robust pro-inflammatory response, and (c) decreasing production of beneficial microbial products such as short-chain fatty acids. Second, once sepsis is established, gut microbiome disruption worsens and increases susceptibility to end-organ dysfunction. Third, there is limited evidence that microbiome-based therapeutics, including probiotics and selective digestive decontamination, may decrease sepsis risk and improve sepsis outcomes in select patient populations, but concerns about safety have limited uptake. Case reports of a different microbiome-based therapy, fecal microbiota transplantation, have shown correlation with gut microbial structure restoration and decreased inflammatory response, but these results require further validation. While much of the evidence linking the gut microbiome and sepsis has been established in pre-clinical studies, clinical evidence is lacking in many areas. To address this, we outline a potential research agenda for further investigating the interaction between the gut microbiome and sepsis.}, }
@article {pmid32486476, year = {2020}, author = {Okahara, K and Ishikawa, D and Nomura, K and Ito, S and Haga, K and Takahashi, M and Shibuya, T and Osada, T and Nagahara, A}, title = {Matching between Donors and Ulcerative Colitis Patients Is Important for Long-Term Maintenance after Fecal Microbiota Transplantation.}, journal = {Journal of clinical medicine}, volume = {9}, number = {6}, pages = {}, pmid = {32486476}, issn = {2077-0383}, support = {JP16K09328//Japan Society for the Promotion of Science/ ; }, abstract = {We previously demonstrated that fresh fecal microbiota transplantation (FMT) following triple antibiotic therapy (amoxicillin, fosfomycin, metronidazole (AFM); A-FMT) resulted in effective colonization of Bacteroidetes species, leading to short-term clinical response in ulcerative colitis (UC). Its long-term efficacy and criteria for donor selection are unknown. Here, we analyzed the long-term efficacy of A-FMT compared to AFM monotherapy (mono-AFM). AFM was administered to patients with mild to severe UC for 2 weeks until 2 days before fresh FMT. Clinical response and efficacy maintenance were defined by the decrease and no exacerbation in clinical activity index. The population for intention-to-treat analysis comprised 92 patients (A-FMT, n = 55; mono-AFM, n = 37). Clinical response was observed at 4 weeks post-treatment (A-FMT, 56.3%; mono-AFM, 48.6%). Maintenance rate of responders at 24 months post-treatment was significantly higher with A-FMT than mono-AFM (p = 0.034). Significant differences in maintenance rate according to the age difference between donors and patients were observed. Additionally, sibling FMT had a significantly higher maintenance rate than parent-child FMT. Microbial analysis of patients who achieved long-term maintenance showed that some exhibited similarity to their donors, particularly Bacteroidetes species. Thus, A-FMT exhibited long-term efficacy. Therefore, matching between donors and UC patients may be helpful in effectively planning the FMT regimen.}, }
@article {pmid32485282, year = {2020}, author = {Wang, MX and Lin, L and Chen, YD and Zhong, YP and Lin, YX and Li, P and Tian, X and Han, B and Xie, ZY and Liao, QF}, title = {Evodiamine has therapeutic efficacy in ulcerative colitis by increasing Lactobacillus acidophilus levels and acetate production.}, journal = {Pharmacological research}, volume = {159}, number = {}, pages = {104978}, doi = {10.1016/j.phrs.2020.104978}, pmid = {32485282}, issn = {1096-1186}, abstract = {Emerging evidence implicates gut microbiota have an important role in ulcerative colitis (UC). Previous study indicated that Evodiamine (EVO) can alleviate colitis through downregulating inflammatory pathways. However, specific relationship between EVO-treated colitis relief and regulation of gut microbiota is still unclear. Here, our goal was to determine the potential role of gut microbiota in the relief of UC by EVO. By using pathology-related indicators, 16S rRNA sequencing and metabolomics profiling, we assessed the pharmacological effect of EVO on dextran sulfate sodium (DSS)-induced colitis rats as well as on the change of gut microbiota and metabolism. Fecal derived from EVO-treated rats was transplanted into colitis rats to verify the effect of EVO on gut microbiota, and 'driver bacteria' was found and validated by 16S rRNA sequencing, metagenome and qRT-PCR. The effect of Lactobacillus acidophilus (L. acidophilus) was investigated by vivo experiment, microbiota analysis, Short-chain fatty acids (SCFAs) quantification and colon transcriptomics. EVO reduced the susceptibility to DSS-induced destruction of epithelial integrity and severe inflammatory response, and regulated the gut microbiota and metabolites. Fecal Microbiota Transplantation (FMT) alleviated DSS-induced colitis, increased the abundance of L. acidophilus and the level of acetate. Furthermore, gavaged with L. acidophilus reduced pro-inflammatory cytokines, promoted the increase of goblet cells and the secretion of antimicrobial peptides, regulated the ratio of Firmicutes/Bacteroidetes and increased the level of acetate. Our results indicated that EVO mitigation of DSS-induced colitis is associated with increased in L. acidophilus and protective acetate production, which may be a promising strategy for treating UC.}, }
@article {pmid32483373, year = {2020}, author = {Burberry, A and Wells, MF and Limone, F and Couto, A and Smith, KS and Keaney, J and Gillet, G and van Gastel, N and Wang, JY and Pietilainen, O and Qian, M and Eggan, P and Cantrell, C and Mok, J and Kadiu, I and Scadden, DT and Eggan, K}, title = {C9orf72 suppresses systemic and neural inflammation induced by gut bacteria.}, journal = {Nature}, volume = {582}, number = {7810}, pages = {89-94}, doi = {10.1038/s41586-020-2288-7}, pmid = {32483373}, issn = {1476-4687}, support = {R01 NS089742/NS/NINDS NIH HHS/United States ; 5R01NS089742/NH/NIH HHS/United States ; K99 MH119327/MH/NIMH NIH HHS/United States ; K99 AG057808/AG/NIA NIH HHS/United States ; 1K99MH119327-01/NH/NIH HHS/United States ; 5K99AG057808-02/NH/NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/genetics/pathology ; Animals ; Anti-Bacterial Agents/pharmacology ; Autoimmunity/drug effects/genetics/immunology ; C9orf72 Protein/*genetics ; Cell Movement/drug effects ; Cytokines/immunology ; Fecal Microbiota Transplantation ; Female ; Frontotemporal Dementia/genetics/pathology ; Gastrointestinal Microbiome/drug effects/immunology/*physiology ; Gliosis/genetics/*microbiology/*pathology/prevention &amp; control ; Inflammation/*genetics/*microbiology/pathology/prevention &amp; control ; Loss of Function Mutation/genetics ; Male ; Mice ; Microglia/immunology/microbiology/pathology ; Spinal Cord/immunology/microbiology/*pathology ; Survival Rate ; }, abstract = {A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia1,2. The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration3-9. The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins5 before its non-canonical translation into neural-toxic dipeptide proteins3,4. The failure of RNA polymerase to read through the mutation also reduces the abundance of the endogenous C9ORF72 gene product, which functions in endolysosomal pathways and suppresses systemic and neural inflammation6-9. Notably, the effects of the repeat expansion act with incomplete penetrance in families with a high prevalence of amyotrophic lateral sclerosis or frontotemporal dementia, indicating that either genetic or environmental factors modify the risk of disease for each individual. Identifying disease modifiers is of considerable translational interest, as it could suggest strategies to diminish the risk of developing amyotrophic lateral sclerosis or frontotemporal dementia, or to slow progression. Here we report that an environment with reduced abundance of immune-stimulating bacteria10,11 protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity. Consistent with C9orf72 functioning to prevent microbiota from inducing a pathological inflammatory response, we found that reducing the microbial burden in mutant mice with broad spectrum antibiotics-as well as transplanting gut microflora from a protective environment-attenuated inflammatory phenotypes, even after their onset. Our studies provide further evidence that the microbial composition of our gut has an important role in brain health and can interact in surprising ways with well-known genetic risk factors for disorders of the nervous system.}, }
@article {pmid32474336, year = {2020}, author = {Lin, H and Wang, Q and Yuan, M and Liu, L and Chen, Z and Zhao, Y and Das, R and Duan, Y and Xu, X and Xue, Y and Luo, Y and Mao, D}, title = {The prolonged disruption of a single-course amoxicillin on mice gut microbiota and resistome, and recovery by inulin, Bifidobacterium longum and fecal microbiota transplantation.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {265}, number = {Pt A}, pages = {114651}, doi = {10.1016/j.envpol.2020.114651}, pmid = {32474336}, issn = {1873-6424}, mesh = {Amoxicillin ; Animals ; *Bifidobacterium longum ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Inulin ; Mice ; RNA, Ribosomal, 16S ; }, abstract = {The usages of antibiotics in treating the pathogenic infections could alter the gut microbiome and associated resistome, causing long term adverse impact on human health. In this study, mice were treated with human-simulated regimen 25.0 mg kg-1 of amoxicillin for seven days, and their gut microbiota and resistome were characterized using the 16S rRNA amplicons sequencing and the high-throughput qPCR, respectively. Meanwhile, the flora restorations after individual applications of inulin, Bifidobacterium longum (B. longum), and fecal microbiota transplantation (FMT) were analyzed for up to 35 days. The results revealed the prolonged negative impact of single course AMX exposure on mice gut microbiota and resistome. To be specific, pathobionts of Klebsiella and Escherichia-Shigella were significantly enriched, while prebiotics of Bifidobacterium and Lactobacillus were dramatically depleted. Furthermore, β-lactam resistance genes and efflux resistance genes were obviously enriched after amoxicillin exposure. Compared to B. longum, FMT and inulin were demonstrated to preferably restore the gut microbiota via reconstituting microbial community and stimulating specific prebiotic respectively. Such variation of microbiome caused their distinct alleviations on resistome alteration. Inulin earned the greatest elimination on AMX induced ARG abundance and diversity enrichment. FMT and B. longum caused remove of particular ARGs such as ndm-1, blaPER. Network analysis revealed that most of the ARGs were prone to be harbored by Firmicutes and Proteobacteria. In general, gut resistome shift was partly associated with the changing bacterial community structures and transposase and integron. Taken together, these results demonstrated the profound disruption of gut microbiota and resistome after single-course amoxicillin treatment and different restoration by inulin, B. longum and FMT.}, }
@article {pmid32468608, year = {2020}, author = {Kragsnaes, MS and Nilsson, AC and Kjeldsen, J and Holt, HM and Rasmussen, KF and Georgsen, J and Ellingsen, T and Holm, DK}, title = {How do I establish a stool bank for fecal microbiota transplantation within the blood- and tissue transplant service?.}, journal = {Transfusion}, volume = {60}, number = {6}, pages = {1135-1141}, doi = {10.1111/trf.15816}, pmid = {32468608}, issn = {1537-2995}, support = {//Odense University Hospital/ ; }, abstract = {Worldwide, there is a rising demand for thoroughly screened, high-quality fecal microbiota transplantation (FMT) products that can be obtained at a reasonable cost. In the light of this evolving therapeutic area of the intestinal microbiota, both private and public stool banks have emerged. However, some of the larger difficulties when establishing stool banks are caused by the absence of or international disagreement on regulation and legislative formalities. In this context, the establishment of a stool bank within a nonprofit blood and tissue transplant service has several advantages. Especially, this setting can ensure that every step of the donation process, laboratory handling, and donor-traceability is in agreement with the current expert guidelines and meets the requirements of the European Union's regulative directives on human cells and tissues. Although safety and documentation are the top priority of the stool bank setup presented here, cost-effectiveness of the production is possible due to a high donor screening success rate and the knowhow, infrastructure, facilities, personnel, and laboratory- and quality-management systems that were already in place. Overall, our experience is that a centralized, nonprofit, blood and tissue transplant service is an ideal and safe facility to run a stool bank of high quality FMT products that are based on stool donations from volunteer, unpaid, healthy, blood donors.}, }
@article {pmid32466801, year = {2020}, author = {Jian, X and Zhu, Y and Ouyang, J and Wang, Y and Lei, Q and Xia, J and Guan, Y and Zhang, J and Guo, J and He, Y and Wang, J and Li, J and Lin, J and Su, M and Li, G and Wu, M and Qiu, L and Xiang, J and Xie, L and Jia, W and Zhou, W}, title = {Alterations of gut microbiome accelerate multiple myeloma progression by increasing the relative abundances of nitrogen-recycling bacteria.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {74}, pmid = {32466801}, issn = {2049-2618}, support = {31900102//National Natural Science Foundation of China/ ; 81570205, 81630007//National Natural Science Foundation of China/ ; 81800209//National Natural Science Foundation of China/ ; 2019M652792//China Postdoctoral Science Foundation/ ; ZLXD2017004//Strategic Priority Research Program of Central South University/ ; }, abstract = {BACKGROUND: Gut microbiome alterations are closely related to human health and linked to a variety of diseases. Although great efforts have been made to understand the risk factors for multiple myeloma (MM), little is known about the role of the gut microbiome and alterations of its metabolic functions in the development of MM.<br><br>RESULTS: Here, in a cohort of newly diagnosed patients with MM and healthy controls (HCs), significant differences in metagenomic composition were discovered, for the first time, with higher bacterial diversity in MM. Specifically, nitrogen-recycling bacteria such as Klebsiella and Streptococcus were significantly enriched in MM. Also, the bacteria enriched in MM were significantly correlated with the host metabolome, suggesting strong metabolic interactions between microbes and the host. In addition, the MM-enriched bacteria likely result from the regulation of urea nitrogen accumulated during MM progression. Furthermore, by performing fecal microbiota transplantation (FMT) into 5TGM1 mice, we proposed a mechanistic explanation for the interaction between MM-enriched bacteria and MM progression via recycling urea nitrogen. Further experiments validated that Klebsiella pneumoniae promoted MM progression via de novo synthesis of glutamine in mice and that the mice fed with glutamine-deficient diet exhibited slower MM progression.<br><br>CONCLUSIONS: Overall, our findings unveil a novel function of the altered gut microbiome in accelerating the malignant progression of MM and open new avenues for novel treatment strategies via manipulation of the intestinal microbiota of MM patients. Video abstract.}, }
@article {pmid32466620, year = {2020}, author = {Nance, CL and Deniskin, R and Diaz, VC and Paul, M and Anvari, S and Anagnostou, A}, title = {The Role of the Microbiome in Food Allergy: A Review.}, journal = {Children (Basel, Switzerland)}, volume = {7}, number = {6}, pages = {}, pmid = {32466620}, issn = {2227-9067}, abstract = {Food allergies are common and estimated to affect 8% of children and 11% of adults in the United States. They pose a significant burden-physical, economic and social-to those affected. There is currently no available cure for food allergies. Emerging evidence suggests that the microbiome contributes to the development and manifestations of atopic disease. According to the hygiene hypothesis, children growing up with older siblings have a lower incidence of allergic disease compared with children from smaller families, due to their early exposure to microbes in the home. Research has also demonstrated that certain environmental exposures, such as a farming environment, during early life are associated with a diverse bacterial experience and reduced risk of allergic sensitization. Dysregulation in the homeostatic interaction between the host and the microbiome or gut dysbiosis appears to precede the development of food allergy, and the timing of such dysbiosis is critical. The microbiome affects food tolerance via the secretion of microbial metabolites (e.g., short chain fatty acids) and the expression of microbial cellular components. Understanding the biology of the microbiome and how it interacts with the host to maintain gut homeostasis is helpful in developing smarter therapeutic approaches. There are ongoing trials evaluating the benefits of probiotics and prebiotics, for the prevention and treatment of atopic diseases to correct the dysbiosis. However, the routine use of probiotics as an intervention for preventing allergic disease is not currently recommended. A new approach in microbial intervention is to attempt a more general modification of the gut microbiome, such as with fecal microbiota transplantation. Developing targeted bacterial therapies for food allergy may be promising for both the treatment and prevention of food allergy. Similarly, fecal microbiota transplantation is being explored as a potentially beneficial interventional approach. Overall, targeted bacterial therapies for food allergy may be promising for both the treatment and prevention of food allergy.}, }
@article {pmid32460890, year = {2020}, author = {Li, M and Li, C and Wu, X and Chen, T and Ren, L and Xu, B and Cao, J}, title = {Microbiota-driven interleukin-17 production provides immune protection against invasive candidiasis.}, journal = {Critical care (London, England)}, volume = {24}, number = {1}, pages = {268}, pmid = {32460890}, issn = {1466-609X}, support = {81722001//National Natural Science Foundation of China/International ; 81572038//National Natural Science Foundation of China/International ; }, abstract = {BACKGROUND: The intestinal microbiota plays a crucial role in human health, which could affect host immunity and the susceptibility to infectious diseases. However, the role of intestinal microbiota in the immunopathology of invasive candidiasis remains unknown.<br><br>METHODS: In this work, an antibiotic cocktail was used to eliminate the intestinal microbiota of conventional-housed (CNV) C57/BL6 mice, and then both antibiotic-treated (ABX) mice and CNV mice were intravenously infected with Candida albicans to investigate their differential responses to infection. Furthermore, fecal microbiota transplantation (FMT) was applied to ABX mice in order to assess its effects on host immunity against invasive candidiasis after restoring the intestinal microbiota, and 16S ribosomal RNA gene sequencing was conducted on fecal samples from both uninfected ABX and CNV group of mice to analyze their microbiomes.<br><br>RESULTS: We found that ABX mice displayed significantly increased weight loss, mortality, and organ damage during invasive candidiasis when compared with CNV mice, which could be alleviated by FMT. In addition, the level of IL-17A in ABX mice was significantly lower than that in the CNV group during invasive candidiasis. Treatment with recombinant IL-17A could improve the survival of ABX mice during invasive candidiasis. Besides, the microbial diversity of ABX mice was significantly reduced, and the intestinal microbiota structure of ABX mice was significantly deviated from the CNV mice.<br><br>CONCLUSIONS: Our data revealed that intestinal microbiota plays a protective role in invasive candidiasis by enhancing IL-17A production in our model system.}, }
@article {pmid32457246, year = {2020}, author = {Abhyankar, MM and Ma, JZ and Scully, KW and Nafziger, AJ and Frisbee, AL and Saleh, MM and Madden, GR and Hays, AR and Poulter, M and Petri, WA}, title = {Immune Profiling To Predict Outcome of Clostridioides difficile Infection.}, journal = {mBio}, volume = {11}, number = {3}, pages = {}, pmid = {32457246}, issn = {2150-7511}, support = {R01 AI124214/AI/NIAID NIH HHS/United States ; }, abstract = {There is a pressing need for biomarker-based models to predict mortality from and recurrence of Clostridioides difficile infection (CDI). Risk stratification would enable targeted interventions such as fecal microbiota transplant, antitoxin antibodies, and colectomy for those at highest risk. Because severity of CDI is associated with the immune response, we immune profiled patients at the time of diagnosis. The levels of 17 cytokines in plasma were measured in 341 CDI inpatients. The primary outcome of interest was 90-day mortality. Increased tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand 5 (CCL-5), suppression of tumorigenicity 2 receptor (sST-2), IL-8, and IL-15 predicted mortality by univariate analysis. After adjusting for demographics and clinical characteristics, the mortality risk (as indicated by the hazard ratio [HR]) was higher for patients in the top 25th percentile for TNF-α (HR = 8.35, P = 0.005) and IL-8 (HR = 4.45, P = 0.01) and lower for CCL-5 (HR = 0.18, P ≤ 0.008). A logistic regression risk prediction model was developed and had an area under the receiver operating characteristic curve (AUC) of 0.91 for 90-day mortality and 0.77 for 90-day recurrence. While limited by being single site and retrospective, our work resulted in a model with a substantially greater predictive ability than white blood cell count. In conclusion, immune profiling demonstrated differences between patients in their response to CDI, offering the promise for precision medicine individualized treatment.IMPORTANCEClostridioides difficile infection is the most common health care-associated infection in the United States with more than 20% patients experiencing symptomatic recurrence. The complex nature of host-bacterium interactions makes it difficult to predict the course of the disease based solely on clinical parameters. In the present study, we built a robust prediction model using representative plasma biomarkers and clinical parameters for 90-day all-cause mortality. Risk prediction based on immune biomarkers and clinical variables may contribute to treatment selection for patients as well as provide insight into the role of immune system in C. difficile pathogenesis.}, }
@article {pmid32453670, year = {2020}, author = {Kaźmierczak-Siedlecka, K and Daca, A and Fic, M and van de Wetering, T and Folwarski, M and Makarewicz, W}, title = {Therapeutic methods of gut microbiota modification in colorectal cancer management - fecal microbiota transplantation, prebiotics, probiotics, and synbiotics.}, journal = {Gut microbes}, volume = {11}, number = {6}, pages = {1518-1530}, pmid = {32453670}, issn = {1949-0984}, abstract = {The link between gut microbiota and the development of colorectal cancer has been investigated. An imbalance in the gut microbiota promotes the progress of colorectal carcinogenesis via multiple mechanisms, including inflammation, activation of carcinogens, and tumorigenic pathways as well as damaging host DNA. Several therapeutic methods are available with which to alter the composition and the activity of gut microbiota, such as administration of prebiotics, probiotics, and synbiotics; these can confer various benefits for colorectal cancer patients. Nowadays, fecal microbiota transplantation is the most modern way of modulating the gut microbiota. Even though data regarding fecal microbiota transplantation in colorectal cancer patients are still rather limited, it has been approved as a clinical method of treatment-recurrent Clostridium difficile infection, which may also occur in these patients. The major benefits of fecal microbiota transplantation include modulation of immunotherapy efficacy, amelioration of bile acid metabolism, and restoration of intestinal microbial diversity. Nonetheless, more studies are needed to assess the long-term effects of fecal microbiota transplantation. In this review, the impact of gut microbiota on the efficiency of anti-cancer therapy and colorectal cancer patients' overall survival is also discussed.}, }
@article {pmid32448639, year = {2020}, author = {Castro Rocha, FA and Duarte-Monteiro, AM and Henrique da Mota, LM and Matias Dinelly Pinto, AC and Fonseca, JE}, title = {Microbes, helminths, and rheumatic diseases.}, journal = {Best practice &amp; research. Clinical rheumatology}, volume = {}, number = {}, pages = {101528}, pmid = {32448639}, issn = {1532-1770}, abstract = {There has been a progressive interest on modifications of the human defense system following insults occurring in the interface between our body and the external environment, as they may provoke or worsen disease states. Studies suggest that billions of germs, which compose the gut microbiota influence one's innate and adaptive immune responses at the intestinal level, but these microorganisms may also impact rheumatic diseases. The microbiota of the skin, respiratory, and urinary tracts may also be relevant in rheumatology. Evidence indicates that changes in the gut microbiome alter the pathogenesis of immune-mediated diseases such as rheumatoid arthritis and ankylosing spondylitis but also of other disorders like atherosclerosis and osteoarthritis. Therapeutic strategies to modify the microbiota, including probiotics and fecal microbiota transplantation, have been received with skepticism, which, in turn, has drawn attention back to previously developed interventions such as antibiotics. Helminths adapted to humans over the evolution process, but their role in disease modulation, particularly immune-mediated diseases, remains to be understood. The present review focuses on data concerning modifications of the immune system induced by interactions with microbes and pluricellular organisms, namely helminths, and their impact on rheumatic diseases. Practical aspects, including specific microbiota-targeted therapies, are also discussed.}, }
@article {pmid32445528, year = {2020}, author = {Ostojic, SM}, title = {Letter: balancing gut hydrogen as a proxy for bacteriotherapy benefits in irritable bowel syndrome.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {51}, number = {12}, pages = {1451-1452}, doi = {10.1111/apt.15782}, pmid = {32445528}, issn = {1365-2036}, mesh = {*Clostridium Infections ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Hydrogen ; *Irritable Bowel Syndrome ; }, }
@article {pmid32443576, year = {2020}, author = {Kløve, S and Genger, C and Mousavi, S and Weschka, D and Bereswill, S and Heimesaat, MM}, title = {Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral Campylobacter coli Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota.}, journal = {Pathogens (Basel, Switzerland)}, volume = {9}, number = {5}, pages = {}, pmid = {32443576}, issn = {2076-0817}, support = {ZIM; ZF4117904 AJ8//Bundesministerium für Forschung und Technologie/ ; Zoonoses research consortium PAC-Campylobacter, IP7/ 01KI1725D//Bundesministerium für Bildung, Wissenschaft und Forschung/ ; }, abstract = {Zoonotic Campylobacter, including C. jejuni and C. coli, are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immune responses, induced by bacterial lipooligosaccharide (LOS). In order to investigate C. coli-host interactions, including the roles of the human gut microbiota and TLR4, upon infection, we applied a clinical acute campylobacteriosis model, and subjected secondary abiotic, TLR4-deficient IL10-/- mice and IL10-/- controls to fecal microbiota transplantation derived from human donors by gavage, before peroral C. coli challenge. Until day 21 post-infection, C. coli could stably colonize the gastrointestinal tract of human microbiota-associated (hma) mice of either genotype. TLR4-deficient IL10-/- mice, however, displayed less severe clinical signs of infection, that were accompanied by less distinct apoptotic epithelial cell and innate as well as adaptive immune cell responses in the colon, as compared to IL10-/- counterparts. Furthermore, C. coli infected IL10-/-, as opposed to TLR4-deficient IL10-/-, mice displayed increased pro-inflammatory cytokine concentrations in intestinal and, strikingly, systemic compartments. We conclude that pathogenic LOS might play an important role in inducing TLR4-dependent host immune responses upon C. coli infection, which needs to be further addressed in more detail.}, }
@article {pmid32440192, year = {2020}, author = {Elsalem, L and Jum'ah, AA and Alfaqih, MA and Aloudat, O}, title = {The Bacterial Microbiota of Gastrointestinal Cancers: Role in Cancer Pathogenesis and Therapeutic Perspectives.}, journal = {Clinical and experimental gastroenterology}, volume = {13}, number = {}, pages = {151-185}, pmid = {32440192}, issn = {1178-7023}, abstract = {The microbiota has an essential role in the pathogenesis of many gastrointestinal diseases including cancer. This effect is mediated through different mechanisms such as damaging DNA, activation of oncogenic pathways, production of carcinogenic metabolites, stimulation of chronic inflammation, and inhibition of antitumor immunity. Recently, the concept of &quot;pharmacomicrobiomics&quot; has emerged as a new field concerned with exploring the interplay between drugs and microbes. Mounting evidence indicates that the microbiota and their metabolites have a major impact on the pharmacodynamics and therapeutic responses toward anticancer drugs including conventional chemotherapy and molecular-targeted therapeutics. In addition, microbiota appears as an attractive target for cancer prevention and treatment. In this review, we discuss the role of bacterial microbiota in the pathogenesis of different cancer types affecting the gastrointestinal tract system. We also scrutinize the evidence regarding the role of microbiota in anticancer drug responses. Further, we discuss the use of probiotics, fecal microbiota transplantation, and antibiotics, either alone or in combination with anticancer drugs for prevention and treatment of gastrointestinal tract cancers.}, }
@article {pmid32437393, year = {2020}, author = {Fretheim, H and Chung, BK and Didriksen, H and Bækkevold, ES and Midtvedt, Ø and Brunborg, C and Holm, K and Valeur, J and Tennøe, AH and Garen, T and Midtvedt, T and Trøseid, M and Zarè, H and Lund, MB and Hov, JR and Lundin, KEA and Molberg, Ø and Hoffmann-Vold, AM}, title = {Fecal microbiota transplantation in systemic sclerosis: A double-blind, placebo-controlled randomized pilot trial.}, journal = {PloS one}, volume = {15}, number = {5}, pages = {e0232739}, pmid = {32437393}, issn = {1932-6203}, mesh = {Bacteria ; Double-Blind Method ; Fatty Acids/metabolism ; Fecal Incontinence/etiology ; *Fecal Microbiota Transplantation/adverse effects ; Feces/chemistry ; Female ; Humans ; Immunoglobulin A/metabolism ; Immunoglobulin M/metabolism ; Leukocyte L1 Antigen Complex/metabolism ; Male ; Middle Aged ; Pilot Projects ; Placebos ; Scleroderma, Systemic/*microbiology/*therapy ; Treatment Outcome ; }, abstract = {OBJECTIVES: Systemic sclerosis (SSc) is an auto-immune, multi organ disease marked by severe gastrointestinal (GI) involvement and gut dysbiosis. Here, we aimed to determine the safety and efficacy of fecal microbiota transplantation (FMT) using commercially-available anaerobic cultivated human intestinal microbiota (ACHIM) in SSc.<br><br>METHODS: Ten patients with SSc were randomized to ACHIM (n = 5) or placebo (n = 5) in a double-blind, placebo-controlled 16-week pilot. All patients had mild to severe upper and lower GI symptoms including diarrhea, distention/bloating and/or fecal incontinence at baseline. Gastroduodenoscopy transfer of ACHIM or placebo was performed at weeks 0 and 2. Primary endpoints were safety and clinical efficacy on GI symptoms assessed at weeks 4 and 16. Secondary endpoints included changes in relative abundance of total, immunoglobulin (Ig) A- and IgM-coated fecal bacteria measured by 16s rRNA sequencing.<br><br>RESULTS: ACHIM side effects were mild and transient. Two placebo controls experienced procedure-related serious adverse events; one developed laryngospasms at week 0 gastroduodenoscopy necessitating study exclusion whilst one encountered duodenal perforation during gastroduodenoscopy at the last study visit (week 16). Decreased bloating, diarrhea and/or fecal incontinence was observed in four of five patients in the FMT group (week 4 or/and 16) and in two of four in the placebo group (week 4 or 16). Relative abundance, richness and diversity of total and IgA-coated and IgM-coated bacteria fluctuated more after FMT, than after placebo.<br><br>CONCLUSIONS: FMT of commercially-available ACHIM is associated with gastroduodenoscopy complications but reduces lower GI symptoms by possibly altering the gut microbiota in patients with SSc.}, }
@article {pmid32434586, year = {2020}, author = {Xiao, HW and Cui, M and Li, Y and Dong, JL and Zhang, SQ and Zhu, CC and Jiang, M and Zhu, T and Wang, B and Wang, HC and Fan, SJ}, title = {Gut microbiota-derived indole 3-propionic acid protects against radiation toxicity via retaining acyl-CoA-binding protein.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {69}, pmid = {32434586}, issn = {2049-2618}, support = {R01 AT005076/AT/NCCIH NIH HHS/United States ; R01 GM063075/GM/NIGMS NIH HHS/United States ; P30 CA196521/CA/NCI NIH HHS/United States ; OCM-094//Centers for Medicare and Medicaid Services/ ; }, abstract = {BACKGROUND: We have proved fecal microbiota transplantation (FMT) is an efficacious remedy to mitigate acute radiation syndrome (ARS); however, the mechanisms remain incompletely characterized. Here, we aimed to tease apart the gut microbiota-produced metabolites, underpin the therapeutic effects of FMT to radiation injuries, and elucidate the underlying molecular mechanisms.<br><br>RESULTS: FMT elevated the level of microbial-derived indole 3-propionic acid (IPA) in fecal pellets from irradiated mice. IPA replenishment via oral route attenuated hematopoietic system and gastrointestinal (GI) tract injuries intertwined with radiation exposure without precipitating tumor growth in male and female mice. Specifically, IPA-treated mice represented a lower system inflammatory level, recuperative hematogenic organs, catabatic myelosuppression, improved GI function, and epithelial integrity following irradiation. 16S rRNA gene sequencing and subsequent analyses showed that irradiated mice harbored a disordered enteric bacterial pattern, which was preserved after IPA administration. Notably, iTRAQ analysis presented that IPA replenishment retained radiation-reprogrammed protein expression profile in the small intestine. Importantly, shRNA interference and hydrodynamic-based gene delivery assays further validated that pregnane X receptor (PXR)/acyl-CoA-binding protein (ACBP) signaling played pivotal roles in IPA-favored radioprotection in vitro and in vivo.<br><br>CONCLUSIONS: These evidences highlight that IPA is a key intestinal microbiota metabolite corroborating the therapeutic effects of FMT to radiation toxicity. Owing to the potential pitfalls of FMT, IPA might be employed as a safe and effective succedaneum to fight against accidental or iatrogenic ionizing ARS in clinical settings. Our findings also provide a novel insight into microbiome-based remedies toward radioactive diseases. Video abstract.}, }
@article {pmid32427675, year = {2020}, author = {Craven, L and Rahman, A and Nair Parvathy, S and Beaton, M and Silverman, J and Qumosani, K and Hramiak, I and Hegele, R and Joy, T and Meddings, J and Urquhart, B and Harvie, R and McKenzie, C and Summers, K and Reid, G and Burton, JP and Silverman, M}, title = {Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000000661}, pmid = {32427675}, issn = {1572-0241}, abstract = {INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability.<br><br>METHODS: Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT.<br><br>RESULTS: There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT.<br><br>DISCUSSION: FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.}, }
@article {pmid32425906, year = {2020}, author = {Sun, Z and Li, J and Dai, Y and Wang, W and Shi, R and Wang, Z and Ding, P and Lu, Q and Jiang, H and Pei, W and Zhao, X and Guo, Y and Liu, J and Tan, X and Mao, T}, title = {Indigo Naturalis Alleviates Dextran Sulfate Sodium-Induced Colitis in Rats via Altering Gut Microbiota.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {731}, pmid = {32425906}, issn = {1664-302X}, abstract = {Ulcerative colitis is a gastrointestinal disorder intricately associated with intestinal dysbiosis, but effective treatments are currently limited. Indigo naturalis, a traditional Chinese medicine derived from indigo plants, has been widely used in the treatment of ulcerative colitis. However, the specific mechanisms have not yet been identified. Accordingly, in this study, we evaluated the effects and mechanisms of indigo naturalis on dextran sulfate sodium (DSS)-induced colitis in rats. Our results showed that indigo naturalis potently alleviated DSS-induced colitis in rats, and reversed DSS-induced intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing. The protective effects of indigo naturalis were gut microbiota dependent, as demonstrated by antibiotic treatments and fecal microbiota transplantation. Depletion of the gut microbiota through a combination of antibiotic treatments blocked the anti-inflammatory effect of indigo naturalis on the DSS-induced colitis, and the recipients of the gut microbiota from indigo naturalis-treated rats displayed a significantly attenuated intestinal inflammation, which was actively responsive to therapeutic interventions with indigo naturalis. Notably, supplement with indigo naturalis greatly increased the levels of feces butyrate, which was positively correlated with the relative abundances of Ruminococcus_1 and Butyricicoccus. We further showed that indigo naturalis-dependent attenuation of colitis was associated with elevated expression of short-chain fatty acid-associated receptors GPR41 and GPR43. Collectively, these results suggested that indigo naturalis alleviates DSS-induced colitis in rats through a mechanism of the microbiota-butyrate axis, particularly alterations in Ruminococcus_1 and Butyricicoccus abundances, and target-specific microbial species may have unique therapeutic promise for ulcerative colitis.}, }
@article {pmid32423189, year = {2020}, author = {Zhang, W and Zou, G and Li, B and Du, X and Sun, Z and Sun, Y and Jiang, X}, title = {Fecal Microbiota Transplantation (FMT) Alleviates Experimental Colitis in Mice by Gut Microbiota Regulation.}, journal = {Journal of microbiology and biotechnology}, volume = {30}, number = {8}, pages = {1132-1141}, doi = {10.4014/jmb.2002.02044}, pmid = {32423189}, issn = {1738-8872}, abstract = {Inflammatory bowel disease (IBD) is an increasing global burden and a predisposing factor to colorectal cancer. Although a number of treatment options are available, the side effects could be considerable. Studies on fecal microbiota transplantation (FMT) as an IBD intervention protocol require further validation as the underlying mechanisms for its attenuating effects remain unclear. This study aims to demonstrate the ameliorative role of FMT in an ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) and elucidate its relative mechanisms in a mouse model. It was shown that FMT intervention decreased disease activity index (DAI) levels and increased the body weight, colon weight and colon length of experimental animals. It also alleviated histopathological changes, reduced key cytokine expression and oxidative status in the colon. A down-regulated expression level of genes associated with NF-κB signaling pathway was also observed. The results of 16S rRNA gene sequencing showed that FMT intervention restored the gut microbiota to the pattern of the control group by increasing the relative abundance of Firmicutes and decreasing the abundances of Bacteroidetes and Proteobacteria. The relative abundances of the genera Lactobacillus, Butyricicoccus, Lachnoclostridium, Olsenella and Odoribacter were upregulated but Helicobacter, Bacteroides and Clostridium were reduced after FMT administration. Furthermore, FMT administration elevated the concentrations of SCFAs in the colon. In conclusion, FMT intervention could be suitable for UC control, but further validations via clinical trials are recommended.}, }
@article {pmid32422097, year = {2020}, author = {Talley, NJ and Irani, M}, title = {In irritable bowel syndrome, fecal microbiota transplantation improved symptoms at 3 months.}, journal = {Annals of internal medicine}, volume = {172}, number = {10}, pages = {JC52}, doi = {10.7326/ACPJ202005190-052}, pmid = {32422097}, issn = {1539-3704}, mesh = {Double-Blind Method ; *Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome ; }, abstract = {SOURCE CITATION: El-Salhy M, Hatlebakk JG, Gilja OH, Bråthen Kristoffersen A, Hausken T. Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut. 2020;69:859-67. 31852769.}, }
@article {pmid32421761, year = {2020}, author = {Bauer, CM and Zhang, X and Long, MD and Sandler, RS}, title = {Characteristics of Fecal Microbiota Transplantation Use in Inflammatory Bowel Disease Cohort.}, journal = {Crohn's &amp; colitis 360}, volume = {2}, number = {2}, pages = {otaa024}, pmid = {32421761}, issn = {2631-827X}, abstract = {Background: There is a growing interest in the role of gut bacteria in a number of diseases and an emerging hypothesis that inflammatory bowel disease (IBD) is triggered by microbial dysbiosis in genetically susceptible individuals. Currently, fecal microbiota transplantation (FMT) is utilized for the treatment of Clostridium difficile colitis. Data on the efficacy of FMT for IBD are mixed, but patients are interested in its use for the treatment of IBD. We sought to describe the use of FMT (self or medical professional administered) in individuals with IBD using IBD Partners, an Internet-based cohort.<br><br>Methods: Patients enrolled in the IBD Partners cohort were offered the opportunity to complete an optional survey on the use of FMT between January 2017 to September 2018 (n = 5430). A cross-sectional analysis was performed within patients who completed the survey and did not have a pouch or ostomy. Patients' demographic characteristics, disease activity and phenotype, mode of FMT delivery, and patient-reported efficacy were compared.<br><br>Results: Among 3274 eligible patients, 51 (1.6%) responded that they had an FMT in the past. Of patients undergoing FMT, 22 patients had the FMT for C. difficile while 29 reported that the FMT was for another indication. Most patients receiving FMT for an indication other than C. difficile had ulcerative colitis/indeterminate colitis (25, 86.2%). Colonoscopy (68.2%) and nasogastric tube (18.2%) were the most common routes of administration for patients receiving FMT for C. difficile colitis. Self-administration (72.4%) and enemas (17.2%) were the most common routes of administration in patients receiving FMT for an alternate indication. Patients reporting FMT for an indication other than C. difficile were less likely to have a physician directing their FMT treatment (20.6%) as compared to patients receiving FMT for C. difficile (86.3%). Patient-reported efficacy was lower for FMT given for a non-C. difficile indication.<br><br>Conclusions: Patients undergoing FMT for an indication other than C. difficile infection were more likely to have ulcerative colitis, self-administer FMT, and were less likely to be receiving FMT under the guidance of a medical professional. FMT was not as effective for symptoms when given for a non-C. difficile indication. Patients should be counseled on potential harms and lack of proven benefit associated with FMT for IBD indications to try to discourage self-administered FMT without proper medical oversite.}, }
@article {pmid32419454, year = {2020}, author = {Liu, Y and Luo, L and Luo, Y and Zhang, J and Wang, X and Sun, K and Zeng, L}, title = {Prebiotic Properties of Green and Dark Tea Contribute to Protective Effects in Chemical-Induced Colitis in Mice: A Fecal Microbiota Transplantation Study.}, journal = {Journal of agricultural and food chemistry}, volume = {68}, number = {23}, pages = {6368-6380}, doi = {10.1021/acs.jafc.0c02336}, pmid = {32419454}, issn = {1520-5118}, abstract = {Green and dark tea extract (GTE/DTE) ameliorate chemical-induced colitis in mice; however, the role of gut microbiota in the anticolitis effects of green and dark tea in mice remains unclear. This study aims to explore the role of modulations in gut microbes mediated by green and dark tea in colitis mice by fecal microbiota transplantation (FMT). Our results indicated that GTE and DTE (5 mg/kg bodyweight/day for 4 weeks) exhibited prebiotic effects on the donor mice. Moreover, the FMT treatments (transferring the microbiota daily from the 1 g/kg bodyweight fecal sample to each recipient) indicated that, compared with the fecal microbiota from the normal diet-treated donor mice, the fecal microbiota from the GTE- and DTE-treated donor mice significantly ameliorate colitis-related symptoms (e.g., loss of bodyweight, colonic inflammation, loss of barrier integrity, and gut microbiota dysbiosis) and downregulated the TLR4/MyD88/NF-κB pathway. Collectively, GTE and DTE ameliorate chemical-induced colitis by modulating gut microbiota.}, }
@article {pmid32418496, year = {2020}, author = {Sharma, RK and Oliveira, AC and Yang, T and Karas, MM and Li, J and Lobaton, GO and Aquino, VP and Robles-Vera, I and de Kloet, AD and Krause, EG and Bryant, AJ and Verma, A and Li, Q and Richards, EM and Raizada, MK}, title = {Gut Pathology and Its Rescue by ACE2 (Angiotensin-Converting Enzyme 2) in Hypoxia-Induced Pulmonary Hypertension.}, journal = {Hypertension (Dallas, Tex. : 1979)}, volume = {76}, number = {1}, pages = {206-216}, pmid = {32418496}, issn = {1524-4563}, support = {R01 HL102033/HL/NHLBI NIH HHS/United States ; R01 HL142776/HL/NHLBI NIH HHS/United States ; R01 HL033610/HL/NHLBI NIH HHS/United States ; R01 HL132448/HL/NHLBI NIH HHS/United States ; R01 HL142887/HL/NHLBI NIH HHS/United States ; }, abstract = {Therapeutic advances for pulmonary hypertension (PH) have been incremental because of the focus on the pulmonary vasculature in PH pathology. Here, we evaluate the concept that PH is, rather, a systemic disorder involving interplay among multiorgan systems, including brain, gut, and lungs. Therefore, the objective of this study was to evaluate the hypothesis that PH is associated with a dysfunctional brain-gut-lung axis and that global overexpression of ACE2 (angiotensin-converting enzyme 2) rebalances this axis and protects against PH. ACE2 knockin and wild-type (WT; C57BL/6) mice were subjected to chronic hypoxia (10% FIO2) or room air for 4 weeks. Cardiopulmonary hemodynamics, histology, immunohistochemistry, and fecal 16S rRNA microbial gene analyses were evaluated. Hypoxia significantly increased right ventricular systolic pressure, sympathetic activity as well as the number and activation of microglia in the paraventricular nucleus of the hypothalamus in WT mice. This was associated with a significant increase in muscularis layer thickening and decreases in both villi length and goblet cells and altered gut microbiota. Global overexpression of ACE2 prevented changes in hypoxia-induced pulmonary and gut pathophysiology and established distinct microbial communities from WT hypoxia mice. Furthermore, WT mice subjected to fecal matter transfer from ACE2 knockin mice were resistant to hypoxia-induced PH compared with their controls receiving WT fecal matter transfer. These observations demonstrate that ACE2 ameliorates these hypoxia-induced pathologies and attenuates PH. The data implicate dysfunctional brain-gut-lung communication in PH and provide novel avenues for therapeutic interventions.}, }
@article {pmid32415349, year = {2020}, author = {Chen, H and Xu, C and Zhang, F and Liu, Y and Guo, Y and Yao, Q}, title = {The gut microbiota attenuates muscle wasting by regulating energy metabolism in chemotherapy-induced malnutrition rats.}, journal = {Cancer chemotherapy and pharmacology}, volume = {85}, number = {6}, pages = {1049-1062}, doi = {10.1007/s00280-020-04060-w}, pmid = {32415349}, issn = {1432-0843}, support = {2017ZZ004//Chinese Medicine Research Program of Zhejiang Province/ ; 2019ZA018//Chinese Medicine Research Program of Zhejiang Province/ ; }, abstract = {BACKGROUND: Malnutrition is a common clinical symptom in cancer patients after chemotherapy, which is characterized by muscle wasting and metabolic dysregulation. The regulation of muscle metabolism by gut microbiota has been studied recently. However, there is no direct convincing evidence proving that manipulating gut microbiota homeostasis could regulate muscle metabolic disorder caused by chemotherapy. Here, we investigate the potential role of gut microbiota in the regulation of the muscle metabolism in 5-fluorouracil (5-Fu)-induced malnutrition rat model.<br><br>METHODS: Male Sprague-Dawley rats were randomly divided into two groups (n = 8/group): control group and 5-Fu group. In the 5-Fu group, rats received 5-Fu (40 mg/kg/day) by intraperitoneal injection for 4 days, and all rats were raised for 8 days. Nutritional status, muscle function, muscle metabolites, and gut microbiota were assessed. Fecal microbiota transplantation (FMT) was applied to explore the potential regulation of gut microbiota on muscle metabolism.<br><br>RESULTS: 5-Fu-treated rats exhibited loss of body weight and food intake compared to control group. 5-Fu decreased the levels of total protein and albumin in serum, and significantly increased the levels of IL-6 and TNF-α in muscle tissue. Rats that received 5-Fu displayed concurrent reduction of muscle function and fiber size. Moreover, 5-Fu group showed a distinct profile of gut microbiota compared to control group, including the relative lower abundance of Firmicutes and a higher abundance of Proteobacteria and Verrucomicrobia. Fourteen differential muscle metabolites were identified between two groups, which were mainly related to glycolysis, amino acid metabolism, and TCA cycle pathway. Furthermore, fecal transplantation from healthy rats improved nutritional status and muscle function in 5-Fu-treated rats. Notably, FMT inhibited the inflammatory response in muscle, and reversed the changes of several differential muscle metabolites and energy metabolism in 5-Fu-treated rats.<br><br>CONCLUSIONS: Our study demonstrated that gut microbiota played an important role in the regulation of muscle metabolism and promoting muscle energy production in 5-Fu-induced malnutrition rats, suggesting the potential attenuation of chemotherapy-induced muscle wasting by manipulating gut microbiota homeostasis.}, }
@article {pmid32407705, year = {2020}, author = {Fritsch, J and Abreu, MT}, title = {Candida in IBD: Friend or Foe?.}, journal = {Cell host &amp; microbe}, volume = {27}, number = {5}, pages = {689-691}, doi = {10.1016/j.chom.2020.04.018}, pmid = {32407705}, issn = {1934-6069}, mesh = {Candida ; *Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Humans ; Inflammation ; }, abstract = {In this issue of Cell Host &amp; Microbe, Leonardi et al. demonstrate ulcerative colitis patients with high Candida responded best to fecal microbial transplant (FMT). However, decreased Candida post-treatment was associated with improved disease-suggesting that Candida reductions are associated with less inflammation. Pre-FMT Candida levels may identify FMT responders.}, }
@article {pmid32406264, year = {2020}, author = {Pereira, FV and Melo, ACL and Silva, MB and de Melo, FM and Terra, FF and Castro, IA and Perandini, LA and Miyagi, MT and Sato, FT and Origassa, CST and Hiyane, MI and Donato, J and Wasinski, F and Araujo, RC and Festuccia, WTL and da Silva, JS and Camara, NOS}, title = {Interleukin-6 and the Gut Microbiota Influence Melanoma Progression in Obese Mice.}, journal = {Nutrition and cancer}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/01635581.2020.1764982}, pmid = {32406264}, issn = {1532-7914}, abstract = {There is a strong correlation between obesity and cancer. Here, we investigated the influence of IL-6 and gut microbiota of obese mice in melanoma development. We first evaluated B16F10 melanoma growth in preclinical models for obesity: mice deficient for leptin (ob/ob) or adiponectin (AdpKO) and in wild-type mice (WT, C57BL/6J) fed a high-fat diet (HFD; 60% kcal from fat) for 12 weeks. The survival rates of ob/ob and HFD-fed mice were lower than those of their respective controls. AdpKO mice also died earlier than WT control mice. We then verified the involvement of IL-6 signaling in obese mice that were inoculated with melanoma cells. Both ob/ob and AdpKO mice had higher circulating IL-6 levels than wild-type mice. Melanoma tumor volumes in IL-6 KO mice fed an HFD were reduced compared to those of WT mice subjected to the same diet. Also evaluated the effect of microbiota in tumor development. Cohousing and fecal matter transfer experiments revealed that microbiota from ob/ob mice can stimulate tumor development in lean WT mice. Taken together, our data show that in some conditions IL-6 and the gut microbiota are key mediators that link obesity and melanoma.}, }
@article {pmid32405509, year = {2020}, author = {Wilcox, MH and McGovern, BH and Hecht, GA}, title = {The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridiumdifficile Infection: Current Understanding and Gap Analysis.}, journal = {Open forum infectious diseases}, volume = {7}, number = {5}, pages = {ofaa114}, doi = {10.1093/ofid/ofaa114}, pmid = {32405509}, issn = {2328-8957}, abstract = {The leading risk factor for Clostridioides (Clostridium) difficile infection (CDI) is broad-spectrum antibiotics, which lead to low microbial diversity, or dysbiosis. Current therapeutic strategies for CDI are insufficient, as they do not address the key role of the microbiome in preventing C. difficile spore germination into toxin-producing vegetative bacteria, which leads to symptomatic disease. Fecal microbiota transplant (FMT) appears to reduce the risk of recurrent CDI through microbiome restoration. However, a wide range of efficacy rates have been reported, and few placebo-controlled trials have been conducted, limiting our understanding of FMT efficacy and safety. We discuss the current knowledge gaps driven by questions around the quality and consistency of clinical trial results, patient selection, diagnostic methodologies, use of suppressive antibiotic therapy, and methods for adverse event reporting. We provide specific recommendations for future trial designs of FMT to provide improved quality of the clinical evidence to better inform treatment guidelines.}, }
@article {pmid32403888, year = {2020}, author = {Fan, LD and Liu, YM and Cheng, ML}, title = {[Probiotics enhance the efficacy of fecal microbiota transplantation in severe acute liver injury].}, journal = {Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology}, volume = {28}, number = {4}, pages = {345-350}, doi = {10.3760/cma.j.cn501113-20190823-00315}, pmid = {32403888}, issn = {1007-3418}, support = {81570543//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Bacteria/classification ; Chemical and Drug Induced Liver Injury/*therapy ; *Fecal Microbiota Transplantation ; Feces ; Gastrointestinal Microbiome ; Liver ; Male ; Mice ; Mice, Inbred BALB C ; Probiotics/*therapeutic use ; RNA, Ribosomal, 16S ; Random Allocation ; }, abstract = {Objective: To observe the changes of gut flora in mice, and explore the outcome of fecal microbiota transplantation combined with probiotics in the intervention of severe acute liver injury. Methods: Forty male BALB/c mice were selected and randomly divided into blank control group (10 mice), model group (10 mice), ordinary fecal microbiota transplantation group (10 mice), and fecal microbiota + probiotics transplantation group (10 mice). An intraperitoneal injection of d-galactosamine (D-GalN 3.0g/kg) was given to every group except the blank control group to induce severe acute liver injury model. Simultaneously, ordinary fecal microbiota transplantation group and fecal microbiota + probiotics transplantation group and modeling group were given enema solutions (once a day). After 48 hours, fetched serum was taken to detect alanine transaminase, aspartate transaminase and total bilirubin, and liver tissue was taken for pathological detection. The colonic content was used to extract DNA for 16S V3-V4 high-throughput sequencing. The results of sequencing were analyzed by using bioinformatics analysis; including OTU cluster analysis, α diversity analysis, β diversity analysis, and linear discriminant analysis effect size (Lefse) to find the bacteria with different colonic content characteristics in different groups of mice. Differences in clinical biochemical indicators between groups were compared using t-test, and the differences between 16S V3-V4 region sequencing results were compared using Wilcoxon test. Results: Model group mice serum biochemical parameters were higher than the other three groups, and the difference was statistically significant (P < 0.05). HE staining of liver sections showed severe inflammatory changes under the microscope in the model group. Ordinary fecal microbiota transplantation group and fecal microbiota + probiotic microbiota transplantation group had low levels of inflammation than the model group. The analysis results of 16S rRNA high-throughput sequencing showed that there was no statistically significant difference in Shannon's index between the blank control and the other three groups. Observed Species difference was statistically significant, and the gut flora composition varied greatly. Species number in the mice gut flora was increased with fecal microbiota transplantation. The results of β - diversity analysis showed that the difference between the blank control group and the other three groups was greater than that between the disease groups. The difference in the structure of the gut flora of the diseased mice in the fecal microbiota + probiotic transplantation group was mostly butyrate-producing bacteria. Conclusion: Fecal microbiota + probiotics enhance the therapeutic effect of fecal microbiota transplantation, improve liver inflammation, and increase the number of butyrate-producing bacteria in the gut.}, }
@article {pmid32402927, year = {2020}, author = {Shan, B and Ai, Z and Zeng, S and Song, Y and Song, J and Zeng, Q and Liao, Z and Wang, T and Huang, C and Su, D}, title = {Gut microbiome-derived lactate promotes to anxiety-like behaviors through GPR81 receptor-mediated lipid metabolism pathway.}, journal = {Psychoneuroendocrinology}, volume = {117}, number = {}, pages = {104699}, doi = {10.1016/j.psyneuen.2020.104699}, pmid = {32402927}, issn = {1873-3360}, abstract = {Accumulating evidence suggests that chronic stress could perturb the composition of the gut microbiota and induce host anxiety- and depression-like behaviors. In particular, microorganism-derived products that can directly or indirectly signal to the nervous system. This study sought to investigate whether high levels of Lactobacillus and lactate in the gut of rats under chronic unpredictable stress (CUS) were the factors leading to anxiety behavior. We collected faeces and blood samples in a sterile laboratory bench to study the microbiome and plasma metabolome from adult male rats age and environment matched healthy individuals. We sequenced the V3 and V4 regions of the 16S rRNA gene from faeces samples. UPLC-MS metabolomics were used to examine plasma samples. Search for potential biomarkers by combining the different data types. Finally, we found a regulated signaling pathway through the relative expression of protein and mRNA. Both lactate feeding and fecal microbiota transplantation caused behavioral abnormalities such as psychomotor malaise, impaired learning and memory in the recipient animals. These rats also showed inhibition of the adenylate cyclase (AC)-protein kinase A (PKA) pathway of lipolysis after activation of G protein-coupled receptor 81 (GPR81) by lactate in the liver, as well as increased tumor necrosis factor α (TNF-α), compared with healthy controls. Furthermore, we showed that sphingosine-1-phosphate receptor 2 (S1PR2) protein expression in hippocampus was reduced in chronic unpredictable stress compared to control group and its expression negatively correlates with symptom severity. Our study suggest that the gut microbiome-derived lactate promotes to anxiety-like behaviors through GPR81 receptor-mediated lipid metabolism pathway.}, }
@article {pmid32402176, year = {2020}, author = {DeFilipp, Z and Bloom, PP and Hohmann, EL and , }, title = {Drug-Resistant Bacteremia after Fecal Microbiota Transplant. Reply.}, journal = {The New England journal of medicine}, volume = {382}, number = {20}, pages = {1961-1962}, doi = {10.1056/NEJMc2002496}, pmid = {32402176}, issn = {1533-4406}, mesh = {*Bacteremia ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid32402175, year = {2020}, author = {Bleibtreu, A and Kapel, N and Galperine, T and , }, title = {Drug-Resistant Bacteremia after Fecal Microbiota Transplant.}, journal = {The New England journal of medicine}, volume = {382}, number = {20}, pages = {1961}, doi = {10.1056/NEJMc2002496}, pmid = {32402175}, issn = {1533-4406}, mesh = {*Bacteremia ; Escherichia coli ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid32402174, year = {2020}, author = {Chiu, CH and Chiu, CT}, title = {Drug-Resistant Bacteremia after Fecal Microbiota Transplant.}, journal = {The New England journal of medicine}, volume = {382}, number = {20}, pages = {1960-1961}, doi = {10.1056/NEJMc2002496}, pmid = {32402174}, issn = {1533-4406}, mesh = {*Bacteremia ; Escherichia coli ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid32402173, year = {2020}, author = {Janket, SJ and Ackerson, LK and Diamandis, EP}, title = {Drug-Resistant Bacteremia after Fecal Microbiota Transplant.}, journal = {The New England journal of medicine}, volume = {382}, number = {20}, pages = {1960}, doi = {10.1056/NEJMc2002496}, pmid = {32402173}, issn = {1533-4406}, mesh = {*Bacteremia ; Escherichia coli ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid32393794, year = {2020}, author = {Kim, SM and DeFazio, JR and Hyoju, SK and Sangani, K and Keskey, R and Krezalek, MA and Khodarev, NN and Sangwan, N and Christley, S and Harris, KG and Malik, A and Zaborin, A and Bouziat, R and Ranoa, DR and Wiegerinck, M and Ernest, JD and Shakhsheer, BA and Fleming, ID and Weichselbaum, RR and Antonopoulos, DA and Gilbert, JA and Barreiro, LB and Zaborina, O and Jabri, B and Alverdy, JC}, title = {Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {2354}, pmid = {32393794}, issn = {2041-1723}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; T32 GM007281/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Butyric Acid/metabolism ; *Fecal Microbiota Transplantation ; Feces/chemistry ; Gastrointestinal Microbiome ; Gastrointestinal Tract/pathology ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; *Immunity ; Interferon Regulatory Factor-3/metabolism ; Male ; Mice, Inbred C57BL ; Sepsis/*immunology/microbiology/*therapy ; Signal Transduction ; Transcription, Genetic ; }, abstract = {Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression.}, }
@article {pmid32392712, year = {2020}, author = {Iruzubieta, P and Medina, JM and Fernández-López, R and Crespo, J and de la Cruz, F}, title = {A Role for Gut Microbiome Fermentative Pathways in Fatty Liver Disease Progression.}, journal = {Journal of clinical medicine}, volume = {9}, number = {5}, pages = {}, pmid = {32392712}, issn = {2077-0383}, support = {BFU2017-86378-P//Ministerio de Ciencia y Tecnología/ ; Gilead Fellowship programme 2018//Gilead Sciences/ ; PI18/01304//Ministerio de Ciencia, Innovación y Universidades/ ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease in which environmental and genetic factors are involved. Although the molecular mechanisms involved in NAFLD onset and progression are not completely understood, the gut microbiome (GM) is thought to play a key role in the process, influencing multiple physiological functions. GM alterations in diversity and composition directly impact disease states with an inflammatory course, such as non-alcoholic steatohepatitis (NASH). However, how the GM influences liver disease susceptibility is largely unknown. Similarly, the impact of strategies targeting the GM for the treatment of NASH remains to be evaluated. This review provides a broad insight into the role of gut microbiota in NASH pathogenesis, as a diagnostic tool, and as a therapeutic target in this liver disease. We highlight the idea that the balance in metabolic fermentations can be key in maintaining liver homeostasis. We propose that an overabundance of alcohol-fermentation pathways in the GM may outcompete healthier, acid-producing members of the microbiota. In this way, GM ecology may precipitate a self-sustaining vicious cycle, boosting liver disease progression.}, }
@article {pmid32390701, year = {2020}, author = {Chen, HT and Huang, HL and Li, YQ and Xu, HM and Zhou, YJ}, title = {Therapeutic advances in non-alcoholic fatty liver disease: A microbiota-centered view.}, journal = {World journal of gastroenterology}, volume = {26}, number = {16}, pages = {1901-1911}, pmid = {32390701}, issn = {2219-2840}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent metabolic disorder with steadily increasing incidence rates worldwide, especially in the West. There are no drugs available at present to treat NAFLD, and the primary therapeutic options include weight loss and the combination of healthy diet and exercise. Therefore, novel interventions are required that can target the underlying risk factors. Gut microbiota is an &quot;invisible organ&quot; of the human body and vital for normal metabolism and immuno-modulation. The number and diversity of microbes differ across the gastrointestinal tract from the mouth to the anus, and is most abundant in the intestine. Since dysregulated gut microbiota is an underlying pathological factor of NAFLD, it is a viable therapeutic target that can be modulated by antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and microbial metabolites. In this review, we summarize the most recent advances in gut microbiota-targeted therapies against NAFLD in clinical and experimental studies, and critically evaluate novel targets and strategies for treating NAFLD.}, }
@article {pmid32388250, year = {2020}, author = {Wang, P and Wang, J and Li, D and Ke, W and Chen, F and Hu, X}, title = {Targeting the gut microbiota with resveratrol: a demonstration of novel evidence for the management of hepatic steatosis.}, journal = {The Journal of nutritional biochemistry}, volume = {81}, number = {}, pages = {108363}, doi = {10.1016/j.jnutbio.2020.108363}, pmid = {32388250}, issn = {1873-4847}, abstract = {Resveratrol is a natural polyphenol that has been reported to reduce the risk of obesity and nonalcoholic fatty liver disease (NAFLD). Recent evidence has demonstrated that the gut microbiota plays an important role in the protection against NAFLD and other metabolic diseases. The present study aimed to investigate the relationship between the gut microbiota and the beneficial effects of resveratrol on the amelioration of NAFLD in mice. We observed marked decreases in body weight and liver steatosis and improved insulin resistance in high-fat diet (HFD)-fed mice treated with resveratrol. Furthermore, we found that resveratrol treatment alleviated NAFLD in HFD-fed mice by improving the intestinal microenvironment, including gut barrier function and gut microbiota composition. On the one hand, resveratrol improved gut intestinal barrier integrity through the repair of intestinal mucosal morphology and increased the expression of physical barrier- and physiochemical barrier-related factors in HFD-fed mice. On the other hand, in HFD-fed mice, resveratrol supplementation modulated the gut bacterial composition. The resveratrol-induced gut microbiota was characterized by a decreased abundance of harmful bacteria, including Desulfovibrio, Lachnospiraceae_NK4A316_group and Alistipes, as well as an increased abundance of short-chain fatty acid (SCFA)-producing bacteria, such as Allobaculum, Bacteroides and Blautia. Moreover, transplantation of the HFDR-microbiota into HFD-fed mice sufficiently decreased body weight, liver steatosis and low-grade inflammation and improved hepatic lipid metabolism. Collectively, resveratrol would provide a potentially dietary intervention strategy against NAFLD through modulating the intestinal microenvironment.}, }
@article {pmid32375675, year = {2020}, author = {Zhang, T and Long, C and Cui, B and Buch, H and Wen, Q and Li, Q and Ding, X and Ji, G and Zhang, F}, title = {Colonic transendoscopic tube-delivered enteral therapy (with video): a prospective study.}, journal = {BMC gastroenterology}, volume = {20}, number = {1}, pages = {135}, pmid = {32375675}, issn = {1471-230X}, support = {81670495//National Natural Science Foundation of China/ ; 81600417//National Natural Science Foundation of China/ ; -//Jiangsu Province Creation Team and Leading Talents project/ ; LGY2017080//Top-notch Talent Research Projects/ ; -//public donated Intestine Initiative Foundation/ ; }, abstract = {BACKGROUND: Colonic transendoscopic enteral tubing (TET) refers to colonic transendoscopic tube-delivered enteral therapy. Colonic TET has been successfully used for frequent colonic administration of drugs or multiple fecal microbiota transplantations (FMTs). This prospective observational study aimed to evaluate possible factors affecting methodology, feasibility and safety of colonic TET.<br><br>METHODS: Patients who underwent colonic TET at our center from October 2014 to November 2018 were included. The feasibility, efficacy, and safety of TET were evaluated.<br><br>RESULTS: In total, 224 patients were analyzed. The success rate of TET was 100%. The median retention time of TET tube within the colonic lumen was 8.5 (IQR 7-11) days in 158 patients with tube falling out spontaneously, and the maximum retention time was up to 28 days. These patients were divided into the short-retention group (≤ 8.5 days) and the long-retention group (> 8.5 days). Univariate and multivariate analysis demonstrated that the type of endoscopic clip (p = 0.001) was an independent factor for the retention time. The larger clips as well as a greater number of clips significantly affected the retention time (p = 0.013). No severe adverse event was observed during and after TET.<br><br>CONCLUSIONS: Colonic TET is a feasible, practical, and safe colon-targeted drug delivery technique with a high degree of patients' satisfaction. Two to four large endoscopic clips are recommended to maintain stability of the TET tube within the colon for over 7 days.}, }
@article {pmid32373209, year = {2020}, author = {Liu, YJ and Tang, B and Wang, FC and Tang, L and Lei, YY and Luo, Y and Huang, SJ and Yang, M and Wu, LY and Wang, W and Liu, S and Yang, SM and Zhao, XY}, title = {Parthenolide ameliorates colon inflammation through regulating Treg/Th17 balance in a gut microbiota-dependent manner.}, journal = {Theranostics}, volume = {10}, number = {12}, pages = {5225-5241}, pmid = {32373209}, issn = {1838-7640}, abstract = {Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays an important pathogenic role. However, the current drugs for IBD treatment are far from optimal. Previous researches indicated that parthenolide (PTL) had not only anti-cancer properties but also strong anti-inflammatory activities. Rationale: To investigate the protective effect of PTL on colon inflammation and demonstrate the underlying gut microbiota-dependent mechanism. Methods: Colon inflammation severity in mouse model was measured by body weight change, mortality, colon length, disease activity index (DAI) score, H&amp;E staining and colonoscopy evaluation. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Luminex cytokine microarray and Enzyme-linked immunosorbent assay (ELISA) were conducted to measure the colon cytokines profile. The frequency of immune cells in lamina propria (LP) and spleen were phenotyped by flow cytometry. Results: The PTL-treated mice showed significantly relieved colon inflammation, as evidenced by a reduction in body weight loss, survival rate, shortening of colon length, DAI score, histology score and colonoscopy score. Notably, when the gut microbiota was depleted using antibiotic cocktails, the protective effect of PTL on colon inflammation disappeared. PTL treatment downregulated the level of proinflammatory cytokines, including IL-1β, TNF-α, IL-6, and IL-17A and upregulated the immunosuppressive cytokine IL-10 in colon tissue. 16S rRNA sequencing indicated that PTL-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased SCFAs production in PTL-treated mice. Additionally, PTL administration selectively upregulated the frequency of colonic regulatory T (Treg) cells as well as downregulated the ratio of colonic T helper type 17 (Th17) cells, improving the Treg/Th17 balance to maintain intestinal homeostasis. Gut microbiota depletion and fecal microbiota transplantation (FMT) was performed to confirm this gut microbiota-dependent mechanism. Conclusions: PTL ameliorated colon inflammation in a gut microbiota-dependent manner. The underlying protective mechanism was associated with the improved Treg/Th17 balance in intestinal mucosa mediated through the increased microbiota-derived SCFAs production. Collectively, our results demonstrated the role of PTL as a potential gut microbiota modulator to prevent and treat IBD.}, }
@article {pmid32368882, year = {2020}, author = {Nakov, R and Segal, JP and Settanni, CR and Bibbò, S and Gasbarrini, A and Cammarota, G and Ianiro, G}, title = {Microbiome: what intensivists should know.}, journal = {Minerva anestesiologica}, volume = {86}, number = {7}, pages = {777-785}, doi = {10.23736/S0375-9393.20.14278-0}, pmid = {32368882}, issn = {1827-1596}, abstract = {The standard conditions of critical illness (including sepsis, acute respiratory distress syndrome, and multiorgan failure) cause enormous global mortality and a growing economic burden. Increasing evidence suggests that critical illness may be associated with loss of commensal microbes and overgrowth of potentially pathogenic and inflammatory bacteria. This state could be associated with poor outcomes. Therefore, microbiota-targeted interventions are potentially attractive novel treatment options. Although the precise mechanisms of microbiome-directed treatments such as prebiotics, probiotics, and fecal microbiota transplantation remain to be determined, they can be utilized in the Intensive Care Unit (ICU) setting. The current review aims to offer intensivists an evidenced-based approach on what we currently know about the role of the microbiome in critical illness and how the microbiome could be targeted in the clinical practice to improve ICU-related outcomes.}, }
@article {pmid32363202, year = {2020}, author = {Chaitman, J and Ziese, AL and Pilla, R and Minamoto, Y and Blake, AB and Guard, BC and Isaiah, A and Lidbury, JA and Steiner, JM and Unterer, S and Suchodolski, JS}, title = {Fecal Microbial and Metabolic Profiles in Dogs With Acute Diarrhea Receiving Either Fecal Microbiota Transplantation or Oral Metronidazole.}, journal = {Frontiers in veterinary science}, volume = {7}, number = {}, pages = {192}, pmid = {32363202}, issn = {2297-1769}, abstract = {The aim was to characterize differences in fecal consistency, and fecal microbiota and metabolome profiles in dogs with acute diarrhea (AD) treated with either fecal microbiota transplantation as enema (FMT; n = 11) or oral metronidazole (MET; n = 7) for 7 days. On days 0, 7, and 28 fecal samples were obtained. Fecal samples from healthy dogs (HC; n = 14) were used for comparison. Samples were analyzed by the previously validated qPCR based canine Dysbiosis Index (DI; increased values indicate microbiota dysbiosis) and 16S rRNA gene sequencing. The fecal metabolome was analyzed using a previously validated targeted canine assay for fecal unconjugated bile acids, and untargeted metabolomics. Fecal consistency improved significantly in dogs treated with FMT and MET by day 7 and day 28 (p < 0.01) compared to day 0. However, on day 28 fecal consistency was significantly better in FMT compared to MET (p = 0.040). At day 0, dogs with AD had an altered microbiota indicated by significantly increased DI, decreased alpha-diversity, and altered beta-diversity. In the FMT group, the DI decreased over time, while MET led to a significant increase in the dysbiosis index at day 7 and 28 compared to FMT. Sequencing data revealed that in FMT microbial diversity and beta-diversity was similar to HC at day 28, while in MET these parameters were still significantly different from HC. In dogs treated with FMT, a decrease in cholic acid and the percentage of primary bile acids was observed, whereas treatment with metronidazole led to an increase in cholic acid at day 7 and an increase in percentage of primary bile acids over time. Based on untargeted metabolomics, dogs with AD had an altered fecal metabolome compared to HC. Dogs treated with FMT clustered closer to HC at day 28, while dogs treated with MET did not. In this pilot study, dogs with AD had significant differences in fecal microbiota and metabolome profiles. Dogs treated with MET still had altered microbial and metabolic profiles at day 28 compared to dogs treated with FMT or healthy dogs.}, }
@article {pmid32359480, year = {2020}, author = {Frisbee, AL and Petri, WA}, title = {Considering the Immune System during Fecal Microbiota Transplantation for Clostridioides difficile Infection.}, journal = {Trends in molecular medicine}, volume = {26}, number = {5}, pages = {496-507}, pmid = {32359480}, issn = {1471-499X}, support = {F31 AI136421/AI/NIAID NIH HHS/United States ; }, abstract = {Our understanding and utilization of fecal microbiota transplantation (FMT) has jump-started over the past two decades. Recent technological advancements in sequencing and metabolomics have allowed for better characterization of our intestinal microbial counterparts, triggering a surge of excitement in the fields of mucosal immunology and microbiology. This excitement is well founded, as demonstrated by 90% relapse-free cure rates in FMT treatment for recurrent Clostridioides difficile infections. Growing evidence suggests that in addition to bacterial factors, the host immune response during C. difficile infection greatly influences disease severity. In this review, we discuss recent advancements in understanding the interplay between immune cells and the microbiota and how they may relate to recovery from C. difficile through FMT therapy.}, }
@article {pmid32357144, year = {2020}, author = {Li, Y and Ning, L and Yin, Y and Wang, R and Zhang, Z and Hao, L and Wang, B and Zhao, X and Yang, X and Yin, L and Wu, S and Guo, D and Zhang, C}, title = {Age-related shifts in gut microbiota contribute to cognitive decline in aged rats.}, journal = {Aging}, volume = {12}, number = {9}, pages = {7801-7817}, pmid = {32357144}, issn = {1945-4589}, abstract = {Cognitive function declines during the aging process, meanwhile, gut microbiota of the elderly changed significantly. Although previous studies have reported the effect of gut microbiota on learning and memory, all the reports were based on various artificial interventions to change the gut microbiota without involvement of aging biological characteristics. Here, we investigated the effect of aged gut microbiota on cognitive function by using fecal microbiota transplantation (FMT) from aged to young rats. Results showed that FMT impaired cognitive behavior in young recipient rats; decreased the regional homogeneity in medial prefrontal cortex and hippocampus; changed synaptic structures and decreased dendritic spines; reduced expression of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate receptor NR1 subunit, and synaptophysin; increased expression of advanced glycation end products (AGEs) and receptor for AGEs (RAGE). All these behavioral, brain structural and functional alterations induced by FMT reflected cognitive decline. In addition, FMT increased levels of pro-inflammatory cytokines and oxidative stress in young rats, indicating that inflammation and oxidative stress may underlie gut-related cognitive decline in aging. This study provides direct evidence for the contribution of gut microbiota to the cognitive decline during normal aging and suggests that restoring microbiota homeostasis in the elderly may improve cognitive function.}, }
@article {pmid32356257, year = {2020}, author = {Agrawal, G}, title = {Fecal Microbiota Transplantation for Clostridioides difficile in High-Risk Older Adults: Treat Early, Treat Often.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-020-06291-6}, pmid = {32356257}, issn = {1573-2568}, }
@article {pmid32354351, year = {2020}, author = {Arnoriaga-Rodríguez, M and Mayneris-Perxachs, J and Burokas, A and Pérez-Brocal, V and Moya, A and Portero-Otin, M and Ricart, W and Maldonado, R and Fernández-Real, JM}, title = {Gut bacterial ClpB-like gene function is associated with decreased body weight and a characteristic microbiota profile.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {59}, pmid = {32354351}, issn = {2049-2618}, abstract = {BACKGROUND: The chaperone ClpB, a bacterial protein, is a conformational antigen-mimetic of α-melanocyte-stimulating hormone (α-MSH) implicated in body weight regulation in mice. We here investigated the potential associations of gut bacterial ClpB-like gene function with obesity status and gut microbiota in humans.<br><br>RESULTS: Gut microbiota ClpB KEGG function was negatively associated with body mass index, waist circumference, and total fat mass (DEXA). The relative abundance (RA) of several phyla and families directly associated with ClpB was decreased in subjects with obesity. Specifically, the RA of Rikenellaceae, Clostridiaceae and not assigned Firmicutes were lower in subjects with obesity and positively associated with gut bacterial ClpB-like gene function (not assigned Firmicutes (r = 0.405, FDR = 2.93 × 10-2), Rikenellaceae (r = 0.217, FDR = 0.031), and Clostridiaceae (r = 0.239, FDR = 0.017)). The gut bacterial ClpB-like gene function was also linked to specific plasma metabolites (hippuric acid and 3-indolepropionic acid) and fecal lupeol. The α-MSH-like epitope similar to that of Escherichia coli ClpB was also identified in some sequences of those bacterial families. After fecal transplantation from humans to mice, the families that more contributed to ClpB-like gene function in humans were also associated with ClpB-like gene function in mice after adjusting for the donor's body mass index (not assigned Firmicutes (r = 0.621, p = 0.003), Prevotellaceae (r = 0.725, p = 4.1 × 10-7), Rikenellaceae (r = 0.702, p = 3.9 × 10-4), and Ruminococcaceae (r = 0.526, p = 0.014)). Clostridiaceae (r = - 0.445, p = 0.038) and Prevotellaceae RA (r = - 0.479, p = 0.024) and were also negatively associated with weight gain in mice. The absolute abundance (AA) of Prevotellaceae in mice was also positively associated with the gut bacterial ClpB-like gene function in mice. DESeq2 identified species of Prevotellaceae, both negatively associated with mice' weight gain and positively with gut bacterial ClpB-like gene function.<br><br>CONCLUSIONS: In summary, gut bacterial ClpB-like gene function is associated with obesity status, a specific gut microbiota composition and a plasma metabolomics profile in humans that could be partially transplanted to mice. Video Abstract.}, }
@article {pmid32354259, year = {2020}, author = {Lee, J and d'Aigle, J and Atadja, L and Quaicoe, V and Honarpisheh, P and Ganesh, BP and Hassan, A and Graf, J and Petrosino, J and Putluri, N and Zhu, L and Durgan, DJ and Bryan, RM and McCullough, LD and Venna, VR}, title = {Gut Microbiota-Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice.}, journal = {Circulation research}, volume = {127}, number = {4}, pages = {453-465}, pmid = {32354259}, issn = {1524-4571}, support = {R01 NS094543/NS/NINDS NIH HHS/United States ; TL1 TR003169/TR/NCATS NIH HHS/United States ; R01 NS103592/NS/NINDS NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; RF1 AG058463/AG/NIA NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; }, abstract = {RATIONALE: The elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outcomes can be influenced by the composition of gut microbiome. However, the potential benefits of manipulating the gut microbiome after injury is unknown.<br><br>OBJECTIVE: To determine if restoring youthful gut microbiota after stroke aids in recovery in aged subjects, we altered the gut microbiome through young fecal transplant gavage in aged mice after experimental stroke. Further, the effect of direct enrichment of selective bacteria producing short-chain fatty acids (SCFAs) was tested as a more targeted and refined microbiome therapy.<br><br>METHODS AND RESULTS: Aged male mice (18-20 months) were subjected to ischemic stroke by middle cerebral artery occlusion. We performed fecal transplant gavage 3 days after middle cerebral artery occlusion using young donor biome (2-3 months) or aged biome (18-20 months). At day 14 after stroke, aged stroke mice receiving young fecal transplant gavage had less behavioral impairment, and reduced brain and gut inflammation. Based on data from microbial sequencing and metabolomics analysis demonstrating that young fecal transplants contained much higher SCFA levels and related bacterial strains, we selected 4 SCFA-producers (Bifidobacterium longum, Clostridium symbiosum, Faecalibacterium prausnitzii, and Lactobacillus fermentum) for transplantation. These SCFA-producers alleviated poststroke neurological deficits and inflammation, and elevated gut, brain and plasma SCFA concentrations in aged stroke mice.<br><br>CONCLUSIONS: This is the first study suggesting that the poor stroke recovery in aged mice can be reversed via poststroke bacteriotherapy following the replenishment of youthful gut microbiome via modulation of immunologic, microbial, and metabolomic profiles in the host.}, }
@article {pmid32353108, year = {2020}, author = {Payen, M and Nicolis, I and Robin, M and Michonneau, D and Delannoye, J and Mayeur, C and Kapel, N and Berçot, B and Butel, MJ and Le Goff, J and Socié, G and Rousseau, C}, title = {Functional and phylogenetic alterations in gut microbiome are linked to graft-versus-host disease severity.}, journal = {Blood advances}, volume = {4}, number = {9}, pages = {1824-1832}, pmid = {32353108}, issn = {2473-9537}, abstract = {Acute graft-versus-host disease (aGVHD) is the main complication of hematopoietic stem cell transplantation (HSCT). Changes in gut microbiota composition have been associated with subsequent aGVHD, and reconstitution of healthy microbiota is currently being explored as a therapeutic approach. However, the specific actors in the intestinal ecosystem involved in the pathologic process at the time of aGVHD onset are not yet fully known. We prospectively collected stool samples from patients who underwent allogeneic HSCT. Patients sampled at aGVHD onset were compared with non-GVHD patients. To identify phylogenetic and functional signatures of the disease process, we determined fecal short-chain fatty acid (SFCA) profiles and used high-throughput DNA sequencing and real-time quantitative polymerase chain reaction to assess the microbiota composition. Microbiota alterations were highly specific of gastrointestinal (GI) aGVHD severity. Bacterial biomass and α-diversity were lower in severe aGVHD. We identified several bacterial signatures associated with severe aGVHD at disease onset; a negative correlation was observed with anaerobic bacteria of the Lachnospiraceae, especially the Blautia genus, and Ruminococcaceae families. In parallel, in severe aGVHD patients, we showed a dramatic decrease in the levels of the main SFCAs: acetate (75.8%), propionate (95.8%), and butyrate (94.6%). Mild aGVHD patients were characterized by conserved levels of propionate and Blautia propionate producers. Butyrate was significantly decreased in all GI aGVHD stages, representing a potential diagnostic marker of the disease. Specific microbiota and metabolic alterations were thus associated with aGVHD severity and may be useful for diagnostic and pathophysiologic purposes.}, }
@article {pmid32350099, year = {2020}, author = {Korach-Rechtman, H and Hreish, M and Fried, C and Gerassy-Vainberg, S and Azzam, ZS and Kashi, Y and Berger, G}, title = {Intestinal Dysbiosis in Carriers of Carbapenem-Resistant Enterobacteriaceae.}, journal = {mSphere}, volume = {5}, number = {2}, pages = {}, pmid = {32350099}, issn = {2379-5042}, abstract = {Infection with carbapenem-resistant Enterobacteriaceae (CRE) has become an important challenge in health care settings and a growing concern worldwide. Since infection is preceded by colonization, an understanding of the latter may reduce CRE infections. We aimed to characterize the gut microbiota in CRE carriers, assuming that microbiota alterations precede CRE colonization. We evaluated the gut microbiota using 16S rRNA gene sequencing extracted of fecal samples collected from hospitalized CRE carriers and two control groups, hospitalized noncarriers and healthy adults. The microbiota diversity and composition in CRE-colonized patients differed from those of the control group participants. These CRE carriers displayed lower phylogenetic diversity and dysbiotic microbiota, enriched with members of the family Enterobacteriaceae Concurrent with the enrichment in Enterobacteriaceae, a depletion of anaerobic commensals was observed. Additionally, changes in several predicted metabolic pathways were observed for the CRE carriers. Concomitantly, we found higher prevalence of bacteremia in the CRE carriers. Several clinical factors that might induce changes in the microbiota were examined and found to be insignificant between the groups. The compositional and functional changes in the microbiota of CRE-colonized patients are associated with increased risk for systemic infection. Our study results provide justification for attempts to restore the dysbiotic microbiota with probiotics or fecal transplantation.IMPORTANCE The gut microbiota plays important roles in the host's normal function and health, including protection against colonization by pathogenic bacteria. Alterations in the gut microbial profile can potentially serve as an early diagnostic tool, as well as a therapeutic strategy against colonization by and carriage of harmful bacteria, including antibiotic-resistant pathogens. Here, we show that the microbiota of hospitalized patients demonstrated specific taxa which differed between carriers of carbapenem-resistant Enterobacteriaceae (CRE) and noncarriers. The difference in the microbiota also dictates alterations in microbiome-specific metabolic capabilities, in association with increased prevalence of systemic infection. Reintroducing specific strains and/or correction of dysbiosis with probiotics or fecal transplantation may potentially lead to colonization by bacterial taxa responsible for protection against or depletion of antibiotic-resistant pathogens.}, }
@article {pmid32346376, year = {2020}, author = {Zhang, Y and Liu, Q and Yu, Y and Wang, M and Wen, C and He, Z}, title = {Early and Short-Term Interventions in the Gut Microbiota Affects Lupus Severity, Progression, and Treatment in MRL/lpr Mice.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {628}, pmid = {32346376}, issn = {1664-302X}, abstract = {There have been attempts to reveal the possible associations between systemic lupus erythematosus (SLE) and gut microbiota. Using MRL/lpr mice, this study was performed to reveal whether early and short-term interventions in gut microbiota affect lupus. MRL/lpr mice were treated with antibiotics or fecal microbiota transplantation (FMT) before onset. Then, prednisone was used to treat the lupus mice with initially different gut microbiota compositions. The compositions of gut microbiota were assessed by the V3-V4 region of 16S rRNA gene sequence. Early and short-term antibiotics exposure aggravated lupus severity by depleting beneficial gut microbiota for lupus, such as Lactobacillus and Bifidobacterium, and enriching harmful gut microbiota for lupus, such as Klebsiella and Proteus. FMT alleviated lupus severity by renovating the antibiotic-induced dysbiosis of gut microbiota in the following 1 week after antibiotics exposure. Besides, short-term antibiotics exposure before onset imposed no significant effects on lupus progression, but the following one week of FMT suppressed lupus progression. Moreover, the short-term antibiotics or FMT before onset inhibited the therapeutic efficiency of prednisone on lupus from 9 to 13 weeks old of MRL/lpr mice. These data demonstrate that the gut microbiota before onset is important for lupus severity, progression and treatment.}, }
@article {pmid32330797, year = {2020}, author = {Wang, H and Zhang, S and Yang, F and Xin, R and Wang, S and Cui, D and Sun, Y}, title = {The gut microbiota confers protection in the CNS against neurodegeneration induced by manganism.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {127}, number = {}, pages = {110150}, doi = {10.1016/j.biopha.2020.110150}, pmid = {32330797}, issn = {1950-6007}, abstract = {Among all types of pollution, heavy metals are considered the greatest threat to human health, and heavy metals are associated with an increased risk of cardiovascular disease, coronary heart disease and neurodegenerative disorders. Manganese (Mn) exposure is well reported to exert neurotoxicity and various neurodegenerative disorders, but the mechanisms are not clear. The gut microbiota plays a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities. The changes in chemical signaling, metabolism and gut microbiota associated with Mn exposure have provided deeper insight into the neurotoxic mechanism of Mn. We observed that Mn exposure increases host manganic bioaccumulation, and β-amyloid (Aβ), receptor-interacting protein kinase 3 (RIP3) and caspase-3 production in the brain, and causes hippocampal degeneration and necrosis. Mn exposure led to decreased gut bacterial richness, especially for Prevotellaceae, Fusobacteriaceae and Lactobacillaceae. In addition, Mn exposure altered the metabolism of tryptamine, taurodeoxycholic acid, β-hydroxypyruvic acid and urocanic acid. Meanwhile, we found correlations between the abundance of certain bacterial species and the level of tryptamine, taurodeoxycholic acid, β-hydroxypyruvic acid and urocanic acid. Fecal microbiome transplantation from normal rats could alleviate the neurotoxicity of Mn exposure by shaping the gut microbiota. Our findings highlight the role of gut dysbiosis-promoted neurotoxicity in Mn exposure and suggest a novel therapeutic strategy of remodeling the gut microbiota.}, }
@article {pmid32330075, year = {2020}, author = {Nie, X and Li, L and Yi, M and Qin, W and Zhao, W and Li, F and Wu, B and Yuan, X}, title = {The Intestinal Microbiota Plays as a Protective Regulator Against Radiation Pneumonitis.}, journal = {Radiation research}, volume = {194}, number = {1}, pages = {52-60}, doi = {10.1667/RR15579.1}, pmid = {32330075}, issn = {1938-5404}, abstract = {Radiation pneumonitis is a common complication of thoracic irradiation for lung cancer patients. The healthy gut microbiota plays an important role in the local mucosal defense process as well as pulmonary immunomodulation of the host. However, the effect of the intestinal microbiota on radiation pneumonitis is not well understood. Here we studied how the intestinal microbiota affected the host response to radiation pneumonitis. C57BL/6 mice were administered antibiotics to induce disequilibrium in the gut microbiota, and subsequently irradiated. We found that the intestinal microbiota served as a protective mediator against radiation pneumonitis, as indicated by decreased body weight and increased mortality in antibiotic-treated mice. In mice with gut microbiota disequilibrium, more serious pathological lung damage was observed at two and four weeks postirradiation. Fecal microbiota transplantation into irradiated mice led to improvement from radiation-induced inflammation two weeks postirradiation. High-throughput sequencing of murine feces displayed conversion of flora diversity, bacterial composition and community structure in the absence of normal intestinal flora. We filtered the potentially important species among the gut microbiota and considered that the tissue-type plasminogen activator might be involved in the inflammatory process. This study reveals that the gut microbiota functions as a protective regulator against radiation pneumonitis. Additionally, fecal microbiota transplantation was shown to alleviate lung injury in the irradiated model. The protective role of the healthy gut microbiota and the utilization of the gut-lung axis show potential for innovative therapeutic strategies in radiation-induced lung injury.}, }
@article {pmid32326509, year = {2020}, author = {Nicco, C and Paule, A and Konturek, P and Edeas, M}, title = {From Donor to Patient: Collection, Preparation and Cryopreservation of Fecal Samples for Fecal Microbiota Transplantation.}, journal = {Diseases (Basel, Switzerland)}, volume = {8}, number = {2}, pages = {}, pmid = {32326509}, issn = {2079-9721}, abstract = {Fecal Microbiota Transplantation (FMT) is suggested as an efficacious therapeutic strategy for restoring intestinal microbial balance, and thus for treating disease associated with alteration of gut microbiota. FMT consists of the administration of fresh or frozen fecal microorganisms from a healthy donor into the intestinal tract of diseased patients. At this time, in according to healthcare authorities, FMT is mainly used to treat recurrent Clostridium difficile. Despite the existence of a few existing stool banks worldwide and many studies of the FMT, there is no standard method for producing material for FMT, and there are a multitude of factors that can vary between the institutions. The main constraints for the therapeutic uses of FMT are safety concerns and acceptability. Technical and logistical issues arise when establishing such a non-standardized treatment into clinical practice with safety and proper governance. In this context, our manuscript describes a process of donor safety screening for FMT compiling clinical and biological examinations, questionnaires and interviews of donors. The potential risk of transmission of SARS-CoV-2 virus by the use of fecal microbiota for transplantation must be taken urgently into consideration. We discuss a standardized procedure of collection, preparation and cryopreservation of fecal samples through to the administration of material to patients, and explore the risks and limits of this method of FMT. The future success of medicine employing microbiota transplantation will be tightly related to its modulation and manipulation to combat dysbiosis. To achieve this goal, standard and strict methods need to be established before performing any type of FMT.}, }
@article {pmid32319703, year = {2020}, author = {Vangoitsenhoven, R and Cresci, GAM}, title = {Role of Microbiome and Antibiotics in Autoimmune Diseases.}, journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition}, volume = {35}, number = {3}, pages = {406-416}, doi = {10.1002/ncp.10489}, pmid = {32319703}, issn = {1941-2452}, support = {R00AA023266//GAC National Institutes of Health, NIAAA/ ; }, abstract = {The global rise in the incidence of autoimmune diseases has paralleled the widespread use of antibiotics. Recently, the gut microbiome has been shown to be key in the development and maturation of a normal immune system, and a range of microbial disturbances have been associated with the development and activity of several autoimmune diseases. Here, we aim to provide an overview of the mechanistic crosstalk between the human microbiome, the immune system, and antibiotics. The disease-associated microbial gut dysbiosis, the potential role of antibiotics in the development and treatment of autoimmune diseases, and the manipulation of the gut microbiome with prebiotics and probiotics is discussed using 2 key autoimmune diseases as an example: inflammatory bowel disease and type 1 diabetes. Although some data suggest that widespread use of antibiotics may facilitate autoimmunity through gut dysbiosis, there are also data to suggest antibiotics may hold the potential to improve disease activity. Currently, the effect of fecal microbiota transplantation on several autoimmune diseases is being studied in clinical trials, and several preclinical studies are revealing promising results with probiotic and prebiotic therapies.}, }
@article {pmid32319196, year = {2020}, author = {Takashima, S and Tanaka, F and Kawaguchi, Y and Usui, Y and Fujimoto, K and Nadatani, Y and Otani, K and Hosomi, S and Nagami, Y and Kamata, N and Taira, K and Tanigawa, T and Watanabe, T and Imoto, S and Uematsu, S and Fujiwara, Y}, title = {Proton pump inhibitors enhance intestinal permeability via dysbiosis of gut microbiota under stressed conditions in mice.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {32}, number = {7}, pages = {e13841}, doi = {10.1111/nmo.13841}, pmid = {32319196}, issn = {1365-2982}, abstract = {BACKGROUND: Intestinal permeability and psychological stress are considered the key mechanism(s) in functional dyspepsia (FD). Although proton pump inhibitors (PPIs) are commonly used for the treatment of FD, the effect of PPIs on intestinal permeability has not been elucidated. This study investigated the effect of PPI on intestinal permeability under stressed conditions.<br><br>METHODS: C57BL/6J mice were subjected to water avoidance stress (WAS) and administered rabeprazole (40 mg/kg) or vehicle treatment (VT). We then evaluated intestinal permeability both in vivo and ex vivo using plasma fluorescein isothiocyanate-dextran and by assessing the paracellular permeability and transepithelial electrical resistance (TEER) in an Ussing chamber, respectively. Furthermore, we evaluated the effect of PPI-treated fecal microbiota transplant (FMT) on intestinal permeability in vivo. Microbiota profiles of donor feces were assessed by 16S rRNA gene analysis using MiSeq and QIIME2.<br><br>KEY RESULTS: In the WAS treatment, PPI significantly enhanced intestinal permeability in vivo compared to that in VT. Moreover, PPI significantly increased paracellular permeability and decreased TEER in the duodenum and jejunum, respectively, compared to those in VT under stressed conditions. Moreover, both vasoactive intestinal peptide (VIP) receptor antagonist and ketotifen significantly reversed the effect of PPI on intestinal permeability. Furthermore, PPI-treated FMT significantly increased the intestinal permeability in vivo compared to that in vehicle-treated FMT. Proton pump inhibitors treatment altered the gut microbiota composition, indicating that PPI induced dysbiosis.<br><br>CONCLUSIONS AND INFERENCES: Under stressed conditions, PPI enhances intestinal permeability via dysbiosis of gut microbiota. Vasoactive intestinal peptide and mast cells are also implicated in the underlying mechanisms.}, }
@article {pmid32318580, year = {2020}, author = {Gerussi, A and Lucà, M and Cristoferi, L and Ronca, V and Mancuso, C and Milani, C and D'Amato, D and O'Donnell, SE and Carbone, M and Invernizzi, P}, title = {New Therapeutic Targets in Autoimmune Cholangiopathies.}, journal = {Frontiers in medicine}, volume = {7}, number = {}, pages = {117}, pmid = {32318580}, issn = {2296-858X}, abstract = {Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are autoimmune cholangiopathies characterized by limited treatment options. A more accurate understanding of the several pathways involved in these diseases has fostered the development of novel and promising targeted drugs. For PBC, the characterization of the role of farnesoid X receptor (FXR) and perixosome-proliferator activated receptor (PPAR) has paved the way to several clinical trials including different molecules with choleretic and antinflammatory action. Conversely, different pathogenetic models have been proposed in PSC such as the &quot;leaky gut&quot; hypothesis, a dysbiotic microbiota or a defect in mechanisms protecting against bile acid toxicity. Along these theories, new treatment approaches have been developed, ranging from drugs interfering with trafficking of lymphocytes from the gut to the liver, fecal microbiota transplantation or new biliary acids with possible immunomodulatory potential. Finally, for both diseases, antifibrotic agents are under investigation. In this review, we will illustrate current understanding of molecular mechanisms in PBC and PSC, focusing on actionable biological pathways for which novel treatments are being developed.}, }
@article {pmid32318067, year = {2020}, author = {Zhou, B and Yuan, Y and Zhang, S and Guo, C and Li, X and Li, G and Xiong, W and Zeng, Z}, title = {Intestinal Flora and Disease Mutually Shape the Regional Immune System in the Intestinal Tract.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {575}, pmid = {32318067}, issn = {1664-3224}, abstract = {The intestinal tract is the largest digestive organ in the human body. It is colonized by, and consistently exposed to, a myriad of microorganisms, including bifidobacteria, lactobacillus, Escherichia coli, enterococcus, clostridium perfringens, and pseudomonas. To protect the body from potential pathogens, the intestinal tract has evolved regional immune characteristics. These characteristics are defined by its unique structure, function, and microenvironment, which differ drastically from those of the common central and peripheral immune organs. The intestinal microenvironment created by the intestinal flora and its products significantly affects the immune function of the region. In turn, specific diseases regulate and influence the composition of the intestinal flora. A constant interplay occurs between the intestinal flora and immune system. Further, the intestinal microenvironment can be reconstructed by probiotic use or microbiota transplantation, functioning to recalibrate the immune homeostasis, while also contributing to the treatment or amelioration of diseases. In this review, we summarize the relationship between the intestinal flora and the occurrence and development of diseases as an in-turn effect on intestinal immunity. We also discuss improved immune function as it relates to non-specific and specific immunity. Further, we discuss the proliferation, differentiation and secretion of immune cells, within the intestinal region following remodeling of the microenvironment as a means to ameliorate and treat diseases. Finally, we suggest strategies for improved utilization of intestinal flora.}, }
@article {pmid32317112, year = {2020}, author = {Gryp, T and De Paepe, K and Vanholder, R and Kerckhof, FM and Van Biesen, W and Van de Wiele, T and Verbeke, F and Speeckaert, M and Joossens, M and Couttenye, MM and Vaneechoutte, M and Glorieux, G}, title = {Gut microbiota generation of protein-bound uremic toxins and related metabolites is not altered at different stages of chronic kidney disease.}, journal = {Kidney international}, volume = {97}, number = {6}, pages = {1230-1242}, doi = {10.1016/j.kint.2020.01.028}, pmid = {32317112}, issn = {1523-1755}, abstract = {Chronic kidney disease (CKD) is characterized by accumulation of protein-bound uremic toxins such as p-cresyl sulfate, p-cresyl glucuronide, indoxyl sulfate and indole-3-acetic acid, which originate in the gut. Intestinal bacteria metabolize aromatic amino acids into p-cresol and indole, (further conjugated in the colon mucosa and liver) and indole-3-acetic acid. Here we measured fecal, plasma and urine metabolite concentrations; the contribution of gut bacterial generation to plasma protein-bound uremic toxins accumulation; and influx into the gut of circulating protein-bound uremic toxins at different stages of CKD. Feces, blood and urine were collected from 14 control individuals and 141 patients with CKD. Solutes were quantified by ultra-high performance liquid chromatography. To assess the rate of bacterial generation of p-cresol, indole and indole-3-acetic acid, fecal samples were cultured ex vivo. With CKD progression, an increase in protein-bound uremic toxins levels was observed in plasma, whereas the levels of these toxins and their precursors remained the same in feces and urine. Anaerobic culture of fecal samples showed no difference in ex vivo p-cresol, indole and indole-3-acetic acid generation. Therefore, differences in plasma protein-bound uremic toxins levels between different CKD stages cannot be explained by differences in bacterial generation rates in the gut, suggesting retention due to impaired kidney function as the main contributor to their increased plasma levels. Thus, as fractional clearance decreased with the progression of CKD, tubular clearance appeared to be more affected than the glomerular filtration rate, and there was no net increase in protein-bound uremic toxins influx into the gut lumen with increased plasma levels.}, }
@article {pmid32316741, year = {2020}, author = {Li, J and Yang, X and Zhou, X and Cai, J}, title = {The Role and Mechanism of Intestinal Flora in Blood Pressure Regulation and Hypertension Development.}, journal = {Antioxidants &amp; redox signaling}, volume = {}, number = {}, pages = {}, doi = {10.1089/ars.2020.8104}, pmid = {32316741}, issn = {1557-7716}, abstract = {Significance: Hypertension (HTN) has a complex etiology that is characterized by genetic and environmental factors. It has become a global health burden leading to cardiovascular diseases and kidney diseases, ultimately progressing to premature death. Accumulating evidence indicated that gut microbiome was associated with metabolic disorders and inflammation, which were closely linked to HTN. Recent Advances: Recent studies using bacterial genomic analysis and fecal microbiota transplantation as well as many lines of seminal evidence demonstrated that aberrant gut microbiome was significantly associated with HTN. The intestinal microbiome of both patients and animals with HTN had decreased bacterial diversity, disordered microbial structure and functions, and altered end products of fermentation. Gut dysbiosis and metabolites of the gut microbiota play an important role in blood pressure (BP) control, and they are therefore responsible for developing HTN. Critical Issues: This study aimed at focusing on the recent advances in understanding the role played by gut bacteria and the mechanisms underlying the pathological milieu that induced elevated BP and led to HTN pathogenesis. Potential intervention strategies targeting the correction of gut dysbiosis to improve HTN development were summarized. Future Directions: Larger numbers of fecal transplants from participants with HTN should be carried out to examine the magnitude of BP changes with the replacement of the gut microbiome. The proposed mechanisms for the gut in regulating BP remain to be verified. Whether intervention strategies using probiotics, dietary interventions, bacteriophages, and fecal transplants are feasible for individuals with HTN remains to be explored.}, }
@article {pmid32310042, year = {2020}, author = {De Musis, C and Granata, L and Dallio, M and Miranda, A and Gravina, AG and Romano, M}, title = {Inflammatory Bowel Diseases: The Role of Gut Microbiota.}, journal = {Current pharmaceutical design}, volume = {26}, number = {25}, pages = {2951-2961}, doi = {10.2174/1381612826666200420144128}, pmid = {32310042}, issn = {1873-4286}, abstract = {Inflammatory bowel diseases (IBD) are chronic multifactorial diseases characterized by partially unclear pathogenic mechanisms including changes in intestinal microbiota. Despite the microbiota, alteration is well established in IBD patients, as reported by 16RNA sequencing analysis, an important goal is to define if it is just a consequence of the disease progression or a trigger factor of the disease itself. To date, gut microbiota composition and gut microbiota-related metabolites seem to affect the host healthy state both by modulating metabolic pathways or acting on the expression of different genes through epigenetic effects. Because of this, it has been suggested that intestinal microbiota might represent a promising therapeutic target for IBD patients. The aim of this review is to summarize both the most recent acquisitions in the field of gut microbiota and its involvement in intestinal inflammation together with the available strategies for the modulation of microbiota, such as prebiotics and/or probiotics administration or fecal microbiota transplantation.}, }
@article {pmid32307472, year = {2020}, author = {Hu, X and Mu, R and Xu, M and Yuan, X and Jiang, P and Guo, J and Cao, Y and Zhang, N and Fu, Y}, title = {Gut microbiota mediate the protective effects on endometritis induced by Staphylococcus aureus in mice.}, journal = {Food &amp; function}, volume = {11}, number = {4}, pages = {3695-3705}, doi = {10.1039/c9fo02963j}, pmid = {32307472}, issn = {2042-650X}, abstract = {Endometritis, the inflammation of the endometrial lining caused by bacterial pathogens, is associated with reproductive failure. Recent studies have shown that gut microbiota play an important role in infectious diseases. However, the roles of the gut microbiota in endometritis remain unclear. Here, we assessed the effects and mechanisms of the gut microbiota during endometritis induced by Staphylococcus aureus (S. aureus). A mouse gut microbiota-dysbiosis model was established by a mixture of antibiotics (Abx) and subsequently, a model of endometritis was established by the uterine perfusion of S. aureus. Fecal microbiota transplantation (FMT) was performed to evaluate the relationship between gut microbiota and endometritis. The results showed that the mice with gut microbiota-dysbiosis developed uterine inflammation, while this inflammatory response of the uterus was alleviated in mice with FMT to gut microbiota-dysbiosis. In addition, S. aureus-induced endometritis was greater in severity in the mice with gut dysbiosis as compared to the untreated mice. Moreover, these effects were reversed in mice with FMT to the gut microbiota-dysbiosis. GC-MS analysis demonstrated that the levels of short-chain fatty acids (SCFAs) in the feces of mice with gut microbiota-dysbiosis significantly decreased and pretreatment with sodium butyrate or sodium propionate increased the concentrations of butyrate or propionate in both the circulation and uterine tissues, thereby reducing the severity of endometritis induced by S. aureus. In addition, the increased pathogen load in the uteri of the mice with gut microbiota-dysbiosis was associated with a reduction in the phagocytic ability and responsiveness of neutrophils. In conclusion, the gut microbiota offer a protective effect against S. aureus-induced endometritis by regulating the levels of SCFAs and maintaining the phagocytic ability and responsiveness of neutrophils.}, }
@article {pmid32306706, year = {2020}, author = {Mahajan, R and Midha, V and Singh, A and Mehta, V and Gupta, Y and Kaur, K and Sudhakar, R and Singh Pannu, A and Singh, D and Sood, A}, title = {Incidental benefits after fecal microbiota transplant for ulcerative colitis.}, journal = {Intestinal research}, volume = {18}, number = {3}, pages = {337-340}, pmid = {32306706}, issn = {1598-9100}, abstract = {Gut dysbiosis can result in several diseases, including infections (Clostridium difficile infection and infectious gastroenteritis), autoimmune diseases (inflammatory bowel disease, diabetes, and allergic disorders), behavioral disorders and other conditions like metabolic syndrome and functional gastrointestinal disorders. Amongst various therapies targeting gut microbiome, fecal microbiota transplantation (FMT) is becoming a focus in the public media and peer reviewed literature. We have been using FMT for induction of remission in patients with moderate to severe active ulcerative colitis (UC) and also for subsequent maintenance of remission. Four cases reported incidental benefits while being treated with FMT for UC. These included weight loss (n=1), improvement in hair loss (n=1), amelioration of axial arthritis (n=1) and improvement in allergic rhinitis (n=1), thereby suggesting potential clinical applications of FMT in treating extraintestinal diseases associated with gut dysbiosis.}, }
@article {pmid32305646, year = {2020}, author = {Wang, P and Gao, J and Ke, W and Wang, J and Li, D and Liu, R and Jia, Y and Wang, X and Chen, X and Chen, F and Hu, X}, title = {Resveratrol reduces obesity in high-fat diet-fed mice via modulating the composition and metabolic function of the gut microbiota.}, journal = {Free radical biology &amp; medicine}, volume = {156}, number = {}, pages = {83-98}, doi = {10.1016/j.freeradbiomed.2020.04.013}, pmid = {32305646}, issn = {1873-4596}, abstract = {Resveratrol (RSV) is a natural polyphenol with anti-obesity effects. However, the mechanisms of anti-obesity remain unclear due to its low bioavailability. Recent evidence demonstrates that gut microbiota plays a key role in obesity. This spurred us to investigate whether the anti-obesity effects of RSV are related to modulations in the gut microbiota and metabolic functions. Here, RSV significantly improved metabolic phenotype and intestinal oxidative stress in the high-fat diet (HFD)-fed mice. A multi-omics approach was used to systematically profile the microbial signatures at both the phylogenetic and functional levels using 16S rRNA gene sequencing and metagenome. At the phylogenetic level, RSV treatment significantly modulated the gut microbiota composition in HFD-fed mice, characterized with increased Blautia abundance and decreased Desulfovibrio and Lachnospiraceae_NK4A136_group abundance. At the functional level, RSV significantly decreased the enrichment of pathways linked to host metabolic disease and increased the enrichment of pathways involved in the generation of small metabolites. Besides, the fecal microbiota transplantation experiment showed anti-obesity and microbiota-modulating effects similar to those observed in the oral RSV-feeding experiment. Furthermore, metabolomic analysis and antibiotic treatment verified that 4-hydroxyphenylacetic acid (4-HPA) and 3-hydroxyphenylpropionic acid (3-HPP) were the two gut metabolites of RSV, which contribute to improving lipid metabolism in vitro. Moreover, the content of 4-HPA and 3-HPP exhibited strong correlation with the intestinal oxidative state. We concluded that the RSV-mediated alteration of gut microbiota, related gut metabolites and redox state of the intestinal environment contributed to prevention of metabolic syndrome in HFD-fed mice.}, }
@article {pmid32300219, year = {2020}, author = {Nazmul Huda, M and Winnike, JH and Crowell, JM and O'Connor, A and Bennett, BJ}, title = {Microbial modulation of host body composition and plasma metabolic profile.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {6545}, pmid = {32300219}, issn = {2045-2322}, abstract = {The gut microbiota is a critical mediator of nutrition and disease risk. Like most complex traits, the microbiome is under genetic regulation and differs between inbred strains of mice. We tested the effect of fecal microbiota transplantation (FMT) on obesity, and plasma glucose. For this study, we collected microbiota from 2 inbred strains of mice which differ in adiposity and glucose tolerance, C57BL/6J and WSB/EiJ. C57BL/6J female mice (n = 18) were first treated with antibiotics for 4 weeks to ablate the microbiota. Following ablation, the mice were transplanted with microbiota from a C57BL/6J or a WSB/EiJ mouse and clinical traits and plasma metabolomic profiles were interrogated at 2- and 4-weeks post-transplantation. Unexpectedly, the mice receiving WSB/EiJ microbiota increased adiposity but decreased plasma glucose. Metabolomic and 16S microbiota profiling indicated broad metabolic changes occurred during and after FMT. Detailed analysis of these interactions demonstrated specific microbiota-host metabolite interactions which may alter disease susceptibility.}, }
@article {pmid32298656, year = {2020}, author = {Leonardi, I and Paramsothy, S and Doron, I and Semon, A and Kaakoush, NO and Clemente, JC and Faith, JJ and Borody, TJ and Mitchell, HM and Colombel, JF and Kamm, MA and Iliev, ID}, title = {Fungal Trans-kingdom Dynamics Linked to Responsiveness to Fecal Microbiota Transplantation (FMT) Therapy in Ulcerative Colitis.}, journal = {Cell host &amp; microbe}, volume = {27}, number = {5}, pages = {823-829.e3}, doi = {10.1016/j.chom.2020.03.006}, pmid = {32298656}, issn = {1934-6069}, support = {R01 DK113136/DK/NIDDK NIH HHS/United States ; R01 DK121977/DK/NIDDK NIH HHS/United States ; R56 AI137157/AI/NIAID NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been successfully applied to ulcerative colitis. However, only a subset of patients responds to FMT, and there is a pressing need for biomarkers of responsiveness. Fungi (the mycobiota) represent a highly immunologically reactive component of the gut microbiota. We analyzed samples from a large randomized controlled trial of FMT for ulcerative colitis (UC). High Candida abundance pre-FMT was associated with a clinical response, whereas decreased Candida abundance post-FMT was indicative of ameliorated disease severity. High pre-FMT Candida was associated with increased bacterial diversity post-FMT, and the presence of genera was linked to FMT responsiveness. Although we detected elevated anti-Candida antibodies in placebo recipients, this increase was abrogated in FMT recipients. Our data suggest that FMT might reduce Candida to contain pro-inflammatory immunity during intestinal disease and highlight the utility of mycobiota-focused approaches to identify FMT responders prior to therapy initiation.}, }
@article {pmid32297646, year = {2020}, author = {Kilinçarslan, S and Evrensel, A}, title = {The effect of fecal microbiota transplantation on psychiatric symptoms among patients with inflammatory bowel disease: an experimental study.}, journal = {Actas espanolas de psiquiatria}, volume = {48}, number = {1}, pages = {1-7}, pmid = {32297646}, issn = {1578-2735}, abstract = {INTRODUCTION: Over the past decade, evidence that supports the relationship between intestinal microbiota and the brain has been obtained. Ageing, stress, nutrition and medicines can alter the composition of bacteria in the intestinal microbiota. This condition, called dysbiosis, can be repaired through prebiotics, probiotics or fecal microbiota transplantation (FMT). FMT is effective in the treatment of inflammatory bowel diseases (IBD). Information on FMT's use with psychiatric disorders is limited. This study aims to investigate changes in the severity of depression, anxiety and obsession of patients who received FMT for the treatment of inflammatory bowel diseases.<br><br>METHODS: This study was conducted with 10 patients with IBD who underwent FMT between March and September 2017. FMT was performed by an experienced gastroenterologist. The patients completed the Beck Depression Inventory (BDI), Symptom Checklist-90-Revised (SCL-90-R) and Maudsley Obsessive Compulsive Inventory (MOCI) before FMT and again at 1 month after FMT.<br><br>RESULTS: Significant decreases were found in BDI (Z=2.49, p=0.013), SCL-90-R (Z=-2.09, p=0.037) and MOCI (Z=2.08, p=0.037) scores after 1 month of FMT. Although the SCL-90-R anxiety subscale scores decreased, this decrease was not statistically significant (Z=-1.55, p=0.121).<br><br>CONCLUSIONS: The severity of anxiety, depression and obsession in IBD patients decreased after FMT. The decrease in psychiatric symptoms may result from the direct neuropsychiatric effect of FMT (primary effect), but also the improvement of gastrointestinal symptoms (secondary effect). Another possibility is that this result is independent of these two conditions. Therefore, the results of our study are not sufficient to establish a cause-effect relationship. More randomised controlled trials with larger samples from patients with anxiety or depression but without comorbid physical illnesses are needed to generalise these results.}, }
@article {pmid32296975, year = {2020}, author = {Fadda, HM}, title = {The Route to Palatable Fecal Microbiota Transplantation.}, journal = {AAPS PharmSciTech}, volume = {21}, number = {3}, pages = {114}, doi = {10.1208/s12249-020-1637-z}, pmid = {32296975}, issn = {1530-9932}, mesh = {Capsules ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; }, abstract = {The community of symbiotic microorganisms that reside in our gastrointestinal tract is integral to human health. Fecal microbiota transplantation (FMT) has been shown to be highly effective in treating recurrent Clostridioides difficile infection (rCDI) and is now recommended by medical societies for patients suffering from rCDI who have failed to respond to conventional therapy. The main challenges with FMT are its accessibility, acceptability, lack of standardization, and regulatory complexity, which will be discussed in this review. Access to FMT is being addressed through the development of frozen and lyophilized FMT preparations that can be prepared at stool banks and shipped to the point of care. Both access and patient acceptance would be enhanced by oral FMT capsules, and there is potential to reduce capsule burden by utilizing colonic release capsules, targeting the site of disease. This review compares the efficacy of different FMT routes of administration: capsules, nasal feeding tubes, enemas, and colonoscopic infusions. FMT is considered investigational by the Food and Drug Administration. In effort to improve access to FMT, physicians may perform FMT outside of an investigational new drug application for treating CDI infections not responsive to standard therapies. The majority of FMT studies report only minor adverse effects; however, there is risk of transmission of infections.}, }
@article {pmid32291810, year = {2020}, author = {Gallo, A and Cancelli, C and Ceron, E and Covino, M and Capoluongo, E and Pocino, K and Ianiro, G and Cammarota, G and Gasbarrini, A and Montalto, M}, title = {Fecal calprotectin and need of multiple microbiota trasplantation infusions in Clostridium difficile infection.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.15072}, pmid = {32291810}, issn = {1440-1746}, abstract = {BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) has proven to be very effective in recurrent Clostridium difficile infection (CDI) when compared with standard antibiotic therapy. However, given the lack of validated criteria, decision regarding number and timing of infusions is currently based on the clinician's experience, severity of infection, and clinical response. We performed a longitudinal assessment of fecal calprotectin concentration (FCC) in CDI patients undergoing FMT. FCCs were correlated with the need for multiple infusions and with the clinical status of the patient.<br><br>METHODS: Fecal calprotectin concentration measurement was performed just before first procedure (T0) and 2 (T1) and 5 (T2) days later. The need for reinfusion was accounted for in the 8 weeks following procedure, and clinical status was evaluated at the end of the given period. Both outcomes were correlated with measured FCCs.<br><br>RESULTS: A total of 28 CDI patients undergoing FMT were enrolled. Median FCCs at T0 were significantly higher in patients who needed repeat FMT, 540 μg/g versus patients who underwent single FMT, 290 μg/g (P < 0.05). Differences were not significant for FCC at T1 and T2 . Regarding correlation with clinical outcome, median FCC at T0 was found to be lower in responders compared with non-responders with a trend towards statistical significance (P = 0.07). Correlation at T1 and T2 was not significant.<br><br>CONCLUSIONS: The use of an easily obtainable parameter such as fecal calprotectin could possibly optimize overall management of FMT procedural framework potentially being able to immediately identify patients who may benefit from repeat infusions.}, }
@article {pmid32282545, year = {2020}, author = {Li, Q and Zhang, T and Ding, X and Xiang, L and Cui, B and Buch, H and Zhang, F}, title = {Enhancing patient adherence to fecal microbiota transplantation maintains the long-term clinical effects in ulcerative colitis.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MEG.0000000000001725}, pmid = {32282545}, issn = {1473-5687}, abstract = {OBJECTIVES: The way to improve the long-term efficacy of fecal microbiota transplantation (FMT) in ulcerative colitis (UC) remains unclear. This study mainly dedicated to the UC patients' satisfaction with FMT and the importance of patients' adherence to repeated FMT for long-term clinical outcomes.<br><br>METHODS: Patients with UC who underwent FMT at our center from November 2012 to September 2018 were included. We assessed patient satisfaction with efficacy, safety, and reliability of FMT, as well as adherence to the repeated FMT.<br><br>RESULTS: One hundred and seventy-six patients were included in the analysis. The median follow-up duration of the study was 25.5 (interquartile range 13.0-46.5) months. The clinical response rate at 1 week, 1 month, 3 months, and 6 months after FMT was 48.9%, 69.3%, 49.4%, and 32.7%, respectively. 3.4% (6/176) of patients underwent colectomy after FMT during our long-term follow-up. Partial Mayo score at 1-month post-FMT (P < 0.001) was an independent factor of patients' satisfaction. The laboratory preparation process was related to the incidence of adverse events (P < 0.05). 23.8% (29/122) of patients with a good adherence followed our recommendation to undergo the second course of FMT and achieved a longer clinical response compared with the patients with poor adherence (P < 0.001).<br><br>CONCLUSION: Patients' good adherence to repeated FMT is important to maintain long-term clinical benefits achieved from FMT in UC. Registration number: NCT01790061.}, }
@article {pmid32280227, year = {2020}, author = {Liu, S and Guo, R and Liu, F and Yuan, Q and Yu, Y and Ren, F}, title = {Gut Microbiota Regulates Depression-Like Behavior in Rats Through the Neuroendocrine-Immune-Mitochondrial Pathway.}, journal = {Neuropsychiatric disease and treatment}, volume = {16}, number = {}, pages = {859-869}, pmid = {32280227}, issn = {1176-6328}, abstract = {Purpose: Gut microbiota affects various physiological functions in the host and has crucial effects on the nervous system. There is increasing evidence of a correlation between gut microbiota and depression; however, the mechanisms underlying the regulation of depression-like behavior by gut microbiota remain unclear. In this study, we assessed the regulatory mechanism of gut microbiota on depression-like behavior in rats.<br><br>Methods: We transplanted fecal microbiota obtained from patients with depression and healthy individuals into germ-free (GF) rats (n=18) through fecal microbiota transplantation technology. Next, we assessed the affective behavior in the rats using the forced swimming test and a sucrose preference test. We used enzyme-linked immunosorbent assay (ELISA) to determine the hippocampal levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and noradrenaline (NE) and the serum levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-1 (IL-1), interleukin-1 (IL-4), and interleukin-1 (IL-10). The mitochondrial morphology of small intestinal epithelial cells was observed through transmission electron microscopy.<br><br>Results: Rats that received fecal microbiota from patients with depression (depression microbiota) exhibited depression-like behavior. They presented decreased levels of hippocampal neurotransmitters, serum CORT levels, and anti-inflammatory cytokine levels, as well as increased ACTH, CRH, and serum levels of multiple pro-inflammatory cytokines. Observation of the mitochondria ultrastructure showed damaged mitochondria in the intestinal epithelial cells, significant endoplasmic reticulum expansion, and border aggregation of nuclear chromatin.<br><br>Conclusion: Our findings suggested that the depression-like behaviors induced by the depression microbiota through the neuroendocrine-immune-mitochondrial pathway, which were associated with neuroendocrine disorders, inflammatory responses, and mitochondrial damage.}, }
@article {pmid32279172, year = {2020}, author = {Chauhan, A and Kumar, R and Sharma, S and Mahanta, M and Vayuuru, SK and Nayak, B and Kumar, S and Shalimar, }, title = {Fecal Microbiota Transplantation in Hepatitis B e Antigen-Positive Chronic Hepatitis B Patients: A Pilot Study.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-020-06246-x}, pmid = {32279172}, issn = {1573-2568}, abstract = {BACKGROUND: Intestinal flora plays a critical role in immunity against hepatitis B virus (HBV). Fecal Microbiota Transplantation (FMT) may be a potential immunomodulatory therapy in patients with chronic hepatitis B (CHB).<br><br>AIM: We aimed to study role of FMT in hepatitis B e antigen (HBeAg)-positive CHB patients in terms of its effect on HBeAg, HBsAg, and HBV DNA.<br><br>METHODS: HBeAg-positive patients despite being on antiviral treatment for > 1 year were given six cycles of FMT via gastroscope (nasoduodenal route) at 4 weekly intervals along with antiviral therapy. Twelve out of 14 included patients in FMT arm completed six cycles. Another 15 HBeAg-positive patients who were on oral antivirals for > 1 year were taken as control-antiviral therapy (AVT) arm. Per-protocol analysis was done.<br><br>RESULTS: The median (interquartile range) age in the FMT and AVT arm were 29 (25-35) and 29(24-38), respectively (P = 0.794). The median (interquartile range) duration of AVT prior to inclusion in the study was 80 (52-104) and 76 (52-114) months in FMT and AVT arm, respectively (P = 0.884). In the FMT arm, 16.7% (2/12) patients had HBeAg clearance in comparison to none in the AVT arm (P = 0.188). None of the patients in either arm had HBsAg loss. The FMT was tolerated well, 42.8% (6/14) patients reported one or more minor adverse events.<br><br>CONCLUSIONS: In this non-randomized pilot study, FMT appears to be safe and potentially effective in terms of viral suppression and HBeAg clearance in patients with HBeAg-positive CHB. Further randomized controlled trials are needed in order to obtain robust conclusions.}, }
@article {pmid32278875, year = {2020}, author = {Ricciuto, A and Sherman, PM and Laxer, RM}, title = {Gut microbiota in chronic inflammatory disorders: A focus on pediatric inflammatory bowel diseases and juvenile idiopathic arthritis.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {215}, number = {}, pages = {108415}, doi = {10.1016/j.clim.2020.108415}, pmid = {32278875}, issn = {1521-7035}, abstract = {The gut microbiota is integral to human health, including maintaining the delicate balance between tolerance and protection against potentially harmful pathogens. A growing body of evidence implicates the intestinal microbiome in immune-mediated inflammatory disorders; these data span the spectrum from genetic and environmental disease risk factors, to animal studies (particularly germ-free and gnotobiotic models) and human studies, including evidence of dysbiosis in diseased individuals compared to healthy populations. In this review, we summarize both animal and human data supporting a link between the gut microbiota and inflammatory bowel diseases (IBD) and systemic inflammatory arthritis, as models for chronic inflammatory disorders, while offering a pediatric focus (pediatric IBD and juvenile idiopathic arthritis). We discuss relevant mechanisms related to the crosstalk between the gut microbiota and the innate and adaptive immune system. We close with a brief discussion of emerging microbe-altering interventions, including fecal microbial transplantation and its immunologic effects.}, }
@article {pmid32277897, year = {2020}, author = {Kelly, CR and Kahn, SA}, title = {Is it unethical to conduct placebo-controlled trials of faecal microbiota transplantation for recurrent Clostridioides difficile infection?.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {5}, number = {5}, pages = {432-433}, doi = {10.1016/S2468-1253(20)30043-1}, pmid = {32277897}, issn = {2468-1253}, mesh = {*Clostridium difficile ; Controlled Clinical Trials as Topic/*ethics ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Placebos/*therapeutic use ; Recurrence ; Therapeutic Equipoise ; }, }
@article {pmid32276499, year = {2020}, author = {Fond, GB and Lagier, JC and Honore, S and Lancon, C and Korchia, T and Sunhary De Verville, PL and Llorca, PM and Auquier, P and Guedj, E and Boyer, L}, title = {Microbiota-Orientated Treatments for Major Depression and Schizophrenia.}, journal = {Nutrients}, volume = {12}, number = {4}, pages = {}, pmid = {32276499}, issn = {2072-6643}, abstract = {BACKGROUND AND SIGNIFICANCE: There is a need to develop new hypothesis-driven treatment for both both major depression (MD) and schizophrenia in which the risk of depression is 5 times higher than the general population. Major depression has been also associated with poor illness outcomes including pain, metabolic disturbances, and less adherence. Conventional antidepressants are partly effective, and 44% of the subjects remain unremitted under treatment. Improving MD treatment efficacy is thus needed to improve the SZ prognosis. Microbiota-orientated treatments are currently one of the most promising tracks.<br><br>METHOD: This work is a systematic review synthetizing data of arguments to develop microbiota-orientated treatments (including fecal microbiota transplantation (FMT)) in major depression and schizophrenia.<br><br>RESULTS: The effectiveness of probiotic administration in MD constitutes a strong evidence for developing microbiota-orientated treatments. Probiotics have yielded medium-to-large significant effects on depressive symptoms, but it is still unclear if the effect is maintained following probiotic discontinuation. Several factors may limit MD improvement when using probiotics, including the small number of bacterial strains administered in probiotic complementary agents, as well as the presence of a disturbed gut microbiota that probably limits the probiotics' impact. FMT is a safe technique enabling to improve microbiota in several gut disorders. The benefit/risk ratio of FMT has been discussed and has been recently improved by capsule administration.<br><br>CONCLUSION: Cleaning up the gut microbiota by transplanting a totally new human gut microbiota in one shot, which is referred to as FMT, is likely to strongly improve the efficacy of microbiota-orientated treatments in MD and schizophrenia and maintain the effect over time. This hypothesis should be tested in future clinical trials.}, }
@article {pmid32275059, year = {2019}, author = {Revolinski, S and Munoz-Price, LS}, title = {Fecal Microbiota Transplantation for Clostridioides difficile Infection in Immunocompromised Hosts.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciz689}, pmid = {32275059}, issn = {1537-6591}, }
@article {pmid32273468, year = {2020}, author = {Bessman, NJ and Mathieu, JRR and Renassia, C and Zhou, L and Fung, TC and Fernandez, KC and Austin, C and Moeller, JB and Zumerle, S and Louis, S and Vaulont, S and Ajami, NJ and Sokol, H and Putzel, GG and Arvedson, T and Sockolow, RE and Lakhal-Littleton, S and Cloonan, SM and Arora, M and Peyssonnaux, C and Sonnenberg, GF}, title = {Dendritic cell-derived hepcidin sequesters iron from the microbiota to promote mucosal healing.}, journal = {Science (New York, N.Y.)}, volume = {368}, number = {6487}, pages = {186-189}, doi = {10.1126/science.aau6481}, pmid = {32273468}, issn = {1095-9203}, support = {R00 HL125899/HL/NHLBI NIH HHS/United States ; R21 CA249274/CA/NCI NIH HHS/United States ; R01 AI145989/AI/NIAID NIH HHS/United States ; R01 AI123368/AI/NIAID NIH HHS/United States ; F32 AI124517/AI/NIAID NIH HHS/United States ; U01 AI095608/AI/NIAID NIH HHS/United States ; U2C ES030859/ES/NIEHS NIH HHS/United States ; R01 AI143842/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cation Transport Proteins/metabolism ; Dendritic Cells/*metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gene Deletion ; Hepcidins/genetics/*metabolism ; Homeostasis ; Intestinal Diseases/*microbiology ; Intestinal Mucosa/*microbiology/*physiology ; Iron/*metabolism ; Mice ; Mice, Mutant Strains ; Phagocytes/metabolism ; }, abstract = {Bleeding and altered iron distribution occur in multiple gastrointestinal diseases, but the importance and regulation of these changes remain unclear. We found that hepcidin, the master regulator of systemic iron homeostasis, is required for tissue repair in the mouse intestine after experimental damage. This effect was independent of hepatocyte-derived hepcidin or systemic iron levels. Rather, we identified conventional dendritic cells (cDCs) as a source of hepcidin that is induced by microbial stimulation in mice, prominent in the inflamed intestine of humans, and essential for tissue repair. cDC-derived hepcidin acted on ferroportin-expressing phagocytes to promote local iron sequestration, which regulated the microbiota and consequently facilitated intestinal repair. Collectively, these results identify a pathway whereby cDC-derived hepcidin promotes mucosal healing in the intestine through means of nutritional immunity.}, }
@article {pmid32272276, year = {2020}, author = {Liu, C and Cheng, L and Ji, L and Li, F and Zhan, Y and Wu, B and Ke, Y and Chen, P and Hua, F and Yuan, L and Min, Z and Sun, L and Chen, H and Cheng, Y}, title = {Intestinal microbiota dysbiosis play a role in pathogenesis of patients with primary immune thrombocytopenia.}, journal = {Thrombosis research}, volume = {190}, number = {}, pages = {11-19}, doi = {10.1016/j.thromres.2020.03.012}, pmid = {32272276}, issn = {1879-2472}, abstract = {BACKGROUND: The intestinal microbiota is essential for the maintenance of the physiology of immune homeostasis. Dysbiosis has been described in some autoimmune diseases, however its role is still elusive in primary immune thrombocytopenia (ITP), which is one kind of autoimmune diseases. This study aimed to characterize the phylogenetic diversity of the fecal microbiota and its relationship with the platelet activation status in patients with ITP.<br><br>METHODS: The platelet activation status was assessed by 2 platelet markers, PAC-1 (antibody that recognizes the activated GPIIb/IIIa complex) and CD62p (Platelet surface P-selectin) by flow cytometry. Total DNA was extracted from fecal samples of ITP patients and healthy controls (HC). Sequencing the V4 hypervariable region of bacterial 16S rRNA genes was used to identify the changes in phylogenetic diversity and composition of the intestinal flora. The obtained sequencing reads were assigned to operational taxonomic units (OTUs, 97% sequence identity) and taxonomically classified to assess composition and diversity.<br><br>RESULTS: The percentage of PAC-1+ platelets in ITP patients was higher than that in control group (p < 0.001), The percentage of CD62p+ and PAC-1+CD62p+ platelets in ITP patients both higher than those in control group (p < 0.001). At the phylum level, eight different phyla were identified in ITP individuals, with a majority of Bacteroidetes (45.96%) and Firmicutes (38.59%), followed by Proteobacteria (11.43%), Fusobacteria(1.29%), and Actinobacteria (1.22%). While in the Healthy volunteers, ten phyla were detected, with a predominance of Firmicutes (50.92%) and Bacteroidetes (34.26%), came before Proteobacteria (13.60%), and Actinobacteria (0.90%). The gut microbiota was skewed in ITP, with an increased proportion of Proteobacteria, Bacteroidetes and Bacteroidetes/Firmicutes ratio, a decreased proportion of Firmicutes compared with HC. Disease specific alterations in diversity was also identified, especially the potential markers (Anaerorhabdus, sutterella, Peptostreptococcaceae, Clostridium_XI and carnobacteriaceae, p < 0.05) for ITP.<br><br>CONCLUSIONS: The results suggested that the distinct microbiota dysbiosis in ITP characterized by alterations in biodiversity and composition, which could provide insights for diet therapy and fecal microbiota transplantation treatment to cure ITP. There might be somehow compensatory enhancement of platelet activation in ITP patients. And there is associate between platelet activation and intestinal microbiota in patients with ITP.}, }
@article {pmid32266849, year = {2020}, author = {Boem, F and Nannini, G and Amedei, A}, title = {Not just 'immunity': how the microbiota can reshape our approach to cancer immunotherapy.}, journal = {Immunotherapy}, volume = {12}, number = {6}, pages = {407-416}, doi = {10.2217/imt-2019-0192}, pmid = {32266849}, issn = {1750-7448}, abstract = {Cancer immunotherapy refers to a set of approaches aiming at enhancing the immune system to fight cancer growth and spread. This variety of therapeutic approaches, especially those inhibiting immune checkpoints, have shown very promising results. Nevertheless, patients may respond differently to treatments and the efficacy of immunotherapy seems to be dependent on several factors that go beyond the molecular targeting of immune cells modulation. Here, we review how the activity of gut microbiota appears to be crucial in determining the effectiveness of some immunotherapeutic treatments, fostering or impeding the conditions under which treatments can work or not. Moreover, we discuss how these findings suggest not only extending the range of immunotherapeutic approaches but also reshaping our understanding of immunotherapy itself.}, }
@article {pmid32266848, year = {2020}, author = {Voth, E and Khanna, S}, title = {Fecal microbiota transplantation for treatment of patients with recurrent Clostridioides difficile infection.}, journal = {Expert review of anti-infective therapy}, volume = {18}, number = {7}, pages = {669-676}, doi = {10.1080/14787210.2020.1752192}, pmid = {32266848}, issn = {1744-8336}, abstract = {INTRODUCTION: Recurrent Clostridiodes difficile infection (rCDI) is a growing public health burden, and is associated with poor patient outcomes. Fecal microbiota transplantation (FMT) is a novel therapy with an aim to restore the disrupted microbiota with demonstrated success in the management of rCDI and a favorable safety profile.<br><br>AREAS COVERED: This review includes a comprehensive overview of a search of the literature including epidemiology of rCDI, basics of the gut microbiome, antibiotic therapy for rCDI along with rationale for safety and efficacy of FMT for rCDI.<br><br>EXPERT OPINION: Patients exposed to risk factors, such as antimicrobial agents, are at risk for disruption of the gut microbiome resulting in the reduction of microbial diversity and dysbiosis. Dysbiotic microbiota predispose to primary and rCDI. Strategies to improve the current and future management of rCDI are under clinical investigation, including narrow-spectrum antibiotics, monoclonal antibodies and FMT, which has shown a high success rate for rCDI. Further investigation is needed to determine optimal standardization of the methodological components of FMT including donor screening, stool preparation, storage and instillation and patient follow-up. Newer methods of microbiota replacement therapies including enema- and capsule-based therapies are under investigation.}, }
@article {pmid32266160, year = {2020}, author = {Vendrik, KEW and Ooijevaar, RE and de Jong, PRC and Laman, JD and van Oosten, BW and van Hilten, JJ and Ducarmon, QR and Keller, JJ and Kuijper, EJ and Contarino, MF}, title = {Fecal Microbiota Transplantation in Neurological Disorders.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {98}, pmid = {32266160}, issn = {2235-2988}, abstract = {Background: Several studies suggested an important role of the gut microbiota in the pathophysiology of neurological disorders, implying that alteration of the gut microbiota might serve as a treatment strategy. Fecal microbiota transplantation (FMT) is currently the most effective gut microbiota intervention and an accepted treatment for recurrent Clostridioides difficile infections. To evaluate indications of FMT for patients with neurological disorders, we summarized the available literature on FMT. In addition, we provide suggestions for future directions. Methods: In July 2019, five main databases were searched for studies and case descriptions on FMT in neurological disorders in humans or animal models. In addition, the ClinicalTrials.gov website was consulted for registered planned and ongoing trials. Results: Of 541 identified studies, 34 were included in the analysis. Clinical trials with FMT have been performed in patients with autism spectrum disorder and showed beneficial effects on neurological symptoms. For multiple sclerosis and Parkinson's disease, several animal studies suggested a positive effect of FMT, supported by some human case reports. For epilepsy, Tourette syndrome, and diabetic neuropathy some studies suggested a beneficial effect of FMT, but evidence was restricted to case reports and limited numbers of animal studies. For stroke, Alzheimer's disease and Guillain-Barré syndrome only studies with animal models were identified. These studies suggested a potential beneficial effect of healthy donor FMT. In contrast, one study with an animal model for stroke showed increased mortality after FMT. For Guillain-Barré only one study was identified. Whether positive findings from animal studies can be confirmed in the treatment of human diseases awaits to be seen. Several trials with FMT as treatment for the above mentioned neurological disorders are planned or ongoing, as well as for amyotrophic lateral sclerosis. Conclusions: Preliminary literature suggests that FMT may be a promising treatment option for several neurological disorders. However, available evidence is still scanty and some contrasting results were observed. A limited number of studies in humans have been performed or are ongoing, while for some disorders only animal experiments have been conducted. Large double-blinded randomized controlled trials are needed to further elucidate the effect of FMT in neurological disorders.}, }
@article {pmid32256746, year = {2020}, author = {Chen, HT and Huang, HL and Xu, HM and Luo, QL and He, J and Li, YQ and Zhou, YL and Nie, YQ and Zhou, YJ}, title = {Fecal microbiota transplantation ameliorates active ulcerative colitis.}, journal = {Experimental and therapeutic medicine}, volume = {19}, number = {4}, pages = {2650-2660}, pmid = {32256746}, issn = {1792-0981}, abstract = {Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota Faecalibacterium prausnitzii (F. prausnitzii) levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, F. prausnitzii levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, F. prausnitzii may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.}, }
@article {pmid32255522, year = {2020}, author = {Du, HX and Liu, Y and Zhang, LG and Zhan, CS and Chen, J and Zhang, M and Chen, XG and Zhang, L and Liang, CZ}, title = {Abnormal gut microbiota composition is associated with experimental autoimmune prostatitis-induced depressive-like behaviors in mice.}, journal = {The Prostate}, volume = {80}, number = {9}, pages = {663-673}, doi = {10.1002/pros.23978}, pmid = {32255522}, issn = {1097-0045}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Behavior, Animal/*physiology ; Chronic Disease ; Depression/immunology/*microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/immunology/*physiology ; Male ; Mice ; Mice, Inbred NOD ; Prostatitis/immunology/*microbiology/*psychology ; Random Allocation ; }, abstract = {BACKGROUND: Depressive symptoms are found in approximately 78% of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients, but the pathological mechanisms remain unknown. Increasing evidence suggests that abnormal gut microbiota may play an important role in depression. Thus, we aimed to investigate whether gut microbiota contributes to CP/CPPS-associated depression by using a mouse model of experimental autoimmune prostatitis (EAP).<br><br>METHODS: Male nonobese diabetic mice were immunized twice by subcutaneous injection of prostate antigen and adjuvant. Behavioral tests consisted of an open field test, sucrose preference test, forced swimming tests, and tail suspension test was used to confirm the depression-like symptoms that were induced by EAP. Then, fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition between control and EAP group. Additionally, fecal bacteria from the control and EAP mice were transplanted into antibiotics-induced pseudo-germ-free mice to investigate the effects on host behaviors and the composition of gut bacteria.<br><br>RESULTS: EAP was successfully established and exhibited depressive-like behaviors in mice. The 16S rRNA analysis of fecal samples indicated the abnormal composition of gut microbiota in the EAP mice compared to the control mice. In the fecal microbiota transplant study, antibiotics-treated pseudo-germ-free mice presented depressive states as compared to naïve mice. Fecal bacteria transplant from EAP mice, but not from control mice, into the pseudo-germ-free mice, significantly exaggerated host depression-like behaviors. Moreover, fecal bacteria transplants from control and EAP mice induced distinct alterations in α-diversity and β-diversity indices. In all, 24 bacteria at six phylogenetic levels were remarkably changed by the fecal bacteria transplantation.<br><br>CONCLUSIONS: Abnormal gut microbiota composition after EAP induction may contribute to the development of depression in mice. A therapeutic strategy that targets gut microbiota may provide an alternative treatment for alleviating this condition.}, }
@article {pmid32253791, year = {2020}, author = {Hughes, KR and Schofield, Z and Dalby, MJ and Caim, S and Chalklen, L and Bernuzzi, F and Alcon-Giner, C and Le Gall, G and Watson, AJM and Hall, LJ}, title = {The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {34}, number = {5}, pages = {7075-7088}, doi = {10.1096/fj.202000042R}, pmid = {32253791}, issn = {1530-6860}, support = {100974/C/13/Z//Wellcome Trust (Wellcome)/ ; BB/J004529/1//Biotechnology and Biological Sciences Research Council (BBSRC)/ ; BB/R012490/1//Biotechnology and Biological Sciences Research Council (BBSRC)/ ; }, abstract = {The early life gut microbiota plays a crucial role in regulating and maintaining the intestinal barrier, with disturbances in these communities linked to dysregulated renewal and replenishment of intestinal epithelial cells. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period, and which host and microbial factors mediate these responses. Surprisingly, neonatal mice (Day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of liposaccharide (LPS), with Day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses. When we profiled microbiota and metabolites, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia, and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes, and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Antibiotic treatment of neonates restored LPS-induced small intestinal cell shedding, whereas adult fecal microbiota transplant alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlights areas for further investigation.}, }
@article {pmid32251667, year = {2020}, author = {Pickert, G and Wirtz, S and Matzner, J and Ashfaq-Khan, M and Heck, R and Rosigkeit, S and Thies, D and Surabattula, R and Ehmann, D and Wehkamp, J and Aslam, M and He, G and Weigert, A and Foerster, F and Klotz, L and Frick, JS and Becker, C and Bockamp, E and Schuppan, D}, title = {Wheat Consumption Aggravates Colitis in Mice via Amylase Trypsin Inhibitor-mediated Dysbiosis.}, journal = {Gastroenterology}, volume = {159}, number = {1}, pages = {257-272.e17}, doi = {10.1053/j.gastro.2020.03.064}, pmid = {32251667}, issn = {1528-0012}, abstract = {BACKGROUND &amp; AIMS: Wheat has become the world's major staple and its consumption correlates with prevalence of noncommunicable disorders such as inflammatory bowel diseases. Amylase trypsin inhibitors (ATIs), a component of wheat, activate the intestine's innate immune response via toll-like receptor 4 (TLR4). We investigated the effects of wheat and ATIs on severity of colitis and fecal microbiota in mice.<br><br>METHODS: C57BL/6 wild-type and Tlr4-/- mice were fed wheat- or ATI-containing diets or a wheat-free (control) diet and then given dextran sodium sulfate to induce colitis; we also studied Il10-/- mice, which develop spontaneous colitis. Changes in fecal bacteria were assessed by taxa-specific quantitative polymerase chain reaction and 16S ribosomal RNA metagenomic sequencing. Feces were collected from mice on wheat-containing, ATI-containing, control diets and transplanted to intestines of mice with and without colitis on control or on ATI-containing diets. Intestinal tissues were collected and analyzed by histology, immunohistochemistry, and flow cytometry. Bacteria with reported immunomodulatory effects were incubated with ATIs and analyzed in radial diffusion assays.<br><br>RESULTS: The wheat- or ATI-containing diets equally increased inflammation in intestinal tissues of C57BL/6 mice with colitis, compared with mice on control diets. The ATI-containing diet promoted expansion of taxa associated with development of colitis comparable to the wheat-containing diet. ATIs inhibited proliferation of specific human commensal bacteria in radial diffusion assays. Transplantation of microbiota from feces of mice fed the wheat- or ATI-containing diets to intestines of mice on control diets increased the severity of colitis in these mice. The ATI-containing diet did not increase the severity of colitis in Tlr4-/- mice.<br><br>CONCLUSIONS: Consumption of wheat or wheat ATIs increases intestinal inflammation in mice with colitis, via TLR4, and alters their fecal microbiota. Wheat-based, ATI-containing diets therefore activate TLR4 signaling and promote intestinal dysbiosis.}, }
@article {pmid32250997, year = {2020}, author = {Shah, A and Macdonald, GA and Morrison, M and Holtmann, G}, title = {Targeting the Gut Microbiome as a Treatment for Primary Sclerosing Cholangitis: A Conceptional Framework.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {6}, pages = {814-822}, pmid = {32250997}, issn = {1572-0241}, mesh = {Anti-Infective Agents/*therapeutic use ; Bile Acids and Salts/*metabolism ; Cholangitis, Sclerosing/immunology/metabolism/microbiology/*therapy ; Dysbiosis/immunology/metabolism/*therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immunity, Mucosal/immunology ; Inflammatory Bowel Diseases/immunology/metabolism/*microbiology ; Intestinal Mucosa/immunology/metabolism/microbiology ; Liver Transplantation ; }, abstract = {Primary sclerosing cholangitis (PSC) is a rare, immune-mediated, chronic cholestatic liver disease associated with a unique phenotype of inflammatory bowel disease that frequently manifests as pancolitis with right-sided predominance. Available data suggest a bidirectional interplay of the gut-liver axis with critical roles for the gastrointestinal microbiome and circulating bile acids (BAs) in the pathophysiology of PSC. BAs shape the gut microbiome, whereas gut microbes have the potential to alter BAs, and there are emerging data that alterations of BAs and the microbiome are not simply a consequence but the cause of PSC. Clustering of PSC in families may suggest that PSC occurs in genetically susceptible individuals. After exposure to an environmental trigger (e.g., microbial byproducts or BAs), an aberrant or exaggerated cholangiocyte-induced immune cascade occurs, ultimately leading to bile duct damage and progressive fibrosis. The pathophysiology can be conceptualized as a triad of (1) gut dysbiosis, (2) altered BA metabolism, and (3) immune-mediated biliary injury. Immune activation seems to be central to the disease process, but immunosuppression does not improve clinical outcomes or alter the natural history of PSC. Currently, orthoptic liver transplantation is the only established life-saving treatment, whereas antimicrobial therapy or fecal transplantation is an emerging therapeutic option for PSC. The beneficial effects of these microbiome-based therapies are likely mediated by a shift of the gut microbiome with favorable effects on BA metabolism. In the future, personalized approaches will allow to better target the interdependence between microbiome, immune function, and BA metabolism and potentially cure patients with PSC.}, }
@article {pmid32250972, year = {2020}, author = {Mennini, M and Fierro, V and Di Nardo, G and Pecora, V and Fiocchi, A}, title = {Microbiota in non-IgE-mediated food allergy.}, journal = {Current opinion in allergy and clinical immunology}, volume = {20}, number = {3}, pages = {323-328}, doi = {10.1097/ACI.0000000000000644}, pmid = {32250972}, issn = {1473-6322}, abstract = {PURPOSE OF REVIEW: To perform a nonsystematic review of the literature on the microbiota in the different types of non-IgE-mediated food allergy.<br><br>RECENT FINDINGS: The commonest non-IgE-mediated disorders managed by allergists include: eosinophilic esophagitis, food protein-induced enteropathy, food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis. The review of the literature describes how at phylum level we observe an increase of Proteobacteria in eosinophilic esophagitis esophageal microbiota and in food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis gut microbiota, while we observe an increase of Bacteroidetes in healthy controls. Several studies endorse the concept that a bloom of Proteobacteria in the gut reflects dysbiosis or an unstable gut microbial community structure. In several studies, the type of diet, the use of probiotics and in a single experience the use of fecal microbiota transplantation has produced significant variations of the microbiota.<br><br>SUMMARY: Genetic factors alone cannot account for the rapid rise in food allergy prevalence and the microbiome might be contributing to allergy risk. Our review showed that common features of the pathological microbiota among different types of non-IgE-mediated food allergy can be identified. These evidences suggest a possible role of the microbiota in the pathogenesis and non-IgE-mediated food allergies and the need to understand the effects of its modulation on the disorders themselves.}, }
@article {pmid32247350, year = {2020}, author = {Cho, JM and Pardi, DS and Khanna, S}, title = {Update on Treatment of Clostridioides difficile Infection.}, journal = {Mayo Clinic proceedings}, volume = {95}, number = {4}, pages = {758-769}, doi = {10.1016/j.mayocp.2019.08.006}, pmid = {32247350}, issn = {1942-5546}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/drug therapy/microbiology/*therapy ; *Clostridium difficile ; Fecal Microbiota Transplantation ; Humans ; Probiotics/therapeutic use ; Recurrence ; }, abstract = {Clostridioides difficile infection (CDI) is the leading cause of health care-associated infections in the United States. The increasing incidence and recurrence rates of CDI together with its associated morbidity and mortality are great concerns. Newer treatment methods, such as narrow-spectrum antibiotics, monoclonal antibodies, and microbial replacement therapies, are being developed and implemented. We searched PubMed to identify published literature from 2010 to 2018 using the following keywords: Clostridium difficile, treatment, and therapy. Cited references were also used to identify relevant literature. This review focuses on the current standard of therapy and emerging therapies for CDI and summarizes the updated guidelines on treatment of CDI.}, }
@article {pmid32245531, year = {2020}, author = {Weir, V and Reddy, KR}, title = {Nonpharmacologic Management of Hepatic Encephalopathy: An Update.}, journal = {Clinics in liver disease}, volume = {24}, number = {2}, pages = {243-261}, doi = {10.1016/j.cld.2020.01.003}, pmid = {32245531}, issn = {1557-8224}, abstract = {Research increasingly shows that the gut-liver-brain axis is a crucial component in the pathophysiology of hepatic encephalopathy (HE). Due to the limitations of current standard-of-care medications, non-pharmacological treatments that target gut dysbiosis, including probiotics, nutritional management, and fecal microbiota transplants, are being considered as alternative and adjunct therapies. Meta-analyses note that probiotics could offer benefits in HE treatment, but have not shown superiority over lactulose. Emerging literature suggests that fecal microbiota transplants could offer a novel strategy to treat gut dysbiosis and favorably impact HE. Finally, liver support devices and liver transplantation could offer a last-resort treatment option for persistent HE.}, }
@article {pmid32245530, year = {2020}, author = {Mahpour, NY and Pioppo-Phelan, L and Reja, M and Tawadros, A and Rustgi, VK}, title = {Pharmacologic Management of Hepatic Encephalopathy.}, journal = {Clinics in liver disease}, volume = {24}, number = {2}, pages = {231-242}, doi = {10.1016/j.cld.2020.01.005}, pmid = {32245530}, issn = {1557-8224}, abstract = {Pharmacologic management of hepatic encephalopathy includes a broad range of therapies. This article covers the specific mainstays of therapies, such as antimicrobials and laxatives, with an established evidence base. This article also covers newer modalities of therapies, such as fecal microbiota transplant, probiotics, bioartificial support systems, small molecular therapies such as l-ornithine l-aspartate, branched chain amino acids, l-carnitine, zinc, and other forms of therapy currently under review.}, }
@article {pmid32239720, year = {2020}, author = {Eltokhi, A and Janmaat, IE and Genedi, M and Haarman, BCM and Sommer, IEC}, title = {Dysregulation of synaptic pruning as a possible link between intestinal microbiota dysbiosis and neuropsychiatric disorders.}, journal = {Journal of neuroscience research}, volume = {98}, number = {7}, pages = {1335-1369}, doi = {10.1002/jnr.24616}, pmid = {32239720}, issn = {1097-4547}, support = {//The Stanley Medical Research Institute and ZonMW/ ; }, abstract = {The prenatal and early postnatal stages represent a critical time window for human brain development. Interestingly, this window partly overlaps with the maturation of the intestinal flora (microbiota) that play a critical role in the bidirectional communication between the central and the enteric nervous systems (microbiota-gut-brain axis). The microbial composition has important influences on general health and the development of several organ systems, such as the gastrointestinal tract, the immune system, and also the brain. Clinical studies have shown that microbiota alterations are associated with a wide range of neuropsychiatric disorders including autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, and bipolar disorder. In this review, we dissect the link between these neuropsychiatric disorders and the intestinal microbiota by focusing on their effect on synaptic pruning, a vital process in the maturation and establishing efficient functioning of the brain. We discuss in detail how synaptic pruning is dysregulated differently in the aforementioned neuropsychiatric disorders and how it can be influenced by dysbiosis and/or changes in the intestinal microbiota composition. We also review that the improvement in the intestinal microbiota composition by a change in diet, probiotics, prebiotics, or fecal microbiota transplantation may play a role in improving neuropsychiatric functioning, which can be at least partly explained via the optimization of synaptic pruning and neuronal connections. Altogether, the demonstration of the microbiota's influence on brain function via microglial-induced synaptic pruning addresses the possibility that the manipulation of microbiota-immune crosstalk represents a promising strategy for treating neuropsychiatric disorders.}, }
@article {pmid32235826, year = {2020}, author = {Zhu, F and Ju, Y and Wang, W and Wang, Q and Guo, R and Ma, Q and Sun, Q and Fan, Y and Xie, Y and Yang, Z and Jie, Z and Zhao, B and Xiao, L and Yang, L and Zhang, T and Feng, J and Guo, L and He, X and Chen, Y and Chen, C and Gao, C and Xu, X and Yang, H and Wang, J and Dang, Y and Madsen, L and Brix, S and Kristiansen, K and Jia, H and Ma, X}, title = {Metagenome-wide association of gut microbiome features for schizophrenia.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {1612}, pmid = {32235826}, issn = {2041-1723}, mesh = {Animals ; Bacteria/classification/genetics ; Behavior, Animal ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/genetics/*physiology ; Humans ; Male ; *Metagenome ; Metagenomics/methods ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S ; ROC Curve ; Risk Factors ; Schizophrenia/*metabolism/*microbiology ; Social Behavior ; Streptococcus ; }, abstract = {Evidence is mounting that the gut-brain axis plays an important role in mental diseases fueling mechanistic investigations to provide a basis for future targeted interventions. However, shotgun metagenomic data from treatment-naïve patients are scarce hampering comprehensive analyses of the complex interaction between the gut microbiota and the brain. Here we explore the fecal microbiome based on 90 medication-free schizophrenia patients and 81 controls and identify a microbial species classifier distinguishing patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.896, and replicate the microbiome-based disease classifier in 45 patients and 45 controls (AUC = 0.765). Functional potentials associated with schizophrenia include differences in short-chain fatty acids synthesis, tryptophan metabolism, and synthesis/degradation of neurotransmitters. Transplantation of a schizophrenia-enriched bacterium, Streptococcus vestibularis, appear to induces deficits in social behaviors, and alters neurotransmitter levels in peripheral tissues in recipient mice. Our findings provide new leads for further investigations in cohort studies and animal models.}, }
@article {pmid32234317, year = {2020}, author = {Liu, J and Miyake, H and Zhu, H and Li, B and Alganabi, M and Lee, C and Pierro, A}, title = {Fecal microbiota transplantation by enema reduces intestinal injury in experimental necrotizing enterocolitis.}, journal = {Journal of pediatric surgery}, volume = {55}, number = {6}, pages = {1094-1098}, doi = {10.1016/j.jpedsurg.2020.02.035}, pmid = {32234317}, issn = {1531-5037}, abstract = {PURPOSE: Necrotizing Enterocolitis (NEC) is a devastating neonatal disease with a high mortality rate. Fecal Microbiota Transplantation (FMT) has been used to treat a variety of gastrointestinal diseases. We aimed to investigate the role of FMT in NEC.<br><br>METHODS: NEC was induced by hypoxia, LPS, and hyperosmolar gavage feeding between postnatal days P5 and P9 (n = 8). Breastfed mice were used as control (n = 7). FMT (30 μl/g) was administered by gavage or enema at P6 during NEC induction. Distal ileum was harvested on P9. Disease severity was evaluated by H&amp;E staining. Gene expression of inflammatory markers IL6 and TNFa was measured. Expression of intestinal barrier function was investigated by measuring Claudin-7. Microbiota composition in ileum and colon was analyzed by quantitative PCR.<br><br>RESULTS: FMT by gavage further increased terminal ileum inflammation and did not improve the histological damage owing to experimental NEC. Conversely, FMT by enema decreased intestinal inflammation and improved histology of the NEC-like injury in the ileum. In addition, compared with NEC alone, FMT by enema increased Claudin-7 expression indicating an improvement in barrier function. These beneficial effects occurred despite no change in microbiota.<br><br>CONCLUSION: Our results show that FMT by enema may be an effective strategy to reduce NEC progression as it attenuates intestinal inflammation and enhances intestinal barrier function. FMT by enema is a potential novel treatment for NEC.<br><br>LEVEL OF EVIDENCE: Level IV, Evidence from well-designed case-control or cohort studies.}, }
@article {pmid32233326, year = {2019}, author = {Trang-Poisson, C}, title = {[Fecal transplantation].}, journal = {La Revue du praticien}, volume = {69}, number = {7}, pages = {792-793}, pmid = {32233326}, issn = {2101-017X}, mesh = {*Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; }, }
@article {pmid32233325, year = {2019}, author = {Barbut, F and Couturier, J}, title = {[Interactions between intestinal microbiota and Clostridioides difficile].}, journal = {La Revue du praticien}, volume = {69}, number = {7}, pages = {784-791}, pmid = {32233325}, issn = {2101-017X}, mesh = {*Clostridium Infections ; *Clostridium difficile/pathogenicity ; Diarrhea ; France ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Interactions between intestinal microbiota and clostridioides difficile. Clostridioides difficile is a spore-forming anaerobic Gram-positive bacillus that is responsible for diarrhea and post-antibiotic colitis. Approximately 20,000 inpatients are infected by C. difficile in France per year. This bacterium is recognized as an emerging pathogen responsible for community-acquired diarrhea. Antibiotic therapy is the main risk factor for C. difficile infection (CDI) because it leads to intestinal dysbiosis and loss of &quot;colonization resistance&quot;. C. difficile from endogenous or exogenous origin can then establish, multiply and produce its two toxins causing enterocyte lesions and a significant inflammatory reaction. The loss of colonization resistance has been associated with the loss of microbial diversity, particularly of some taxa that play a protective role. These variations of bacterial communities lead to changes in functions that can be explored by metabolomic or metagenomic approaches. Data from these experiments led to mechanistic assumptions about resistance or susceptibility to CDI. Microbiota studies have also pushed physicians to develop therapeutic approaches based on biotherapies. These therapies aim at repopulating the colon by a healthy microbiota either by fecal microbiota transplantation or by the administration of strains and cocktails of strains to restore the colonization resistance effect.}, }
@article {pmid32230951, year = {2020}, author = {Hiippala, K and Kainulainen, V and Suutarinen, M and Heini, T and Bowers, JR and Jasso-Selles, D and Lemmer, D and Valentine, M and Barnes, R and Engelthaler, DM and Satokari, R}, title = {Isolation of Anti-Inflammatory and Epithelium Reinforcing Bacteroides and Parabacteroides Spp. from A Healthy Fecal Donor.}, journal = {Nutrients}, volume = {12}, number = {4}, pages = {}, pmid = {32230951}, issn = {2072-6643}, support = {304490//Academy of Finland/ ; 323156//Academy of Finland/ ; 285632//Academy of Finland/ ; Reetta Satokari//Sigrid Juséliuksen Säätiö/ ; }, abstract = {Altered intestinal microbiota is associated with systemic and intestinal diseases, such as inflammatory bowel disease (IBD). Dysbiotic microbiota with enhanced proinflammatory capacity is characterized by depletion of anaerobic commensals, increased proportion of facultatively anaerobic bacteria, as well as reduced diversity and stability. In this study, we developed a high-throughput in vitro screening assay to isolate intestinal commensal bacteria with anti-inflammatory capacity from a healthy fecal microbiota transplantation donor. Freshly isolated gut bacteria were screened for their capacity to attenuate Escherichia coli lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) release from HT-29 cells. The screen yielded a number of Bacteroides and Parabacteroides isolates, which were identified as P.distasonis, B.caccae, B. intestinalis, B.uniformis, B. fragilis, B.vulgatus and B.ovatus using whole genome sequencing. We observed that a cell-cell contact with the epithelium was not necessary to alleviate in vitro inflammation as spent culture media from the isolates were also effective and the anti-inflammatory action did not correlate with the enterocyte adherence capacity of the isolates. The anti-inflammatory isolates also exerted enterocyte monolayer reinforcing action and lacked essential genes to synthetize hexa-acylated, proinflammatory lipid A, part of LPS. Yet, the anti-inflammatory effector molecules remain to be identified. The Bacteroides strains isolated and characterized in this study have potential to be used as so-called next-generation probiotics.}, }
@article {pmid32228321, year = {2020}, author = {Morissette, A and Kropp, C and Songpadith, JP and Junges Moreira, R and Costa, J and Mariné-Casadó, R and Pilon, G and Varin, TV and Dudonné, S and Boutekrabt, L and St-Pierre, P and Levy, E and Roy, D and Desjardins, Y and Raymond, F and Houde, VP and Marette, A}, title = {Blueberry proanthocyanidins and anthocyanins improve metabolic health through a gut microbiota-dependent mechanism in diet-induced obese mice.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {318}, number = {6}, pages = {E965-E980}, doi = {10.1152/ajpendo.00560.2019}, pmid = {32228321}, issn = {1522-1555}, support = {//CIHR/Canada ; }, abstract = {Blueberry consumption can prevent obesity-linked metabolic diseases, and it has been proposed that the polyphenol content of blueberries may contribute to these effects. Polyphenols have been shown to favorably impact metabolic health, but the role of specific polyphenol classes and whether the gut microbiota is linked to these effects remain unclear. We aimed to evaluate the impact of whole blueberry powder and blueberry polyphenols on the development of obesity and insulin resistance and to determine the potential role of gut microbes in these effects by using fecal microbiota transplantation (FMT). Sixty-eight C57BL/6 male mice were assigned to one of the following diets for 12 wk: balanced diet (Chow); high-fat, high-sucrose diet (HFHS); or HFHS supplemented with whole blueberry powder (BB), anthocyanidin (ANT)-rich extract, or proanthocyanidin (PAC)-rich extract. After 8 wk, mice were housed in metabolic cages, and an oral glucose tolerance test (OGTT) was performed. Sixty germ-free mice fed HFHS diet received FMT from one of the above groups biweekly for 8 wk, followed by an OGTT. PAC-treated mice were leaner than HFHS controls although they had the same energy intake and were more physically active. This observation was reproduced in germ-free mice receiving FMT from PAC-treated mice. PAC- and ANT-treated mice showed improved insulin responses during OGTT, and this finding was also reproduced in germ-free mice following FMT. These results show that blueberry PAC and ANT polyphenols can reduce diet-induced body weight and improve insulin sensitivity and that at least part of these beneficial effects are explained by modulation of the gut microbiota.}, }
@article {pmid32228039, year = {2020}, author = {Hinton, R}, title = {A case report looking at the effects of faecal microbiota transplantation in a patient with bipolar disorder.}, journal = {The Australian and New Zealand journal of psychiatry}, volume = {54}, number = {6}, pages = {649-650}, doi = {10.1177/0004867420912834}, pmid = {32228039}, issn = {1440-1614}, mesh = {*Bipolar Disorder ; Depression ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid32222124, year = {2020}, author = {Dale, HF and Lied, GA}, title = {Gut microbiota and therapeutic approaches for dysbiosis in irritable bowel syndrome: Recent developments and future perspectives.}, journal = {Turkish journal of medical sciences}, volume = {}, number = {}, pages = {}, doi = {10.3906/sag-2002-57}, pmid = {32222124}, issn = {1303-6165}, abstract = {Increased knowledge regarding the implications of gut microbiota in irritable bowel syndrome (IBS), suggest that a disturbed intestinal microenvironment (dysbiosis) might promote the development and maintenance of IBS symptoms and effects several pathways in the pathology of this multifactorial disease. Accordingly, manipulation of the gut microbiota in order to improve IBS symptoms has the last decade evolved as a novel treatment strategy. Several different approaches have been investigated in order to improve the gut microbiota composition. Dietary modifications including supplementation with fibers, prebiotics and probiotics are shown to improve symptoms and composition of gut microbiota in IBS, however the exact probiotic mixture beneficial for each individual remains to be identified. The use of antibiotics still needs confirmation, although promising results have been reported with use of rifaximin. Fecal microbiota transplantation (FMT) has recently gained a lot of attention, and several placebo-controlled trials investigating FMT pose promising results regarding symptom reduction and gut microbiota manipulation in IBS. However, more data regarding long-term effects is needed before FMT can be integrated as a customised treatment for IBS in the clinical routine.}, }
@article {pmid32218321, year = {2020}, author = {Polimeno, L and Barone, M and Mosca, A and Viggiani, MT and Joukar, F and Mansour-Ghanaei, F and Mavaddati, S and Daniele, A and Debellis, L and Bilancia, M and Santacroce, L and Di Leo, A}, title = {Soy Metabolism by Gut Microbiota from Patients with Precancerous Intestinal Lesions.}, journal = {Microorganisms}, volume = {8}, number = {4}, pages = {}, pmid = {32218321}, issn = {2076-2607}, support = {PON-BIOMIS 2018 (Project: Costituzione della Biobanca del Microbiota intestinale e salivare umano: dalla disbiosi alla simbiosi).//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) requires the presence of a variety of factors predisposing a tumorigenic milieu. Excluding familial clustering and hereditary CRC syndromes, the development of sporadic CRC from precancerous lesions is influenced by tissue inflammation, modulation of intestinal immunity, hormones, dietary habits and gut microbiota composition. As concerning the last two aspects, the intestinal presence of equol, the most biologically active metabolite of the soy isoflavone daidzein and the presence of a genetic determinant of gut microbiota able to metabolize daidzein, seem to lower the CRC risk. It has been hypothesized that the anaerobic microorganisms of the Bacteroides genus play a role in equol production.<br><br>AIM: To evaluate the presence of (i) anaerobic gut microbiota and (ii) the urinary levels of soy isoflavones (daidzein, genistein and equol) in patients with and without precancerous lesions, challenged with a daidzein-rich soy extract.<br><br>METHODS: Consecutive subjects undergoing colonoscopy participated to the study. Feces were collected from all patients one week before colonoscopy for gut microbiota studies. After the endoscopy examination and the histological evaluation, 40 subjects, 20 with sporadic colorectal adenomas (SCA/P group) and 20 without proliferative lesions (control group) were enrolled for the study. Urine levels of soy isoflavones daidzein, genistein and their metabolite equol, were determined by high performance liquid chromatographic (HPLC) analysis and gut microbiota analysis was performed by Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) procedure.<br><br>RESULTS: Seventeen different bacterial species were identified in the fecal samples of the forty subjects participating to the study. Ten bacterial species resulted anaerobic Gram-negative bacteria, all belonging to the Bacteroides genus. A significant difference of bacteria species was evidenced in the fecal samples of the two groups of subjects. Particularly important was the evidence of Parabacteroidesdistasonis, Clostridiumclostridioforme and Pediococcuspentasaceus only in control fecal samples, such as the presence of Bacteroides fragilis and Prevotellamelaningenica only in SCA/P fecal samples. Concerning the soy isoflavones levels, no statistically significant differences were revealed in the genistein and daidzein urinary levels between the two groups of subjects. On the contrary, urinary equol levels were undetectable in ten SCA/P subjects and in two controls; moreover, when present, the levels of urinary equol were significantly lower in SCA/P subjects compared to controls (0.24 ± 0.27 mg/24 hrs vs. 21.25 ± 4.3 mg/24 hrs, respectively, p = 1.12 × 10-6).<br><br>CONCLUSIONS: Our results suggest that the presence of anaerobic Bacteroides in the colon, and the production of equol from soy, could determine a milieu able to contrast the development of colonic mucosa proliferative lesions.}, }
@article {pmid32215122, year = {2020}, author = {Kukla, M and Adrych, K and Dobrowolska, A and Mach, T and Reguła, J and Rydzewska, G}, title = {Guidelines for Clostridium difficile infection in adults.}, journal = {Przeglad gastroenterologiczny}, volume = {15}, number = {1}, pages = {1-21}, pmid = {32215122}, issn = {1895-5770}, abstract = {Clostridium difficile infection (CDI) has become a serious medical and epidemiological problem, especially in well developed countries. There has been evident increase in incidence and severity of CDI. Prevention, proper diagnosis and effective treatment are necessary to reduce the risk for the patients, deplete the spreading of infection and diminish the probability of recurrent infection. Antibiotics are the fundamental treatment of CDI. In patients who had recurrent CDI fecal microbiota transplantation seems to be promising and efficient strategy. These guidelines systematize existing data and include recent changes implemented in the management of CDI.}, }
@article {pmid32207794, year = {2020}, author = {Slomski, A}, title = {&quot;Superdonor&quot; Fecal Microbiota Transplant Effective for IBS.}, journal = {JAMA}, volume = {323}, number = {12}, pages = {1124}, doi = {10.1001/jama.2020.2812}, pmid = {32207794}, issn = {1538-3598}, }
@article {pmid32205337, year = {2020}, author = {Huang, Z and Chen, J and Li, B and Zeng, B and Chou, CH and Zheng, X and Xie, J and Li, H and Hao, Y and Chen, G and Pei, F and Shen, B and Kraus, VB and Wei, H and Zhou, X and Cheng, L}, title = {Faecal microbiota transplantation from metabolically compromised human donors accelerates osteoarthritis in mice.}, journal = {Annals of the rheumatic diseases}, volume = {79}, number = {5}, pages = {646-656}, pmid = {32205337}, issn = {1468-2060}, support = {P30 AG028716/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Biomarkers/analysis ; Biopsy, Needle ; Disease Models, Animal ; Disease Progression ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Menisci, Tibial/pathology/surgery ; Metabolic Syndrome/*complications/pathology ; Mice, Inbred C57BL ; Multivariate Analysis ; Osteoarthritis, Knee/pathology/*therapy ; Random Allocation ; Reference Values ; Regression Analysis ; Risk Assessment ; }, abstract = {OBJECTIVES: Emerging evidence suggests that the microbiome plays an important role in the pathogenesis of osteoarthritis (OA). We aimed to test the two-hit model of OA pathogenesis and potentiation in which one 'hit' is provided by an adverse gut microbiome that activates innate immunity; the other 'hit' is underlying joint damage.<br><br>METHODS: Medical history, faecal and blood samples were collected from human healthy controls (OA-METS-, n=4), knee OA without metabolic syndrome (OA+METS-, n=7) and knee OA with metabolic syndrome (OA+METS+, n=9). Each group of human faecal samples, whose microbial composition was identified by 16S rRNA sequencing, was pooled and transplanted into germ-free mice 2 weeks prior to meniscal/ligamentous injury (MLI) (n≥6 per group). Eight weeks after MLI, mice were evaluated for histological OA severity and synovitis, systemic inflammation and gut permeability.<br><br>RESULTS: Histological OA severity following MLI was minimal in germ-free mice. Compared with the other groups, transplantation with the OA+METS+ microbiome was associated with higher mean systemic concentrations of inflammatory biomarkers (interleukin-1β, interleukin-6 and macrophage inflammatory protein-1α), higher gut permeability and worse OA severity. A greater abundance of Fusobacterium and Faecalibaterium and lesser abundance of Ruminococcaceae in transplanted mice were consistently correlated with OA severity and systemic biomarkers concentrations.<br><br>CONCLUSION: The study clearly establishes a direct gut microbiome-OA connection that sets the stage for a new means of exploring OA pathogenesis and potentially new OA therapeutics. Alterations of Fusobacterium, Faecalibaterium and Ruminococcaceae suggest a role of these particular microbes in exacerbating OA.}, }
@article {pmid32204538, year = {2020}, author = {Tsai, MC and Liu, YY and Lin, CC and Wang, CC and Wu, YJ and Yong, CC and Chen, KD and Chuah, SK and Yao, CC and Huang, PY and Chen, CH and Hu, TH and Chen, CL}, title = {Gut Microbiota Dysbiosis in Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study in Taiwan.}, journal = {Nutrients}, volume = {12}, number = {3}, pages = {}, pmid = {32204538}, issn = {2072-6643}, support = {CMRPG8H1111//Kaohsiung Chang Gung Memorial Hospital/ ; CMRPG8J1571//Kaohsiung Chang Gung Memorial Hospital/ ; CMRPG8K0661//Kaohsiung Chang Gung Memorial Hospital/ ; }, abstract = {The gut microbiota plays a role in nonalcoholic fatty liver disease (NAFLD), but data about gut dysbiosis in Asians with NAFLD remains scarce. We analyzed the differences in fecal microbiota between adults with and without NAFLD. This cross-sectional study examined adults with histology-proven NAFLD (25 nonalcoholic fatty liver (NAFL) patients, 25 nonalcoholic steatohepatitis (NASH) patients, and 25 living liver donors (healthy controls)). The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The NAFL and NASH groups showed lower total bacterial diversity and richness than the controls. NAFLD patients had higher levels of the phylum Bacteroidetes and lower levels of Firmicutes than controls. The genus RuminococcaceaeUCG-010, family Ruminococcaceae, order Clostridiales, and class Clostridia were less abundant in patients with NAFL or NASH than healthy individuals. The lipopolysaccharide biosynthesis pathway was differentially enriched in the NASH group. This study examined the largest number of Asian patients with biopsy-proven NAFL and NASH in terms of dysbiosis of the gut microbiota in NAFLD patients. NAFLD patients had higher levels of Bacteroidetes and lower levels of Firmicutes. These results are different from research from western countries and could provide different targets for therapies by region.}, }
@article {pmid32203111, year = {2020}, author = {Hui, S and Liu, Y and Huang, L and Zheng, L and Zhou, M and Lang, H and Wang, X and Yi, L and Mi, M}, title = {Resveratrol enhances brown adipose tissue activity and white adipose tissue browning in part by regulating bile acid metabolism via gut microbiota remodeling.}, journal = {International journal of obesity (2005)}, volume = {44}, number = {8}, pages = {1678-1690}, doi = {10.1038/s41366-020-0566-y}, pmid = {32203111}, issn = {1476-5497}, abstract = {OBJECTIVE: Current evidence has linked dietary resveratrol (RSV) intake to the activation of brown adipose tissue (BAT) and induction of white adipose tissue (WAT) browning, which may be a potential means of improving glucose homeostasis. However, the underlying mechanisms remain unclear.<br><br>METHODS: A diet containing RSV was fed to db/db mice for 10 weeks, following which the body weight, adipose tissue accumulation, bile acid (BA) profiles, and markers of BA metabolism were analyzed. Oral glucose tolerance testing, immunohistochemistry, and gut microbiota sequencing were also performed.<br><br>RESULTS: RSV intervention improved glucose homeostasis in db/db mice, which was linked to the enhanced BAT activity and WAT browning. Moreover, RSV-treated mice exhibited altered plasma and fecal BA compositions and significant remodeling of the gut microbiota, the latter confirmed by a higher level of lithocholic acid (LCA) in the plasma and feces. LCA was identified to be the agonist of Takeda G-protein coupled receptor 5 (TGR5), which mediated the BAT activation and WAT browning by upregulating uncoupling protein 1 (UCP1) expression. Furthermore, depletion of the gut microbiota using antibiotics partially abolished the beneficial effects of RSV against glucose intolerance. Finally, microbiota transplantation experiments demonstrated that the RSV-induced beneficial effects were transferable, indicating that these effects were largely dependent on the gut microbiota.<br><br>CONCLUSIONS: These data indicate that RSV administration improves glucose homeostasis by enhancing BAT activation and WAT browning, a mechanism that might partially be mediated by the gut microbiota-BA-TGR5/UCP1 pathway.}, }
@article {pmid32200611, year = {2020}, author = {Zybura, J and Dyla, A and Mielnicki, W}, title = {Fecal microbiota transplantation is feasible even in critically ill patients with toxic megacolon due to Clostridium difficile infection.}, journal = {Anaesthesiology intensive therapy}, volume = {52}, number = {2}, pages = {177-180}, doi = {10.5114/ait.2020.93712}, pmid = {32200611}, issn = {1731-2531}, }
@article {pmid32197802, year = {2020}, author = {Khoruts, A and Bajaj, JS}, title = {Reply to: &quot; 'You know my name, but not my story' - Deciding on an accurate nomenclature for faecal microbiota transplantation&quot;: Intestinal microbiota transplantation: Naming a new paradigm.}, journal = {Journal of hepatology}, volume = {72}, number = {6}, pages = {1213-1214}, doi = {10.1016/j.jhep.2020.02.014}, pmid = {32197802}, issn = {1600-0641}, }
@article {pmid32192627, year = {2020}, author = {Ianiro, G and Mullish, BH and Kelly, CR and Sokol, H and Kassam, Z and Ng, SC and Fischer, M and Allegretti, JR and Masucci, L and Zhang, F and Keller, J and Sanguinetti, M and Costello, SP and Tilg, H and Gasbarrini, A and Cammarota, G}, title = {Screening of faecal microbiota transplant donors during the COVID-19 outbreak: suggestions for urgent updates from an international expert panel.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {5}, number = {5}, pages = {430-432}, doi = {10.1016/S2468-1253(20)30082-0}, pmid = {32192627}, issn = {2468-1253}, mesh = {Betacoronavirus/*isolation &amp; purification ; Coronavirus Infections/epidemiology/*virology ; Fecal Microbiota Transplantation/*methods/standards ; Feces/microbiology/virology ; Humans ; Living Donors ; Mass Screening/methods ; Pandemics ; Pneumonia, Viral/epidemiology/*virology ; }, }
@article {pmid32189316, year = {2020}, author = {Konturek, P and Konturek, K and Zopf, Y and Harsch, IA}, title = {[Intestinal microbiota - a vital &quot;organ&quot; with manifold functions].}, journal = {MMW Fortschritte der Medizin}, volume = {162}, number = {Suppl 4}, pages = {9-14}, doi = {10.1007/s15006-020-0228-y}, pmid = {32189316}, issn = {1613-3560}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics ; }, abstract = {BACKGROUND: The intestinal microbiota must be seen as an elementary component of our health.<br><br>METHOD: Review article RESULTS AND CONCLUSIONS: An abnormal gut microbiota (dysbiosis) plays an essential role in the pathogenesis of functional and inflammatory bowel diseases. It is often also associated with diseases outside the intestine. The exact causality remains unclear (&quot;chicken and egg problem&quot;). With the help of prebiotics, probiotics or fecal microbiota therapy, relevant therapeutic effects can be achieved in chronic, dysbiosis-associated diseases. The choice of the preparation depends on the clinical symptoms, the duration of the treatment depends on the particular clinical picture.}, }
@article {pmid32185143, year = {2020}, author = {Dorsaz, S and Charretier, Y and Girard, M and Gaïa, N and Leo, S and Schrenzel, J and Harbarth, S and Huttner, B and Lazarevic, V}, title = {Changes in Microbiota Profiles After Prolonged Frozen Storage of Stool Suspensions.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {77}, pmid = {32185143}, issn = {2235-2988}, abstract = {Introduction: Fecal microbiota transplantation (FMT) is recommended as safe and effective treatment for recurrent Clostridioides difficile infections. Freezing the FMT preparation simplifies the process, allowing a single stool sample to be used for multiple receivers and over an extended period of time. We aimed to assess the effect of long-term frozen storage on bacterial taxonomic profiles of a stool suspension prepared for FMT. Methods: DNA was extracted from a stool suspension before freezing and sequentially during the 18-month storage period at -80°C. Two different protocols were used for DNA extraction. The first relied on a classical mechanical and chemical cell disruption to extract both intra- and extracellular DNA; the second included specific pre-treatments aimed at removing free DNA and DNA from human and damaged bacterial cells. Taxonomic profiling of bacterial communities was performed by sequencing of V3-V4 16S rRNA gene amplicons. Results: Microbiota profiles obtained by whole DNA extraction procedure remained relatively stable during frozen storage. When DNA extraction procedure included specific pre-treatments, microbiota similarity between fresh and frozen samples progressively decreased with longer frozen storage times; notably, the abundance of Bacteroidetes decreased in a storage duration-dependent manner. The abundance of Firmicutes, the main butyrate producers in the colon, were not much affected by frozen storage for up to 1 year. Conclusion: Our data show that metataxonomic analysis of frozen stool suspensions subjected to specific pre-treatments prior to DNA extractions might provide an interesting indication of bacterial resistance to stress conditions and thus of chances of survival in FMT recipients.}, }
@article {pmid32185104, year = {2020}, author = {Liu, X and Lv, Q and Ren, H and Gao, L and Zhao, P and Yang, X and Yang, G and Xu, D and Wang, G and Yang, W and Wang, P and Wang, Z and Xing, S}, title = {The altered gut microbiota of high-purine-induced hyperuricemia rats and its correlation with hyperuricemia.}, journal = {PeerJ}, volume = {8}, number = {}, pages = {e8664}, pmid = {32185104}, issn = {2167-8359}, abstract = {Some studies on the hyperuricemia (HUA) have focused on intestinal bacteria. To better understand the correlation between gut microbiota and HUA, we established a HUA rat model with high-purine diet, and used 16S rRNA genes sequencing to analyze gut microbiota changes in HUA rats. To analyze the potential role played by gut microbiota in HUA, we altered the gut microbiota of HUA rats with antibiotics, and compared the degree of uric acid elevation between HUA and antibiotic-fed HUA rats (Ab+HUA). Finally, we established a recipient rat model, in which we transplanted fecal microbiota of HUA and normal rats into recipient rats. Three weeks later, we compared the uric acid content of recipient rats. As a result, the diversity and abundance of the gut microbiota had changed in HUA rats. The Ab-fed HUA rats had significantly lower uric acid content compared to the HUA rats, and gut microbiota from HUA rats increased uric acid content of recipient rats. The genera Vallitalea, Christensenella and Insolitispirillum may associate with HUA. Our findings highlight the association between gut microbiota and HUA, and the potential role played by gut microbiota in HUA. We hope that this finding will promote the isolation and culture of HUA-related bacteria and orient HUA-related studies from being correlational to mechanistic. These steps will therefore make it possible for us to treat HUA using gut microbiota as the target.}, }
@article {pmid32182248, year = {2020}, author = {Dang, X and Xu, M and Liu, D and Zhou, D and Yang, W}, title = {Assessing the efficacy and safety of fecal microbiota transplantation and probiotic VSL#3 for active ulcerative colitis: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {15}, number = {3}, pages = {e0228846}, pmid = {32182248}, issn = {1932-6203}, mesh = {Administration, Oral ; Colitis, Ulcerative/*therapy ; Combined Modality Therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/drug effects ; Humans ; Probiotics/*administration &amp; dosage/pharmacology ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation is an effective treatment for many gastrointestinal diseases, such as Clostridium difficile infection and inflammatory bowel disease, especially ulcerative colitis. Changes in colonic microflora may play an important role in the pathogenesis of ulcerative colitis, and improvements in the intestinal microflora may relieve the disease. Fecal bacterial transplants and oral probiotics are becoming important ways to relieve active ulcerative colitis.<br><br>PURPOSE: This systematic review with meta-analysis compared the efficacy and safety of basic treatment combined with fecal microbiota transplantation or mixed probiotics therapy in relieving mild to moderate ulcerative colitis.<br><br>METHODS: The PubMed, Embase, and Cochrane libraries (updated September 2019) were searched to identify randomized, placebo-controlled, or head-to-head trials assessing fecal microbiota transplantation or probiotic VSL#3 as induction therapy in active ulcerative colitis. We analyze data using the R program to obtain evidence of direct comparison and to generate intermediate variables for indirect treatment comparisons.<br><br>RESULTS: Seven randomized, double-blind, placebo-controlled trials were used as the sources of the induction data. All treatments were superior to placebo. In terms of clinical remission and clinical response to active ulcerative colitis, direct comparisons showed fecal microbiota transplantation (OR = 3.47, 95% CI = 1.93-6.25) (OR = 2.48, 95% CI = 1.18-5.21) and mixed probiotics VSL#3 (OR = 2.40, 95% CI = 1.49-3.88) (OR = 3.09, 95% CI = 1.53-6.25) to have better effects than the placebo. Indirect comparison showed fecal microbiota transplantation and probiotic VSL#3 did not reach statistical significance either in clinical remission (RR = 1.20, 95% CI = 0.70-2.06) or clinical response (RR = 0.95, 95% CI = 0.62-1.45). In terms of safety, fecal microbiota transplantation (OR = 1.15, 95% CI = 0.51-2.61) and VSL #3 (OR = 0.90, 95% CI = 0.33-2.49) showed no statistically significant increase in adverse events compared with the control group. In terms of serious adverse events, there was no statistical difference between the fecal microbiota transplantation group and the control group (OR = 1.29, 95% CI = 0.46-3.57). The probiotics VSL#3 seems more safer than fecal microbiota transplantation, because serious adverse events were not reported in the VSL#3 articles.<br><br>CONCLUSIONS: Fecal microbiota transplantation or mixed probiotics VSL#3 achieved good results in clinical remission and clinical response in active ulcerative colitis, and there was no increased risk of adverse reactions. There was no statistical difference between the therapeutic effect of fecal microbiota transplantation and that of mixed probiotics VSL#3. However, the use of fecal microbiota transplantation and probiotics still has many unresolved problems in clinical applications, and more randomized controlled trials are required to confirm its efficacy.}, }
@article {pmid32179403, year = {2020}, author = {Ávila, PRM and Michels, M and Vuolo, F and Bilésimo, R and Burger, H and Milioli, MVM and Sonai, B and Borges, H and Carneiro, C and Abatti, M and Santana, IVV and Michelon, C and Dal-Pizzol, F}, title = {Protective effects of fecal microbiota transplantation in sepsis are independent of the modulation of the intestinal flora.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {73}, number = {}, pages = {110727}, doi = {10.1016/j.nut.2020.110727}, pmid = {32179403}, issn = {1873-1244}, abstract = {OBJECTIVE: The aim of this study was to investigate the protective effects of probiotics and fecal transplantation on inflammatory and oxidative parameters in the intestines of two rat models of sepsis.<br><br>METHODS: Rats were treated with prebiotics, probiotics, or symbiotics and exposed to lipopolysaccharide (LPS) or zymosan after 15 d to induce endotoxemia. Oxidative damage and inflammation were analyzed, and histologic examination of the intestinal tissue was performed. Fecal microbiota transplantation (FMT) was carried out in LPS- and zymosan-induced rat models of sepsis.<br><br>RESULTS: Supplementation with symbiotics for 15 d effectively reduced the inflammatory parameters compared with supplementation for 7 d. Probiotics, prebiotics, and symbiotics exerted different effects on the evaluated parameters. In general, Lactobacillus rhamnosus and L. casei exerted better local protective effects. Evaluation of the role of the intestinal microbiota through FMT revealed its protective effects irrespective of the previous treatment with probiotics.<br><br>CONCLUSION: Probiotic strains significantly differ among themselves and exert different effects on the host's health. Symbiotics and FMT could offer additional immunomodulatory benefits to drug therapy, thus serving as a new therapeutic alternative in pediatric patients with sepsis.}, }
@article {pmid32176868, year = {2020}, author = {Chen, Y and Zhang, S and Zeng, B and Zhao, J and Yang, M and Zhang, M and Li, Y and Ni, Q and Wu,  and Li, Y}, title = {Transplant of microbiota from long-living people to mice reduces aging-related indices and transfers beneficial bacteria.}, journal = {Aging}, volume = {12}, number = {6}, pages = {4778-4793}, pmid = {32176868}, issn = {1945-4589}, abstract = {A close relationship between age and gut microbiota exists in invertebrates and vertebrates, including humans. Long-living people are a model for studying healthy aging; they also have a distinctive microbiota structure. The relationship between the microbiota of long-living people and aging phenotype remains largely unknown. Herein, the feces of long-living people were transplanted into mice, which were then examined for aging-related indices and beneficial bacteria. Mice transplanted with fecal matter from long-living people (L group) had greater α diversity, more probiotic genera (Lactobacillus and Bifidobacterium), and short-chain fatty acid producing genera (Roseburia, Faecalibacterium, Ruminococcus, Coprococcus) than the control group. L group mice also accumulated less lipofuscin and β-galactosidase and had longer intestinal villi. This study indicates the effects that the gut microbiota from long-living people have on healthy aging.}, }
@article {pmid32170542, year = {2020}, author = {Tamez-Torres, KM and Ponce-de-Leon, A and Torres-Gonzalez, P and Perez-Garcia, E and Torres-Veintimilla, E and Valle, MB and Sifuentes-Osornio, J}, title = {High prevalence of MDR gram-negative bacteria in feces of healthy blood donors in Mexico.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {39}, number = {8}, pages = {1439-1444}, doi = {10.1007/s10096-020-03858-z}, pmid = {32170542}, issn = {1435-4373}, support = {289673//Consejo Nacional de Ciencia y Tecnología/ ; }, abstract = {During the initial stage of a study to recruit universal intestinal microbiota donors in Mexico City, we found multiple &quot;healthy&quot; subjects that colonized with MDRO (Multidrug-resistant organisms). We aimed to describe clinical and demographic characteristics of these individuals. This was a prospective observational study. Participants were consecutively recruited among blood donors. A fecal sample was collected from each subject and analyzed at the same day in search of MDRO through chromographic culture media and, if growth observed, later confirmed by MALDI-TOF and susceptibility testing in Vitek 2 system. From July 2018 to March 2019, 85 individuals were screened for fecal colonization. Median age was 35 years (IQR 27-46 years), and 48/85 (56.4%) were males. Seventy-two (84.7%) subjects harbored at least one MDRO. ESBL-producing microorganisms were found in 72/85 (84.3%) subjects, and E. coli was the most frequent (63/85, 74.1%). Four samples (2 E. coli, 2 P. aeruginosa, 2.4% each) harbored carbapenem-resistant Enterobacteriaceae (CRE), together with an ESBL-producing microorganism. Antibiotic use (p = 0.06) and PPIs or H2-blockers intake (p = 0.03) were more common in the colonized subjects during the previous 6-month period. We report a high incidence of enteric colonization of healthy subjects with MDRO, a condition that may be related to antibiotics or PPIs/H2-blockers consumption. This surprisingly high MDRO colonization rate in potential FMT donors emphasizes the need for careful screening of donors to avoid possible transmission to FMT recipients.}, }
@article {pmid32170474, year = {2020}, author = {Allegretti, JR and Mehta, SR and Kassam, Z and Kelly, CR and Kao, D and Xu, H and Fischer, M}, title = {Risk Factors that Predict the Failure of Multiple Fecal Microbiota Transplantations for Clostridioides difficile Infection.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-020-06198-2}, pmid = {32170474}, issn = {1573-2568}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI); however, a small percentage of patients fail to achieve cure even after two FMTs. This high-risk cohort remains poorly understood.<br><br>METHODS: We performed a multicenter, multinational retrospective review of patients that underwent at least one FMT for a CDI indication at four academic FMT referrals. Patients' data including CDI, FMT, and FMT variables were assessed. The primary outcome was FMT failure after a second FMT defined as persistent diarrhea and positive laboratory test for C. difficile (PCR or toxin) despite a second FMT within 8 weeks of the first FMT. A multivariable logistic regression model was performed to determine predictors of second FMT failure.<br><br>RESULTS: A total of 540 patients received at least one FMT during the study period, of which 432 patients had success following the first FMT, 108 had documented failure (25%). Among those who failed the first FMT, 63 patients received a second FMT, of which 36 achieved cure, and 24 had documented failure after the second FMT. Patients that failed the first FMT but did not receive a second FMT and those lost to follow-up were excluded leaving 492 patients included in the analysis. The second FMT failure rate was 4.8% (24/492). Risk factors for second FMT failure identified by multivariable logistic regression included: inpatient status (OR 7.01, 95% CI: 2.37-20.78), the presence of pseudomembranes (OR 3.53, 95% CI: 1.1-11.33), and immunocompromised state (OR 3.56, 95% CI: 1.45-8.72) at the time of first FMT.<br><br>CONCLUSION: This study identifies clinically relevant risk factors predictive of failing a second FMT. Clinicians can use these variables to help identify high-risk patients and provide a better-informed consent regarding the possibility of needing multiple FMTs.}, }
@article {pmid32169506, year = {2020}, author = {Li, Y and Su, X and Gao, Y and Lv, C and Gao, Z and Liu, Y and Wang, Y and Li, S and Wang, Z}, title = {The potential role of the gut microbiota in modulating renal function in experimental diabetic nephropathy murine models established in same environment.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1866}, number = {6}, pages = {165764}, doi = {10.1016/j.bbadis.2020.165764}, pmid = {32169506}, issn = {1879-260X}, abstract = {Recent studies have shown that laboratory murine autoimmunity models under the same environment display different outcomes. We established diabetic nephropathy model mice under the same environment using the classic streptozotocin method. Renal dysfunction was different among the mice. Proteinuria was more significant in the severe proteinuria group (SP) than in the mild proteinuria group (MP). We hypothesized a role for the gut microbiota in the outcome and reproducibility of induced DN models. 16S rDNA gene sequencing technology was used to analyze the differences in the gut microbiota between the two groups. Here, through fecal microbiota transplantation (FMT) and gas chromatography mass spectrometry (GC-MS), we verified the role of the gut microbiota and its short-chain fatty acid (SCFA) generation in DN mouse renal dysfunction. In the SP group, there was a reduced abundance of Firmicutes (P < 0.0001), and the dominant genus Allobaculum [linear discriminant analysis (LDA) >3, P < 0.05] was positively correlated with body weight (Rho = 0.767, P < 0.01) and blood glucose content (Rho = 0.648, P < 0.05), while the dominant genus Anaerosporobacter (LDA > 3, P < 0.05) was positively correlated with 24-hour urinary protein content (Rho = 0.773, P < 0.01). In the MP group, the dominant genus Blautia (LDA > 3, P < 0.05) was negatively correlated with 24-hour urinary protein content (Rho = -0.829, P < 0.05). The results indicated that Allobaculum and Anaerosporobacter may worsen renal function, while Blautia may be a protective factor in DN. These findings suggested that the gut microbiota may contribute to the heterogeneity of the induced response since we observed potential disease-associated microbial taxonomies and correlations with DN.}, }
@article {pmid32168885, year = {2020}, author = {Jo, YJ and Tagele, SB and Pham, HQ and Jung, Y and Ibal, JC and Choi, S and Kang, GU and Park, S and Kang, Y and Kim, S and Koh, H and Shin, JH}, title = {In Situ Profiling of the Three Dominant Phyla Within the Human Gut Using TaqMan PCR for Pre-Hospital Diagnosis of Gut Dysbiosis.}, journal = {International journal of molecular sciences}, volume = {21}, number = {6}, pages = {}, pmid = {32168885}, issn = {1422-0067}, support = {2018M3A9H3025030//National Research Foundation, Korea/ ; 918010-4//Strategic Initiative for Microbiomes in Agriculture and Food, Korea/ ; }, abstract = {A microbial imbalance called dysbiosis leads to inflammatory bowel disease (IBD), which can include ulcerative colitis (UC). Fecal microbiota transplantation (FMT), a novel therapy, has recently been successful in treating gut dysbiosis in UC patients. For the FMT technique to be successful, the gut microbiota of both the healthy donors and UC patients must be characterized. For decades, next-generation sequencing (NGS) has been used to analyze gut microbiota. Despite the popularity of NGS, the cost and time constraints make it difficult to use in emergency services and activities related to the periodic monitoring of microbiota profile alterations. Hence, in this study, we developed a multiplex TaqMan qPCR assay (MTq-PCR) with novel probes to simultaneously determine the relative proportions of the three dominant microbial phyla in the human gut: Bacteroidetes, Firmicutes, and Proteobacteria. The relative proportions of the three phyla in fecal samples of either healthy volunteers or UC patients were similar when assessed NGS and the MTq-PCR. Thus, our MTq-PCR assay could be a practical microbiota profiling alternative for diagnosing and monitoring gut dysbiosis in UC patients during emergency situations, and it could have a role in screening stool from potential FMT donors.}, }
@article {pmid32167008, year = {2020}, author = {Yu, L and Wang, L and Yi, H and Wu, X}, title = {Beneficial effects of LRP6-CRISPR on prevention of alcohol-related liver injury surpassed fecal microbiota transplant in a rat model.}, journal = {Gut microbes}, volume = {11}, number = {4}, pages = {1015-1029}, pmid = {32167008}, issn = {1949-0984}, abstract = {Alcohol intake can modify gut microbiota composition, increase gut permeability, and promote liver fibrogenesis. LRP6 is a signal transmembrane protein and a co-receptor for the canonical Wnt signaling pathway. This study compared the curative effect of LRP6-CRISPR on alcohol-related liver injury with that of traditional fecal microbiota transplant (FMT) and investigated the alteration of the gut microbiome following the treatment. A rat model of alcohol-related liver injury was established and injected with lentiviral vectors expressing LRP6-CRISPR or administered with fecal filtrate from healthy rats, with healthy rat served as the control. Liver tissues of rats were examined by HE staining, Sirius staining, and Oil red O staining, respectively. The expression of LRP6 and fibrosis biomarkers were tested by PCR. The fecal sample of rats was collected and examined by 16S rRNA sequencing. Our data indicated that LRP6-CRISPR was more efficient in the prevention of alcohol-related liver injury than FMT. Microbiome analysis showed that alcohol-related liver injury related to gut microbiota dysbiosis, while treatment with LRP6-CRISPR or FMT increased gut microflora diversity and improved gut symbiosis. Further, bacteria specific to the disease stages were identified. Genera Romboutsia, Escherichia-Shigella, Pseudomonas, Turicibacter, and Helicobacter were prevalent in the intestine of rats with alcohol-related liver injury, while the domination of Lactobacillus was found in rats treated with LRP6-CRISPR or FMT. Besides, Lactobacillus and genera belonging to family Lachnospiraceae, Bacteroidales S24-7 group, and Ruminococcaceae were enriched in healthy rats. LRP6-CRISPR and FMT have beneficial effects on the prevention of alcohol-related liver injury, and correspondently, both treatments altered the disrupted gut microflora to a healthy one.}, }
@article {pmid32166622, year = {2020}, author = {Ramai, D and Zakhia, K and Fields, PJ and Ofosu, A and Patel, G and Shahnazarian, V and Lai, JK and Dhaliwal, A and Reddy, M and Chang, S}, title = {Fecal Microbiota Transplantation (FMT) with Colonoscopy Is Superior to Enema and Nasogastric Tube While Comparable to Capsule for the Treatment of Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-020-06185-7}, pmid = {32166622}, issn = {1573-2568}, abstract = {BACKGROUND: Several routes of fecal microbiota transplantation (FMT) administration are available for treating recurrent Clostridioides difficile infections (CDI), the most recent of which are capsules.<br><br>AIM: To assess the efficacy of colonoscopy, capsule, enema, and nasogastric tube (NGT) FMT for the treatment of recurrent CDI.<br><br>METHODS: We reported clinical outcomes of colonoscopy, capsule, enema, and NGT FMT for the treatment of recurrent CDI according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. During January 2000 to January 2018, three databases were searched: PubMed, EMBASE, and CINAHL. Primary outcome was overall cure rate which was assessed using a random effects model; secondary outcomes included adverse effects as well as subgroup analyses comparing donor relationship, sample preparation, and study design.<br><br>RESULTS: Twenty-six studies (1309 patients) were included in the study. FMT was administered using colonoscopy in 16 studies (483 patients), NGT in five studies (149 patients), enema in four studies (360 patients), and capsules in four studies (301 patients). The random effects of pooled FMT cure rates were colonoscopy 94.8% (CI 92.4-96.8%; I2 15.6%), capsule 92.1% (CI 88.6-95.0%; I2 7.1%), enema 87.2% (CI 83.4-90.5%; I2 0%), and NGT/NDT 78.1% (CI 71.6-84.1%; I2 0%). On subgroup analysis of colonoscopy FMT, sample preparation methods had comparable cure rates: fresh 94.9% compared to 94.5%. Similarly, cure rates were unaffected by donor relationship: mixed 94.5% compared to unrelated donor 95.7%.<br><br>CONCLUSION: CDI cure rates with FMT performed with colonoscopy are superior to enema and NGT FMT, while those with FMT with colonoscopy and capsule are comparable.}, }
@article {pmid32158569, year = {2020}, author = {AlQahtani, H and Baloch, S and Tabb, D}, title = {Treatment of Recurrent Clostridium difficile Infection in an Immunocompromised Patient with Severe Neutropenia Not Responding to Standard Therapy.}, journal = {Case reports in infectious diseases}, volume = {2020}, number = {}, pages = {3089023}, pmid = {32158569}, issn = {2090-6625}, abstract = {One of the most effective strategies in reducing the risk of Clostridium difficile infection (CDI) recurrence is fecal microbiota transplantation (FMT). However, several adverse events have been reported post FMT, and data on the efficacy and safety of FMT in immunocompromised patients with hematological malignancies are rare. This report presents FMT treatment for refractory CDI in a severely immunocompromised patient. A 69-year-old female presented to the emergency department complaining of foul smelling, intractable, watery diarrhea and generalized abdominal pain. She was recently diagnosed with high-risk myelodysplastic Syndrome (MDS) requiring daily blood transfusions and reported multiple CDI episodes in the past treated successfully with metronidazole and vancomycin as mono- or combotherapy. During this admission, treatment with oral vancomycin (high dose) and intravenous metronidazole was unsuccessful, so FMT was administered. The patient recovered well despite an absolute neutrophil count (ANC) < 0.25 × 109/L, and chemotherapy was initiated soon after. FMT was successful and safe in this patient, with no relapse and adverse events seen in 8 weeks of follow-up via phone calls and office visits.}, }
@article {pmid32156514, year = {2020}, author = {Ren, K}, title = {Commentary on Ma et al. Resveratrol brings back happy bug's harmony.}, journal = {Brain, behavior, and immunity}, volume = {87}, number = {}, pages = {197-198}, doi = {10.1016/j.bbi.2020.03.005}, pmid = {32156514}, issn = {1090-2139}, }
@article {pmid32155205, year = {2020}, author = {McKinney, CA and Oliveira, BCM and Bedenice, D and Paradis, MR and Mazan, M and Sage, S and Sanchez, A and Widmer, G}, title = {The fecal microbiota of healthy donor horses and geriatric recipients undergoing fecal microbial transplantation for the treatment of diarrhea.}, journal = {PloS one}, volume = {15}, number = {3}, pages = {e0230148}, pmid = {32155205}, issn = {1932-6203}, support = {R21 AI125891/AI/NIAID NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Colitis/therapy/veterinary ; Diarrhea/*therapy/veterinary ; Dysbiosis/therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/genetics ; High-Throughput Nucleotide Sequencing/methods ; Horses/microbiology ; Microbiota ; RNA, Ribosomal, 16S/genetics ; Tissue Donors ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Fecal microbial transplantation (FMT), a treatment for certain gastrointestinal conditions associated with dysbiosis in people, is also empirically employed in horses with colitis. This study used microbiota high-throughput sequencing to compare the fecal microbial profile of healthy horses to that of geriatric microbial transplant recipients experiencing diarrhea and tested whether FMT restores microbiota diversity.<br><br>METHODS: To evaluate the effect of environment and donor characteristics on the intestinal microbiota, fecal samples were collected per rectum from 15 healthy young-adult (2-12 years) and 15 geriatric (≥20 years) horses. Additionally, FMT was performed for 3 consecutive days in 5 geriatric horses with diarrhea using feces from the same healthy donor. Fecal samples were collected from both donor and recipient prior to each FMT and from recipients 24 hours following the last FMT. The profile of the fecal bacterial microbiota was compared using 16S amplicon sequencing.<br><br>RESULTS AND CONCLUSIONS: In contrast to diet and farm location, age did not significantly affect the healthy equine fecal microbiota, indicating that both healthy geriatric and young-adult horses may serve as FMT donors. The fecal microbiota of horses with diarrhea was significantly more variable in terms of β-diversity than that of healthy horses. An inverse correlation between diarrhea score and relative abundance of Verrucomicrobia was identified in surviving FMT recipients. At study completion, the fecal microbiota of horses which responded to FMT had a higher α-diversity than prior to treatment and was phylogenetically more similar to that of the donor.}, }
@article {pmid32154322, year = {2020}, author = {Keen, EC and Tasoff, P and Hink, T and Reske, KA and Burnham, CD and Dantas, G and Kwon, JH and Dubberke, ER}, title = {Microbiome Restoration by RBX2660 Does Not Preclude Recurrence of Multidrug-Resistant Urinary Tract Infection Following Subsequent Antibiotic Exposure: A Case Report.}, journal = {Open forum infectious diseases}, volume = {7}, number = {3}, pages = {ofaa042}, pmid = {32154322}, issn = {2328-8957}, support = {R01 HD092414/HD/NICHD NIH HHS/United States ; }, abstract = {A 62-year-old woman received RBX2660, an investigational microbiome restoration therapeutic, for recurrent multidrug-resistant (MDR) urinary tract infection (UTI). RBX2660 increased gut microbiome diversity but did not eliminate uropathogen carriage, and MDR UTI recurred after subsequent antibiotic exposure. Thus, restoration of microbiome diversity does not preclude disease recurrence by residual MDR pathogens.}, }
@article {pmid32150549, year = {2020}, author = {Yu, EW and Gao, L and Stastka, P and Cheney, MC and Mahabamunuge, J and Torres Soto, M and Ford, CB and Bryant, JA and Henn, MR and Hohmann, EL}, title = {Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial.}, journal = {PLoS medicine}, volume = {17}, number = {3}, pages = {e1003051}, pmid = {32150549}, issn = {1549-1676}, support = {P30 DK040561/DK/NIDDK NIH HHS/United States ; UL1 TR001102/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Biomarkers/blood ; Boston ; Double-Blind Method ; *Energy Metabolism ; *Fecal Microbiota Transplantation/adverse effects ; Female ; *Gastrointestinal Microbiome ; Humans ; *Insulin Resistance ; Intestines/*microbiology ; Male ; Middle Aged ; Obesity/diagnosis/metabolism/microbiology/*therapy ; Pilot Projects ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: There is intense interest about whether modulating gut microbiota can impact systemic metabolism. We investigated the safety of weekly oral fecal microbiota transplantation (FMT) capsules from healthy lean donors and their ability to alter gut microbiota and improve metabolic outcomes in patients with obesity.<br><br>METHODS AND FINDINGS: FMT-TRIM was a 12-week double-blind randomized placebo-controlled pilot trial of oral FMT capsules performed at a single US academic medical center. Between August 2016 and April 2018, we randomized 24 adults with obesity and mild-moderate insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] between 2.0 and 8.0) to weekly healthy lean donor FMT versus placebo capsules for 6 weeks. The primary outcome, assessed by intention to treat, was change in insulin sensitivity between 0 and 6 weeks as measured by hyperinsulinemic euglycemic clamps. Additional metabolic parameters were evaluated at 0, 6, and 12 weeks, including HbA1c, body weight, body composition by dual-energy X-ray absorptiometry, and resting energy expenditure by indirect calorimetry. Fecal samples were serially collected and evaluated via 16S V4 rRNA sequencing. Our study population was 71% female, with an average baseline BMI of 38.8 ± 6.7 kg/m2 and 41.3 ± 5.1 kg/m2 in the FMT and placebo groups, respectively. There were no statistically significant improvements in insulin sensitivity in the FMT group compared to the placebo group (+5% ± 12% in FMT group versus -3% ± 32% in placebo group, mean difference 9%, 95% CI -5% to 28%, p = 0.16). There were no statistically significant differences between groups for most of the other secondary metabolic outcomes, including HOMA-IR (mean difference 0.2, 95% CI -0.9 to 0.9, p = 0.96) and body composition (lean mass mean difference -0.1 kg, 95% CI -1.9 to 1.6 kg, p = 0.87; fat mass mean difference 1.2 kg, 95% CI -0.6 to 3.0 kg, p = 0.18), over the 12-week study. We observed variable engraftment of donor bacterial groups among FMT recipients, which persisted throughout the 12-week study. There were no significant differences in adverse events (AEs) (10 versus 5, p = 0.09), and no serious AEs related to FMT. Limitations of this pilot study are the small sample size, inclusion of participants with relatively mild insulin resistance, and lack of concurrent dietary intervention.<br><br>CONCLUSIONS: Weekly administration of FMT capsules in adults with obesity results in gut microbiota engraftment in most recipients for at least 12 weeks. Despite engraftment, we did not observe clinically significant metabolic effects during the study.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT02530385.}, }
@article {pmid32148376, year = {2020}, author = {Gupta, A and Saha, S and Khanna, S}, title = {Therapies to modulate gut microbiota: Past, present and future.}, journal = {World journal of gastroenterology}, volume = {26}, number = {8}, pages = {777-788}, pmid = {32148376}, issn = {2219-2840}, abstract = {The human gut microbiota comprises of a complex and diverse array of microorganisms, and over the years the interaction between human diseases and the gut microbiota has become a subject of growing interest. Disturbed microbial milieu in the gastrointestinal tract is central to the pathogenesis of several diseases including antibiotic-associated diarrhea and Clostridioides difficile infection (CDI). Manipulation of this microbial milieu to restore balance by microbial replacement therapies has proven to be a safe and effective treatment for recurrent CDI. There is considerable heterogeneity in various aspects of stool processing and administration for fecal microbiota transplantation (FMT) across different centers globally, and standardized microbioal replacement therapies offer an attractive alternative. The adverse effects associated with FMT are usually mild. However, there is paucity of data on long term safety of FMT and there is a need for further studies in this regard. With our increasing understanding of the host-microbiome interaction, there is immense potential for microbial replacement therapies to emerge as a treatment option for several diseases. The role of microbioal replacement therapies in diseases other than CDI is being extensively studied in ongoing clinical trials and it may be a potential treatment option for inflammatory bowel disease, irritable bowel syndrome, obesity, multidrug resistant infections, and neuropsychiatric illnesses. Fecal microbiota transplantation for non-CDI disease states should currently be limited only to research settings.}, }
@article {pmid32146836, year = {2020}, author = {Giuffrè, M and Campigotto, M and Campisciano, G and Comar, M and Crocè, LS}, title = {A story of liver and gut microbes: how does the intestinal flora affect liver disease? A review of the literature.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {318}, number = {5}, pages = {G889-G906}, doi = {10.1152/ajpgi.00161.2019}, pmid = {32146836}, issn = {1522-1547}, mesh = {Animals ; Bacteria/metabolism/*pathogenicity ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Intestines/*microbiology ; Liver/metabolism/*microbiology/pathology ; Liver Diseases/metabolism/*microbiology/pathology/therapy ; Probiotics/therapeutic use ; }, abstract = {Each individual is endowed with a unique gut microbiota (GM) footprint that mediates numerous host-related physiological functions, such as nutrient metabolism, maintenance of the structural integrity of the gut mucosal barrier, immunomodulation, and protection against microbial pathogens. Because of increased scientific interest in the GM, its central role in the pathophysiology of many intestinal and extraintestinal conditions has been recognized. Given the close relationship between the gastrointestinal tract and the liver, many pathological processes have been investigated in the light of a microbial-centered hypothesis of hepatic damage. In this review we introduce to neophytes the vast world of gut microbes, including prevalent bacterial distribution in healthy individuals, how the microbiota is commonly analyzed, and the current knowledge of the role of GM in liver disease pathophysiology. Also, we highlight the potentials and downsides of GM-based therapy.}, }
@article {pmid32132347, year = {2020}, author = {Zhang, F and Zhai, M and Wu, Q and Jia, X and Wang, Y and Wang, N}, title = {Protective Effect of Tong-Qiao-Huo-Xue Decoction on Inflammatory Injury Caused by Intestinal Microbial Disorders in Stroke Rats.}, journal = {Biological &amp; pharmaceutical bulletin}, volume = {43}, number = {5}, pages = {788-800}, doi = {10.1248/bpb.b19-00847}, pmid = {32132347}, issn = {1347-5215}, abstract = {Tong-Qiao-Huo-Xue Decoction (TQHXD) is a classic traditional Chinese medicine prescription for treating cerebral ischemia. The purpose of this study was to investigate the effect of TQHXD on intervening inflammatory response of ischemic stroke by regulating intestinal flora and repairing the intestinal barrier. A rat model of cerebral ischemia was established using middle cerebral artery occlusion (MCAO) and behavioral scores were performed. Additionally, the high throughput 16S ribosomal DNA (rDNA) sequence of intestinal bacteria in fecal samples of rat was also carried out. Our results showed that TQHXD could change the main components of intestinal flora in stroke rats, and reduced the excessive increase of Bacteroidetes, and also regulated the abnormal changes of abundance of some flora as well. In addition, the intestinal epithelial barrier was damaged after stroke, allowing bacterial metabolites to enter the blood, while TQHXD had an improved effect on this phenomenon. Meanwhile, pathological changes in the brain tissue and infarct volume were also alleviated by TQHXD. Due to the disorder of the intestinal flora and the destruction of the barrier, the peripheral immune imbalance caused an inflammatory reaction. TQHXD improved the imbalance of T cells, and inhibited the inflammatory response. Finally, the therapeutic transplantation of fecal microbiota also improved the outcome of stroke in rats. Our presented results suggest that TQHXD may improve the gut microbiota disorder and its induced inflammatory response after stroke, which could be a new target and mechanism for the treatment of stroke.}, }
@article {pmid32130695, year = {2020}, author = {Baffy, G}, title = {Gut Microbiota and Cancer of the Host: Colliding Interests.}, journal = {Advances in experimental medicine and biology}, volume = {1219}, number = {}, pages = {93-107}, doi = {10.1007/978-3-030-34025-4_5}, pmid = {32130695}, issn = {0065-2598}, mesh = {Dysbiosis ; Gastrointestinal Microbiome/immunology/*physiology ; Humans ; Intestines/immunology/microbiology ; Neoplasms/immunology/*metabolism/therapy ; Tumor Microenvironment ; }, abstract = {Cancer develops in multicellular organisms from cells that ignore the rules of cooperation and escape the mechanisms of anti-cancer surveillance. Tumorigenesis is jointly encountered by the host and microbiota, a vast collection of microorganisms that live on the external and internal epithelial surfaces of the body. The largest community of human microbiota resides in the gastrointestinal tract where commensal, symbiotic and pathogenic microorganisms interact with the intestinal barrier and gut mucosal lymphoid tissue, creating a tumor microenvironment in which cancer cells thrive or perish. Aberrant composition and function of the gut microbiota (dysbiosis) has been associated with tumorigenesis by inducing inflammation, promoting cell growth and proliferation, weakening immunosurveillance, and altering food and drug metabolism or other biochemical functions of the host. However, recent research has also identified several mechanisms through which gut microbiota support the host in the fight against cancer. These mechanisms include the use of antigenic mimicry, biotransformation of chemotherapeutic agents, and other mechanisms to boost anti-cancer immune responses and improve the efficacy of cancer immunotherapy. Further research in this rapidly advancing field is expected to identify additional microbial metabolites with tumor suppressing properties, map the complex interactions of host-microbe 'transkingdom network' with cancer cells, and elucidate cellular and molecular pathways underlying the impact of specific intestinal microbial configurations on immune checkpoint inhibitor therapy.}, }
@article {pmid32126303, year = {2020}, author = {Ebrahimzadeh Leylabadlo, H and Sanaie, S and Sadeghpour Heravi, F and Ahmadian, Z and Ghotaslou, R}, title = {From role of gut microbiota to microbial-based therapies in type 2-diabetes.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {81}, number = {}, pages = {104268}, doi = {10.1016/j.meegid.2020.104268}, pmid = {32126303}, issn = {1567-7257}, abstract = {The incidence of type 2 diabetes mellitus (T2DM) has increased dramatically at an alarming level around the world.T2DM is associated with changeable risk factors in lifestyle as well as genetic and family associated risk factors. More importantly, imbalanced or impaired gut microbial distribution (dysbiosis) has been reported as a contributing risk factor in insulin resistance progression in T2DM. Dysbiosis may restructure the metabolic and functional pathways in the intestine which are involved in the development of T2DM. However, several studies have indicated the constructive and helpful effect of prebiotics, probiotics, and fecal microbiota transplantation (FMT) on the improvement of gut microbiota (GM) and accordingly host metabolism. In this review, the association between GM and T2DM have been evaluated and the role of prebiotics, probiotics and FMT, as potential therapeutic approaches have been discussed. Relevant studies were obtained randomly from online databases such as PubMed/Medline and ISI Web of Science.}, }
@article {pmid32117913, year = {2020}, author = {Adamberg, K and Raba, G and Adamberg, S}, title = {Use of Changestat for Growth Rate Studies of Gut Microbiota.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {8}, number = {}, pages = {24}, pmid = {32117913}, issn = {2296-4185}, abstract = {Human colon microbiota, composed of hundreds of different species, is closely associated with several health conditions. Controlled in vitro cultivation and up-to-date analytical methods make possible the systematic evaluation of the underlying mechanisms of complex interactions between the members of microbial consortia. Information on reproducing fecal microbial consortia can be used for various clinical and biotechnological applications. In this study, chemostat and changestat cultures were used to elucidate the effects of the physiologically relevant range of dilution rates on the growth and metabolism of adult fecal microbiota. The dilution rate was kept either at D = 0.05 or D = 0.2 1/h in chemostat cultures, while gradually changing from 0.05 to 0.2 1/h in the A-stat and from 0.2 to 0.05 1/h in the De-stat. Apple pectin as a substrate was used in the chemostat experiments and apple pectin or birch xylan in the changestat experiments, in the presence of porcine mucin in all cases. The analyses were comprised of HPLC for organic acids, UPLC for amino acids, GC for gas composition, 16S-rDNA sequencing for microbial composition, and growth parameter calculations. It was shown that the abundance of most bacterial taxa was determined by the dilution rate on both substrates. Bacteroides ovatus, Bacteroides vulgatus, and Faecalibacterium were prevalent within the whole range of dilution rates. Akkermansia muciniphila and Ruminococcaceae UCG-013 were significantly enriched at D = 0.05 1/h, while Bacteroides caccae, Lachnospiraceae unclassified and Escherichia coli clearly preferred D = 0.2 1/h. In the chemostat cultures, the production of organic acids and gases from pectin was related to the dilution rate. The ratio of acetate, propionate and butyrate was 5:2:1 (D = 0.05 1/h) and 14:2:1 (D = 0.2 1/h). It was shown that the growth rate-related characteristics of the fecal microbiota were concise in both directions between D = 0.05 and 0.2 1/h. Reproducible adaptation of the fecal microbiota was shown in the continuous culture with a changing dilution rate: changestat. Consortia cultivation is a promising approach for research purposes and several biotechnological applications, including the production of multi-strain probiotics and fecal transplantation mixtures.}, }
@article {pmid32117102, year = {2020}, author = {Tsigalou, C and Konstantinidis, T and Stavropoulou, E and Bezirtzoglou, EE and Tsakris, A}, title = {Potential Elimination of Human Gut Resistome by Exploiting the Benefits of Functional Foods.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {50}, pmid = {32117102}, issn = {1664-302X}, abstract = {Recent advances in technology over the last decades have strived to elucidate the diverse and abundant ecosystem of the human microbiome. The intestinal microbiota represents a densely inhabited environment that offers a plethora of beneficial effects to the host's wellbeing. On the other hand, it can serve as a potential reservoir of Multi-Drug Resistant (MDR) bacteria and their antibiotic-resistant genes (ARgenes), which comprise the &quot;gut resistome.&quot; ARgenes, like antibiotics, have been omnipresent in the environment for billions of years. In the context of the gut microbiome, these genes may conflate into exogenous MDR or emerge in commensals due to mutations or gene transfers. It is currently generally accepted that Antimicrobial Resistance (AMR) poses a serious threat to public health worldwide. It is of paramount importance that researchers focus on, amongst other parameters, elaborating strategies to manage the gut resistome, particularly focusing on the diminution of AMR. Potential interventions in the gut microbiome field by Fecal Microbiota Transplant (FMT) or functional foods are newly emerged candidates for the uprooting of MDR strains and restoring dysbiosis and resilience. Probiotic nutrition is thought to diminish gut colonization from pathobionts. Yet only a few studies have explored the effects of antibiotics use on the reservoir of AR genes and the demanding time for return to normal by gut microbiota-targeted strategies. Regular administration of probiotic bacteria has recently been linked to restoration of the gut ecosystem and decrease of the gut resistome and AR genes carriers. This review summarizes the latest information about the intestinal resistome and the intriguing methods of fighting against AMR through probiotic-based methods and gut microbial shifts that have been proposed. This study contains some key messages: (1) AMR currently poses a lethal threat to global health, and it is pivotal for the scientific community to do its utmost in fighting against it; (2) human gut microbiome research, within the last decade especially, seems to be preoccupied with the interface of numerous diseases and identifying a potential target for a variety of interventions; (3) the gut resistome, comprised of AR genesis, presents very early on in life and is prone to shifts due to the use of antibiotics or dietary supplements; and (4) future strategies involving functional foods seem promising for the battle against AMR through intestinal resistome diminution.}, }
@article {pmid32115244, year = {2020}, author = {Neff, AS}, title = {Technical and Theoretic Limitations of the Experimental Evidence Supporting a Gut Bacterial Etiology in Mental Illness.}, journal = {Clinical therapeutics}, volume = {42}, number = {4}, pages = {e74-e81}, doi = {10.1016/j.clinthera.2020.02.002}, pmid = {32115244}, issn = {1879-114X}, abstract = {The impact of gut bacteria on the brain and behavior has become the subject of intense research. The brain is sensitive to biochemical and physiologic changes in the body, for example, changes in blood oxygenation or nutritional status. The collection of microorganisms residing within the digestive tract (the gut microbiome) is increasingly considered a major contributor to human physiology. These 2 considerations have led to the hypothesis that human psychology, including complex constructs like emotion and mental illness, could be influenced by the composition or function of gut bacteria. Five lines of evidence have been used to support the concept, including human correlational research, probiotic supplementation, antibiotic use, germ-free animal research, and fecal transplantation. Results from these experiments do not provide substantial support for the theory that complex human psychology is under the influence of gut bacteria. Placebo-controlled interventional research in humans, in particular fecal microbiota transplantation, will be required before a stronger conclusion can be reached.}, }
@article {pmid32114770, year = {2020}, author = {Jiménez-Avalos, JA and Arrevillaga-Boni, G and González-López, L and García-Carvajal, ZY and González-Avila, M}, title = {Classical methods and perspectives for manipulating the human gut microbial ecosystem.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-25}, doi = {10.1080/10408398.2020.1724075}, pmid = {32114770}, issn = {1549-7852}, abstract = {A healthy Human Gut Microbial Ecosystem (HGME) is a necessary condition for maintaining the orderly function of the whole body. Major alterations in the normal gut microbial composition, activity and functionality (dysbiosis) by an environmental or host-related disruptive event, can compromise metabolic, inflammatory, and neurological processes, causing disorders such as obesity, inflammatory bowel disease, colorectal cancer, and depressive episodes. The restore or the maintaining of the homeostatic balance of Gut Microbiota (GM) populations (eubiosis) is possible through diet, the use of probiotics, prebiotics, antibiotics, and even Fecal Microbiota Transplantation (FMT). Although these &quot;classic methods&quot; represent an effective and accepted way to modulate GM, the complexity of HGME requires new approaches to control it in a more appropriate way. Among the most promising emergent strategies for modulating GM are the use of engineered nanomaterials (metallic nanoparticles (NP), polymeric-NP, quantum dots, micelles, dendrimers, and liposomes); phagotherapy (i.e., phages linked with the CRISPR/Cas9 system), and the use of antimicrobial peptides, non-antibiotic drugs, vaccines, and immunoglobulins. Here we review the current state of development, implications, advantages, disadvantages, and perspectives of the different approaches for manipulating HGME.}, }
@article {pmid32109968, year = {2020}, author = {Zhao, X and Jiang, Y and Xi, H and Chen, L and Feng, X}, title = {Exploration of the Relationship Between Gut Microbiota and Polycystic Ovary Syndrome (PCOS): a Review.}, journal = {Geburtshilfe und Frauenheilkunde}, volume = {80}, number = {2}, pages = {161-171}, pmid = {32109968}, issn = {0016-5751}, abstract = {Polycystic ovary syndrome (PCOS) is an endocrine and metabolic syndrome (MS) with a complex etiology, and its pathogenesis is not yet clear. In recent years, the correlation between gut microbiota (GM) and metabolic disease has become a hot topic in research, leading to a number of new ideas about the etiology and pathological mechanisms of PCOS. The literature shows that GM can cause insulin resistance, hyperandrogenism, chronic inflammation and metabolic syndrome (obesity, diabetes) and may contribute to the development of PCOS by influencing energy absorption, the pathways of short chain fatty acids (SCFA), lipopolysaccharides, choline and bile acids, intestinal permeability and the brain-gut axis. As part of the treatment of PCOS, fecal microbiota transplantation, supplementation with prebiotics and traditional Chinese medicine can be used to regulate GM and treat disorders. This article reviews possible mechanisms and treatment options for PCOS, based on methods which target the GM, and offers new ideas for the treatment of PCOS.}, }
@article {pmid32107473, year = {2020}, author = {König, J and Brummer, RJ}, title = {Faecal microbiota transplantation in IBS - new evidence for success?.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {17}, number = {4}, pages = {199-200}, doi = {10.1038/s41575-020-0282-z}, pmid = {32107473}, issn = {1759-5053}, mesh = {Double-Blind Method ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome ; }, }
@article {pmid32107336, year = {2020}, author = {Merli, P and Putignani, L and Ruggeri, A and Del Chierico, F and Gargiullo, L and Galaverna, F and Gaspari, S and Pagliara, D and Russo, A and Pane, S and Strocchio, L and Algeri, M and Rea, F and Romeo, EF and Bernaschi, P and Onetti Muda, A and Dallapiccola, B and Locatelli, F}, title = {Decolonization of multi-drug resistant bacteria by fecal microbiota transplantation in five pediatric patients before allogeneic hematopoietic stem cell transplantation: gut microbiota profiling, infectious and clinical outcomes.}, journal = {Haematologica}, volume = {}, number = {}, pages = {}, doi = {10.3324/haematol.2019.244210}, pmid = {32107336}, issn = {1592-8721}, }
@article {pmid32106123, year = {2020}, author = {Yan, PG and Li, JN}, title = {Advances in the understanding of the intestinal micro-environment and inflammatory bowel disease.}, journal = {Chinese medical journal}, volume = {133}, number = {7}, pages = {834-841}, pmid = {32106123}, issn = {2542-5641}, abstract = {The human gastrointestinal tract accommodates an entire micro-environment for divergent physiologic processes, the dysbiosis of this micro-ecology has a strong inter-action with the pathogenesis of inflammatory bowel disease (IBD). In the past few years, with the advances in the understanding of microbiome, its metabolites and further application of next generation sequencing, analysis of dynamic alteration of gut micro-environment was realized, which provides numerous information beyond simple microbiota structure or metabolites differences under chronic colitis status. The subsequent intervention strategies targeting the modulation of intestinal micro-environment have been explored as a potential therapy. In this review, we will summarize the recent knowledge about multi-dimensional dysbiosis, the inter-action between fungus and bacteria under inflamed mucosa, and the clinical application of probiotics and fecal microbiota transplantation as a promising therapeutic approach in IBD.}, }
@article {pmid32104162, year = {2020}, author = {Cheng, YW and Fischer, M}, title = {Fecal Microbiota Transplantation: Redefining Surgical Management of Refractory Clostridium difficile Infection.}, journal = {Clinics in colon and rectal surgery}, volume = {33}, number = {2}, pages = {92-97}, pmid = {32104162}, issn = {1531-0043}, abstract = {Fecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a diseased individual for therapeutic purposes. It has a clearly defined role in the treatment of recurrent Clostridium difficile (reclassified as &quot; Clostridioides difficile &quot;) infection (CDI), with cure rates over 90% and decreased rates of subsequent recurrence compared with anti-CDI antibiotics. There is emerging evidence that FMT is also effective in the treatment of severe and fulminant CDI, with associated decreases in mortality and colectomy rates compared with standard antibiotic therapy. FMT shows promise as salvage therapy for critically-ill CDI patients refractory to maximum medical therapy and not deemed to be surgical candidates. FMT should be considered early in the course of severe CDI and should be delivered immediately in patients with signs of refractory CDI. Expansion of FMT's use along the spectrum of CDI severity has potential to decrease associated rates of mortality and colectomy.}, }
@article {pmid32101664, year = {2020}, author = {Peled, JU and Gomes, ALC and Devlin, SM and Littmann, ER and Taur, Y and Sung, AD and Weber, D and Hashimoto, D and Slingerland, AE and Slingerland, JB and Maloy, M and Clurman, AG and Stein-Thoeringer, CK and Markey, KA and Docampo, MD and Burgos da Silva, M and Khan, N and Gessner, A and Messina, JA and Romero, K and Lew, MV and Bush, A and Bohannon, L and Brereton, DG and Fontana, E and Amoretti, LA and Wright, RJ and Armijo, GK and Shono, Y and Sanchez-Escamilla, M and Castillo Flores, N and Alarcon Tomas, A and Lin, RJ and Yáñez San Segundo, L and Shah, GL and Cho, C and Scordo, M and Politikos, I and Hayasaka, K and Hasegawa, Y and Gyurkocza, B and Ponce, DM and Barker, JN and Perales, MA and Giralt, SA and Jenq, RR and Teshima, T and Chao, NJ and Holler, E and Xavier, JB and Pamer, EG and van den Brink, MRM}, title = {Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation.}, journal = {The New England journal of medicine}, volume = {382}, number = {9}, pages = {822-834}, pmid = {32101664}, issn = {1533-4406}, support = {1R01CA228308-01/CA/NCI NIH HHS/United States ; P01-AG052359 (Project 2)/AG/NIA NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; R01 AI137269-01//National Institute of Allergy and Infectious Diseases/International ; K08HL143189-01A1/HL/NHLBI NIH HHS/United States ; P30 AG028716/AG/NIA NIH HHS/United States ; P01-CA023766 (Project 4)/CA/NCI NIH HHS/United States ; U01 AI124275/CA/NCI NIH HHS/United States ; KL2 TR001115-03/TR/NCATS NIH HHS/United States ; 17K09945//Japan Society for the Promotion of Science/International ; 17H04206//Japan Society for the Promotion of Science/International ; 2016-013/US/United States/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; 1R01HL124112-01A/HL/NHLBI NIH HHS/United States ; R01 AI032135/AI/NIAID NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01CA203950-01/CA/NCI NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; KL2 TR001115/TR/NCATS NIH HHS/United States ; R01-HL125571/HL/NHLBI NIH HHS/United States ; R01-HL125571/CA/NCI NIH HHS/United States ; R01 AI100288/AI/NIAID NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 CA203950/CA/NCI NIH HHS/United States ; R01-HL123340/HL/NHLBI NIH HHS/United States ; 2P30AG028716-11/AG/NIA NIH HHS/United States ; R01 AI032135/NH/NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; 1R01CA228358-01/CA/NCI NIH HHS/United States ; AI095706//National Institute of Allergy and Infectious Diseases/International ; }, mesh = {Adult ; Biodiversity ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Hematopoietic Stem Cell Transplantation/*mortality ; Humans ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Survival Analysis ; Transplantation, Homologous/mortality ; }, abstract = {BACKGROUND: Relationships between microbiota composition and clinical outcomes after allogeneic hematopoietic-cell transplantation have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable.<br><br>METHODS: The microbiota composition of fecal samples obtained from patients who were undergoing allogeneic hematopoietic-cell transplantation at four centers was profiled by means of 16S ribosomal RNA gene sequencing. In an observational study, we examined associations between microbiota diversity and mortality using Cox proportional-hazards analysis. For stratification of the cohorts into higher- and lower-diversity groups, the median diversity value that was observed at the study center in New York was used. In the analysis of independent cohorts, the New York center was cohort 1, and three centers in Germany, Japan, and North Carolina composed cohort 2. Cohort 1 and subgroups within it were analyzed for additional outcomes, including transplantation-related death.<br><br>RESULTS: We profiled 8767 fecal samples obtained from 1362 patients undergoing allogeneic hematopoietic-cell transplantation at the four centers. We observed patterns of microbiota disruption characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota was associated with a lower risk of death in independent cohorts (cohort 1: 104 deaths among 354 patients in the higher-diversity group vs. 136 deaths among 350 patients in the lower-diversity group; adjusted hazard ratio, 0.71; 95% confidence interval [CI], 0.55 to 0.92; cohort 2: 18 deaths among 87 patients in the higher-diversity group vs. 35 deaths among 92 patients in the lower-diversity group; adjusted hazard ratio, 0.49; 95% CI, 0.27 to 0.90). Subgroup analyses identified an association between lower intestinal diversity and higher risks of transplantation-related death and death attributable to graft-versus-host disease. Baseline samples obtained before transplantation already showed evidence of microbiome disruption, and lower diversity before transplantation was associated with poor survival.<br><br>CONCLUSIONS: Patterns of microbiota disruption during allogeneic hematopoietic-cell transplantation were similar across transplantation centers and geographic locations; patterns were characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota at the time of neutrophil engraftment was associated with lower mortality. (Funded by the National Cancer Institute and others.).}, }
@article {pmid32100127, year = {2020}, author = {Chen, K and Fu, Y and Wang, Y and Liao, L and Xu, H and Zhang, A and Zhang, J and Fan, L and Ren, J and Fang, B}, title = {Therapeutic Effects of the In Vitro Cultured Human Gut Microbiota as Transplants on Altering Gut Microbiota and Improving Symptoms Associated with Autism Spectrum Disorder.}, journal = {Microbial ecology}, volume = {80}, number = {2}, pages = {475-486}, doi = {10.1007/s00248-020-01494-w}, pmid = {32100127}, issn = {1432-184X}, support = {81770558//National Natural Science Foundation of China/ ; 3502Z20149031//Xiamen Joint Projects for Major Diseases/ ; }, abstract = {Autism spectrum disorder (ASD) is a brain-based neurodevelopmental disorder characterized by behavioral abnormalities. Accumulating studies show that the gut microbiota plays a vital role in the pathogenesis of ASD, and gut microbiota transplantation (GMT) is a promising technique for the treatment of ASD. In clinical applications of GMT, it is challenging to obtain effective transplants because of the high costs of donor selection and heterogeneity of donors' gut microbiota, which can cause different clinical responses. In vitro batch culture is a fast, easy-to-operate, and repeatable method to culture gut microbiota. Thus, the present study investigates the feasibility of treating ASD with in vitro cultured gut microbiota as transplants. We cultured gut microbiota via the in vitro batch culture method and performed GMT in the maternal immune activation (MIA)-induced ASD mouse model with original donor microbiota and in vitro cultured microbiota. Open field, three-chamber social, marble burying, and self-grooming tests were used for behavioral improvement assessment. Serum levels of chemokines were detected. Microbial total DNA was extracted from mouse fecal samples, and 16S rDNA was sequenced using Illumina. Our results showed that GMT treatment with original and cultured donor gut microbiota significantly ameliorated anxiety-like and repetitive behaviors and improved serum levels of chemokines including GRO-α (CXCL1), MIP-1α (CCL3), MCP-3 (CCL7), RANTES (CCL5), and Eotaxin (CCL11) in ASD mice. Meanwhile, the gut microbial communities of the two groups that received GMT treatment were changed compared with the ASD mice groups. In the group treated with in vitro cultured donor gut microbiota, there was a significant decrease in the relative abundance of key differential taxa, including S24-7, Clostridiaceae, Prevotella_other, and Candidatus Arthromitus. The relative abundance of these taxa reached close to the level of healthy mice. Prevotella_other also decreased in the group treated with original donor gut microbiota, with a significant increase in Ruminococcaceae and Oscillospira. The present study demonstrated that GMT with in vitro cultured microbiota also improved behavioral abnormalities and chemokine disorders in an ASD mouse model compared with GMT with original donor gut microbiota. In addition, it significantly modified several key differential taxa in gut microbial composition.}, }
@article {pmid32099702, year = {2020}, author = {Ueckermann, V and Hoosien, E and De Villiers, N and Geldenhuys, J}, title = {Fecal Microbial Transplantation for the Treatment of Persistent Multidrug-Resistant Klebsiella pneumoniae Infection in a Critically Ill Patient.}, journal = {Case reports in infectious diseases}, volume = {2020}, number = {}, pages = {8462659}, pmid = {32099702}, issn = {2090-6625}, abstract = {Dysbiosis of the microbiome is a common finding in critically ill patients, who receive broad-spectrum antibiotics and various forms of organ support. Multidrug-resistant (MDR) organisms are a growing threat in all areas of medicine, but most markedly in the critically ill, where there is both loss of host defences and widespread use of broad spectrum antibiotics. We present a case of a critically ill patient with persistent MDR Klebsiella pneumoniae infection, successfully treated with fecal microbiota transplantation (FMT), using stool of a rigorously-screened, healthy donor. FMT for Clostridium difficile colitis has been well described in the literature and is an established therapy for recurrent infections with Clostridium difficile. The use of FMT for other multidrug-resistant organisms is less frequently described, particularly in the context of critically ill patients. In our case, we have culture-documented clearance of the MDR Klebsiella pneumoniae form a patient of FMT.}, }
@article {pmid32089675, year = {2020}, author = {Mazzawi, T and Eikrem, Ø and Lied, GA and Hausken, T}, title = {Abnormal Uroguanylin Immunoreactive Cells Density in the Duodenum of Patients with Diarrhea-Predominant Irritable Bowel Syndrome Changes following Fecal Microbiota Transplantation.}, journal = {Gastroenterology research and practice}, volume = {2020}, number = {}, pages = {3520686}, pmid = {32089675}, issn = {1687-6121}, abstract = {Altered densities of enteroendocrine cells play an important role in patients with irritable bowel syndrome (IBS). Uroguanylin activates guanylate cyclase-C to regulate intestinal electrolyte and water transport. Aim. To quantify uroguanylin immunoreactive cells density in the duodenum of diarrhea-predominant IBS (IBS-D) patients compared to controls and to investigate the effect of fecal microbiota transplantation (FMT) on these cell densities. Method. Twelve patients with IBS-D according to Rome III criteria were included. The cause was identified as post infectious (PI, n = 6) or idiopathic (n = 6). They completed the IBS-symptom questionnaire before and 3 weeks after FMT. Thirty grams of fresh feces donated from healthy relatives were diluted with 60 ml normal saline and instilled via endoscope into the duodenum. Biopsies were taken from the patients' duodenum before and 3 weeks after FMT. Duodenal biopsies taken from eight healthy controls were also included. The biopsies were immunostained for uroguanylin and quantified using computerized image analysis. Results. Uroguanylin immunoreactive cells were found both in duodenal villi and crypts in both controls and IBS-D patients. The densities of uroguanylin immunoreactive cells were significantly lower in the villi (P < 0.0001) and higher in the crypts (P < 0.0001) for the patients than the controls. Following FMT, the densities of uroguanylin immunoreactive cells for the total group and idiopathic subgroup decreased significantly in the duodenal crypts (P = 0.049 and 0.04, respectively) but not in the villi. No significant changes were shown in the PI-IBS subgroups. The cells density in only the crypts correlated with diarrhea (r = 0.97, P = 0.001) and bloating (r = -0.91, P = 0.01) in the PI-IBS subgroup before FMT and with abdominal pain (r = 0.63, P = 0.03) in the total group of IBS-D patients after FMT. Conclusion. Altered uroguanylin immunoreactive cells density was found in IBS-D patients compared to controls. Changes in these cells density following FMT correlated with IBS symptoms (diarrhea, bloating, and abdominal pain).}, }
@article {pmid32089055, year = {2020}, author = {Chen, EB and Shapiro, KE and Wun, K and Kuntz, T and Theriault, BR and Nooromid, MJ and Leone, VA and Harris, KG and Jiang, Q and Spedale, M and Xiong, L and Gilbert, JA and Chang, EB and Ho, KJ}, title = {Microbial Colonization of Germ-Free Mice Restores Neointimal Hyperplasia Development After Arterial Injury.}, journal = {Journal of the American Heart Association}, volume = {9}, number = {5}, pages = {e013496}, pmid = {32089055}, issn = {2047-9980}, support = {UL1 TR001422/TR/NCATS NIH HHS/United States ; K08 HL130601/HL/NHLBI NIH HHS/United States ; R01 DK097268/DK/NIDDK NIH HHS/United States ; T32 HL094293/HL/NHLBI NIH HHS/United States ; R56 DK102872/DK/NIDDK NIH HHS/United States ; }, abstract = {Background The potential role of the gut microbiome in cardiovascular diseases is increasingly evident. Arterial restenosis attributable to neointimal hyperplasia after cardiovascular procedures such as balloon angioplasty, stenting, and bypass surgery is a common cause of treatment failure, yet whether gut microbiota participate in the development of neointimal hyperplasia remains largely unknown. Methods and Results We performed fecal microbial transplantation from conventionally raised male C57BL/6 mice to age-, sex-, and strain-matched germ-free mice. Five weeks after inoculation, all mice underwent unilateral carotid ligation. Neointimal hyperplasia development was quantified after 4 weeks. Conventionally raised and germ-free cohorts served as comparison groups. Conclusions Germ-free mice have significantly attenuated neointimal hyperplasia development compared with conventionally raised mice. The arterial remodeling response is restored by fecal transplantation. Our results describe a causative role of gut microbiota in contributing to the pathogenesis of neointimal hyperplasia.}, }
@article {pmid32083498, year = {2020}, author = {Lopetuso, LR and Ianiro, G and Allegretti, JR and Bibbò, S and Gasbarrini, A and Scaldaferri, F and Cammarota, G}, title = {Fecal transplantation for ulcerative colitis: current evidence and future applications.}, journal = {Expert opinion on biological therapy}, volume = {20}, number = {4}, pages = {343-351}, doi = {10.1080/14712598.2020.1733964}, pmid = {32083498}, issn = {1744-7682}, abstract = {Introduction: Established evidence suggests that gut microbiota plays a role in ulcerative colitis (UC). Fecal microbiota transplantation (FMT) is clearly recognized as a highly effective treatment for patients with recurrent Clostridium difficile infection and has been investigated also in patients with UC, with promising results.Areas covered: Literature review was performed to select publications concerning current evidence on the role of gut microbiota in the pathogenesis of UC, and on the effectiveness of FMT in this disorder.Expert opinion: The randomized controlled trials published investigating the use of FMT suggested a potential role for FMT in the treatment of mild to moderate UC. However, given several unanswered questions regarding donor selection, dose, route of administration and duration of therapy, this is not yet recommended as a viable therapy option. FMT has allowed for more in depth investigation with regards to the role the gut microbiota may be playing in UC. This knowledge is critical to identifying where FMT may appropriately fit in the UC treatment paradigm. As our understanding of the role the microbiome plays in this chronic disease, FMT, and then eventually defined microbes, will hopefully serve in a complementary role to conventional IBD therapies.}, }
@article {pmid32079318, year = {2020}, author = {Pilmis, B and Le Monnier, A and Zahar, JR}, title = {Gut Microbiota, Antibiotic Therapy and Antimicrobial Resistance: A Narrative Review.}, journal = {Microorganisms}, volume = {8}, number = {2}, pages = {}, pmid = {32079318}, issn = {2076-2607}, abstract = {Antimicrobial resistance is a major concern. Epidemiological studies have demonstrated direct relationships between antibiotic consumption and emergence/dissemination of resistant strains. Within the last decade, authors confounded spectrum activity and ecological effects and did not take into account several other factors playing important roles, such as impact on anaerobic flora, biliary elimination and sub-inhibitory concentration. The ecological impact of antibiotics on the gut microbiota by direct or indirect mechanisms reflects the breaking of the resistance barrier to colonization. To limit the impact of antibiotic therapy on gut microbiota, consideration of the spectrum of activity and route of elimination must be integrated into the decision. Various strategies to prevent (antimicrobial stewardship, action on residual antibiotics at colonic level) or cure dysbiosis (prebiotic, probiotic and fecal microbiota transplantation) have been introduced or are currently being developed.}, }
@article {pmid32078714, year = {2020}, author = {Luo, Y and Tixier, EN and Grinspan, AM}, title = {Fecal Microbiota Transplantation for Clostridioides difficile in High-Risk Older Adults Is Associated with Early Recurrence.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-020-06147-z}, pmid = {32078714}, issn = {1573-2568}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI). CDI disproportionately affects the elderly; however, there is a paucity of data on FMT effectiveness in older adults, especially subpopulations at highest risk for CDI-related morbidity and mortality.<br><br>AIM: To assess the efficacy and safety of FMT for CDI in older adults.<br><br>METHODS: A retrospective, long-term follow-up study was performed. The high-risk subpopulation included patients who were immunocompromised, patients with inflammatory bowel disease, and patients presenting with severe or fulminant colitis. Outcome measures included primary cure rates, early (< 12 weeks) and late (> 12 weeks) recurrence rates, adverse events, and subgroup analysis of higher-risk populations.<br><br>RESULTS: Our cohort included 75 patients (72% female) with a mean age of 76.4 and Charlson comorbidity index score of 5.4. There were 34 patients in our higher-risk subpopulation as defined above with an adjusted recurrence rate of 32.1%. FMT was performed for severe or fulminant disease in 30.6% of patients with a 3-month survival rate of 73.9%. Overall, the adjusted primary cure rate was 67.2% and the adjusted CDI recurrence was 29.9% in our cohort (90% of recurrences occurred early). Most adverse events in our study were rehospitalizations for recurrent CDI.<br><br>CONCLUSION: Compared with previous studies of FMT efficacy, our cohort had a lower primary cure rate and higher CDI recurrence rate than previously reported, likely driven by our higher-risk subpopulations. Nevertheless, FMT should be considered early to prevent progression of CDI severity and recurrence, especially in patients who present with severe and fulminant disease.}, }
@article {pmid32078445, year = {2020}, author = {Yan, X and Jin, J and Su, X and Yin, X and Gao, J and Wang, X and Zhang, S and Bu, P and Wang, M and Zhang, Y and Wang, Z and Zhang, Q}, title = {Intestinal Flora Modulates Blood Pressure by Regulating the Synthesis of Intestinal-Derived Corticosterone in High Salt-Induced Hypertension.}, journal = {Circulation research}, volume = {126}, number = {7}, pages = {839-853}, doi = {10.1161/CIRCRESAHA.119.316394}, pmid = {32078445}, issn = {1524-4571}, abstract = {RATIONALE: High-salt diet is one of the most important risk factors for hypertension. Intestinal flora has been reported to be associated with high salt-induced hypertension (hSIH). However, the detailed roles of intestinal flora in hSIH pathogenesis have not yet been fully elucidated.<br><br>OBJECTIVE: To reveal the roles and mechanisms of intestinal flora in hSIH development.<br><br>METHODS AND RESULTS: The abovementioned issues were investigated using various techniques including 16S rRNA gene sequencing, untargeted metabolomics, selective bacterial culture, and fecal microbiota transplantation. We found that high-salt diet induced hypertension in Wistar rats. The fecal microbiota of healthy rats could dramatically lower blood pressure (BP) of hypertensive rats, whereas the fecal microbiota of hSIH rats had opposite effects. The composition, metabolism, and interrelationship of intestinal flora in hSIH rats were considerably reshaped, including the increased corticosterone level and reduced Bacteroides and arachidonic acid levels, which tightly correlated with BP. The serum corticosterone level was also significantly increased in rats with hSIH. Furthermore, the above abnormalities were confirmed in patients with hypertension. The intestinal Bacteroides fragilis could inhibit the production of intestinal-derived corticosterone induced by high-salt diet through its metabolite arachidonic acid.<br><br>CONCLUSIONS: hSIH could be transferred by fecal microbiota transplantation, indicating the pivotal roles of intestinal flora in hSIH development. High-salt diet reduced the levels of B fragilis and arachidonic acid in the intestine, which increased intestinal-derived corticosterone production and corticosterone levels in serum and intestine, thereby promoting BP elevation. This study revealed a novel mechanism different from inflammation/immunity by which intestinal flora regulated BP, namely intestinal flora could modulate BP by affecting steroid hormone levels. These findings enriched the understanding of the function of intestinal flora and its effects on hypertension.}, }
@article {pmid32076145, year = {2020}, author = {Lavelle, A and Sokol, H}, title = {Gut microbiota-derived metabolites as key actors in inflammatory bowel disease.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {17}, number = {4}, pages = {223-237}, doi = {10.1038/s41575-019-0258-z}, pmid = {32076145}, issn = {1759-5053}, mesh = {Animals ; Bile Acids and Salts/metabolism ; Fatty Acids, Volatile/physiology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/metabolism/microbiology ; Humans ; Inflammatory Bowel Diseases/diagnosis/metabolism/*microbiology/therapy ; Metabolomics/methods ; Probiotics/therapeutic use ; Tryptophan/metabolism ; }, abstract = {A key role of the gut microbiota in the establishment and maintenance of health, as well as in the pathogenesis of disease, has been identified over the past two decades. One of the primary modes by which the gut microbiota interacts with the host is by means of metabolites, which are small molecules that are produced as intermediate or end products of microbial metabolism. These metabolites can derive from bacterial metabolism of dietary substrates, modification of host molecules, such as bile acids, or directly from bacteria. Signals from microbial metabolites influence immune maturation, immune homeostasis, host energy metabolism and maintenance of mucosal integrity. Alterations in the composition and function of the microbiota have been described in many studies on IBD. Alterations have also been described in the metabolite profiles of patients with IBD. Furthermore, specific classes of metabolites, notably bile acids, short-chain fatty acids and tryptophan metabolites, have been implicated in the pathogenesis of IBD. This Review aims to define the key classes of microbial-derived metabolites that are altered in IBD, describe the pathophysiological basis of these associations and identify future targets for precision therapeutic modulation.}, }
@article {pmid32071279, year = {2020}, author = {Madhusoodanan, J}, title = {News Feature: Editing the microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {7}, pages = {3345-3348}, pmid = {32071279}, issn = {1091-6490}, mesh = {Bacteria/*genetics/metabolism ; Bacteriophages/physiology ; Clostridium Infections/*microbiology/therapy ; Clostridium difficile/physiology/virology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Phage Therapy ; Plasmids/genetics/metabolism ; }, }
@article {pmid32068018, year = {2020}, author = {Liu, X and Liu, Y and Chen, X and Wang, C and Chen, X and Liu, W and Huang, K and Chen, H and Yang, J}, title = {Multi-walled carbon nanotubes exacerbate doxorubicin-induced cardiotoxicity by altering gut microbiota and pulmonary and colonic macrophage phenotype in mice.}, journal = {Toxicology}, volume = {435}, number = {}, pages = {152410}, doi = {10.1016/j.tox.2020.152410}, pmid = {32068018}, issn = {1879-3185}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Antibiotics, Antineoplastic/*toxicity ; Apoptosis/drug effects ; Cells, Cultured ; Chemokine CCL2/blood ; Colon/*drug effects/immunology/metabolism/microbiology ; Doxorubicin/*toxicity ; Dysbiosis ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Heart Diseases/blood/*chemically induced/immunology/microbiology ; Interleukin-1beta/blood ; Lung/*drug effects/immunology/metabolism ; Macrophages/*drug effects/immunology/metabolism ; Male ; Mice, Inbred C57BL ; Myocytes, Cardiac/*drug effects/metabolism/pathology ; Nanotubes, Carbon/*toxicity ; Phenotype ; Tumor Necrosis Factor-alpha/blood ; }, abstract = {Epidemiologic studies show that the levels of air pollutants and particulate matter are positively associated with the morbidity and mortality of cardiovascular diseases. Here we demonstrate that the intratracheal instillation of multi-walled carbon nanotubes (MWCNTs), a standard fine particle, exacerbate doxorubicin (DOX)-induced cardiotoxicity in mice through altering gut microbiota and pulmonary and colonic macrophage phenotype. MWCNTs (25 μg/kg per day, 5 days a week for 3 weeks) promoted cardiotoxicity and apoptosis in the DOX (2 mg/kg, twice a week for 5 weeks)-treated C57BL/6 mice. MWCNTs exaggerated DOX-induced gut microbiota dysbiosis characterized by the increased abundances of Helicobacteraceae and Coriobacteriaceae. In addition, MWCNTs promoted DOX-induced M1-like polarization of colonic macrophages with an increase in TNF-α, IL-1β and CC chemokine ligand 2 in peripheral blood. Importantly, treatment with the antibiotics attenuated MWCNTs plus DOX-induced apoptosis of cardiomyocytes and M1-like polarization of colonic macrophages. The fecal microbiota transplantation demonstrated that MWCNTs exaggerated DOX-induced cardiotoxicity with M1-like polarization of colonic macrophages. The conditioned medium from MWCNTs-treated pulmonary macrophages promoted DOX-induced gut microbiota dysbiosis and colonic macrophage polarization. Furthermore, the co-culture of macrophages and fecal bacteria promoted M1-like macrophage polarization and their production of TNF-α and IL-1β, and thereby exacerbated the effects of MWCNTs. Moreover, IL-1β and TNF-α blockade, either alone or in combination attenuated MWCNTs-exacerbated cardiotoxicity. In summary, MWCNTs exacerbate DOX-induced cardiotoxicity in mice through gut microbiota and pulmonary and colonic macrophage interaction. Our findings identify a novel mechanism of action of inhaled particle-driven cardiotoxicity.}, }
@article {pmid32066679, year = {2020}, author = {Xiao, J and Wang, T and Xu, Y and Gu, X and Li, D and Niu, K and Wang, T and Zhao, J and Zhou, R and Wang, HL}, title = {Long-term probiotic intervention mitigates memory dysfunction through a novel H3K27me3-based mechanism in lead-exposed rats.}, journal = {Translational psychiatry}, volume = {10}, number = {1}, pages = {25}, pmid = {32066679}, issn = {2158-3188}, support = {31401671//National Science Foundation of China | Young Scientists Fund/International ; 81773475, 21477031//National Science Foundation of China | Major Research Plan/International ; }, abstract = {Chronic lead exposure is associated with the development of neurodegenerative diseases, characterized by the long-term memory decline. However, whether this pathogenesis could be prevented through adjusting gut microbiota is not yet understood. To address the issue, pregnant rats and their female offspring were treated with lead (125 ppm) or separately the extra probiotics (1010 organisms/rat/day) till adulthood. For results, memory dysfunction was alleviated by the treatment of multispecies probiotics. Meanwhile, the gut microbiota composition was partially normalized against lead-exposed rats, which in turn mediated the memory repairment via fecal transplantation trials. In the molecular aspect, the decreased H3K27me3 (trimethylation of histone H3 Lys 27) in the adult hippocampus was restored with probiotic intervention, an epigenetic event mediated by EZH2 (enhancer of zeste homolog 2) at early developmental stage. In a neural cellular model, EZH2 overexpression showed the similar rescue effect with probiotics, whereas its blockade led to the neural re-damages. Regarding the gut-brain inflammatory mediators, the disrupted IL-6 (interleukin 6) expression was resumed by probiotic treatment. Intraperitoneal injection of tocilizumab, an IL-6 receptor antagonist, upregulated the hippocampal EZH2 level and consequently alleviated the memory injuries. In conclusion, reshaping gut microbiota could mitigate memory dysfunction caused by chronic lead exposure, wherein the inflammation-hippocampal epigenetic pathway of IL-6-EZH2-H3K27me3, was first proposed to mediate the studied gut-brain communication. These findings provided insight with epigenetic mechanisms underlying a unique gut-brain interaction, shedding light on the safe and non-invasive treatment of neurodegenerative disorders with environmental etiology.}, }
@article {pmid32063856, year = {2019}, author = {Wu, H and Rao, Q and Ma, GC and Yu, XH and Zhang, CE and Ma, ZJ}, title = {Effect of Triptolide on Dextran Sodium Sulfate-Induced Ulcerative Colitis and Gut Microbiota in Mice.}, journal = {Frontiers in pharmacology}, volume = {10}, number = {}, pages = {1652}, pmid = {32063856}, issn = {1663-9812}, abstract = {Triptolide is beneficial for the treatment of ulcerative colitis (UC), which is closely related to the gut microbiota. However, whether the therapeutic effects of triptolide involve the regulation of the gut microbiota is still unclear. In the present study, animal models of UC mice induced by dextran sodium sulfate (DSS) were established, the changes of gut microbiota in mice were detected by high-throughput sequencing. The effects of triptolide on DSS-induced UC mouse and its gut microbiota were studied. As a result, we found that triptolide exerted anti-inflammatory and therapeutic effects on UC mice. Sequencing results for the gut microbiota showed that the composition of the gut microbiota from DSS group was disordered as compared with that from the control group, consistent with a decrease in the abundance of flora. Triptolide treatment accelerated the recovery of the population of the gut microbiota and significantly improved the microbial diversity. At the phylum level, the population of Bacteroidetes decreased and that of Firmicutes increased. At the genus level, Bacteroides and Lachnospiraceae counts decreased. Thus, triptolide could regulate the composition of the gut microbiota, accelerate the recovery of microbiota, and exert good therapeutic effects in UC mice. Our results also revealed that fecal transplantation from triptolide-treated mice could relieve UC. This study provides a reference for the rational use of triptolide for the treatment of UC.}, }
@article {pmid32061326, year = {2020}, author = {Olesen, SW and Panchal, P and Chen, J and Budree, S and Osman, M}, title = {Global disparities in faecal microbiota transplantation research.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {5}, number = {3}, pages = {241}, doi = {10.1016/S2468-1253(19)30452-2}, pmid = {32061326}, issn = {2468-1253}, mesh = {Adolescent ; Adult ; Child ; Child, Preschool ; Clinical Trials as Topic ; Clostridium Infections/epidemiology/microbiology/*therapy ; Clostridium difficile/isolation &amp; purification ; Fecal Microbiota Transplantation/*methods/statistics &amp; numerical data/trends ; Health Services Accessibility/statistics &amp; numerical data ; Healthcare Disparities ; Humans ; Infant ; Infant, Newborn ; Inflammatory Bowel Diseases/epidemiology/microbiology/*therapy ; Registries ; }, }
@article {pmid32057278, year = {2020}, author = {Cheng, YW and Fischer, M}, title = {Clinical management of severe, fulminant, and refractory Clostridioides difficile infection.}, journal = {Expert review of anti-infective therapy}, volume = {18}, number = {4}, pages = {323-333}, doi = {10.1080/14787210.2020.1730814}, pmid = {32057278}, issn = {1744-8336}, abstract = {Introduction: Up to 15% of hospitalized patients with Clostridioides difficile infection (CDI) develop severe CDI (SCDI) or Fulminant CDI (FCDI). Due to high rates of mortality in medically-refractory CDI cases, 30% of patients with severe infection historically require surgical intervention. However, colectomy itself is an imperfect solution because it is difficult to predict who will fail medical therapy, patients with SCDI are more likely to have underlying medical conditions that make them poor surgical candidates, and post-surgical mortality still approaches 30-50%.Areas covered: This review will serve as a clinically-based review of severe and fulminant CDI management including discussion of models to predict severe infection, emerging treatments, novel targets for therapy, and innovations in surgical management.Expert opinion: Among the most promising studies to emerge in the last decade have involved fecal microbiota transplantation (FMT), which is already recommended by multiple society guidelines for recurrent CDI (RCDI). In the case of SCDI/FCDI, multiple studies have safely and successfully utilized FMT to produce rates of cure in the 70-90% range. Additionally, patients who have FCDI refractory to medical therapy and are poor candidates for colectomy may benefit from FMT as salvage therapy.}, }
@article {pmid32056091, year = {2020}, author = {Saurman, V and Margolis, KG and Luna, RA}, title = {Autism Spectrum Disorder as a Brain-Gut-Microbiome Axis Disorder.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {818-828}, doi = {10.1007/s10620-020-06133-5}, pmid = {32056091}, issn = {1573-2568}, support = {R01 NS015547/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Autism Spectrum Disorder/*microbiology/psychology/therapy ; Brain/*microbiology/physiology ; Fecal Microbiota Transplantation/trends ; Gastrointestinal Diseases/*microbiology/psychology/therapy ; *Gastrointestinal Microbiome/physiology ; Gastrointestinal Tract/*microbiology/physiology ; Humans ; Probiotics/administration &amp; dosage ; }, abstract = {While there are numerous medical comorbidities associated with ASD, gastrointestinal (GI) issues have a significant impact on quality of life for these individuals. Recent findings continue to support the relationship between the gut microbiome and both GI symptoms and behavior, but the heterogeneity within the autism spectrum requires in-depth clinical characterization of these clinical cohorts. Large, diverse, well-controlled studies in this area of research are still needed. Although there is still much to discover about the brain-gut-microbiome axis in ASD, microbially mediated therapies, specifically probiotics and fecal microbiota transplantation have shown promise in the treatment of GI symptoms in ASD, with potential benefit to the core behavioral symptoms of ASD as well. Future research and clinical trials must increasingly consider complex phenotypes in ASD in stratification of large datasets as well as in design of inclusion criteria for individual therapeutic interventions.}, }
@article {pmid32055962, year = {2020}, author = {Shin, JH and Lee, YK and Shon, WJ and Kim, B and Jeon, CO and Cho, JY and Morse, HC and Choi, EY and Shin, DM}, title = {Gut microorganisms and their metabolites modulate the severity of acute colitis in a tryptophan metabolism-dependent manner.}, journal = {European journal of nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00394-020-02194-4}, pmid = {32055962}, issn = {1436-6215}, support = {HI16C0047//Ministry of Health and Welfare/ ; }, abstract = {PURPOSE: Growing evidence shows that nutrient metabolism affects inflammatory bowel diseases (IBD) development. Previously, we showed that deficiency of indoleamine 2,3-dioxygenase 1 (Ido1), a tryptophan-catabolizing enzyme, reduced the severity of dextran sulfate sodium (DSS)-induced colitis in mice. However, the roles played by intestinal microbiota in generating the differences in disease progression between Ido1+/+ and Ido1-/- mice are unknown. Therefore, we aimed to investigate the interactions between the intestinal microbiome and host IDO1 in governing intestinal inflammatory responses.<br><br>METHODS: Microbial 16s rRNA sequencing was conducted in Ido1+/+ and Ido1-/- mice after DSS treatment. Bacteria-derived tryptophan metabolites were measured in urine. Transcriptome analysis revealed the effects of the metabolite and IDO1 expression in HCT116 cells. Colitis severity of Ido1+/+ was compared to Ido1-/- mice following fecal microbiota transplantation (FMT).<br><br>RESULTS: Microbiome analysis through 16S-rRNA gene sequencing showed that IDO1 deficiency increased intestinal bacteria that use tryptophan preferentially to produce indolic compounds. Urinary excretion of 3-indoxyl sulfate, a metabolized form of gut bacteria-derived indole, was significantly higher in Ido1-/- than in Ido1+/+ mice. Transcriptome analysis showed that tight junction transcripts were significantly increased by indole treatment in HCT116 cells; however, the effects were diminished by IDO1 overexpression. Using FMT experiments, we demonstrated that bacteria from Ido1-/- mice could directly attenuate the severity of DSS-induced colitis.<br><br>CONCLUSIONS: Our results provide evidence that a genetic defect in utilizing tryptophan affects intestinal microbiota profiles, altering microbial metabolites, and colitis development. This suggests that the host and intestinal microbiota communicate through shared nutrient metabolic networks.}, }
@article {pmid32053787, year = {2020}, author = {Carlson, PE}, title = {Regulatory Considerations for Fecal Microbiota Transplantation Products.}, journal = {Cell host &amp; microbe}, volume = {27}, number = {2}, pages = {173-175}, doi = {10.1016/j.chom.2020.01.018}, pmid = {32053787}, issn = {1934-6069}, mesh = {Clostridium Infections/prevention &amp; control ; Clostridium difficile ; *Fecal Microbiota Transplantation/methods/trends ; Feces/*microbiology ; Gastrointestinal Microbiome ; Living Donors ; Safety ; Social Control, Formal ; Treatment Outcome ; }, abstract = {Fecal microbiota for transplantation (FMT) is being studied as a potential intervention for numerous conditions. The regulation of FMT by the FDA is discussed along with FMT donor screening and manufacturing considerations. The FDA is committed to ensuring that FMT products can be safely tested in clinical trials.}, }
@article {pmid32053786, year = {2020}, author = {Markey, KA and van den Brink, MRM and Peled, JU}, title = {Therapeutics Targeting the Gut Microbiome: Rigorous Pipelines for Drug Development.}, journal = {Cell host &amp; microbe}, volume = {27}, number = {2}, pages = {169-172}, doi = {10.1016/j.chom.2020.01.022}, pmid = {32053786}, issn = {1934-6069}, support = {P01 AG052359/AG/NIA NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; R01 HL125571/HL/NHLBI NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; R01 HL147584/HL/NHLBI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; }, mesh = {Drug Development ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; }, abstract = {Restoration of the gut microbiome is a promising preventive and therapeutic strategy in a number of clinical scenarios. We discuss here the scientific and clinical challenges of engineering and implementing these strategies.}, }
@article {pmid32047670, year = {2020}, author = {Meighani, A and Alimirah, M and Ramesh, M and Salgia, R}, title = {Fecal Microbiota Transplantation for Clostridioides Difficile Infection in Patients with Chronic Liver Disease.}, journal = {International journal of hepatology}, volume = {2020}, number = {}, pages = {1874570}, pmid = {32047670}, issn = {2090-3448}, abstract = {Background: Fecal microbiota transplantation (FMT) is a well-established therapeutic option for patients with antibiotic resistant Clostridioides difficile infection (CDI). However, the efficacy of FMT in patients with chronic liver disease remains elusive.<br><br>Aims: We studied the effect of FMT on chronic liver disease (CLD) patients with CDI at our tertiary medical center.<br><br>Methods: A cohort of all patients who received FMT from December 2012 to May 2014 for refractory or recurrent CDI was identified. Patients were monitored for a year after FMT. Descriptive analysis was conducted to compare the effect of FMT in patients with and without CLD.<br><br>Results: A total of 201 patients with CDI received FMT, 14 of which had a history of CLD. Nine of these patients exhibited cirrhosis of the liver with a mean Child-Turcotte-Pugh score of 8. CDI development in these patients was associated with recent exposure to antibiotics and was observed to be significantly different between both groups (17% of CLD patients vs. 58% in the general cohort, p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%), p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%).<br><br>Conclusion: FMT is a safe and effective therapy against CDI for patients with CLD and cirrhosis.}, }
@article {pmid32047611, year = {2020}, author = {Quigley, EMM and Gajula, P}, title = {Recent advances in modulating the microbiome.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {}, pmid = {32047611}, issn = {2046-1402}, abstract = {We are in the midst of &quot;the microbiome revolution&quot;-not a day goes by without some new revelation on the potential role of the gut microbiome in some disease or disorder. From an ever-increasing recognition of the many roles of the gut microbiome in health and disease comes the expectation that its modulation could treat or prevent these very same diseases. A variety of interventions could, at least in theory, be employed to alter the composition or functional capacity of the microbiome, ranging from diet to fecal microbiota transplantation (FMT). For some, such as antibiotics, prebiotics, and probiotics, an extensive, albeit far from consistent, literature already exists; for others, such as other dietary supplements and FMT, high-quality clinical studies are still relatively few in number. Not surprisingly, researchers have turned to the microbiome itself as a source for new entities that could be used therapeutically to manipulate the microbiome; for example, some probiotic strains currently in use were sourced from the gastrointestinal tract of healthy humans. From all of the extant studies of interventions targeted at the gut microbiome, a number of important themes have emerged. First, with relatively few exceptions, we are still a long way from a precise definition of the role of the gut microbiome in many of the diseases where a disturbed microbiome has been described-association does not prove causation. Second, while animal models can provide fascinating insights into microbiota-host interactions, they rarely recapitulate the complete human phenotype. Third, studies of several interventions have been difficult to interpret because of variations in study population, test product, and outcome measures, not to mention limitations in study design. The goal of microbiome modulation is a laudable one, but we need to define our targets, refine our interventions, and agree on outcomes.}, }
@article {pmid32044171, year = {2020}, author = {Ding, X and Li, Q and Li, P and Chen, X and Xiang, L and Bi, L and Zhu, J and Huang, X and Cui, B and Zhang, F}, title = {Fecal microbiota transplantation: A promising treatment for radiation enteritis?.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {143}, number = {}, pages = {12-18}, doi = {10.1016/j.radonc.2020.01.011}, pmid = {32044171}, issn = {1879-0887}, abstract = {BACKGROUND: Increasing evidence has indicated that gut microbiota is closely associated with radiation-induced bowel injury. We aimed to evaluate the safety and efficacy of fecal microbiota transplantation (FMT) in patients with chronic radiation enteritis (CRE).<br><br>METHODS: A pilot study of FMT for CRE was performed. The primary outcomes were safety and response to FMT which was defined as a ≥1-grade reduction in Radiation Therapy Oncology Group (RTOG/EORTC) late toxicity grade from baseline, by 8 weeks post-FMT. The secondary outcomes included a decrease in the severity of four common symptoms (diarrhea, rectal hemorrhage, abdominal/rectal pain and fecal incontinence) in CRE and changes in Karnofsky Performance Status (KPS) score. Microbial analyses were performed by 16S rRNA sequencing.<br><br>RESULTS: Five female patients underwent FMT from January to November 2018 with a median age of 58 (range 45-81) years. The median baseline RTOG/EORTC grade was 2 (range 2-4). Three patients responded to FMT and experienced improvement in diarrhea, rectal hemorrhage, abdominal/rectal pain and fecal incontinence as well as a decrease in KPS score. No FMT-related death and infectious complications occurred. One mild FMT-related AE was observed during a follow-up ranged from 8 to 18 months. 16S rRNA sequencing indicated that FMT altered the composition of gut microbiota of patients.<br><br>CONCLUSION: The present case series first demonstrated that FMT might be safe and effective to improve intestinal symptoms and mucosal injury in patients with CRE for a period of time. Trial registration ID: NCT03516461.}, }
@article {pmid32043638, year = {2020}, author = {Han, J and Wang, X and Tang, S and Lu, C and Wan, H and Zhou, J and Li, Y and Ming, T and Wang, ZJ and Su, X}, title = {Protective effects of tuna meat oligopeptides (TMOP) supplementation on hyperuricemia and associated renal inflammation mediated by gut microbiota.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {34}, number = {4}, pages = {5061-5076}, doi = {10.1096/fj.201902597RR}, pmid = {32043638}, issn = {1530-6860}, support = {LY19C010003//Natural Science Foundation of Zhejiang Province/ ; LY18C010001//Natural Science Foundation of Zhejiang Province/ ; 2018YFD0901102//National Key R&amp;D Program of China/ ; //Open Fund of State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products/ ; 2019C10064//Public Welfare Project of Ningbo city/ ; //Ningbo University/ ; }, abstract = {Recently, interest in using whole food-derived mixtures to alleviate chronic metabolic syndrome through potential synergistic interactions among different components is increasing. In this study, the effects and mechanisms of tuna meat oligopeptides (TMOP) on hyperuricemia and associated renal inflammation were investigated in mice. Dietary administration of TMOP alleviated hyperuricemia and renal inflammation phenotypes, reprogramed uric acid metabolism pathways, inhibited the activation of NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling pathways, and suppressed the phosphorylation of p65-NF-κB. In addition, TMOP treatments repaired the intestinal epithelial barrier, reversed the gut microbiota dysbiosis and increased the production of short-chain fatty acids. Moreover, the antihyperuricemia effects of TMOP were transmissible by transplanting the fecal microbiota from TMOP-treated mice, indicating that the protective effects were at least partially mediated by the gut microbiota. Thus, for the first time, we clarify the potential effects of TMOP as a whole food derived ingredient on alleviating hyperuricemia and renal inflammation in mice, and additional efforts are needed to confirm the beneficial effects of TMOP on humans.}, }
@article {pmid32040664, year = {2020}, author = {Abu-Sbeih, H and Wang, Y}, title = {Gut Microbiome and Immune Checkpoint Inhibitor-Induced Enterocolitis.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {797-799}, doi = {10.1007/s10620-020-06103-x}, pmid = {32040664}, issn = {1573-2568}, mesh = {Animals ; Antineoplastic Agents, Immunological/*adverse effects/*immunology ; Enterocolitis/*chemically induced/*immunology/microbiology ; Gastrointestinal Microbiome/*drug effects/*immunology ; Humans ; }, abstract = {The gut microbiome is increasingly being described as one of the underlying mechanisms for development of immune checkpoint inhibitor (ICI)-induced colitis. Similarities in gut microbiome profiles have been found among various diseases associated with intestinal inflammation, including inflammatory bowel disease. Certain bacterial species have been reported to be preventive for colitis, as well as beneficial for cancer outcome, in patients receiving ICI therapy. Alternatively, other bacterial classes have been shown to be associated with immunologic alterations causing intestinal inflammation with subsequent increase in the risk of ICI-related colitis. Gut microbiome manipulation by fecal transplantation has been proposed as one of the modalities to ameliorate inflammation in patients with ICI-related colitis refractory to immunosuppressive therapy. Additional investigations are needed to clarify the role of gut microbiome in the pathogenesis of ICI-related colitis.}, }
@article {pmid32040250, year = {2020}, author = {Guo, XY and Liu, XJ and Hao, JY}, title = {Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment.}, journal = {Journal of digestive diseases}, volume = {21}, number = {3}, pages = {147-159}, doi = {10.1111/1751-2980.12849}, pmid = {32040250}, issn = {1751-2980}, support = {81300294//Youth Program of National Natural Science Foundation of China/ ; XXT11//Project of Digestive Medical Coordinated Development Center of Beijing Hospitals Authority/ ; PX2018011//Incubation Program Project of Beijing Municipal Administration of Hospitals of China/ ; 7192072//Beijing Natural Science Foundation/ ; }, abstract = {Gut microbiota constitute the largest reservoir of the human microbiome and are an abundant and stable ecosystem-based on its diversity, complexity, redundancy, and host interactions This ecosystem is indispensable for human development and health. The integrity of the intestinal mucosal barrier depends on its interactions with gut microbiota. The commensal bacterial community is implicated in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC). The dysbiosis of microbes is characterized by reduced biodiversity, abnormal composition of gut microbiota, altered spatial distribution, as well as interactions among microbiota, between different strains of microbiota, and with the host. The defects in microecology, with the related metabolic pathways and molecular mechanisms, play a critical role in the innate immunity of the intestinal mucosa in UC. Fecal microbiota transplantation (FMT) has been used to treat many diseases related to gut microbiota, with the most promising outcome reported in antibiotic-associated diarrhea, followed by IBD. This review evaluated the results of various reports of FMT in UC. The efficacy of FMT remains highly controversial, and needs to be regularized by integrated management, standardization of procedures, and individualization of treatment.}, }
@article {pmid32039372, year = {2019}, author = {Schwenger, KJ and Clermont-Dejean, N and Allard, JP}, title = {The role of the gut microbiome in chronic liver disease: the clinical evidence revised.}, journal = {JHEP reports : innovation in hepatology}, volume = {1}, number = {3}, pages = {214-226}, pmid = {32039372}, issn = {2589-5559}, abstract = {Recent research has suggested a role for the intestinal microbiota in the pathogenesis and potential treatment of a wide range of liver diseases. The intestinal microbiota and bacterial products may contribute to the development of liver diseases through multiple mechanisms including increased intestinal permeability, chronic systemic inflammation, production of short-chain fatty acids and changes in metabolism. This suggests a potential role for pre-, pro- and synbiotic products in the prevention or treatment of some liver diseases. In addition, there is emerging evidence on the effects of faecal microbial transplant. Herein, we discuss the relationship between the intestinal microbiota and liver diseases, as well as reviewing intestinal microbiota-based treatment options that are currently being investigated.}, }
@article {pmid32036124, year = {2020}, author = {Wang, Y and Xu, L and Sun, X and Wan, X and Sun, G and Jiang, R and Li, W and Tian, Y and Liu, X and Kang, X}, title = {Characteristics of the fecal microbiota of high- and low-yield hens and effects of fecal microbiota transplantation on egg production performance.}, journal = {Research in veterinary science}, volume = {129}, number = {}, pages = {164-173}, doi = {10.1016/j.rvsc.2020.01.020}, pmid = {32036124}, issn = {1532-2661}, mesh = {Animal Feed/analysis ; Animals ; Chickens/*microbiology/physiology ; Fecal Microbiota Transplantation/*veterinary ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; *Oviposition ; }, abstract = {The microbiota that resides in the digestive tract plays pivotal role in maintaining intestinal environmental stability by promoting nutrition digestion and intestinal mucosal immunity. However, whether the intestinal microbiota in laying hens affects egg laying- performance is not known. In this study, 16S rDNA gene sequencing and fecal microbiota transplantation were used to determine the structure of the intestinal microbiota and the effect of the intestinal microbiota on egg production. The results revealed that Firmicutes were dominant in both the H (high egg laying rates) and L (low egg laying rates) groups, while Bacteroides, Actinobacteria and Proteobacteria were significantly enriched in the L group compared to the H group. The laying rates were weakly affected in H hens transplanted with the fecal microbiota from L hens, except for temporary fluctuation, while the egg laying rates were significantly increased in L hens transplanted with the fecal microbiota from H hens. Therefore, we concluded that the population structure of the intestinal microbiota varied between the H and L groups, and the intestinal microbiota of high-yield laying hens had significant effects on low-yield laying hens performance.}, }
@article {pmid32031511, year = {2020}, author = {Stallmach, A and Steube, A and Grunert, P and Hartmann, M and Biehl, LM and Vehreschild, MJGT}, title = {Fecal Microbiota Transfer.}, journal = {Deutsches Arzteblatt international}, volume = {117}, number = {3}, pages = {31-38}, pmid = {32031511}, issn = {1866-0452}, mesh = {Clostridium Infections/*therapy ; *Clostridium difficile ; *Fecal Microbiota Transplantation ; Germany ; Humans ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transfer (FMT) is increasingly being used in Ger- many, as in other countries, for the treatment of recurrent Clostridioides difficile infection (rCDI). FMT is now being performed both for research and in individual patients outside of clinical trials. No compulsory standards have been established to date for donor screening or for the method of fecal transfer. Given the potential dangers of FMT, this would seem to be urgently necessary.<br><br>METHODS: This review is based on pertinent literature retrieved by a selective search, including the reports of consensus conferences from Germany and abroad.<br><br>RESULTS: Because of its high efficacy, FMT is the treatment of choice for rCDI. It is largely free of adverse side effects, even in immune-deficient patients, as long as comprehensive and repeated donor screening has been carried out, with extensive clinical and microbiological testing and with the use of structured questionnaires. The ingestion of frozen, encapsulated microbiota is just as effective as other modes of delivery for the treatment of rCDI.<br><br>CONCLUSION: Encapsulation of the fecal microbiome (FM) and storage at -20°C is the method of choice, because it can be standardized with the necessary quality controls and it is readily available. Patients with rCDI should undergo FMT by orally ingesting the capsules. There are ongoing research efforts to identify the active e FM. It is not yet clear when the ultimate goal of recombinant production can be achieved.}, }
@article {pmid32024322, year = {2020}, author = {Park, S and Kang, Y and Koh, H and Kim, S}, title = {Increasing incidence of inflammatory bowel disease in children and adolescents: significance of environmental factors.}, journal = {Clinical and experimental pediatrics}, volume = {63}, number = {9}, pages = {337-344}, pmid = {32024322}, issn = {2713-4148}, abstract = {Inflammatory bowel disease (IBD) is a chronic relapsing immune-mediated disease of the intestinal tract. Although its prevalence is reportedly lower in Asia than in Western countries, the rapid increase in the incidence of IBD has drawn attention to its etiology, including genetic susceptibility and environmental factors. Specifically, recent studies concerning dietary treatments and intestinal microbiota suggest that these factors may interact with the immune system, and the imbalance of this relationship may lead to immune dysregulation in IBD. Changes in diet or alterations in the composition of the intestinal microbiota may be associated with the increasing incidence of IBD in Asia. Here, we aim to review recent studies on the role of diet and intestinal microbiota in IBD pathogenesis and the results of the investigations performed to modulate these factors.}, }
@article {pmid32024079, year = {2020}, author = {Swarte, JC and Douwes, RM and Hu, S and Vich Vila, A and Eisenga, MF and van Londen, M and Gomes-Neto, AW and Weersma, RK and Harmsen, HJM and Bakker, SJL}, title = {Characteristics and Dysbiosis of the Gut Microbiome in Renal Transplant Recipients.}, journal = {Journal of clinical medicine}, volume = {9}, number = {2}, pages = {}, pmid = {32024079}, issn = {2077-0383}, abstract = {Renal transplantation is life-changing in many aspects. This includes changes to the gut microbiome likely due to exposure to immunosuppressive drugs and antibiotics. As a consequence, renal transplant recipients (RTRs) might suffer from intestinal dysbiosis. We aimed to investigate the gut microbiome of RTRs and compare it with healthy controls and to identify determinants of the gut microbiome of RTRs. Therefore, RTRs and healthy controls participating in the TransplantLines Biobank and Cohort Study (NCT03272841) were included. We analyzed the gut microbiome using 16S rRNA sequencing and compared the composition of the gut microbiome of RTRs to healthy controls using multivariate association with linear models (MaAsLin). Fecal samples of 139 RTRs (50% male, mean age: 58.3 ± 12.8 years) and 105 healthy controls (57% male, mean age: 59.2 ± 10.6 years) were collected. Median time after transplantation of RTRs was 6.0 (1.5-12.5)years. The microbiome composition of RTRs was significantly different from that of healthy controls, and RTRs had a lower diversity of the gut microbiome (p < 0.01). Proton-pump inhibitors, mycophenolate mofetil, and estimated glomerular filtration rate (eGFR) are significant determinants of the gut microbiome of RTRs (p < 0.05). Use of mycophenolate mofetil correlated to a lower diversity (p < 0.01). Moreover, significant alterations were found in multiple bacterial taxa between RTRs and healthy controls. The gut microbiome of RTRs contained more Proteobacteria and less Actinobacteria, and there was a loss of butyrate-producing bacteria in the gut microbiome of RTRs. By comparing the gut microbiome of RTRs to healthy controls we have shown that RTRs suffer from dysbiosis, a disruption in the balance of the gut microbiome.}, }
@article {pmid32023967, year = {2020}, author = {Kachrimanidou, M and Tsintarakis, E}, title = {Insights into the Role of Human Gut Microbiota in Clostridioides difficile Infection.}, journal = {Microorganisms}, volume = {8}, number = {2}, pages = {}, pmid = {32023967}, issn = {2076-2607}, abstract = {Clostridioides difficile infection (CDI) has emerged as a major health problem worldwide. A major risk factor for disease development is prior antibiotic use, which disrupts the normal gut microbiota by altering its composition and the gut's metabolic functions, leading to the loss of colonization resistance and subsequent CDI. Data from human studies have shown that the presence of C. difficile, either as a colonizer or as a pathogen, is associated with a decreased level of gut microbiota diversity. The investigation of the gut's microbial communities, in both healthy subjects and patients with CDI, elucidate the role of microbiota and improve the current biotherapeutics for patients with CDI. Fecal microbiota transplantation has a major role in managing CDI, aiming at re-establishing colonization resistance in the host gastrointestinal tract by replenishing the gut microbiota. New techniques, such as post-genomics, proteomics and metabolomics analyses, can possibly determine in the future the way in which C. difficile eradicates colonization resistance, paving the way for the development of new, more successful treatments and prevention. The aim of the present review is to present recent data concerning the human gut microbiota with a focus on its important role in health and disease.}, }
@article {pmid32023228, year = {2020}, author = {Pimentel, M and Saad, RJ and Long, MD and Rao, SSC}, title = {ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {2}, pages = {165-178}, doi = {10.14309/ajg.0000000000000501}, pmid = {32023228}, issn = {1572-0241}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Blind Loop Syndrome/*diagnosis/*therapy ; Breath Tests ; Culture Techniques ; *Diet Therapy ; *Fecal Microbiota Transplantation ; Humans ; Hydrogen/analysis ; Intestine, Small ; Methane/analysis ; Probiotics/*therapeutic use ; Suction ; }, abstract = {Small intestinal bacterial overgrowth is defined as the presence of excessive numbers of bacteria in the small bowel, causing gastrointestinal symptoms. This guideline statement evaluates criteria for diagnosis, defines the optimal methods for diagnostic testing, and summarizes treatment options for small intestinal bacterial overgrowth. This guideline provides an evidence-based evaluation of the literature through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. In instances where the available evidence was not appropriate for a formal GRADE recommendation, key concepts were developed using expert consensus.}, }
@article {pmid32020359, year = {2020}, author = {Lechner, S and Yee, M and Limketkai, BN and Pham, EA}, title = {Fecal Microbiota Transplantation for Chronic Liver Diseases: Current Understanding and Future Direction.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {897-905}, doi = {10.1007/s10620-020-06100-0}, pmid = {32020359}, issn = {1573-2568}, mesh = {Chronic Disease ; Fecal Microbiota Transplantation/methods/*trends ; Forecasting ; Gastrointestinal Microbiome/*physiology ; Humans ; Liver Diseases/*microbiology/pathology/*therapy ; }, abstract = {Chronic liver disease is a major cause of morbidity and mortality worldwide. Even though effective treatments are now available for most chronic viral hepatitis, treatment options for other causes of chronic liver disease remain inadequate. Recent research has revealed a previously unappreciated role that the human intestinal microbiome plays in mediating the development and progression of chronic liver diseases. The recent remarkable success of fecal microbiota transplantation (FMT) in treating Clostridioides difficile demonstrates that the intestinal microbiota can be manipulated to obtain favorable therapeutic benefits and that FMT may become an important component of a total therapeutic approach to effectively treat hepatic disorders.}, }
@article {pmid32019832, year = {2020}, author = {Ghimire, S and Roy, C and Wongkuna, S and Antony, L and Maji, A and Keena, MC and Foley, A and Scaria, J}, title = {Identification of Clostridioides difficile-Inhibiting Gut Commensals Using Culturomics, Phenotyping, and Combinatorial Community Assembly.}, journal = {mSystems}, volume = {5}, number = {1}, pages = {}, pmid = {32019832}, issn = {2379-5077}, abstract = {A major function of the gut microbiota is to provide colonization resistance, wherein pathogens are inhibited or suppressed below infectious levels. However, the fraction of gut microbiota required for colonization resistance remains unclear. We used culturomics to isolate a gut microbiota culture collection comprising 1,590 isolates belonging to 102 species. This culture collection represents 34.57% of the taxonomic diversity and 70% functional capacity, as estimated by metagenomic sequencing of the fecal samples used for culture. Using whole-genome sequencing, we characterized species representatives from this collection and predicted their phenotypic traits, further characterizing isolates by defining nutrient utilization profiles and short-chain fatty acid production. When screened with a coculture assay, 66 species in our culture collection inhibited Clostridioides difficile Several phenotypes, particularly, growth rate, production of SCFAs, and the utilization of mannitol, sorbitol, or succinate, correlated with C. difficile inhibition. We used a combinatorial community assembly approach to formulate defined bacterial mixes inhibitory to C. difficile We tested 256 combinations and found that both species composition and blend size were important in inhibition. Our results show that the interaction of bacteria with one another in a mix and with other members of gut commensals must be investigated to design defined bacterial mixes for inhibiting C. difficilein vivoIMPORTANCE Antibiotic treatment causes instability of gut microbiota and the loss of colonization resistance, thus allowing pathogens such as Clostridioides difficile to colonize and causing recurrent infection and mortality. Although fecal microbiome transplantation has been shown to be an effective treatment for C. difficile infection (CDI), a more desirable approach would be the use of a defined mix of inhibitory gut bacteria. The C. difficile-inhibiting species and bacterial combinations identified herein improve the understanding of the ecological interactions controlling colonization resistance against C. difficile and could aid in the design of defined bacteriotherapy as a nonantibiotic alternative against CDI.}, }
@article {pmid32017248, year = {2020}, author = {You, JHS and Jiang, X and Lee, WH and Chan, PKS and Ng, SC}, title = {Cost-effectiveness analysis of fecal microbiota transplantation for recurrent Clostridium difficile infection in patients with inflammatory bowel disease.}, journal = {Journal of gastroenterology and hepatology}, volume = {35}, number = {9}, pages = {1515-1523}, doi = {10.1111/jgh.15002}, pmid = {32017248}, issn = {1440-1746}, abstract = {BACKGROUND AND AIM: Inflammatory bowel disease (IBD) patients are at risk for recurrent Clostridium difficile infection (RCDI). We aimed to evaluate the potential health economic and clinical outcomes of four strategies for management of RCDI in IBD patients from the perspective of public health-care provider in Hong Kong.<br><br>METHODS: A decision-analytic model was designed to simulate outcomes of adult IBD patients with first RCDI treated with vancomycin, vancomycin plus bezlotoxumab, fidaxomicin and fecal microbiota transplantation (FMT). Model inputs were derived from literature and public data. Primary model outcomes were C. difficile infection (CDI)-related direct medical cost and quality-adjusted life-years (QALYs) loss. Base-case and sensitivity analysis were performed.<br><br>RESULTS: Comparing to vancomycin, fidaxomicin and vancomycin plus bezlotoxumab, FMT saved 0.00318, 0.00149 and 0.00306 QALYs and reduced cost by USD3180, USD3790 and USD5514, respectively, in base-case analysis. In probabilistic sensitivity analysis, FMT was cost-saving when comparing to vancomycin, fidaxomicin and vancomycin plus bezlotoxumab by USD3765 (95% confidence interval [CI] 3732-3798; P < 0.001), USD3854 (95%CI 3827-3883; P < 0.001) and USD6501 (95%CI 6465-6,536; P < 0.001), respectively. The QALYs saved by FMT (vs vancomycin) were 0.00386 QALYs (95%CI 0.00384-0.00388; P < 0.001), (vs fidaxomicin) 0.00179 QALYs (95%CI 0.00177-0.00180; P < 0.001) and (vs vancomycin plus bezlotoxumab) 0.00376 QALYs (95%CI 0.00374-0.00378; P < 0.001). FMT was found to save QALYs at lower cost in 99.3% (vs vancomycin), 99.7% (vs fidaxomicin) and 100.0% (vs vancomycin plus bezlotoxumab) of the 10 000 Monte Carlo simulations.<br><br>CONCLUSIONS: FMT for IBD patients with RCDI appeared to save both direct medical cost and QALYs when comparing to vancomycin (with or without bezlotoxumab) and fidaxomicin.}, }
@article {pmid32016290, year = {2020}, author = {Peng, Y and Thomas, AS and Wei, D and Tan, D and Wang, Y}, title = {An Aggressive Approach Toward a Case of Refractory Ulcerative Colitis With Uncertain Etiology in the Context of Chronic Myeloid Leukemia.}, journal = {Inflammatory bowel diseases}, volume = {26}, number = {4}, pages = {e26-e27}, doi = {10.1093/ibd/izaa016}, pmid = {32016290}, issn = {1536-4844}, }
@article {pmid32015948, year = {2020}, author = {Li, B and Yin, GF and Wang, YL and Tan, YM and Huang, CL and Fan, XM}, title = {Impact of fecal microbiota transplantation on TGF-β1/Smads/ERK signaling pathway of endotoxic acute lung injury in rats.}, journal = {3 Biotech}, volume = {10}, number = {2}, pages = {52}, pmid = {32015948}, issn = {2190-572X}, abstract = {Acute lung injury (ALI) is a common clinical disease with high morbidity in both humans and animals. Studies have shown that intestinal microbiota affect the pathology and immune function of respiratory diseases through the &quot;gut-lung axis&quot;. The authors investigated the therapeutic effect of fecal microbiota transplantation (FMT) in rats with ALI induced by lipopolysaccharide (LPS). Rats were treated with FMT, and then measured lung wet/dry ratio, PaO2 in artery, proinflammatory marker, and TGF-β1, Smad3, Smad7, and phosphorylated ERK (p-ERK) protein levels, as well as a histopathologic analysis and high-throughput sequencing of intestinal microbiota. FMT significantly reduced lung wet/dry ratio and TNF-α, IL-1β, and IL-6 levels, but increased the levels of PaO2 in artery. In addition, FMT significantly decreased the expression of TGF-β1, Smad3, and p-ERK, while increased the levels of Smad7. Lung histopathological analyses showed that FMT reduced the inflammatory cell infiltration and interstitial lung exudates. High-throughput sequencing of intestinal microbiota analyses showed that FMT reconstructed the structure of intestinal microbiota, and increased the gene abundance of the bacterial community. Therefore, FMT may act on the TGF-β1/Smads/ERK pathway by regulating intestinal microbiota, inhibiting immune inflammation, reducing the production of inflammatory markers in the body and release, and reducing alveolar epithelial damage and repair, thereby improving the endotoxic ALI in rats induced by LPS.}, }
@article {pmid32014035, year = {2020}, author = {Sokol, H and Landman, C and Seksik, P and Berard, L and Montil, M and Nion-Larmurier, I and Bourrier, A and Le Gall, G and Lalande, V and De Rougemont, A and Kirchgesner, J and Daguenel, A and Cachanado, M and Rousseau, A and Drouet, É and Rosenzwajg, M and Hagege, H and Dray, X and Klatzman, D and Marteau, P and ,  and Beaugerie, L and Simon, T}, title = {Fecal microbiota transplantation to maintain remission in Crohn's disease: a pilot randomized controlled study.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {12}, doi = {10.1186/s40168-020-0792-5}, pmid = {32014035}, issn = {2049-2618}, abstract = {BACKGROUND: The role of the gut microbiota in Crohn's disease (CD) is established and fecal microbiota transplantation (FMT) is an attractive therapeutic strategy. No randomized controlled clinical trial results are available. We performed a randomized, single-blind, sham-controlled pilot trial of FMT in adults with colonic or ileo-colonic CD.<br><br>METHOD: Patients enrolled while in flare received oral corticosteroid. Once in clinical remission, patients were randomized to receive either FMT or sham transplantation during a colonoscopy. Corticosteroids were tapered and a second colonoscopy was performed at week 6. The primary endpoint was the implantation of the donor microbiota at week 6 (Sorensen index > 0.6).<br><br>RESULTS: Eight patients received FMT and nine sham transplantation. None of the patients reached the primary endpoint. The steroid-free clinical remission rate at 10 and 24 weeks was 44.4% (4/9) and 33.3% (3/9) in the sham transplantation group and 87.5% (7/8) and 50.0% (4/8; one patient loss of follow-up while in remission at week 12 and considered in flare at week 24) in the FMT group. Crohn's Disease Endoscopic Index of Severity decreased 6 weeks after FMT (p = 0.03) but not after sham transplantation (p = 0.8). Conversely, the CRP level increased 6 weeks after sham transplantation (p = 0.008) but not after FMT (p = 0.5). Absence of donor microbiota engraftment was associated with flare. No safety signal was identified.<br><br>CONCLUSION: The primary endpoint was not reached for any patient. In this pilot study, higher colonization by donor microbiota was associated with maintenance of remission. These results must be confirmed in larger studies (NCT02097797). Video abstract.}, }
@article {pmid32011405, year = {2020}, author = {Perler, BK and Chen, B and Phelps, E and Allegretti, JR and Fischer, M and Ganapini, V and Krajiceck, E and Kumar, V and Marcus, J and Nativ, L and Kelly, CR}, title = {Long-Term Efficacy and Safety of Fecal Microbiota Transplantation for Treatment of Recurrent Clostridioides difficile Infection.}, journal = {Journal of clinical gastroenterology}, volume = {54}, number = {8}, pages = {701-706}, doi = {10.1097/MCG.0000000000001281}, pmid = {32011405}, issn = {1539-2031}, abstract = {GOALS: We investigated the long-term efficacy and safety of fecal microbiota transplant (FMT) for the treatment of recurrent Clostridioides difficile infection (rCDI).<br><br>BACKGROUND: FMT has emerged as a promising therapy for patients with rCDI unresponsive to standard medical therapy, though long-term efficacy and safety data are scarce.<br><br>MATERIALS AND METHODS: A multicenter retrospective study was performed on patients treated with FMT for rCDI with ≥6 months of clinical follow-up post-FMT. Patients were contacted to document sustained efficacy, potential adverse events, and antibiotic exposure. The electronic medical record was reviewed to confirm patient-reported outcomes and obtain additional data. The primary outcome was sustained cure, as defined by the absence of Clostridioides difficile infection (CDI) at any timepoint after FMT.<br><br>RESULTS: Of 528 patients treated, 207 were successfully contacted. The mean follow-up post-FMT was 34 (range: 6 to 84) months. One hundred fifty-seven patients (75.8%) reported sustained cure at the time of follow-up. One hundred patients (48%) reported the use of antibiotics for non-CDI indications post-FMT, of whom 11 (11%) had experienced CDI post-FMT. Fifty-two of the original 528 patients (9.8%) treated with FMT had died at the time of follow-up contact; none were felt attributable to the procedure. New medical conditions or diagnoses post-FMT were reported in 105 patients (50.5%). Fifteen reported improvement post-FMT in previously diagnosed medical conditions.<br><br>CONCLUSIONS: In this largest and longest study to date on efficacy and safety after FMT for treatment of rCDI, we found that the majority of patients experienced long-term cure. Although a number of new conditions developed post-FMT, there was no clustering of diseases associated with dysbiosis.}, }
@article {pmid32010641, year = {2019}, author = {Wang, H and Lu, Y and Yan, Y and Tian, S and Zheng, D and Leng, D and Wang, C and Jiao, J and Wang, Z and Bai, Y}, title = {Promising Treatment for Type 2 Diabetes: Fecal Microbiota Transplantation Reverses Insulin Resistance and Impaired Islets.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {455}, pmid = {32010641}, issn = {2235-2988}, mesh = {Animals ; Apoptosis ; Blood Glucose/metabolism ; Cytokines ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2/*therapy ; Diet, High-Fat ; Energy Metabolism ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/genetics/physiology ; Glycated Hemoglobin A ; Inflammation/pathology ; Insulin/metabolism ; *Insulin Resistance ; Islets of Langerhans/pathology ; Mice ; }, abstract = {Type 2 diabetes is a common metabolic disorder related to insulin resistance, or deficiency of insulin secretion, caused by decreased insulin sensitivity and destruction of islet structure and function. As the second human genome, the microbiota has been observed to have a growing relationship with diabetes in recent years. Microbiota imbalance has been hypothesized to be involved in the regulation of energy metabolism and the inflammatory immune response in diabetes. The present study aimed to investigate whether fecal microbiota transplantation (FMT) could alleviate the symptoms associated with type 2 diabetes. To this end, a type 2 diabetes mouse model was first established through the consumption of a high-fat diet combined with streptozotocin (100 mg/kg), and FMT was used to rebuild the gut microbiota of diabetic mice. Fasting blood glucose, oral glucose tolerance tests, and HbA1c levels were monitored, while the hypoglycemic effects of FMT were also observed. Insulin levels were tested by ELISA and related indexes such as HOMA-IR, HOMA-IS, and HOMA-β were calculated. We found that insulin resistance and pancreatic islet β-cells were improved after FMT treatment. Meanwhile, the markers of inflammation in the pancreatic tissue were detected by ELISA and immunohistochemistry, which indicated that inflammatory response decreased following FMT treatment. Furthermore, flow cytometry and western blot results revealed that FMT inhibited the β-cell apoptosis. Here, the effect of FMT on hypoglycemia in type 2 diabetes was addressed by improving insulin resistance and repairing impaired islets, thereby providing a potential treatment strategy for type 2 diabetes.}, }
@article {pmid32010434, year = {2020}, author = {Zama, D and Bossù, G and Leardini, D and Muratore, E and Biagi, E and Prete, A and Pession, A and Masetti, R}, title = {Insights into the role of intestinal microbiota in hematopoietic stem-cell transplantation.}, journal = {Therapeutic advances in hematology}, volume = {11}, number = {}, pages = {2040620719896961}, pmid = {32010434}, issn = {2040-6207}, abstract = {The gut microbiota (GM) is able to modulate the human immune system. The development of novel investigation methods has provided better characterization of the GM, increasing our knowledge of the role of GM in the context of hematopoietic stem-cell transplantation (HSCT). In particular, the GM influences the development of the major complications seen after HSCT, having an impact on overall survival. In fact, this evidence highlights the possible therapeutic implications of modulation of the GM during HSCT. Insights into the complex mechanisms and functions of the GM are essential for the rational design of these therapeutics. To date, preemptive and curative approaches have been tested. The current state of understanding of the impact of the GM on HSCT, and therapies targeting the GM balance is reviewed herein.}, }
@article {pmid32009472, year = {2020}, author = {Zhou, HY and Guo, B and Lufumpa, E and Li, XM and Chen, LH and Meng, X and Li, BZ}, title = {Comparative of the Effectiveness and Safety of Biological Agents, Tofacitinib, and Fecal Microbiota Transplantation in Ulcerative Colitis: Systematic Review and Network Meta-Analysis.}, journal = {Immunological investigations}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/08820139.2020.1714650}, pmid = {32009472}, issn = {1532-4311}, abstract = {BACKGROUND: Biological agents are commonly used for the treatment of ulcerative colitis (UC). As new treatments, tofacitinib, and fecal microbiota transplantation (FMT) have demonstrated efficacy in treating UC. This network meta-analysis aims to determine the efficacy and safety of biological agents, tofacitinib, and FMT.<br><br>METHODS: A network meta-analysis was conducted by systematically searching the PubMed, Embase, and Cochrane Libraries. According to strict inclusion and exclusion criteria, we included randomized controlled trials (RCTs) of biological agents, tofacitinib, and FMT in UC. A random-effect model was chosen by the network meta-analysis and sensitivity analysis. Heterogeneity test and publication bias test were performed to determine the efficacy of treatments.<br><br>RESULTS: Data were extracted from 16 RCTs and we found that all treatments were more effective than the placebos. A total of 21 comparisons were made to determine efficiency. We found that infliximab, vedolizumab, and FMT performed better curative effect in terms of absolute effects and relative ranks. Furthermore, there was no statistical difference in the efficacy of biological agents, tofacitinib, and FMT. Moreover, no treatments were found to increase the occurrence of adverse events when compared with placebos, except infliximab. However, vedolizumab seemed to reduce the occurrence of adverse events compared with infliximab.<br><br>CONCLUSION: Of the biological agents, vedolizumab and infliximab were the most effective, suggesting that biological agents are still a better choice. Nevertheless, tofacitinib and FMT may be promising alternatives with high efficacies. However, more safety and maintenance studies need to be conducted in future for the acquisition of more accurate results.Abbreviations: FMT: Fecal microbiota transplantation; UC: Ulcerative colitis; RCTs: Randomized controlled trials; IBD: Inflammatory bowel disease; CD: Crohn's disease; IBS: Irritable bowel syndrome; CDI: Clostridium difficile infections; ITT: Intention-to-treat; RR: Relative risk; CI: Confidence interval; CrI: Credible intervals; IFX: Infliximab; ADA: Adalimumab; TFB: Tofacitinib; GLM: Golimumab; VDZ: Vedolizumab; PBO: Placebo; wk: week; F: Female; M: Male; AEs: Adverse events; SAEs: Serious adverse events; anti-TNF: Anti-tumor necrosis factors.}, }
@article {pmid32008133, year = {2020}, author = {DuPont, HL and Jiang, ZD and DuPont, AW and Utay, NS}, title = {Abnormal Intestinal Microbiome in Medical Disorders and Potential Reversibility by Fecal Microbiota Transplantation.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {741-756}, doi = {10.1007/s10620-020-06102-y}, pmid = {32008133}, issn = {1573-2568}, mesh = {Fecal Microbiota Transplantation/*methods/trends ; Gastrointestinal Diseases/*microbiology/*therapy ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology/*physiology ; Humans ; Living Donors ; }, abstract = {Reduction in diversity of the intestinal microbiome (dysbiosis) is being identified in many disease states, and studies are showing important biologic contributions of microbiome to health and disease. Fecal microbiota transplantation (FMT) is being evaluated as a way to reverse dysbiosis in diseases and disorders in an attempt to improve health. The published literature was reviewed to determine the value of FMT in the treatment of medical disorders for which clinical trials have recently been conducted. FMT is effective in treating recurrent C. difficile infection in one or two doses, with many healthy donors providing efficacious fecal-derived products. In inflammatory bowel disease (IBD), FMT may lead to remission in approximately one-third of moderate-to-severe illnesses with one study suggesting that more durable FMT responses may be seen when used once medical remissions have been achieved. Donor products differ in their efficacy in treatment of IBD. Combining donor products has been one way to increase the potential value of FMT in treating chronic disorders. FMT is being explored in a variety of clinical settings affecting different organ systems outside CDI, with positive preliminary signals, in treatment of functional constipation, immunotherapy-induced colitis, neurodegenerative disease, as well as prevention of cancer-related disorders like graft versus host disease and decolonization of patients with recurrent urinary tract infection due to antibiotic-resistant bacteria. Currently, intense research is underway to see how the microbiome products like FMT can be harnessed for health benefits.}, }
@article {pmid32006212, year = {2020}, author = {Oka, A and Sartor, RB}, title = {Microbial-Based and Microbial-Targeted Therapies for Inflammatory Bowel Diseases.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {757-788}, doi = {10.1007/s10620-020-06090-z}, pmid = {32006212}, issn = {1573-2568}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/adverse effects ; Dysbiosis/microbiology/therapy ; *Fecal Microbiota Transplantation/trends ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Prebiotics/*administration &amp; dosage/microbiology ; Probiotics/*administration &amp; dosage ; Randomized Controlled Trials as Topic/methods ; }, abstract = {Inflammatory bowel diseases (IBD), including Crohn's disease, ulcerative colitis, and pouchitis, are chronic, relapsing intestinal inflammatory disorders mediated by dysregulated immune responses to resident microbiota. Current standard therapies that block immune activation with oral immunosuppressives or biologic agents are generally effective, but each therapy induces a sustained remission in only a minority of patients. Furthermore, these approaches can have severe adverse events. Recent compelling evidence of a role of unbalanced microbiota (dysbiosis) driving immune dysfunction and inflammation in IBD supports the therapeutic rationale for manipulating the dysbiotic microbiota. Traditional approaches using currently available antibiotics, probiotics, prebiotics, and synbiotics have not produced optimal results, but promising outcomes with fecal microbiota transplant provide a proof of principle for targeting the resident microbiota. Rationally designed oral biotherapeutic products (LBPs) composed of mixtures of protective commensal bacterial strains demonstrate impressive preclinical results. Resident microbial-based and microbial-targeted therapies are currently being studied with increasing intensity for IBD primary therapy with favorable early results. This review presents current evidence and therapeutic mechanisms of microbiota modulation, emphasizing clinical studies, and outlines prospects for future IBD treatment using new approaches, such as LBPs, bacteriophages, bacterial function-editing substrates, and engineered bacteria. We believe that the optimal clinical use of microbial manipulation may be as adjuvants to immunosuppressive for accelerated and improved induction of deep remission and as potential safer solo approaches to sustained remission using personalized regimens based on an individual patient's microbial profile.}, }
@article {pmid32003951, year = {2020}, author = {Mounsey, A and Lacy Smith, K and Reddy, VC and Nickolich, S}, title = {Clostridioides difficile Infection: Update on Management.}, journal = {American family physician}, volume = {101}, number = {3}, pages = {168-175}, pmid = {32003951}, issn = {1532-0650}, mesh = {Adult ; Age Factors ; Aged ; Anti-Bacterial Agents/administration &amp; dosage ; Antimicrobial Stewardship ; Child ; Clostridium Infections/*diagnosis/physiopathology/*prevention &amp; control ; Clostridium difficile/*pathogenicity ; Fidaxomicin/administration &amp; dosage ; Humans ; Infant ; Practice Guidelines as Topic ; Risk Factors ; Severity of Illness Index ; Vancomycin/administration &amp; dosage ; }, abstract = {Guidelines for the diagnosis and treatment of Clostridioides difficile infection have recently been updated. Risk factors include recent exposure to health care facilities or antibiotics, especially clindamycin. C. difficile infection is characterized by a wide range of symptoms, from mild or moderate diarrhea to severe disease with pseudomembranous colitis, colonic ileus, toxic megacolon, sepsis, or death. C. difficile infection should be considered in patients who are not taking laxatives and have three or more episodes of unexplained, unformed stools in 24 hours. Testing in these patients should start with enzyme immunoassays for glutamate dehydrogenase and toxins A and B or nucleic acid amplification testing. In children older than 12 months, testing is recommended only for those with prolonged diarrhea and risk factors. Treatment depends on whether the episode is an initial vs. recurrent infection and on the severity of the infection based on white blood cell count, serum creatinine level, and other clinical signs and symptoms. For an initial episode of nonsevere C. difficile infection, oral vancomycin or oral fidaxomicin is recommended. Metronidazole is no longer recommended as first-line therapy for adults. Fecal microbiota transplantation is a reasonable treatment option with high cure rates in patients who have had multiple recurrent episodes and have received appropriate antibiotic therapy for at least three of the episodes. Good antibiotic stewardship is a key strategy to decrease rates of C. difficile infection. In routine or endemic settings, hands should be cleaned with either soap and water or an alcohol-based product, but during outbreaks soap and water is superior. The Infectious Diseases Society of America does not recommend the use of probiotics for prevention of C. difficile infection.}, }
@article {pmid32001342, year = {2020}, author = {Ma, Y and Liu, S and Shu, H and Crawford, J and Xing, Y and Tao, F}, title = {Resveratrol alleviates temporomandibular joint inflammatory pain by recovering disturbed gut microbiota.}, journal = {Brain, behavior, and immunity}, volume = {87}, number = {}, pages = {455-464}, doi = {10.1016/j.bbi.2020.01.016}, pmid = {32001342}, issn = {1090-2139}, abstract = {Patients with temporomandibular disorders (TMDs) often experience persistent facial pain. However, the treatment of TMD pain is still inadequate. In recent years, the disturbance of gut microbiota has been shown to play an important role in the pathogenesis of different neurological diseases including chronic pain. In the present study, we investigated the involvement of gut microbiota in the development of temporomandibular joint (TMJ) inflammation. Intra-temporomandibular joint injection of complete Freund's adjuvant (CFA) was employed to induce TMJ inflammation. Resveratrol (RSV), a natural bioactive compound with anti-inflammatory property, was used to treat the CFA-induced TMJ inflammation. We observed that CFA injection not only induces persistent joint pain, but also causes the reduction of short-chain fatty acids (SCFAs, including acetic acid, propionic acid and butyric acid) in the gut as well as decreases relevant gut bacteria Bacteroidetes and Lachnospiraceae. Interestingly, systemic administration of RSV (i.p.) dose-dependently inhibits CFA-induced TMJ inflammation, reverses CFA-caused reduction of SCFAs and these gut bacteria. Moreover, CFA injection causes blood-brain barrier (BBB) leakage, activates microglia and enhances tumor necrosis factor alpha (TNFα) release in the spinal trigeminal nucleus caudalis (Sp5C). The RSV treatment restores the BBB integrity, inhibits microglial activation and decreases the release of TNFα in the Sp5C. Furthermore, fecal microbiota transplantation with feces from RSV-treated mice significantly diminishes the CFA-induced TMJ inflammation. Taken together, our results suggest that gut microbiome perturbation is critical for the development of TMJ inflammation and that recovering gut microbiome to normal levels could be a new therapeutic approach for treating such pain.}, }
@article {pmid31996833, year = {2020}, author = {Dolgin, E}, title = {Fighting cancer with microbes.}, journal = {Nature}, volume = {577}, number = {7792}, pages = {S16-S18}, doi = {10.1038/d41586-020-00199-x}, pmid = {31996833}, issn = {1476-4687}, mesh = {Animals ; Bacteria/virology ; Bacteriophages/physiology ; Fecal Microbiota Transplantation/trends ; Gastrointestinal Microbiome/*physiology ; Host Microbial Interactions/*physiology ; Humans ; Mice ; Neoplasms/*microbiology/*therapy ; }, }
@article {pmid31996829, year = {2020}, author = {Svoboda, E}, title = {Could the gut microbiome be linked to autism?.}, journal = {Nature}, volume = {577}, number = {7792}, pages = {S14-S15}, doi = {10.1038/d41586-020-00198-y}, pmid = {31996829}, issn = {1476-4687}, mesh = {Animals ; Autistic Disorder/*microbiology/therapy ; Biodiversity ; Fecal Microbiota Transplantation/trends ; Gastrointestinal Microbiome/*physiology ; *Host Microbial Interactions ; Humans ; Mice ; }, }
@article {pmid31993446, year = {2019}, author = {Pilla, R and Suchodolski, JS}, title = {The Role of the Canine Gut Microbiome and Metabolome in Health and Gastrointestinal Disease.}, journal = {Frontiers in veterinary science}, volume = {6}, number = {}, pages = {498}, pmid = {31993446}, issn = {2297-1769}, abstract = {The gut microbiome contributes to host metabolism, protects against pathogens, educates the immune system, and, through these basic functions, affects directly or indirectly most physiologic functions of its host. Molecular techniques have allowed us to expand our knowledge by unveiling a wide range of unculturable bacteria that were previously unknown. Most bacterial sequences identified in the canine gastrointestinal (GI) tract fall into five phyla: Firmicutes, Fusobacteria, Bacteroidetes, Proteobacteria, and Actinobacteria. While there are variations in the microbiome composition along the GI tract, most clinical studies concentrate on fecal microbiota. Age, diet, and many other environmental factors may play a significant role in the maintenance of a healthy microbiome, however, the alterations they cause pale in comparison with the alterations found in diseased animals. GI dysfunctions are the most obvious association with gut dysbiosis. In dogs, intestinal inflammation, whether chronic or acute, is associated with significant differences in the composition of the intestinal microbiota. Gut dysbiosis happens when such alterations result in functional changes in the microbial transcriptome, proteome, or metabolome. Commonly affected metabolites include short-chain fatty acids, and amino acids, including tryptophan and its catabolites. A recently developed PCR-based algorithm termed &quot;Dysbiosis Index&quot; is a tool that allows veterinarians to quantify gut dysbiosis and can be used to monitor disease progression and response to treatment. Alterations or imbalances in the microbiota affect immune function, and strategies to manipulate the gut microbiome may be useful for GI related diseases. Antibiotic usage induces a rapid and significant drop in taxonomic richness, diversity, and evenness. For that reason, a renewed interest has been put on probiotics, prebiotics, and fecal microbiota transplantation (FMT). Although probiotics are typically unable to colonize the gut, the metabolites they produce during their transit through the GI tract can ameliorate clinical signs and modify microbiome composition. Another interesting development is FMT, which may be a promising tool to aid recovery from dysbiosis, but further studies are needed to evaluate its potential and limitations.}, }
@article {pmid31993375, year = {2019}, author = {Albouery, M and Buteau, B and Grégoire, S and Cherbuy, C and Pais de Barros, JP and Martine, L and Chain, F and Cabaret, S and Berdeaux, O and Bron, AM and Acar, N and Langella, P and Bringer, MA}, title = {Age-Related Changes in the Gut Microbiota Modify Brain Lipid Composition.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {444}, pmid = {31993375}, issn = {2235-2988}, mesh = {Age Factors ; Aging/*metabolism ; Animals ; Brain/*metabolism ; Cholesterol/metabolism ; Fatty Acid Desaturases/genetics ; Fatty Acid Elongases/genetics ; Fatty Acids/metabolism ; Fatty Acids, Monounsaturated/metabolism ; Fatty Acids, Unsaturated/metabolism ; Gastrointestinal Microbiome/genetics/*physiology ; Gene Expression ; Germ-Free Life ; *Lipid Metabolism ; Lipids ; Liver/metabolism ; Male ; Mice ; Stearoyl-CoA Desaturase/genetics ; }, abstract = {Understanding the molecular mechanisms underlying the changes observed during aging is a prerequisite to design strategies to prevent age-related diseases. Aging is associated with metabolic changes, including alteration in the brain lipid metabolism. These alterations may contribute to the development of pathophysiological conditions. Modifications in the gut microbiota composition are also observed during aging. As communication axes exist between the gut microbiota and the brain and knowing that microbiota influences the host metabolism, we speculated on whether age-associated modifications in the gut microbiota could be involved in the lipid changes observed in aging brain. For that purpose, germ-free mice were colonized by the fecal microbiota of young or old donor mice. Lipid classes and fatty acid profiles were determined in the brain (cortex), plasma and liver by thin-layer chromatography on silica gel-coated quartz rods and gas chromatography. Gut colonization by microbiota of old mice resulted in a significant increase in total monounsaturated fatty acids (MUFA) and a significant decrease in the relative amounts of cholesterol and total polyunsaturated fatty acids (PUFA) in the cortex. Among the eight most represented fatty acids in the cortex, the relative abundances of five (C18:1n-9, C22:6n-3, C20:4n-6, C18:1n-7, and C20:1n-9) were significantly altered in mice inoculated with an aged microbiota. Liquid chromatography analyses revealed that the relative abundance of major species among phosphatidyl and plasmenylcholine (PC 16:0/18:1), phosphatidyl and plasmenylethanolamine (PE 18:0/22:6), lysophosphatidylethanolamine (LPE 22:6) and sphingomyelins (SM d18:1/18:0) were significantly altered in the cortex of mice colonized by the microbiota obtained from aged donors. Transplantation of microbiota from old mice also modified the lipid class and fatty acid content in the liver. Finally, we found that the expression of several genes involved in MUFA and PUFA synthesis (Scd1, Fads1, Fads2, Elovl2, and Elovl5) was dysregulated in mice inoculated with an aged microbiota. In conclusion, our data suggest that changes in gut microbiota that are associated with aging can impact brain and liver lipid metabolisms. Lipid changes induced by an aged microbiota recapitulate some features of aging, thus pointing out the potential role of microbiota alterations in the age-related degradation of the health status.}, }
@article {pmid31993353, year = {2019}, author = {Xi, D and Michail, S}, title = {Fecal microbiota transplantation in children does not significantly alter body mass index.}, journal = {Translational pediatrics}, volume = {8}, number = {5}, pages = {398-401}, pmid = {31993353}, issn = {2224-4344}, abstract = {Background: Fecal microbiota transplantation (FMT) is nowadays a promising therapy for Clostridium difficile infection (CDI) and a potential treatment for ulcerative colitis. However, it is still unclear whether the changes in intestinal microbiome will affect energy homeostasis or metabolism. This brings an intriguing question whether FMT from healthy donors affects recipient's body mass index (BMI).<br><br>Methods: In our randomized placebo-controlled study children patients with CDI or ulcerative colitis were randomly divided into control and FMT groups. The change of post-FMT BMI percentile at 1, 3, 6, 12 months was calculated. The age range of CDI cohort was 1 to 17 years, while the range was 8 to 21 years for ulcerative colitis cohort.<br><br>Results: We found that the BMI percentile was insignificantly changed by ‒0.7%, ‒1.8%, 1.3%, 4.6% in CDI, while by 3.6%, ‒3.3%, 3.7%, 7.1% in ulcerative colitis at 1, 3, 6, 12 months after FMT (&quot;‒&quot; means decrease).<br><br>Conclusions: We concluded that FMT from healthy donors does not significantly alter BMI in children with CDI and ulcerative colitis over 12 months.}, }
@article {pmid31992630, year = {2020}, author = {Oliphant, K and Cochrane, K and Schroeter, K and Daigneault, MC and Yen, S and Verdu, EF and Allen-Vercoe, E}, title = {Effects of Antibiotic Pretreatment of an Ulcerative Colitis-Derived Fecal Microbial Community on the Integration of Therapeutic Bacteria In Vitro.}, journal = {mSystems}, volume = {5}, number = {1}, pages = {}, pmid = {31992630}, issn = {2379-5077}, abstract = {Fecal microbiota transplantation (FMT) is a proposedly useful strategy for the treatment of gastrointestinal (GI) disorders through remediation of the patient gut microbiota. However, its therapeutic success has been variable, necessitating research to uncover mechanisms that improve patient response. Antibiotic pretreatment has been proposed as one method to enhance the success rate by increasing niche availability for introduced species. Several limitations hinder exploring this hypothesis in clinical studies, such as deleterious side effects and the development of antimicrobial resistance in patients. Thus, the purpose of this study was to evaluate the use of an in vitro, bioreactor-based, colonic ecosystem model as a form of preclinical testing by determining how pretreatment with the antibiotic rifaximin influenced engraftment of bacterial strains sourced from a healthy donor into an ulcerative colitis-derived defined microbial community. Distinct species integrated under the pretreated and untreated conditions, with the relative rifaximin resistance of the microbial strains being an important influencer. However, both conditions resulted in the integration of taxa from Clostridium clusters IV and XIVa, a concomitant reduction of Proteobacteria, and similar decreases in metabolites associated with poor health status. Our results agree with the findings of similar research in the clinic by others, which observed no difference in primary patient outcomes whether or not patients were given rifaximin prior to FMT. We therefore conclude that our model is useful for screening for antibiotics that could improve efficacy of FMT when used as a pretreatment.IMPORTANCE Patients with gastrointestinal disorders often exhibit derangements in their gut microbiota, which can exacerbate their symptoms. Replenishing these ecosystems with beneficial bacteria through fecal microbiota transplantation is thus a proposedly useful therapeutic; however, clinical success has varied, necessitating research into strategies to improve outcomes. Antibiotic pretreatment has been suggested as one such approach, but concerns over harmful side effects have hindered testing this hypothesis clinically. Here, we evaluate the use of bioreactors supporting defined microbial communities derived from human fecal samples as models of the colonic microbiota in determining the effectiveness of antibiotic pretreatment. We found that relative antimicrobial resistance was a key determinant of successful microbial engraftment with rifaximin (broad-spectrum antibiotic) pretreatment, despite careful timing of the application of the therapeutic agents, resulting in distinct species profiles from those of the control but with similar overall outcomes. Our model had results comparable to the clinical findings and thus can be used to screen for useful antibiotics.}, }
@article {pmid31991615, year = {2020}, author = {Feehan, A and Garcia-Diaz, J}, title = {Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms.}, journal = {Microorganisms}, volume = {8}, number = {2}, pages = {}, pmid = {31991615}, issn = {2076-2607}, abstract = {Antibiotics have revolutionized human and animal healthcare, but their utility is reduced as bacteria evolve resistance mechanisms over time. Thankfully, there are novel antibiotics in the pipeline to overcome resistance, which are mentioned elsewhere in this special issue, but eventually bacteria are expected to evolve resistance to most new compounds as well. Multidrug resistant organisms (MDROs) that cause infections increase morbidity, mortality, and readmissions as compared with susceptible organisms. Consequently, many research and development pipelines are focused on non-antibiotic strategies, including fecal microbiota transplantation (FMT), probiotics and prebiotics, and a range of therapies in between. Studies reviewed here focus on efforts to directly treat or prevent MDRO infections or colonization. The studies were collected through clinicaltrials.gov, PubMed, and the International Conference on the Harmonisation Good Clinical Practice website (ichgcp.net). While the gold standard of clinical research is randomized controlled trials (RCTs), several pilot studies are included because the field is so young. Although a vast preclinical body of research has led to studies in humans, animal and in vitro studies are not within the scope of this review. This narrative review discusses microbiome-modifying therapies targeting MDROs in the gut and includes current results, ongoing clinical trials, companies with therapies in the pipeline specifically for MDROs, and commentary on clinical implementation and challenges.}, }
@article {pmid31991477, year = {2020}, author = {Fitzgibbon, G and Mills, KHG}, title = {The microbiota and immune-mediated diseases: Opportunities for therapeutic intervention.}, journal = {European journal of immunology}, volume = {50}, number = {3}, pages = {326-337}, doi = {10.1002/eji.201948322}, pmid = {31991477}, issn = {1521-4141}, support = {16/IA/4468/SFI_/Science Foundation Ireland/Ireland ; 12/RI/2340/SFI_/Science Foundation Ireland/Ireland ; }, mesh = {Animals ; Humans ; Microbiota/*immunology ; }, abstract = {A multitude of diverse microorganisms, termed the microbiota, reside in the gut, respiratory tract, skin, and genital tract of humans and other animals. Recent advances in metagenomic sequencing and bioinformatics have enabled detailed characterization of these vital microbial communities. Studies in animal models have uncovered vital previously unrecognized roles for the microbiota in normal function of the immune responses, and when perturbed, in the pathogenesis of diseases of the gastrointestinal tract and lungs, but also at distant sites in the body including the brain. The composition of gut and respiratory microbiota can influence systemic inflammatory responses that mediate asthma, allergy, inflammatory bowel disease, obesity-related diseases, and neurodevelopmental or neurodegenerative conditions. Experiments in mouse models as well as emerging clinical studies have revealed that therapeutic manipulation of the microbiota, using fecal microbiota transplantation, probiotics, or engineered probiotics represent effective nontoxic approaches for the treatment or prevention of Clostridium difficile infection, allergy, and autoimmune diseases and may enhance the efficacy of certain cancer immunotherapeutics. This review discusses how commensal bacteria can influence immune responses that mediate a range of human diseases and how the microbiota are being targeted to treat these diseases, especially those resistant to pharmacological therapies.}, }
@article {pmid31986084, year = {2020}, author = {Schwabkey, ZI and Jenq, RR}, title = {Microbiome Anomalies in Allogeneic Hematopoietic Cell Transplantation.}, journal = {Annual review of medicine}, volume = {71}, number = {}, pages = {137-148}, doi = {10.1146/annurev-med-052918-122440}, pmid = {31986084}, issn = {1545-326X}, abstract = {The microbiome is an integrated part of the human body that can modulate a variety of disease processes and affect prognosis, treatment response, complications, and outcomes. The importance of allogeneic hematopoietic cell transplantation in cancer treatment has resulted in extensive investigations on the interaction between the microbiome and this treatment modality. These investigations are beginning to lead to clinical trials of microbiome-targeted interventions. Here we review some of these discoveries and describe strategies being investigated to manipulate the microbiome for favorable outcomes, such as the proper selection and timing of antibiotics, type of diet and route of administration, probiotics, prebiotics, and fecal microbiota transplantation.}, }
@article {pmid31982069, year = {2020}, author = {Allegretti, JR and Mullish, BH}, title = {Faecal microbiota transplantations and urinary tract infections - Authors' reply.}, journal = {Lancet (London, England)}, volume = {395}, number = {10220}, pages = {271}, doi = {10.1016/S0140-6736(19)32978-2}, pmid = {31982069}, issn = {1474-547X}, mesh = {*Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; *Urinary Tract Infections ; }, }
@article {pmid31982066, year = {2020}, author = {Lagier, JC and Raoult, D}, title = {Faecal microbiota transplantations and urinary tract infections.}, journal = {Lancet (London, England)}, volume = {395}, number = {10220}, pages = {270-271}, doi = {10.1016/S0140-6736(19)32992-7}, pmid = {31982066}, issn = {1474-547X}, mesh = {*Fecal Microbiota Transplantation ; Feces ; Humans ; *Urinary Tract Infections ; }, }
@article {pmid31980603, year = {2020}, author = {Yu, M and Malik Tyagi, A and Li, JY and Adams, J and Denning, TL and Weitzmann, MN and Jones, RM and Pacifici, R}, title = {PTH induces bone loss via microbial-dependent expansion of intestinal TNF+ T cells and Th17 cells.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {468}, pmid = {31980603}, issn = {2041-1723}, support = {R01 DK112946/DK/NIDDK NIH HHS/United States ; S10 RR028009/RR/NCRR NIH HHS/United States ; U54 AG062334/AG/NIA NIH HHS/United States ; R01 DK108842/DK/NIDDK NIH HHS/United States ; R01 AR068157/AR/NIAMS NIH HHS/United States ; R01 AR070091/AR/NIAMS NIH HHS/United States ; I01 BX000105/BX/BLRD VA/United States ; R01 DK098391/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*immunology ; Germ-Free Life ; Gram-Positive Endospore-Forming Rods/immunology ; Hyperparathyroidism, Primary/complications/immunology/microbiology ; Intestines/immunology/microbiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Osteoporosis/*etiology/immunology/microbiology ; Parathyroid Hormone/*immunology ; T-Lymphocyte Subsets/*immunology ; Th17 Cells/*immunology ; Tumor Necrosis Factor-alpha/immunology ; }, abstract = {Bone loss is a frequent but not universal complication of hyperparathyroidism. Using antibiotic-treated or germ-free mice, we show that parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched by the Th17 cell-inducing taxa segmented filamentous bacteria (SFB). SFB+ microbiota enabled PTH to expand intestinal TNF+ T and Th17 cells and increase their S1P-receptor-1 mediated egress from the intestine and recruitment to the bone marrow (BM) that causes bone loss. CXCR3-mediated TNF+ T cell homing to the BM upregulated the Th17 chemoattractant CCL20, which recruited Th17 cells to the BM. This study reveals mechanisms for microbiota-mediated gut-bone crosstalk in mice models of hyperparathyroidism that may help predict its clinical course. Targeting the gut microbiota or T cell migration may represent therapeutic strategies for hyperparathyroidism.}, }
@article {pmid31978342, year = {2020}, author = {Walter, J and Armet, AM and Finlay, BB and Shanahan, F}, title = {Establishing or Exaggerating Causality for the Gut Microbiome: Lessons from Human Microbiota-Associated Rodents.}, journal = {Cell}, volume = {180}, number = {2}, pages = {221-232}, doi = {10.1016/j.cell.2019.12.025}, pmid = {31978342}, issn = {1097-4172}, support = {//CIHR/Canada ; }, mesh = {Animals ; Disease/etiology ; Dysbiosis/*microbiology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Mice ; Microbiota/physiology ; Models, Animal ; Rats ; Rodentia/*microbiology ; }, abstract = {Human diseases are increasingly linked with an altered or &quot;dysbiotic&quot; gut microbiota, but whether such changes are causal, consequential, or bystanders to disease is, for the most part, unresolved. Human microbiota-associated (HMA) rodents have become a cornerstone of microbiome science for addressing causal relationships between altered microbiomes and host pathology. In a systematic review, we found that 95% of published studies (36/38) on HMA rodents reported a transfer of pathological phenotypes to recipient animals, and many extrapolated the findings to make causal inferences to human diseases. We posit that this exceedingly high rate of inter-species transferable pathologies is implausible and overstates the role of the gut microbiome in human disease. We advocate for a more rigorous and critical approach for inferring causality to avoid false concepts and prevent unrealistic expectations that may undermine the credibility of microbiome science and delay its translation.}, }
@article {pmid31976518, year = {2020}, author = {Stoma, I and Littmann, ER and Peled, JU and Giralt, S and van den Brink, MRM and Pamer, EG and Taur, Y}, title = {Compositional flux within the intestinal microbiota and risk for bloodstream infection with gram-negative bacteria.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa068}, pmid = {31976518}, issn = {1537-6591}, support = {K08 HL143189/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Gram-negative bloodstream infections represent a significant complication facing allogeneic hematopoietic cell transplant (allo-HCT) recipients, as a result of intestinal translocation during neutropenia. In this study we sought to better understand how the composition of the intestinal microbiota is connected to risk of gram-negative bloodstream infections, expanding on our prior work in these patients.<br><br>METHODS: Fecal specimens were collected from recipients of allo-HCT and analyzed using 16SrRNA gene sequencing. Samples and clinical data extending from the pre-transplant conditioning period through stem cell engraftment were used in the analysis. Intestinal domination (relative abundance ≥30%) by gram-negative bacteria was used as predictor of gram-negative bloodstream infection using Cox proportional hazards modelling. Further analysis of microbiota composition was performed at the genus level.<br><br>RESULTS: 708 allo-HCT subjects were studied (7.5% develop gram-negative infection), with 4,768 fecal samples for analysis. Gram-negative intestinal domination was associated with subsequent bloodstream infection, which was observed overall and individually at the genus level: Escherichia, Klebsiella, Enterobacter, Pseudomonas, and Stenotrophomonas. Fluoroquinolone prophylaxis was associated with decreased bloodstream infection and intestinal colonization by gram-negative microbes. In fluoroquinolone-prophylaxed patients, Escherichia coli was more frequently observed as breakthrough, both in terms of intestinal colonization and bloodstream infections, compared with non-prophylaxed patients. Initial colonization by members of Ruminococcaceae and Bacteroidetes were associated with protection against gram-negative bloodstream infection.<br><br>CONCLUSION: Gram-negative intestinal colonization is highly predictive of bloodstream infection, in the setting of allo-HCT. Fluoroquinolones appear to reduce these infections by influencing gut colonization.}, }
@article {pmid31976311, year = {2019}, author = {Garza-González, E and Mendoza-Olazarán, S and Morfin-Otero, R and Ramírez-Fontes, A and Rodríguez-Zulueta, P and Flores-Treviño, S and Bocanegra-Ibarias, P and Maldonado-Garza, H and Camacho-Ortiz, A}, title = {Intestinal Microbiome Changes in Fecal Microbiota Transplant (FMT) vs. FMT Enriched with Lactobacillus in the Treatment of Recurrent Clostridioides difficile Infection.}, journal = {Canadian journal of gastroenterology &amp; hepatology}, volume = {2019}, number = {}, pages = {4549298}, pmid = {31976311}, issn = {2291-2797}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Clostridium difficile ; Double-Blind Method ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; *Lactobacillus ; Male ; Middle Aged ; Pilot Projects ; RNA, Ribosomal, 16S ; Recurrence ; Treatment Outcome ; Young Adult ; }, abstract = {Aim: In this study, we conducted a comparative study to explore the differences in therapeutic efficacy and intestinal microbiome of fecal microbiota transplant (FMT) vs. FMT in addition with Lactobacillus (FMT-L) for treatment of recurrent Clostridioides difficile infection (R-CDI).<br><br>Methods: We designed a double-blinded randomized comparative two-arm pilot multicenter study to assess the efficacy and impact in the intestinal microbiome of standard capsules of FMT vs. FMT-L enriched with 3 species of Lactobacillus for patients with R-CDI. A 90-day follow-up of 21 patients was performed, starting at the beginning of the study. From the selected patients, fecal samples were obtained at days 0, 3, 7, and 28 after treatment. Fecal samples and FMT were analyzed by 16S rRNA sequencing.<br><br>Results: We included 21 patients (13 in the FMT group and 8 in the FMT-L group). Overall, both groups had a reduction in bowel movements per day, from 8.6 to 3.2 in the first 48 h (62.7% reduction, p=0.001). No severe adverse reactions or recurrences were recorded. Firmicutes were the most abundant phylum in donors. A low relative abundance of Proteobacteria was detected and mostly found in patients even at higher proportions than the donor. The donor's pool also had relatively few Bacteroidetes, and some patients showed a higher abundance of this phylum. Based on the ANOSIM R values, there is a significant difference between the microbial communities of basal samples and samples collected on day 7 (p=0.045) and at day 28 (0.041).<br><br>Conclusion: Fecal microbiota transplant by capsules was clinically and genomically similar between traditional FMT and enriched FMT with Lactobacillus spp. Restoration of bacterial diversity and resolution of dysbiosis at days 7 and 28 were observed. Patients with a first episode of recurrence treated with FMT had an excellent response without severe adverse events; FMT should be considered as an early treatment during R-CDI.}, }
@article {pmid31975529, year = {2020}, author = {Groves, HE and Allen, UD}, title = {Winning with poo? Fecal microbiome transplantation as an emerging strategy for the management of recurrent Clostridioides difficile infection in children.}, journal = {Pediatric transplantation}, volume = {24}, number = {1}, pages = {e13651}, doi = {10.1111/petr.13651}, pmid = {31975529}, issn = {1399-3046}, mesh = {Child, Preschool ; *Clostridium Infections ; *Clostridium difficile ; Fecal Microbiota Transplantation ; *Heart Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid31974041, year = {2020}, author = {Lou, JM and Ren, ZG and Li, A and Rao, BC and Yu, ZJ}, title = {Fecal microbiota transplantation has therapeutic effects on chronic hepatits B patients via altering composition of gut microbiota.}, journal = {Hepatobiliary &amp; pancreatic diseases international : HBPD INT}, volume = {19}, number = {5}, pages = {486-487}, doi = {10.1016/j.hbpd.2019.12.008}, pmid = {31974041}, issn = {1499-3872}, }
@article {pmid31973773, year = {2020}, author = {Stalder, T and Kapel, N and Diaz, S and Grenouillet, F and Koch, S and Limat, S and Daval, F and Vuitton, L and Nerich, V}, title = {A systematic review of economic evaluation in fecal microbiota transplantation.}, journal = {Infection control and hospital epidemiology}, volume = {41}, number = {4}, pages = {458-466}, doi = {10.1017/ice.2019.371}, pmid = {31973773}, issn = {1559-6834}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective therapy in recurrent Clostridium difficile infection (rCDI). It is only recommended for this indication by European and American guidelines. Other indications of FMT are being studied, such as inflammatory bowel disease (IBD), and they have shown promising results.<br><br>OBJECTIVES: To identify and review published FMT-related economic evaluations (EEs) to assess their quality and the economic impact of FMT in the treatment of these diseases.<br><br>DATA SOURCES: The systematic literature research was conducted in both PubMed and Cochrane to identify EEs published before July 1, 2019.<br><br>STUDY ELIGIBILITY CRITERIA: Articles were included if they concerned FMT (whatever the disease and its line of treatment), if they reported full or partial EEs, and if they were written in English. Articles were excluded if they did not concern FMT; if they did not report an EE; or if they were a systematic review, editorial, comment, letter to the editor, practice point, or poster.<br><br>METHODS: A measurement tool, AMSTAR, was used to optimize the quality of this systematic review. Based on the CHEERS checklist, data were identified and extracted from articles. The quality of each EE was assessed using the Drummond checklist.<br><br>RESULTS: Overall, 9 EEs were included: all EEs were full evaluations and 8 were cost-utility analyses (CUAs). All EEs had a Drummond score ≥ 7, which indicated high quality. All CUAs related to rCDI and IBD concluded that FMT was cost-effective compared with other reference treatments, at a threshold ≤$50,000/QALY. One EE about initial CDI showed that FMT was dominated by metronidazole.<br><br>CONCLUSIONS: Despite a limited number of EEs, FMT seems to be a promising and cost-effective treatment for rCDI. More EE studies on other diseases like IBD are necessary to address FMT efficiency for new indications. Therefore, our systematic review provides a framework for healthcare decision making.}, }
@article {pmid31973214, year = {2020}, author = {Safari, Z and Bruneau, A and Monnoye, M and Mariadassou, M and Philippe, C and Zatloukal, K and Gérard, P}, title = {Murine Genetic Background Overcomes Gut Microbiota Changes to Explain Metabolic Response to High-Fat Diet.}, journal = {Nutrients}, volume = {12}, number = {2}, pages = {}, pmid = {31973214}, issn = {2072-6643}, support = {W1226//FWF/ ; }, abstract = {Interactions of diet, gut microbiota, and host genetics play essential roles in the development of metabolic diseases. A/J and C57BL/6J (C57) are two mouse strains known to display different susceptibilities to metabolic disorders. In this context, we analyzed gut microbiota composition in A/J and C57 mice, and assessed its responses to high-fat diet (HFD) and antibiotic (AB) treatment. We also exchanged the gut microbiota between the two strains following AB treatment to evaluate its impact on the metabolism. We showed that A/J and C57 mice have different microbiome structure and composition at baseline. Moreover, A/J and C57 microbiomes responded differently to HFD and AB treatments. Exchange of the gut microbiota between the two strains was successful as recipients' microbiota resembled donor-strain microbiota. Seven weeks after inoculation, the differences between recipients persisted and were still closer from the donor-strain microbiota. Despite effective microbiota transplants, the response to HFD was not markedly modified in C57 and A/J mice. Particularly, body weight gain and glucose intolerance in response to HFD remained different in the two mouse strains whatever the changes in microbiome composition. This indicated that genetic background has a much stronger impact on metabolic responses to HFD than gut microbiome composition.}, }
@article {pmid31972620, year = {2020}, author = {Ekekezie, C and Perler, BK and Wexler, A and Duff, C and Lillis, CJ and Kelly, CR}, title = {Understanding the Scope of Do-It-Yourself Fecal Microbiota Transplant.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {4}, pages = {603-607}, pmid = {31972620}, issn = {1572-0241}, support = {DP5 OD026420/OD/NIH HHS/United States ; }, mesh = {Adult ; Clostridium Infections/*therapy ; Clostridium difficile ; Cross-Sectional Studies ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; *Self Care ; Social Media ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) has emerged as an effective treatment option for Clostridioides difficile infection (CDI) and is considered an investigational therapy for a number of other diseases. Social media has facilitated widespread exposure of the public to the gut microbiome and FMT, ultimately acting as a catalyst for the Do-It-Yourself (DIY)-FMT movement. The aims of this study were to identify factors that influenced willingness to pursue DIY-FMT including common indications, screening processes, sample preparation, and self-reported efficacy and safety outcomes.<br><br>METHODS: A twenty-five-point cross-sectional survey was posted online through the websites and social media pages of the Peggy Lillis Foundation, The Fecal Transplant Foundation, and The Power of Poop. Responses were cataloged through the Research Electronic Data Capture tool, and descriptive analyses were performed.<br><br>RESULTS: Eighty-four respondents completed the survey between January 2018 and February 2019. The majority were female (71%) and white (92%). Most (80%) reported performing FMT on themselves; 87% used Internet resources to assist in the process, and 92% knew their stool donor. Inflammatory bowel disease (35%) and irritable bowel syndrome (29%) were the 2 most common conditions that respondents attempted to treat. Only 12% reported adverse events, whereas 82% reported improvement in their condition.<br><br>DISCUSSION: DIY-FMT is being used for many indications, including those for which there is little evidence. There was a high self-reported success rate among respondents with few adverse events. There is a need for increased awareness around DIY-FMT and research around this phenomenon, which may impact public health.}, }
@article {pmid31968211, year = {2020}, author = {Antushevich, H}, title = {Fecal microbiota transplantation in disease therapy.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {503}, number = {}, pages = {90-98}, doi = {10.1016/j.cca.2019.12.010}, pmid = {31968211}, issn = {1873-3492}, mesh = {Fecal Microbiota Transplantation/adverse effects/*methods ; Gastrointestinal Diseases/therapy ; Humans ; Metabolic Syndrome/therapy ; Neoplasms/therapy ; Nervous System Diseases/therapy ; Parkinson Disease/therapy ; Therapeutics/adverse effects/*methods ; }, abstract = {Fecal microbiota transplantation (FMT) is the introduction (transplantation) of gut microbiota obtained from the faeces of a healthy donor into the patient's gastrointestinal tract. Most often, such therapy is used the treatment of gastrointestinal diseases caused by the activity of pathogenic or conditionally pathogenic microorganisms, however, recently an increasing number of studies have reported the use of fecal microbiota transplantation for the treatment of diseases such as metabolic syndrome, diabetes, cancer and Parkinson's disease. This review article presents the results of studies concerning the impact of FMT on weight gain, immunological response and the treatment of neurological and gastrointestinal diseases and cancer. The procedure of fecal microbiota transplantation and possible side effects that may appear in FMT recipients are also described.}, }
@article {pmid31964766, year = {2020}, author = {Bircher, L and Schwab, C and Geirnaert, A and Greppi, A and Lacroix, C}, title = {Planktonic and Sessile Artificial Colonic Microbiota Harbor Distinct Composition and Reestablish Differently upon Frozen and Freeze-Dried Long-Term Storage.}, journal = {mSystems}, volume = {5}, number = {1}, pages = {}, pmid = {31964766}, issn = {2379-5077}, abstract = {Biofilm-associated, sessile communities represent the major bacterial lifestyle, whereas planktonic cells mainly appear during initial colonization of new surfaces. Previous research, mainly performed with pathogens, demonstrated increased environmental stress tolerance of biofilm-growing compared to planktonic bacteria. The lifestyle-specific stress response of colonic microbiota, both natural and fermentation produced, has not been addressed before. Planktonic and sessile &quot;artificial&quot; colonic microbiota delivered by PolyFermS continuous fermentation models can provide a controllable and reproducible alternative to fecal transplantation in treating gastrointestinal disorders. We therefore characterized planktonic and sessile microbiota produced in two PolyFermS models inoculated with immobilized fecal microbiota and comparatively tested their levels of tolerance of frozen storage (-80°C) and freeze-dried storage (4°C) for 9 months to mimic preservation strategies for therapeutic applications. Sessile microbiota harbored next to shared taxa a unique community distinguishable from planktonic microbiota. Synergistetes and Proteobacteria were highly represented in sessile microbiota, while Firmicutes were more abundant in planktonic microbiota. The community structure and metabolic activity of both microbiota, monitored during standardized reactivation batch fermentations, were better preserved after frozen storage than dried storage, indicated by higher Bray-Curtis similarity and enhanced recovery of metabolite production. For both lifestyles, reestablishment of Bacteroidaceae was impaired after frozen and dried storage along with reduced propionate formation. In contrast, butyrate production was maintained after reactivation despite compositional rearrangements within the butyrate-producing community. Unexpectedly, the rate of recovery of metabolite production was lower after preservation of sessile than planktonic microbiota. We speculate that higher functional dependencies between microbes might have led to the lower stress tolerance of sessile than planktonic microbiota.IMPORTANCE Fecal microbiota transplantation has been successfully applied in the treatment of recurrent Clostridium difficile infection and has been suggested as an alternative therapy for other intestinal disorders such as inflammatory bowel disease or metabolic syndrome. &quot;Artificial&quot; colonic microbiota delivered by PolyFermS continuous fermentation models can provide a controllable and reproducible alternative to fecal transplantation, but effective preservation strategies must be developed. In this study, we systematically investigated the response of sessile and planktonic artificial colonic microbiota to cryopreservation and lyophilization. We suggest that functional redundancy is an important factor in providing functional stability with respect to exposure to stress during processing and storage. Functional redundancy in compositionally reduced microbial systems may be considered when designing microbial products for therapy.}, }
@article {pmid31963653, year = {2020}, author = {Xu, R and Wan, J and Lin, C and Su, Y}, title = {Effects of Early Intervention with Antibiotics and Maternal Fecal Microbiota on Transcriptomic Profiling Ileal Mucusa in Neonatal Pigs.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {9}, number = {1}, pages = {}, pmid = {31963653}, issn = {2079-6382}, support = {31572414 and 31872362//National Natural Science Foundation of China/ ; }, abstract = {This study aimed to investigate the effects of early intervention with antibiotics and maternal fecal microbiota on ileal morphology and barrier function, and transcriptomic profiling in neonatal piglets. Piglets in the amoxicillin (AM), fecal microbiota transplantation (FMT), and control (CO) groups were orally administrated with amoxicillin solution (6.94 mg/mL), maternal fecal microbiota suspension [>109 colony forming unit (CFU)/mL], and physiological saline, respectively. Compared with the CO group, early intervention with AM or FMT significantly decreased ileal crypt depth on day 7 and altered gene expression profiles in ileum on days 7 and 21, and especially promoted the expression of chemokines (CCL5, CXCL9, and CXCL11) involved in the toll-like receptor signaling pathway on day 21. FMT changed major immune activities from B cell immunity on day 7 to T cell immunity on day 21 in the ileum. On the other hand, both AM and FMT predominantly downregulated the gene expression of toll-like receptor 4 (TLR4). In summary, both early interventions modulated intestinal barrier function and immune system in the ileum with a low impact on ileal morphology and development.}, }
@article {pmid31961792, year = {2020}, author = {Barcán, L and Ducatenzeiler, L and Bangher, MDC and Barcelona, L and Cornistein, W and Daciuk, L and De Paula, J and Desse, J and Dictar, M and Fernández-Canigia, L and Nacinovich, F and Scapellato, P and Martínez, JV and ,  and ,  and ,  and ,  and ,  and ,  and ,  and ,  and ,  and , }, title = {[Intersociety guidelines for diagnosis, treatment and prevention of Clostridioides difficile infections].}, journal = {Medicina}, volume = {80 Suppl 1}, number = {}, pages = {1-32}, pmid = {31961792}, issn = {1669-9106}, mesh = {Argentina ; Clinical Laboratory Techniques ; Clostridium Infections/*diagnosis/prevention &amp; control/*therapy ; Humans ; Risk Factors ; Societies, Medical ; }, abstract = {Clostridioides difficile infections (CDI) are among the leading causes of health care-associated infections. The epidemiology of CDI has undergone major changes in the last decade, showing an increase in incidence, severity, and rate of relapse. These guidelines were developed by specialists from four scientific societies: Sociedad Argentina de Infectología (SADI), Sociedad Argentina de Gastroenterología (SAGE), Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas (SADEBAC) and Asociación de Enfermeras en Control de Infecciones (ADECI). The objective of these intersociety guidelines is to provide national recommendations on CDI diagnosis, treatment and prevention. The methodology used involved the systematic review of the bibliography available up to December 2018, which was performed by six groups formed ad hoc: Epidemiology, Diagnosis, Treatment, Fecal Microbiota Transplantation, Special Populations, and Infection Control. The conclusions were presented and discussed in meetings held by each individual group and plenary meetings. In this document, updated diagnosis algorithms, therapeutic options (including fecal microbiota transplant) for immunocompetent and immunocompromised patients are presented, as well as strategies for the control of C. difficile infection.}, }
@article {pmid31958930, year = {2020}, author = {Chen, QY and Tian, HL and Yang, B and Lin, ZL and Zhao, D and Ma, CL and Chen, X and Jiang, J and Qin, HL and Li, N}, title = {[Diagnosis and treatment of superior mesenteric artery compression syndrome secondary to chronic constipation (Lee's triad syndrome)].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {1}, pages = {44-50}, doi = {10.3760/cma.j.issn.1671-0274.2020.01.008}, pmid = {31958930}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; }, mesh = {Chronic Disease ; Cohort Studies ; Constipation/*complications ; Enteral Nutrition ; Fecal Microbiota Transplantation ; Humans ; Knee-Chest Position ; Mesenteric Artery, Superior/diagnostic imaging ; Quality of Life ; Superior Mesenteric Artery Syndrome/*diagnosis/diagnostic imaging/etiology/*therapy ; Syndrome ; Treatment Outcome ; }, abstract = {Objective: To summarize the experience of diagnosis and treatment of superior mesenteric artery compression syndrome (SMACS) secondary to chronic constipation according to the concept of Lee's triad syndrome. Methods: The concept of Lee's triad syndrome: (1) clinical symptoms: triad of constipation, malnutrition, upper gastrointestinal obstruction (vomiting, difficulty in eating); (2) anatomical manifestations: with triple anatomy anomaly of transverse colon sagging, elevated spleen flexure, and mesentery arterial compression; (3) treatment: with triple treatment of enteral nutrition support, chest-knee posture and fecal microbiota transplantation. A descriptive cohort study was performed. According to Lee's triad syndrome criteria, clinical data of 78 patients with superior mesenteric artery compression syndrome secondary to chronic constipation in the Tenth People's Hospital of Tongji University and General Hospital of Eastern Theater Command from June 2004 to November 2018 were prospectively collected, including basic information, symptoms and signs, imaging findings, nutritional indicators, gastrointestinal quality of life index (GIQLI) and Wexner defecation score. The above parameters based on Lee's triad syndrome criteria were followed up and recorded at 1, 3, 6, 12 months after comprehensive treatment. Results: All the patients had Lee's triple symptoms of constipation, malnutrition, upper gastrointestinal obstruction (vomiting, eating difficulties), and triple anatomy anomaly of transverse colon sagging, elevated spleen curvature, and mesentery arterial compression before treatment. After triple treatment of enteral nutrition support, chest-knee posture, and fecal microbiota transplantation, 69 (88.5%) patients had a significant improvement of symptoms, and 9 patients had no significant improvement of symptoms and then eventually received surgery. The 69 cases without operation received follow-up for 12 months. All the patients eventually returned to normal eating, and upper gastrointestinal angiography and superior mesenteric artery imaging showed duodenal compression disappeared. After 1 month, the constipation-related indexes were improved. After 12 months, the number of autonomous defecation per week increased from 1.0±0.8 to 5.0±1.6 (P<0.001). The GIQLI score increased from 52.7±8.5 to 93.2±7.5 (P<0.001), and the Wexner score decreased from 19.1±2.5 to 6.2±2.1 (P<0.001). After 1 month, nutritional indexes were improved gradually. After 12 months, the BMI increased from (17.9±1.8) kg/m(2) to (21.0±1.3) kg/m(2), total protein increased from (65.2±5.7) g/L to (68.3±4.2) g/L, albumin increased from (32.1±5.1) g/L to (40.4±3.0) g/L, prealbumin increased from (163.2±53.7) mg/L to (259.1±45.6) mg/L, fibrinogen increased from (1.9±0.5) g/L to (2.4±0.5) g/L, whose differences were statistically significant (all P<0.001). Upper gastrointestinal angiography and superior mesenteric artery imaging showed duodenal compression were relieved. The angle between superior mesenteric artery and abdominal aorta increased from (17.4±3.8)° to (37.8±5.8)° (t=-22.26, P<0.001). Conclusion: When patients with SMACS secondary to chronic constipation have Lee's triple symptoms and triple anatomy anomaly, the triple combination treatment of enteral nutrition support, chest-knee posture and fecal microbiota transplantation should be applied.}, }
@article {pmid31958765, year = {2020}, author = {Chen, H and Zhang, F and Li, R and Liu, Y and Wang, X and Zhang, X and Xu, C and Li, Y and Guo, Y and Yao, Q}, title = {Berberine regulates fecal metabolites to ameliorate 5-fluorouracil induced intestinal mucositis through modulating gut microbiota.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {124}, number = {}, pages = {109829}, doi = {10.1016/j.biopha.2020.109829}, pmid = {31958765}, issn = {1950-6007}, abstract = {Berberine (BBR) is an isoquinoline alkaloid, which has been used in the treatment of intestinal mucositis. However, BBR on chemotherapy-induced mucositis in cancer patients remains largely unknown. Here, we investigated the effect of BBR on intestinal mucositis induced by 5-fluorouracil (5-Fu) using rat model. We detected the degree of intestinal mucosal damage and inflammatory response in 5-Fu treated rats with or without BBR administration, and investigated the changes of fecal metabolites and gut microbiota using 1H NMR spectroscopy and 16S rRNA. The mechanism was further explored by fecal microbiota transplantation (FMT). Results showed that BBR treated rats displayed less weight loss, lower diarrhea score and longer colon length in 5-Fu treated rats. Meanwhile, BBR treatment significantly increased the expression of Occludin in ileum and decreased the d-lactate content in serum. Moreover, the expression of IL-1β, IL-6 and TNF-α in ileum were suppressed by BBR treatment. The pattern of fecal metabolism changed obviously after treated with 5-Fu, which was reversed by BBR. Importantly, BBR significantly increased the levels of butyrate and glutamine in feces from 5-Fu treated rats. In terms of gut microbiota, BBR enriched the relative abundance of Firmicutes and decreased Proteobacteria at the phylum level. Meanwhile, BBR increased the propotion of unclassified_f_ Porphyromonadaceae, unclassified_f_ Lachnospiraceae, Lactobacillus, unclassified_o_ Clostridiales, Ruminococcus, Prevotella, Clostridium IV, and decreased Escherichia/Shigella at the genera level. Furthermore, principal component analysis (PCA) showed that fecal transplantation led to changes in fecal metabolites. Fecal transplantation from BBR treated rats had low diarrhea score, reduced inflammatory response in ileum, and relieved intestinal mucosal injury, which may be caused by the increased of butyrate level in fecal metabolites. In conclusion, our study provides evidence that BBR regulates fecal metabolites to ameliorate 5-Fu induced intestinal mucositis by modifying gut microbiota.}, }
@article {pmid31957587, year = {2019}, author = {Khoruts, A and Hoffmann, DE and Palumbo, FB}, title = {The Impact of Regulatory Policies on the Future of Fecal Microbiota Transplantation.}, journal = {The Journal of law, medicine &amp; ethics : a journal of the American Society of Law, Medicine &amp; Ethics}, volume = {47}, number = {4}, pages = {482-504}, doi = {10.1177/1073110519897726}, pmid = {31957587}, issn = {1748-720X}, abstract = {In this article, the authors explore the impact of a potential future regulatory decision by FDA whether or not to continue its enforcement discretion policy allowing physicians to perform, and stool banks to sell, stool product for fecal microbiota transplantation as a treatment for recurrent Clostridium Difficile infection without an Investigative New Drug (IND) application. The paper looks at the Agency's regulatory options in light of the current gut microbiota based products that are in t