@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},
doi = {10.1186/s13054-020-02977-5},
pmid = {32460890},
issn = {1466-609X},
support = {81722001//National Natural Science Foundation of China/ ; 81572038//National Natural Science Foundation of China/ ; },
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.

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.

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.

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 = {},
doi = {10.1128/mBio.00905-20},
pmid = {32457246},
issn = {2150-7511},
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 = {},
number = {},
pages = {1-13},
doi = {10.1080/19490976.2020.1764309},
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 {pmid31439276,
year = {2019},
author = {Li, J and Hu, FB},
title = {Research digest: reshaping the gut microbiota.},
journal = {The lancet. Diabetes & endocrinology},
volume = {7},
number = {9},
pages = {671},
doi = {10.1016/S2213-8587(19)30270-0},
pmid = {31439276},
issn = {2213-8595},
mesh = {Biomedical Research ; Dysbiosis/*microbiology/physiopathology ; Fecal Microbiota Transplantation/trends ; Feces/*microbiology ; Gastrointestinal Microbiome/immunology/*physiology ; Humans ; Immune System Diseases/*microbiology ; Inflammation/immunology/*microbiology ; Mental Disorders/*microbiology ; Metabolic Diseases/*microbiology ; Nutritional Physiological Phenomena ; },
}

Biomedical Research
Dysbiosis/*microbiology/physiopathology
Fecal Microbiota Transplantation/trends
Feces/*microbiology
Gastrointestinal Microbiome/immunology/*physiology
Humans
Immune System Diseases/*microbiology
Inflammation/immunology/*microbiology
Mental Disorders/*microbiology
Metabolic Diseases/*microbiology
Nutritional Physiological Phenomena

@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 & research. Clinical rheumatology},
volume = {},
number = {},
pages = {101528},
doi = {10.1016/j.berh.2020.101528},
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 {pmid31612528,
year = {2019},
author = {Tixier, EN and Verheyen, E and Ungaro, RC and Grinspan, AM},
title = {Faecal microbiota transplant decreases mortality in severe and fulminant Clostridioides difficile infection in critically ill patients.},
journal = {Alimentary pharmacology & therapeutics},
volume = {50},
number = {10},
pages = {1094-1099},
pmid = {31612528},
issn = {1365-2036},
support = {K23 DK111995/DK/NIDDK NIH HHS/United States ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/epidemiology/*mortality/*therapy ; *Clostridium difficile/pathogenicity ; Cohort Studies ; Critical Illness/*mortality/*therapy ; *Fecal Microbiota Transplantation/mortality/statistics & numerical data ; Female ; Humans ; Intensive Care Units/statistics & numerical data ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Tertiary Care Centers ; Treatment Outcome ; },
abstract = {BACKGROUND: Severe and fulminant Clostridioides difficile infection is associated with high mortality rates. While faecal microbiota transplant has been shown to be effective for recurrent C difficile infection, there is little data on the utility of faecal microbiota transplant in severe or fulminant C difficile infection.

AIM: To compare the outcomes of antibiotics and faecal microbiota transplantation vs antibiotics alone (standard of care) in critically ill patients with severe or fulminant C difficile infection.

METHODS: This was a retrospective, matched cohort study in one urban tertiary academic care centre including 48 patients hospitalised with severe or fulminant C difficile infection who required care in intensive care unit.

RESULTS: Patients who received faecal microbiota transplantation (n = 16) had a 77% decrease in odds for mortality (OR 0.23, 95% CI 0.06-0.97) with a number needed to treat of 3 to prevent one death.

CONCLUSIONS: Faecal microbiota transplantation provides mortality benefit over standard of care for severe and fulminant C difficile infection and should be considered in critically ill patients.},
}

Adult
Aged
Aged, 80 and over
Anti-Bacterial Agents/therapeutic use
Clostridium Infections/epidemiology/*mortality/*therapy
*Clostridium difficile/pathogenicity
Cohort Studies
Critical Illness/*mortality/*therapy
*Fecal Microbiota Transplantation/mortality/statistics & numerical data
Female
Humans
Intensive Care Units/statistics & numerical data
Male
Middle Aged
Retrospective Studies
Severity of Illness Index
Tertiary Care Centers
Treatment Outcome

@article {pmid31328778,
year = {2019},
author = {Pebenito, AM and Liu, M and Nazzal, L and Blaser, MJ},
title = {Development of a Humanized Murine Model for the Study of Oxalobacter formigenes Intestinal Colonization.},
journal = {The Journal of infectious diseases},
volume = {220},
number = {11},
pages = {1848-1858},
pmid = {31328778},
issn = {1537-6613},
support = {U54 DK083908/DK/NIDDK NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Carrier State/*microbiology ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome ; Gram-Negative Bacterial Infections/*microbiology ; Intestines/*microbiology ; Mice, Inbred C57BL ; *Models, Animal ; Oxalobacter formigenes/*growth & development ; },
abstract = {BACKGROUND: Oxalobacter formigenes are bacteria that colonize the human gut and degrade oxalate, a component of most kidney stones. Findings of clinical and epidemiological studies suggest that O. formigenes colonization reduces the risk for kidney stones. We sought to develop murine models to allow investigating O. formigenes in the context of its native human microbiome.

METHODS: For humanization, we transplanted pooled feces from healthy, noncolonized human donors supplemented with a human O. formigenes strain into recipient mice. We transplanted microbiota into mice that were treated with broad-spectrum antibiotics to suppress their native microbiome, were germ free, or received humanization without pretreatment or received sham gavage (controls).

RESULTS: All humanized mice were stably colonized with O. formigenes through 8 weeks after gavage, whereas mice receiving sham gavage remained uncolonized (P < .001). Humanization significantly changed the murine intestinal microbial community structure (P < .001), with humanized germ-free and antibiotic-treated groups overlapping in β-diversity. Both germ-free and antibiotic-treated mice had significantly increased numbers of human species compared with sham-gavaged mice (P < .001).

CONCLUSIONS: Transplanting mice with human feces and O. formigenes introduced new microbial populations resembling the human microbiome, with stable O. formigenes colonization; such models can define optimal O. formigenes strains to facilitate clinical trials.},
}

Animals
Carrier State/*microbiology
Fecal Microbiota Transplantation/methods
Feces/microbiology
Gastrointestinal Microbiome
Gram-Negative Bacterial Infections/*microbiology
Intestines/*microbiology
Mice, Inbred C57BL
*Models, Animal
Oxalobacter formigenes/*growth & development

@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 = {},
doi = {10.3390/pathogens9050386},
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},
doi = {10.2147/CEG.S243337},
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 "pharmacomicrobiomics" 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},
doi = {10.1371/journal.pone.0232739},
pmid = {32437393},
issn = {1932-6203},
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.

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.

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.

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},
doi = {10.1186/s40168-020-00845-6},
pmid = {32434586},
issn = {2049-2618},
support = {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.

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.

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 {pmid32433272,
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 = {},
number = {},
pages = {},
doi = {10.14309/ajg.0000000000000689},
pmid = {32433272},
issn = {1572-0241},
}

@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.

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.

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.

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},
doi = {10.3389/fmicb.2020.00731},
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 = {},
number = {},
pages = {},
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 the fecal microbiota transplantation (FMT) as an IBD intervention protocol require further validation as the underlying mechanisms for its attenuating effects remain unclear. This study thus 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 contents of SCFAs in the colon. In conclusion, FMT intervention could be suitable for UC control, but further validations via clinical trials are recommended.},
}

@article {pmid32421966,
year = {2019},
author = {Akash, MSH and Fiayyaz, F and Rehman, K and Sabir, S and Rasool, MH},
title = {Gut Microbiota and Metabolic Disorders: Advances in Therapeutic Interventions.},
journal = {Critical reviews in immunology},
volume = {39},
number = {4},
pages = {223-237},
doi = {10.1615/CritRevImmunol.2019030614},
pmid = {32421966},
issn = {1040-8401},
abstract = {Human gut microbiota consist of numerous microorganisms, but the most abundant species are Bacteroides and Firmicutes. Each human possesses a specific gut microbiota, which can be altered by diet, antibiotics, lifestyle, and genetic background. Gut microbiota perform vital functions, but in this article, we aimed to elaborate the effects of modified composition of microbiota on host metabolism. Ligands for G protein coupled receptors (GPCRs) are short-chain fatty acids (SCFAs) located on endocrine glands, epithelial cells, and adipocytes. SCFAs are produced in the distal gut by bacterial fermentation of nondigestible polysaccharides; they induce the various beneficial effects including decrease serum glucose level, insulin resistance, as well as inflammation; and they increase glucagon-like peptide-1 (GLP-1) secretion. Fasting-induced adipose factor (FIAF) is suppressed by gut microbiota and results in the increased storage of fatty acids in the adipose tissues and liver. An increased lipopolysaccharide level due to altered gut microflora cause the initiation of inflammation associated with type 2 diabetes mellitus (T2DM). Intestinal dysbiosis and metabolic endotoxemia are considered key mechanisms that seem to be associated with the development of T2DM and obesity. Therapeutic interventions that can be used for the treatment of diabetes include metformin, dietary modulation, probiotics, prebiotics, fecal microbiota transplantation and bariatric surgery.},
}

@article {pmid31373710,
year = {2019},
author = {Koopman, N and Molinaro, A and Nieuwdorp, M and Holleboom, AG},
title = {Review article: can bugs be drugs? The potential of probiotics and prebiotics as treatment for non-alcoholic fatty liver disease.},
journal = {Alimentary pharmacology & therapeutics},
volume = {50},
number = {6},
pages = {628-639},
doi = {10.1111/apt.15416},
pmid = {31373710},
issn = {1365-2036},
support = {016.146.327//ZONMW-VIDI/International ; //Dutch Heart Foundation/International ; //Gilead Research scholarship/International ; //Amsterdam UMC Fellowship/International ; //TKI-PPP/International ; },
mesh = {Animals ; Bariatric Surgery ; Fecal Microbiota Transplantation ; Humans ; Microbiota ; Non-alcoholic Fatty Liver Disease/*therapy ; *Prebiotics ; Probiotics/*therapeutic use ; Synbiotics ; },
abstract = {BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver condition. A major current research effort is ongoing to find potential strategies to treat NAFLD-non-alcoholic steatohepatitis (NASH), with special attention to the gut microbiota. Multiple animal studies and pilot clinical trials are assessing different gut microbiota modulating strategies such as faecal microbiota transplantation, antibiotics, probiotics, prebiotics and synbiotics.

AIM: To review the role of microbiota in NAFLD-NASH and determine whether pro- and prebiotics have potential as treatment METHODS: Information was obtained from critically reviewing literature on PubMed on targeting the gut microbiota in NAFLD. Search terms included NAFLD, NASH, non-alcoholic fatty liver disease, steatohepatitis; combined with microbiome, microbiota, gut bacteria, probiotics and prebiotics.

RESULTS: Animal studies and the first emerging studies in humans show promising results for both the common probiotics Lactobacillus, Bifidobacterium and Streptococci as for short chain fatty acid (SCFA) butyrate-producing bacteria. Also, prebiotics have positive effects on different mechanisms underlying NAFLD-NASH.

CONCLUSIONS: The most promising strategies thus far developed to alter the microbiome in NAFLD-NASH are probiotics and prebiotics. However, pre- and probiotic treatment of NAFLD-NASH is relatively new and still under development. Actual understanding of the involved mechanisms is lacking and changes in the intestinal microbiota composition after treatment are rarely measured. Furthermore, large clinical trials with comparative endpoints are unavailable. Personalised treatment based on metagenomics gut microbiota analysis will probably be part of the future diagnosis and treatment of NAFLD-NASH.},
}

Animals
Bariatric Surgery
Fecal Microbiota Transplantation
Humans
Microbiota
Non-alcoholic Fatty Liver Disease/*therapy
*Prebiotics
Probiotics/*therapeutic use
Synbiotics

@article {pmid31361420,
year = {2019},
author = {Ooijevaar, RE and van Rossen, TM and Vandenbroucke-Grauls, CMJE and Budding, AE and Kneepkens, CMF and de Meij, TGJ},
title = {[Faecal transplants for children with recurrent infections].},
journal = {Nederlands tijdschrift voor geneeskunde},
volume = {163},
number = {},
pages = {},
pmid = {31361420},
issn = {1876-8784},
mesh = {Adolescent ; Anti-Bacterial Agents/adverse effects ; Child, Preschool ; Clostridium Infections/chemically induced/microbiology/*therapy ; Clostridium difficile ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Otitis Media/drug therapy ; Recurrence ; },
abstract = {BACKGROUND: Clostridioides difficile infection is a relatively rare cause of diarrhoea in children, but there are frequent recurrences when it occurs, despite targeted antibiotic treatment.

CASE DESCRIPTIONS: A 2-year-old boy with concomitant motility disorder and a 14-year-old girl with Down syndrome experienced several infections with C. difficile, respectively after the use of antibiotics for otitis media and extended use of antibiotics in addition to chemotherapy. Both were treated successfully with faecal transplants.

CONCLUSION: Clostridioides difficile infections occur in children, mainly after extended use of antibiotics or when the immune system is impaired. In case of recurring C. difficile infections, children can be treated safely and effectively with faecal transplants.},
}

Adolescent
Anti-Bacterial Agents/adverse effects
Child, Preschool
Clostridium Infections/chemically induced/microbiology/*therapy
Clostridium difficile
*Fecal Microbiota Transplantation
Female
Humans
Male
Otitis Media/drug therapy
Recurrence

@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},
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 & colitis 360},
volume = {2},
number = {2},
pages = {otaa024},
doi = {10.1093/crocol/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.

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.

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.

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 = {The Prebiotic Properties of Green and Dark Tea Contribute to The Protective Effects in Chemical-Induced Colitis in Mice: A Fecal Microbiota Transplantation Study.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
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 on the anti-colitis 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 a 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 1g/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 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 = {},
number = {},
pages = {HYPERTENSIONAHA12014931},
doi = {10.1161/HYPERTENSIONAHA.120.14931},
pmid = {32418496},
issn = {1524-4563},
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 {pmid30666959,
year = {2019},
author = {Lavoie, S and Conway, KL and Lassen, KG and Jijon, HB and Pan, H and Chun, E and Michaud, M and Lang, JK and Gallini Comeau, CA and Dreyfuss, JM and Glickman, JN and Vlamakis, H and Ananthakrishnan, A and Kostic, A and Garrett, WS and Xavier, RJ},
title = {The Crohn's disease polymorphism, ATG16L1 T300A, alters the gut microbiota and enhances the local Th1/Th17 response.},
journal = {eLife},
volume = {8},
number = {},
pages = {},
pmid = {30666959},
issn = {2050-084X},
support = {DK097485/NH/NIH HHS/United States ; DK105653/NH/NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; F31 DK105653/DK/NIDDK NIH HHS/United States ; R01 DK092405/DK/NIDDK NIH HHS/United States ; CA154426/NH/NIH HHS/United States ; P30 DK036836/DK/NIDDK NIH HHS/United States ; DK110499/NH/NIH HHS/United States ; R01 CA154426/CA/NCI NIH HHS/United States ; Smith Family Foundation Award for Excellence in Biomedical Research//Richard and Susan Smith Family Foundation/International ; DK092405/NH/NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; R01 DK097485/DK/NIDDK NIH HHS/United States ; },
mesh = {Alleles ; Animals ; Autophagy-Related Proteins/*genetics ; Bacteroides ; Crohn Disease/*genetics/*microbiology ; Dysbiosis/genetics/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Gene Knock-In Techniques ; Genotype ; Humans ; Immune System ; Mice ; Polymorphism, Genetic ; Risk ; Th1 Cells/*cytology/microbiology ; Th17 Cells/*cytology/microbiology ; },
abstract = {Inflammatory bowel disease (IBD) is driven by dysfunction between host genetics, the microbiota, and immune system. Knowledge gaps remain regarding how IBD genetic risk loci drive gut microbiota changes. The Crohn's disease risk allele ATG16L1 T300A results in abnormal Paneth cells due to decreased selective autophagy, increased cytokine release, and decreased intracellular bacterial clearance. To unravel the effects of ATG16L1 T300A on the microbiota and immune system, we employed a gnotobiotic model using human fecal transfers into ATG16L1 T300A knock-in mice. We observed increases in Bacteroides ovatus and Th1 and Th17 cells in ATG16L1 T300A mice. Association of altered Schaedler flora mice with B. ovatus specifically increased Th17 cells selectively in ATG16L1 T300A knock-in mice. Changes occur before disease onset, suggesting that ATG16L1 T300A contributes to dysbiosis and immune infiltration prior to disease symptoms. Our work provides insight for future studies on IBD subtypes, IBD patient treatment and diagnostics.},
}

Alleles
Animals
Autophagy-Related Proteins/*genetics
Bacteroides
Crohn Disease/*genetics/*microbiology
Dysbiosis/genetics/microbiology
Fecal Microbiota Transplantation
Feces/microbiology
*Gastrointestinal Microbiome
Gene Knock-In Techniques
Genotype
Humans
Immune System
Mice
Polymorphism, Genetic
Risk
Th1 Cells/*cytology/microbiology
Th17 Cells/*cytology/microbiology

@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 = {},
number = {},
pages = {},
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.

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.

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.

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 {pmid31326346,
year = {2019},
author = {Moayyedi, P},
title = {Faecal microbiota transplantation for IBS: still a long way to go.},
journal = {The lancet. Gastroenterology & hepatology},
volume = {4},
number = {9},
pages = {656-657},
doi = {10.1016/S2468-1253(19)30226-2},
pmid = {31326346},
issn = {2468-1253},
mesh = {Diarrhea ; Double-Blind Method ; *Fecal Microbiota Transplantation ; Feces ; Humans ; *Irritable Bowel Syndrome ; },
}

Diarrhea
Double-Blind Method
*Fecal Microbiota Transplantation
Feces
Humans
*Irritable Bowel Syndrome

@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/ ; },
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 {pmid31136009,
year = {2019},
author = {Ianiro, G and Eusebi, LH and Black, CJ and Gasbarrini, A and Cammarota, G and Ford, AC},
title = {Systematic review with meta-analysis: efficacy of faecal microbiota transplantation for the treatment of irritable bowel syndrome.},
journal = {Alimentary pharmacology & therapeutics},
volume = {50},
number = {3},
pages = {240-248},
doi = {10.1111/apt.15330},
pmid = {31136009},
issn = {1365-2036},
mesh = {Adult ; Colitis, Ulcerative/epidemiology/microbiology/therapy ; *Fecal Microbiota Transplantation/methods/statistics & numerical data ; Feces/microbiology ; Gastrointestinal Microbiome/physiology ; Humans ; Irritable Bowel Syndrome/epidemiology/microbiology/*therapy ; Randomized Controlled Trials as Topic/statistics & numerical data ; Treatment Outcome ; },
abstract = {BACKGROUND: Increasing evidence supports the role of the gut microbiota in the aetiology of irritable bowel syndrome (IBS). Faecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridioides difficile infection in randomised controlled trials (RCTs), and may be beneficial in ulcerative colitis. However, its efficacy in IBS is uncertain.

AIM: To perform a systematic review and meta-analysis to examine this issue.

METHODS: We searched MEDLINE, EMBASE, EMBASE Classic, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov through to March 2019. RCTs recruiting adults with IBS, which compared FMT with placebo, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% CI.

RESULTS: The search strategy identified 322 citations. Five RCTs were eligible for inclusion, containing 267 patients. Overall, 92.2% of included patients had IBS-D or IBS-M, and only 7.8% IBS-C. When data were pooled for all patients, irrespective of stool type, the RR of IBS symptoms not improving was 0.98 (95% CI 0.58-1.66). Placebo capsules administered orally were superior to capsules containing donor stool in two pooled trials (RR = 1.96; 95% CI 1.19-3.20). FMT from donor stool delivered via colonoscopy was superior to autologous stool in two pooled RCTs (RR = 0.63; 95% CI 0.43-0.93). FMT from donor stool via nasojejunal tube showed a trend towards a benefit over autologous stool in one trial (RR = 0.69; 95% CI 0.46-1.02).

CONCLUSIONS: Fresh or frozen donor stool delivered via colonoscopy or nasojejunal tube may be beneficial in IBS. Larger, more rigorously conducted trials of FMT in IBS are needed.},
}

Adult
Colitis, Ulcerative/epidemiology/microbiology/therapy
*Fecal Microbiota Transplantation/methods/statistics & numerical data
Feces/microbiology
Gastrointestinal Microbiome/physiology
Humans
Irritable Bowel Syndrome/epidemiology/microbiology/*therapy
Randomized Controlled Trials as Topic/statistics & numerical data
Treatment Outcome

@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},
}

@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},
}

@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},
}

@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},
}

@article {pmid31051514,
year = {2019},
author = {Khoruts, A and Sadowsky, MJ},
title = {Letter to the Editor.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {69},
number = {12},
pages = {2232-2233},
doi = {10.1093/cid/ciz366},
pmid = {31051514},
issn = {1537-6591},
mesh = {*Clostridium difficile ; *Fecal Microbiota Transplantation ; },
}

*Clostridium difficile
*Fecal Microbiota Transplantation

@article {pmid31051032,
year = {2019},
author = {Khanna, S and Tariq, R and Pardi, DS},
title = {Reply to Khoruts and Sadowsky.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {69},
number = {12},
pages = {2233-2234},
doi = {10.1093/cid/ciz367},
pmid = {31051032},
issn = {1537-6591},
mesh = {*Clostridium difficile ; Diagnostic Tests, Routine ; *Fecal Microbiota Transplantation ; },
}

*Clostridium difficile
Diagnostic Tests, Routine
*Fecal Microbiota Transplantation

@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},
doi = {10.1038/s41467-020-15545-w},
pmid = {32393794},
issn = {2041-1723},
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 = {},
doi = {10.3390/jcm9051369},
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},
doi = {10.3748/wjg.v26.i16.1901},
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 "invisible organ" 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 {pmid31775890,
year = {2019},
author = {Le Roy, T and Lécuyer, E and Chassaing, B and Rhimi, M and Lhomme, M and Boudebbouze, S and Ichou, F and Haro Barceló, J and Huby, T and Guerin, M and Giral, P and Maguin, E and Kapel, N and Gérard, P and Clément, K and Lesnik, P},
title = {The intestinal microbiota regulates host cholesterol homeostasis.},
journal = {BMC biology},
volume = {17},
number = {1},
pages = {94},
pmid = {31775890},
issn = {1741-7007},
mesh = {Animals ; Cholesterol/*metabolism ; Dyslipidemias/*metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; *Homeostasis ; Intestines/*microbiology ; Mice ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Management of blood cholesterol is a major focus of efforts to prevent cardiovascular diseases. The objective of this study was to investigate how the gut microbiota affects host cholesterol homeostasis at the organism scale.

RESULTS: We depleted the intestinal microbiota of hypercholesterolemic female Apoe-/- mice using broad-spectrum antibiotics. Measurement of plasma cholesterol levels as well as cholesterol synthesis and fluxes by complementary approaches showed that the intestinal microbiota strongly regulates plasma cholesterol level, hepatic cholesterol synthesis, and enterohepatic circulation. Moreover, transplant of the microbiota from humans harboring elevated plasma cholesterol levels to recipient mice induced a phenotype of high plasma cholesterol levels in association with a low hepatic cholesterol synthesis and high intestinal absorption pattern. Recipient mice phenotypes correlated with several specific bacterial phylotypes affiliated to Betaproteobacteria, Alistipes, Bacteroides, and Barnesiella taxa.

CONCLUSIONS: These results indicate that the intestinal microbiota determines the circulating cholesterol level and may thus represent a novel therapeutic target in the management of dyslipidemia and cardiovascular diseases.},
}

Animals
Cholesterol/*metabolism
Dyslipidemias/*metabolism
Fecal Microbiota Transplantation
Gastrointestinal Microbiome/*physiology
*Homeostasis
Intestines/*microbiology
Mice
Mice, Inbred C57BL

@article {pmid31467135,
year = {2019},
author = {Wang, S and Lv, D and Jiang, S and Jiang, J and Liang, M and Hou, F and Chen, Y},
title = {Quantitative reduction in short-chain fatty acids, especially butyrate, contributes to the progression of chronic kidney disease.},
journal = {Clinical science (London, England : 1979)},
volume = {133},
number = {17},
pages = {1857-1870},
doi = {10.1042/CS20190171},
pmid = {31467135},
issn = {1470-8736},
mesh = {Animals ; Butyrates/blood/*metabolism ; Case-Control Studies ; Disease Models, Animal ; Fatty Acids, Volatile/blood/*metabolism ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/genetics ; Humans ; Kidney/physiopathology ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Renal Insufficiency, Chronic/*etiology/metabolism/pathology/physiopathology ; },
abstract = {Chronic kidney disease (CKD) affects 10-15% of the population worldwide, results in high morbidity and mortality, and requires costly treatment and renal replacement therapy. Glomerulosclerosis, tubulointerstitial fibrosis, and persistent intestinal flora disturbance are common in CKD. Short-chain fatty acids (SCFAs), produced by the intestinal microbiota, have been previously reported to ameliorate kidney injury; however, the specific concentrations and types that are required to improve renal function remain unknown. The present study aims to evaluate the levels of SCFAs in healthy and CKD patients, and to test the hypothesis that SCFAs play a critical role in delaying CKD progression. One hundred and twenty-seven patients with CKD and 63 healthy controls from China were enrolled in the present study. Butyrate, which is considered beneficial to humans, was almost three-times higher in healthy volunteers than that in CKD5 subjects (P=0.001). Moreover, the serum SCFA levels in controls were significantly higher than that in CKD patients (P<0.05), and the butyrate level among CKD5 patients (1.48 ± 0.60 μmol/l) was less than half of that in controls (3.44 ± 2.12 μmol/l, P<0.001). In addition, we observed an inverse correlation between butyrate level and renal function (P<0.05). A CKD rat model transplanted with microbiota obtained from CKD patients exhibited accelerated CKD progression via increased production of trimethylamine N-oxide (TMAO), which was reversed by supplementation with extra butyrate. Our results showed that SCFA levels were reduced in CKD patients and that butyrate supplementation might delay CKD progression.},
}

Animals
Butyrates/blood/*metabolism
Case-Control Studies
Disease Models, Animal
Fatty Acids, Volatile/blood/*metabolism
Fecal Microbiota Transplantation
Female
Gastrointestinal Microbiome/genetics
Humans
Kidney/physiopathology
Male
Middle Aged
RNA, Ribosomal, 16S/genetics
Rats
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction
Renal Insufficiency, Chronic/*etiology/metabolism/pathology/physiopathology

@article {pmid31273774,
year = {2019},
author = {Kirby, TO and Brown, M and Ochoa-Repáraz, J and Roullet, JB and Gibson, KM},
title = {Microbiota Manipulation as a Metagenomic Therapeutic Approach for Rare Inherited Metabolic Disorders.},
journal = {Clinical pharmacology and therapeutics},
volume = {106},
number = {3},
pages = {505-507},
pmid = {31273774},
issn = {1532-6535},
support = {R01 EY027476/EY/NEI NIH HHS/United States ; },
mesh = {4-Aminobutyrate Transaminase/deficiency ; Amino Acid Metabolism, Inborn Errors/physiopathology/therapy ; Animals ; Developmental Disabilities/physiopathology/therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Metabolism, Inborn Errors/*physiopathology/therapy ; Mice ; Prebiotics/administration & dosage ; Probiotics/administration & dosage ; RNA, Ribosomal, 16S/metabolism ; Rare Diseases/*physiopathology/therapy ; Severity of Illness Index ; Succinate-Semialdehyde Dehydrogenase/deficiency ; },
}

4-Aminobutyrate Transaminase/deficiency
Amino Acid Metabolism, Inborn Errors/physiopathology/therapy
Animals
Developmental Disabilities/physiopathology/therapy
Fecal Microbiota Transplantation/methods
Gastrointestinal Microbiome/*physiology
Humans
Metabolism, Inborn Errors/*physiopathology/therapy
Mice
Prebiotics/administration & dosage
Probiotics/administration & dosage
RNA, Ribosomal, 16S/metabolism
Rare Diseases/*physiopathology/therapy
Severity of Illness Index
Succinate-Semialdehyde Dehydrogenase/deficiency

@article {pmid30897248,
year = {2019},
author = {Alrafas, HR and Busbee, PB and Nagarkatti, M and Nagarkatti, PS},
title = {Resveratrol modulates the gut microbiota to prevent murine colitis development through induction of Tregs and suppression of Th17 cells.},
journal = {Journal of leukocyte biology},
volume = {106},
number = {2},
pages = {467-480},
pmid = {30897248},
issn = {1938-3673},
support = {R01 AI129788/AI/NIAID NIH HHS/United States ; R01 MH094755/MH/NIMH NIH HHS/United States ; P20 GM103641/GM/NIGMS NIH HHS/United States ; P01 AT003961/AT/NCCIH NIH HHS/United States ; R01 AT006888/AT/NCCIH NIH HHS/United States ; R01 AI123947/AI/NIAID NIH HHS/United States ; },
mesh = {Animals ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology ; Biomarkers ; Colitis/*etiology/metabolism/pathology/prevention & control ; Colonoscopy ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects/*immunology ; Humans ; Immunomodulation/*drug effects ; Metagenomics/methods ; Mice ; Resveratrol/*pharmacology ; T-Lymphocyte Subsets/immunology/metabolism ; T-Lymphocytes, Regulatory/drug effects/*immunology/metabolism ; Th17 Cells/drug effects/*immunology/metabolism ; },
abstract = {Inflammatory diseases of the gastrointestinal tract are often associated with microbial dysbiosis. Thus, dietary interactions with intestinal microbiota, to maintain homeostasis, play a crucial role in regulation of clinical disorders such as colitis. In the current study, we investigated if resveratrol, a polyphenol found in a variety of foods and beverages, would reverse microbial dysbiosis induced during colitis. Administration of resveratrol attenuated colonic inflammation and clinical symptoms in the murine model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Resveratrol treatment in mice with colitis led to an increase in CD4+ FOXP3+ and CD4+ IL-10+ T cells, and a decrease in CD4+ IFN-γ+ and CD4+ IL-17+ T cells. 16S rRNA gene sequencing to investigate alterations in the gut microbiota revealed that TNBS caused significant dysbiosis, which was reversed following resveratrol treatment. Analysis of cecal flush revealed that TNBS administration led to an increase in species such as Bacteroides acidifaciens, but decrease in species such as Ruminococcus gnavus and Akkermansia mucinphilia, as well as a decrease in SCFA i-butyric acid. However, resveratrol treatment restored the gut bacteria back to homeostatic levels, and increased production of i-butyric acid. Fecal transfer experiments confirmed the protective role of resveratrol-induced microbiota against colitis inasmuch as such recipient mice were more resistant to TNBS-colitis and exhibited polarization toward CD4+ FOXP3+ T cells and decreases in CD4+ IFN-γ+ and CD4+ IL-17+ T cells. Collectively, these data demonstrate that resveratrol-mediated attenuation of colitis results from reversal of microbial dysbiosis induced during colitis and such microbiota protect the host from colonic inflammation by inducing Tregs while suppressing inflammatory Th1/Th17 cells.},
}

Animals
Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
Biomarkers
Colitis/*etiology/metabolism/pathology/prevention & control
Colonoscopy
Disease Models, Animal
Fecal Microbiota Transplantation
Female
Gastrointestinal Microbiome/*drug effects/*immunology
Humans
Immunomodulation/*drug effects
Metagenomics/methods
Mice
Resveratrol/*pharmacology
T-Lymphocyte Subsets/immunology/metabolism
T-Lymphocytes, Regulatory/drug effects/*immunology/metabolism
Th17 Cells/drug effects/*immunology/metabolism

@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},
doi = {10.1186/s12876-020-01285-0},
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.

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.

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.

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 {pmid31375137,
year = {2019},
author = {Lavelle, A and Hoffmann, TW and Pham, HP and Langella, P and Guédon, E and Sokol, H},
title = {Baseline microbiota composition modulates antibiotic-mediated effects on the gut microbiota and host.},
journal = {Microbiome},
volume = {7},
number = {1},
pages = {111},
pmid = {31375137},
issn = {2049-2618},
mesh = {Amoxicillin-Potassium Clavulanate Combination/*administration & dosage ; Animals ; Anti-Bacterial Agents/*administration & dosage ; Bacteria/classification/*drug effects ; Bacterial Physiological Phenomena ; Colon/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Gene Expression Profiling ; Germ-Free Life ; Humans ; Male ; Mice ; *Microbiota ; },
abstract = {BACKGROUND: Normal mammalian development and homeostasis are dependent upon the gut microbiota. Antibiotics, essential for the treatment and prophylaxis of bacterial infections, can have collateral effects on the gut microbiota composition, which can in turn have far-reaching and potentially deleterious consequences for the host. However, the magnitude and duration of such collateral effects appear to vary between individuals. Furthermore, the degree to which such perturbations affect the host response is currently unclear. We aimed to test the hypothesis that different human microbiomes have different responses to a commonly prescribed antibiotic and that these differences may impact the host response.

METHODS: Germ-free mice (n = 30) humanized with the microbiota of two unrelated donors (A and B) were subjected to a 7-day antibiotic challenge with amoxicillin-clavulanate ("co-amoxiclav"). Microbiome and colonic transcriptome analysis was performed, pre (day 0) and post antibiotics (day 8) and subsequently into recovery (days 11 and 18).

RESULTS: Unique community profiles were evident depending upon the donor, with donor A recipient mice being dominated by Prevotella and Faecalibacterium and donor B recipient mice dominated by Bacteroides and Parabacteroides. Donor A mice underwent a marked destabilization of their microbiota following antibiotic treatment, while donor B mice maintained a more stable profile. Dramatic and overlapping alterations in the host transcriptome were apparent following antibiotic challenge in both groups. Despite this overlap, donor A mice experienced a more significant alteration in gene expression and uniquely showed correlations between host pathways and key microbial genera.

CONCLUSIONS: Germ-free mice humanized by different donor microbiotas maintain distinct microbiome profiles, which respond in distinct ways to antibiotic challenge and evince host responses that parallel microbiome disequilibrium. These results suggest that inter-individual variation in the gut microbiota may contribute to personalized host responses following microbiota perturbation.},
}

Amoxicillin-Potassium Clavulanate Combination/*administration & dosage
Animals
Anti-Bacterial Agents/*administration & dosage
Bacteria/classification/*drug effects
Bacterial Physiological Phenomena
Colon/microbiology
Fecal Microbiota Transplantation
Feces/microbiology
Gastrointestinal Microbiome/*drug effects
Gene Expression Profiling
Germ-Free Life
Humans
Male
Mice
*Microbiota

@article {pmid31234928,
year = {2019},
author = {Paetzold, B and Willis, JR and Pereira de Lima, J and Knödlseder, N and Brüggemann, H and Quist, SR and Gabaldón, T and Güell, M},
title = {Skin microbiome modulation induced by probiotic solutions.},
journal = {Microbiome},
volume = {7},
number = {1},
pages = {95},
pmid = {31234928},
issn = {2049-2618},
mesh = {Adult ; Bacteria/classification/isolation & purification ; Bacterial Load ; Female ; Healthy Volunteers ; Humans ; Male ; *Microbiota ; Probiotics/*administration & dosage/therapeutic use ; Propionibacteriaceae ; Skin/*microbiology ; Skin Diseases/therapy ; Young Adult ; },
abstract = {BACKGROUND: The skin is colonized by a large number of microorganisms, most of which are beneficial or harmless. However, disease states of skin have specific microbiome compositions that are different from those of healthy skin. Gut microbiome modulation through fecal transplant has been proven as a valid therapeutic strategy in diseases such as Clostridium difficile infections. Therefore, techniques to modulate the skin microbiome composition may become an interesting therapeutic option in diseases affecting the skin such as psoriasis or acne vulgaris.

METHODS: Here, we have used mixtures of different skin microbiome components to alter the composition of recipient skin microbiomes.

RESULTS: We show that after sequential applications of a donor microbiome, the recipient microbiome becomes more similar to the donor. After intervention, an initial week-long phase is characterized by the dominance of donor strains. The level of engraftment depends on the composition of the recipient and donor microbiomes, and the applied bacterial load. We observed higher engraftment using a multi-strain donor solution with recipient skin rich in Cutibacterium acnes subtype H1 and Leifsonia.

CONCLUSIONS: We have demonstrated the use of living bacteria to modulate skin microbiome composition.},
}

Adult
Bacteria/classification/isolation & purification
Bacterial Load
Female
Healthy Volunteers
Humans
Male
*Microbiota
Probiotics/*administration & dosage/therapeutic use
Propionibacteriaceae
Skin/*microbiology
Skin Diseases/therapy
Young Adult

@article {pmid30545582,
year = {2019},
author = {Benavent Boladeras, R and Ariño Blasco, S},
title = {[Faecal transplantation in geriatrics].},
journal = {Revista espanola de geriatria y gerontologia},
volume = {54},
number = {2},
pages = {119-120},
doi = {10.1016/j.regg.2018.10.005},
pmid = {30545582},
issn = {1578-1747},
mesh = {Aged, 80 and over ; *Clostridium difficile ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Male ; },
}

Aged, 80 and over
*Clostridium difficile
Enterocolitis, Pseudomembranous/*therapy
*Fecal Microbiota Transplantation
Humans
Male

@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},
doi = {10.7150/thno.43716},
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&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 {pmid31169660,
year = {2019},
author = {Kuijper, EJ and Coia, JE and Vehreschild, MJGT and Keller, J and Terveer, L},
title = {Treatment of (recurrent) Clostridioides difficile Infections in Children and Adults.},
journal = {Journal of pediatric gastroenterology and nutrition},
volume = {69},
number = {2},
pages = {e57-e58},
doi = {10.1097/MPG.0000000000002387},
pmid = {31169660},
issn = {1536-4801},
mesh = {Child ; *Clostridium Infections ; *Clostridium difficile ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; *Gastroenterology ; Humans ; United States ; },
}

Child
*Clostridium Infections
*Clostridium difficile
*Enterocolitis, Pseudomembranous
Fecal Microbiota Transplantation
*Gastroenterology
Humans
United States

@article {pmid31169659,
year = {2019},
author = {Kociolek, LK and Davidovics, ZH and Kahn, SA and Kellermayer, R},
title = {Response to: Treatment of (Recurrent) Clostridioides difficile Infections in Children and Adults.},
journal = {Journal of pediatric gastroenterology and nutrition},
volume = {69},
number = {2},
pages = {e58-e59},
doi = {10.1097/MPG.0000000000002388},
pmid = {31169659},
issn = {1536-4801},
mesh = {Child ; *Clostridium Infections ; *Clostridium difficile ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; *Gastroenterology ; Humans ; United States ; },
}

Child
*Clostridium Infections
*Clostridium difficile
*Enterocolitis, Pseudomembranous
Fecal Microbiota Transplantation
*Gastroenterology
Humans
United States

@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 = {},
number = {},
pages = {},
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 {pmid31210950,
year = {2019},
author = {Peri, R and Aguilar, RC and Tüffers, K and Erhardt, A and Link, A and Ehlermann, P and Angeli, W and Frank, T and Storr, M and Glück, T and Sturm, A and Rosien, U and Tacke, F and Bachmann, O and Solbach, P and Stallmach, A and Goeser, F and Vehreschild, MJ and , },
title = {The impact of technical and clinical factors on fecal microbiota transfer outcomes for the treatment of recurrent Clostridioides difficile infections in Germany.},
journal = {United European gastroenterology journal},
volume = {7},
number = {5},
pages = {716-722},
pmid = {31210950},
issn = {2050-6406},
mesh = {Age Factors ; Aged ; Aged, 80 and over ; Clostridium Infections/*therapy ; *Clostridium difficile ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Secondary Prevention ; Treatment Failure ; },
abstract = {Introduction: Fecal microbiota transfer (FMT) is highly effective in the treatment and prevention of recurrent Clostridioides difficile infection (rCDI) with cure rates of about 80% after a single treatment. Nevertheless, the reasons for failure in the remaining 20% remain largely elusive. The aim of the present study was to investigate different potential clinical predictors of response to FMT in Germany.

Methods: Information was extracted from the MicroTrans Registry (NCT02681068), a retrospective observational multicenter study, collecting data from patients undergoing FMT for recurrent or refractory CDI in Germany. We performed binary logistic regression with the following covariates: age, gender, ribotype 027, Eastern Co-operative Oncology Group score, immunosuppression, preparation for FMT by use of proton pump inhibitor, antimotility agents and bowel lavage, previous recurrences, severity of CDI, antibiotic induction treatment, fresh or frozen FMT preparation, and route of application.

Results: Treatment response was achieved in 191/240 evaluable cases (79.6%) at day 30 (D30) post FMT and 78.1% at day 90 (D90) post FMT. Assessment of clinical predictors for FMT failure by forward and confirmatory backward-stepwise regression analysis yielded higher age as an independent predictor of FMT failure (p = 0.001; OR 1.060; 95%CI 1.025-1.097).

Conclusion: FMT in Germany is associated with high cure rates at D30 and D90. No specific pre-treatment, preparation or application strategy had an impact on FMT success. Only higher age was identified as an independent risk factor for treatment failure. Based on these and external findings, future studies should focus on the assessment of microbiota and microbiota-associated metabolites as factors determining FMT success.},
}

Age Factors
Aged
Aged, 80 and over
Clostridium Infections/*therapy
*Clostridium difficile
*Fecal Microbiota Transplantation/adverse effects
Female
Humans
Male
Middle Aged
Retrospective Studies
Risk Factors
Secondary Prevention
Treatment Failure

@article {pmid31028093,
year = {2019},
author = {Jimenez, M and Langer, R and Traverso, G},
title = {Microbial therapeutics: New opportunities for drug delivery.},
journal = {The Journal of experimental medicine},
volume = {216},
number = {5},
pages = {1005-1009},
pmid = {31028093},
issn = {1540-9538},
mesh = {Bifidobacterium ; Clostridium ; Clostridium Infections/microbiology/*therapy ; Drug Compounding ; *Drug Delivery Systems ; Drug Dosage Calculations ; Escherichia coli ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Humans ; *Vaccines, Live, Unattenuated ; },
abstract = {With >40 clinical trials underway, we are nearing the first FDA-approved live microbial therapeutic. Here, Giovanni Traverso, MIT and Harvard Medical School Assistant Professor, and colleagues Miguel Jimenez and Institute Professor Robert Langer from MIT discuss the significant challenges of administering live microorganisms to patients and the opportunities for drug delivery of these new complex therapeutics.},
}

Bifidobacterium
Clostridium
Clostridium Infections/microbiology/*therapy
Drug Compounding
*Drug Delivery Systems
Drug Dosage Calculations
Escherichia coli
Fecal Microbiota Transplantation/*methods
Gastrointestinal Microbiome
Humans
*Vaccines, Live, Unattenuated

@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},
doi = {10.3389/fvets.2020.00192},
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},
doi = {10.1016/j.molmed.2020.01.009},
pmid = {32359480},
issn = {1471-499X},
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 = {},
pages = {},
doi = {10.18632/aging.103093},
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},
doi = {10.1186/s40168-020-00837-6},
pmid = {32354351},
issn = {2049-2618},
support = {CP19/00190//Instituto de Salud Calos III, Río Hortega/ ; CP18/00009//Instituto de Salud Carlos III, Miguel Servet/ ; PI15/01934//Instituto de Salud Carlos III/ ; },
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.

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.

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, JF 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 Post-Stroke Recovery in Aged Mice.},
journal = {Circulation research},
volume = {},
number = {},
pages = {},
doi = {10.1161/CIRCRESAHA.119.316448},
pmid = {32354259},
issn = {1524-4571},
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. 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 (young FTG) 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. Methods and Results: Aged male mice (18-20 months) were subjected to ischemic stroke by middle cerebral artery occlusion (MCAO). We performed FTG three days after MCAO using young donor biome (2-3 months) or aged biome (18-20 months). At day 14 after stroke, aged stroke mice receiving young FTG 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 four SCFA-producers (Bifidobacterium longum, Clostridium symbiosum, Faecalibacterium prausnitzii and Lactobacillus fermentum) for transplantation. These SCFA-producers alleviated post-stroke neurological deficits and inflammation, and elevated gut, brain and plasma SCFA concentrations in aged stroke mice. Conclusions:This is the first study suggesting that the poor stroke recovery in aged mice can be reversed via "post-stroke 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},
doi = {10.1182/bloodadvances.2020001531},
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 = {},
doi = {10.1128/mSphere.00173-20},
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},
doi = {10.3389/fmicb.2020.00628},
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 {pmid31873192,
year = {2020},
author = {Hill, C},
title = {Balancing the risks and rewards of live biotherapeutics.},
journal = {Nature reviews. Gastroenterology & hepatology},
volume = {17},
number = {3},
pages = {133-134},
doi = {10.1038/s41575-019-0254-3},
pmid = {31873192},
issn = {1759-5053},
mesh = {*Bacteremia ; Escherichia coli ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Reward ; },
}

*Bacteremia
Escherichia coli
Fecal Microbiota Transplantation
Humans
*Microbiota
Reward

@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.},
}

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

@article {pmid31712445,
year = {2019},
author = {Sobhani, I and Bergsten, E and Couffin, S and Amiot, A and Nebbad, B and Barau, C and de'Angelis, N and Rabot, S and Canoui-Poitrine, F and Mestivier, D and Pédron, T and Khazaie, K and Sansonetti, PJ},
title = {Colorectal cancer-associated microbiota contributes to oncogenic epigenetic signatures.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {116},
number = {48},
pages = {24285-24295},
pmid = {31712445},
issn = {1091-6490},
mesh = {Animals ; Cohort Studies ; Colorectal Neoplasms/*genetics/*microbiology ; DNA Methylation ; Dysbiosis/genetics/microbiology/pathology ; *Epigenesis, Genetic ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Gene Expression Regulation ; Germ-Free Life ; Humans ; Intestinal Mucosa/metabolism/pathology ; Male ; Mice, Inbred C3H ; Promoter Regions, Genetic ; RNA, Ribosomal, 16S ; },
abstract = {Sporadic colorectal cancer (CRC) is a result of complex interactions between the host and its environment. Environmental stressors act by causing host cell DNA alterations implicated in the onset of cancer. Here we investigate the stressor ability of CRC-associated gut dysbiosis as causal agent of host DNA alterations. The epigenetic nature of these alterations was investigated in humans and in mice. Germ-free mice receiving fecal samples from subjects with normal colonoscopy or from CRC patients were monitored for 7 or 14 wk. Aberrant crypt foci, luminal microbiota, and DNA alterations (colonic exome sequencing and methylation patterns) were monitored following human feces transfer. CRC-associated microbiota induced higher numbers of hypermethylated genes in murine colonic mucosa (vs. healthy controls' microbiota recipients). Several gene promoters including SFRP1,2,3, PENK, NPY, ALX4, SEPT9, and WIF1 promoters were found hypermethylated in CRC but not in normal tissues or effluents from fecal donors. In a pilot study (n = 266), the blood methylation levels of 3 genes (Wif1, PENK, and NPY) were shown closely associated with CRC dysbiosis. In a validation study (n = 1,000), the cumulative methylation index (CMI) of these genes was significantly higher in CRCs than in controls. Further, CMI appeared as an independent risk factor for CRC diagnosis as shown by multivariate analysis that included fecal immunochemical blood test. Consequently, fecal bacterial species in individuals with higher CMI in blood were identified by whole metagenomic analysis. Thus, CRC-related dysbiosis induces methylation of host genes, and corresponding CMIs together with associated bacteria are potential biomarkers for CRC.},
}

Animals
Cohort Studies
Colorectal Neoplasms/*genetics/*microbiology
DNA Methylation
Dysbiosis/genetics/microbiology/pathology
*Epigenesis, Genetic
Fecal Microbiota Transplantation
Feces/microbiology
Female
Gastrointestinal Microbiome/*genetics
Gene Expression Regulation
Germ-Free Life
Humans
Intestinal Mucosa/metabolism/pathology
Male
Mice, Inbred C3H
Promoter Regions, Genetic
RNA, Ribosomal, 16S

@article {pmid31554900,
year = {2019},
author = {Zachariassen, LF and Hansen, AK and Krych, L and Nielsen, DS and Holm, TL and Tougaard, P and Hansen, CHF},
title = {Cesarean section increases sensitivity to oxazolone-induced colitis in C57BL/6 mice.},
journal = {Mucosal immunology},
volume = {12},
number = {6},
pages = {1348-1357},
doi = {10.1038/s41385-019-0207-8},
pmid = {31554900},
issn = {1935-3456},
mesh = {Animals ; Cesarean Section/*adverse effects ; Colitis/*chemically induced/immunology/metabolism/microbiology ; Colon/*immunology/metabolism/microbiology/pathology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Inflammation Mediators/metabolism ; Intestinal Mucosa/*immunology/metabolism/microbiology/pathology ; Mice, Inbred C57BL ; *Oxazolone ; Peroxidase/metabolism ; Pregnancy ; Severity of Illness Index ; Tumor Necrosis Factor-alpha/metabolism ; },
abstract = {Children born by cesarean section (CS) have an increased risk of developing inflammatory bowel disease (IBD), possibly due to skewed microbial colonization during birth and consequently impaired bacterial stimulation of the developing immune system. The aim of this study was to investigate the association between CS and experimental colitis in a murine model of IBD. It was hypothesized that CS aggravates colonic inflammation due to a change in gut microbiota (GM) composition. C57BL/6 mice, delivered by CS or vaginal delivery (VD), were intra-rectally challenged with oxazolone at 8 weeks of age and monitored for colitis symptoms. The results showed that CS delivered mice experienced an increased body weight loss and colon weight, together with higher colonic concentrations of TNF-α and MPO compared with VD mice. Increased infiltration of inflammatory cells was present in CS delivered mice, as well as a downregulation in expression of the gut integrity genes occludin and tight junction protein 1 indicative of an impaired barrier function. The GM from CS delivered mice without colitis partly contributed to the increase in colitis symptoms when inoculated into germ-free recipient mice. In conclusion, CS increased sensitivity to oxazolone induced colitis in mice.},
}

Animals
Cesarean Section/*adverse effects
Colitis/*chemically induced/immunology/metabolism/microbiology
Colon/*immunology/metabolism/microbiology/pathology
Disease Models, Animal
Fecal Microbiota Transplantation
Female
Gastrointestinal Microbiome
Inflammation Mediators/metabolism
Intestinal Mucosa/*immunology/metabolism/microbiology/pathology
Mice, Inbred C57BL
*Oxazolone
Peroxidase/metabolism
Pregnancy
Severity of Illness Index
Tumor Necrosis Factor-alpha/metabolism

@article {pmid31501515,
year = {2019},
author = {Spalinger, MR and Schwarzfischer, M and Hering, L and Shawki, A and Sayoc, A and Santos, A and Gottier, C and Lang, S and Bäbler, K and Geirnaert, A and Lacroix, C and Leventhal, GE and Dai, X and Rawlings, D and Chan, AA and Rogler, G and McCole, DF and Scharl, M},
title = {Loss of PTPN22 abrogates the beneficial effect of cohousing-mediated fecal microbiota transfer in murine colitis.},
journal = {Mucosal immunology},
volume = {12},
number = {6},
pages = {1336-1347},
doi = {10.1038/s41385-019-0201-1},
pmid = {31501515},
issn = {1935-3456},
mesh = {Animals ; Bacteria/*growth & development/immunology ; Cells, Cultured ; Colitis/enzymology/genetics/microbiology/*therapy ; Colon/*enzymology/immunology/microbiology ; Dextran Sulfate ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Genotype ; *Housing, Animal ; Intestinal Mucosa/*enzymology/immunology/microbiology ; Mice, Inbred C57BL ; Mice, Knockout ; Protein Tyrosine Phosphatase, Non-Receptor Type 22/*deficiency/genetics ; Th1 Cells/immunology/metabolism/microbiology ; },
abstract = {Fecal microbiota transfer (FMT) is a very efficient approach for the treatment of severe and recurring C. difficile infections. However, the beneficial effect of FMT in other disorders such as ulcerative colitis (UC) or Crohn's disease remains unclear. Furthermore, it is currently unknown how disease-associated genetic variants in donors or recipients influence the effect of FMT. We found that bacteria-transfer from wild-type (WT) donors via cohousing was efficient in inducing recovery from colitis in WT mice, but not in mice deficient in protein-tyrosine phosphatase non-receptor type 22 (PTPN22), a known risk gene for several chronic inflammatory diseases. Also cohousing of PTPN22-deficient mice with diseased WT mice failed to induce faster recovery. Our data indicate that the genetic background of the donor and the recipient influences the outcome of microbiota transfer, and offers a potential explanation why transfer of fecal microbes from some, but not all donors is efficient in UC patients.},
}

Animals
Bacteria/*growth & development/immunology
Cells, Cultured
Colitis/enzymology/genetics/microbiology/*therapy
Colon/*enzymology/immunology/microbiology
Dextran Sulfate
Disease Models, Animal
*Fecal Microbiota Transplantation
*Gastrointestinal Microbiome
Genotype
*Housing, Animal
Intestinal Mucosa/*enzymology/immunology/microbiology
Mice, Inbred C57BL
Mice, Knockout
Protein Tyrosine Phosphatase, Non-Receptor Type 22/*deficiency/genetics
Th1 Cells/immunology/metabolism/microbiology

@article {pmid30835680,
year = {2019},
author = {Wallace, DJ and Sayre, NL and Patterson, TT and Nicholson, SE and Hilton, D and Grandhi, R},
title = {Spinal cord injury and the human microbiome: beyond the brain-gut axis.},
journal = {Neurosurgical focus},
volume = {46},
number = {3},
pages = {E11},
doi = {10.3171/2018.12.FOCUS18206},
pmid = {30835680},
issn = {1092-0684},
support = {IK2 BX003240/BX/BLRD VA/United States ; },
mesh = {Animals ; Bacterial Translocation ; Brain Injuries, Traumatic/microbiology ; Burns/microbiology ; Dysbiosis/complications/immunology/microbiology/therapy ; Fecal Microbiota Transplantation ; Feedback, Physiological ; *Gastrointestinal Microbiome ; Humans ; Immunity, Mucosal/immunology ; Intestinal Mucosa/immunology/microbiology ; Mice ; Probiotics/therapeutic use ; Rats ; Sepsis/etiology/microbiology ; Species Specificity ; Spinal Cord Injuries/complications/immunology/*microbiology ; Stroke/microbiology/therapy ; },
abstract = {In addition to standard management for the treatment of the acute phase of spinal cord injury (SCI), implementation of novel neuroprotective interventions offers the potential for significant reductions in morbidity and long-term health costs. A better understanding of the systemic changes after SCI could provide insight into mechanisms that lead to secondary injury. An emerging area of research involves the complex interplay of the gut microbiome and the CNS, i.e., a brain-gut axis, or perhaps more appropriately, a CNS-gut axis. This review summarizes the relevant literature relating to the gut microbiome and SCI. Experimental models in stroke and traumatic brain injury demonstrate the bidirectional communication of the CNS to the gut with postinjury dysbiosis, gastrointestinal-associated lymphoid tissue-mediated neuroinflammatory responses, and bacterial-metabolite neurotransmission. Similar findings are being elucidated in SCI as well. Experimental interventions in these areas have shown promise in improving functional outcomes in animal models. This commensal relationship between the human body and its microbiome, particularly the gut microbiome, represents an exciting frontier in experimental medicine.},
}

Animals
Bacterial Translocation
Brain Injuries, Traumatic/microbiology
Burns/microbiology
Dysbiosis/complications/immunology/microbiology/therapy
Fecal Microbiota Transplantation
Feedback, Physiological
*Gastrointestinal Microbiome
Humans
Immunity, Mucosal/immunology
Intestinal Mucosa/immunology/microbiology
Mice
Probiotics/therapeutic use
Rats
Sepsis/etiology/microbiology
Species Specificity
Spinal Cord Injuries/complications/immunology/*microbiology
Stroke/microbiology/therapy

@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 & pharmacotherapy = Biomedecine & 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 = {},
number = {},
pages = {},
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 = {},
doi = {10.3390/diseases8020009},
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 {pmid31749279,
year = {2020},
author = {Quaranta, G and Fancello, G and Ianiro, G and Graffeo, R and Gasbarrini, A and Cammarota, G and Sanguinetti, M and Masucci, L},
title = {Laboratory handling practice for faecal microbiota transplantation.},
journal = {Journal of applied microbiology},
volume = {128},
number = {3},
pages = {893-898},
doi = {10.1111/jam.14522},
pmid = {31749279},
issn = {1365-2672},
mesh = {Bacterial Load ; Biological Specimen Banks/standards ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Gastrointestinal Microbiome ; Humans ; Laboratories/*standards ; Specimen Handling/*methods ; Workflow ; },
abstract = {AIMS: Faecal microbiota transplantation (FMT) consists of the infusion of faeces from a healthy donor to the gastrointestinal tract of a recipient patient to treat disease associated with alterations in gut microbiota. The objective of this article was to describe laboratory workflow of an FMT laboratory to provide tips for preparing the faecal suspensions to be infused.

METHODS AND RESULTS: Twenty-stool solutions obtained from ten donors were prepared using two different protocols: magnet plate emulsion (MPE) and Seward StomacherTM Emulsion (SSE). We evaluated parameters such as preparation time, handiness, and aerobic and anaerobic microbial count. For three donors, we monitored bacterial counts after defrosting at different time-points. MPE requires more time than SSE. In terms of microbial load, both methods showed similar values, with small and statistically differences (P ≤ 0·05) regarding anaerobes in favour of SSE. Frozen aliquots showed the same bacterial load values after defrosting.

CONCLUSION: Although both methods allow an easy and available preparation of a stool suspension, SSE seems more suitable, particularly for stool banking. Aerobic and anaerobic species are preserved with both protocols; and safety for laboratory operators is guaranteed.

In recent years, FMT has become a fascinating and interesting subject. Nevertheless, there are no real guidelines describing laboratory facilities and procedures. This paper aims to be a useful and simple guide to increase the number FMT centres as much possible.},
}

Bacterial Load
Biological Specimen Banks/standards
*Fecal Microbiota Transplantation
Feces/*microbiology
Gastrointestinal Microbiome
Humans
Laboratories/*standards
Specimen Handling/*methods
Workflow

@article {pmid31711971,
year = {2019},
author = {Seekatz, AM},
title = {Development of an alternative animal model to investigate host-microbe interactions.},
journal = {EBioMedicine},
volume = {50},
number = {},
pages = {7-8},
doi = {10.1016/j.ebiom.2019.10.027},
pmid = {31711971},
issn = {2352-3964},
support = {K01 DK111794/DK/NIDDK NIH HHS/United States ; },
mesh = {Animals ; *Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Inflammatory Bowel Diseases/*therapy ; Rats ; },
}

Animals
*Disease Models, Animal
Fecal Microbiota Transplantation/*methods
Gastrointestinal Microbiome
Host-Pathogen Interactions
Humans
Inflammatory Bowel Diseases/*therapy
Rats

@article {pmid31144984,
year = {2019},
author = {Tashiro, H and Cho, Y and Kasahara, DI and Brand, JD and Bry, L and Yeliseyev, V and Abu-Ali, G and Huttenhower, C and Shore, SA},
title = {Microbiota Contribute to Obesity-related Increases in the Pulmonary Response to Ozone.},
journal = {American journal of respiratory cell and molecular biology},
volume = {61},
number = {6},
pages = {702-712},
pmid = {31144984},
issn = {1535-4989},
support = {P30 ES000002/ES/NIEHS NIH HHS/United States ; R01 ES013307/ES/NIEHS NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; T32 HL007118/HL/NHLBI NIH HHS/United States ; R21 ES024032/ES/NIEHS NIH HHS/United States ; },
mesh = {Airway Resistance ; Animals ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Asthma/etiology/therapy ; Cellulose/administration & dosage ; Dietary Fiber/administration & dosage ; Fecal Microbiota Transplantation ; Female ; Fermentation ; Gastrointestinal Microbiome/drug effects/*physiology ; Germ-Free Life ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/*complications/genetics/microbiology/physiopathology ; Ozone/*toxicity ; Pectins/administration & dosage/therapeutic use ; Receptors, Leptin/deficiency ; Respiratory Hypersensitivity/chemically induced/diet therapy/*etiology/microbiology ; },
abstract = {Obesity is a risk factor for asthma, especially nonatopic asthma, and attenuates the efficacy of standard asthma therapeutics. Obesity also augments pulmonary responses to ozone, a nonatopic asthma trigger. The purpose of this study was to determine whether obesity-related alterations in gut microbiota contribute to these augmented responses to ozone. Ozone-induced increases in airway responsiveness, a canonical feature of asthma, were greater in obese db/db mice than in lean wild-type control mice. Depletion of gut microbiota with a cocktail of antibiotics attenuated obesity-related increases in the response to ozone, indicating a role for microbiota. Moreover, ozone-induced airway hyperresponsiveness was greater in germ-free mice that had been reconstituted with colonic contents of db/db than in wild-type mice. In addition, compared with dietary supplementation with the nonfermentable fiber cellulose, dietary supplementation with the fermentable fiber pectin attenuated obesity-related increases in the pulmonary response to ozone, likely by reducing ozone-induced release of IL-17A. Our data indicate a role for microbiota in obesity-related increases in the response to an asthma trigger and suggest that microbiome-based therapies such as prebiotics may provide an alternative therapeutic strategy for obese patients with asthma.},
}

Airway Resistance
Animals
Anti-Bacterial Agents/pharmacology/therapeutic use
Asthma/etiology/therapy
Cellulose/administration & dosage
Dietary Fiber/administration & dosage
Fecal Microbiota Transplantation
Female
Fermentation
Gastrointestinal Microbiome/drug effects/*physiology
Germ-Free Life
Mice
Mice, Inbred C57BL
Mice, Obese
Obesity/*complications/genetics/microbiology/physiopathology
Ozone/*toxicity
Pectins/administration & dosage/therapeutic use
Receptors, Leptin/deficiency
Respiratory Hypersensitivity/chemically induced/diet therapy/*etiology/microbiology

@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 ; },
}

Child, Preschool
*Clostridium Infections
*Clostridium difficile
Fecal Microbiota Transplantation
*Heart Transplantation
Humans
*Microbiota

@article {pmid31780599,
year = {2019},
author = {Tamilarasan, AG and Irving, P and Meadows, CI and Goldenberg, S},
title = {Faecal microbiota transplantation for refractory Clostridiumdifficile infection.},
journal = {BMJ case reports},
volume = {12},
number = {11},
pages = {},
doi = {10.1136/bcr-2019-231027},
pmid = {31780599},
issn = {1757-790X},
mesh = {Aged ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; },
abstract = {Faecal microbiota transplantation (FMT) has become a part of the treatment algorithm for Clostridium difficile infection (CDI), particularly for recurrent infections when antibiotics have diminishing efficacy. Notably, despite a significant proportion of patients suffering from refractory disease, there is a general lack of evidence describing the use of FMT in this patient cohort. We present here a case of successful treatment of refractory CDI in a patient under critical care.},
}

Aged
Clostridium Infections/*therapy
*Fecal Microbiota Transplantation
Female
Humans

@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 = {},
number = {},
pages = {},
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 = {},
number = {},
pages = {e13841},
doi = {10.1111/nmo.13841},
pmid = {32319196},
issn = {1365-2982},
support = {//EA Pharma Co., Ltd./ ; //Daiichi Sankyo Corp., Ltd./ ; },
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.

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.

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.

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},
doi = {10.3389/fmed.2020.00117},
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 "leaky gut" 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},
doi = {10.3389/fimmu.2020.00575},
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 = {},
number = {},
pages = {},
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 on blood pressure regulation and hypertension development.},
journal = {Antioxidants & redox signaling},
volume = {},
number = {},
pages = {},
doi = {10.1089/ars.2020.8104},
pmid = {32316741},
issn = {1557-7716},
abstract = {SIGNIFICANCE: Hypertension (HTN) has a complex etiology 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 control, and are therefore responsible for developing HTN.

CRITICAL ISSUES: This study aimed to focus on the recent advances in understanding the role played by gut bacteria and the mechanisms underlying the pathological milieu that induced elevated blood pressure 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 blood pressure changes with the replacement of gut microbiome. The proposed mechanisms for gut in regulating blood pressure 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 {pmid30789675,
year = {2019},
author = {Stern, JM and Urban-Maldonado, M and Usyk, M and Granja, I and Schoenfeld, D and Davies, KP and Agalliu, I and Asplin, J and Burk, R and Suadicani, SO},
title = {Fecal transplant modifies urine chemistry risk factors for urinary stone disease.},
journal = {Physiological reports},
volume = {7},
number = {4},
pages = {e14012},
pmid = {30789675},
issn = {2051-817X},
support = {NIH R21 DK108097-02/NH/NIH HHS/United States ; },
mesh = {Animals ; Calcium/urine ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Absorption ; Gastrointestinal Microbiome ; Male ; Mice ; Mice, Inbred C57BL ; Rats ; Rats, Zucker ; Urinary Calculi/prevention & control/*therapy ; Urine/chemistry/microbiology ; },
abstract = {Urinary stone disease (USD) is a major health concern. There is a need for new treatment modalities. Recently, our group provided evidence for an association between the GMB composition and USD. The accessibility of the Gut Microbiome (GMB) makes it an attractive target for investigation and therefore, in these studies we have evaluated the extent to which the whole gut microbial community in fecal transplants can affect urinary stone risk parameters in an animal model. Fresh fecal pellets were collected from Zucker lean rats, homogenized in PBS (100 mg/mL), filtered through a 70 μm strainer and then orally gavaged into C57BL/6NTac germ-free mice. Twenty-four hours urine collections and GMB analysis were performed over time for 1 month. Kidney and gut tissue were harvested from transplanted mice for western blot analysis of expression levels of the Slc26a6 transporter involved in oxalate balance. Urinary calcium decreased after fecal transplant by 55% (P < 0.001). Urinary oxalate levels were on average 24% lower than baseline levels (P < 0.001). Clostridiaceae family was negatively correlated with urinary oxalate at 4 weeks after transplant (r = -0.83, P < 0.01). There was a 0.6 unit average increase in urinary pH from a baseline of 5.85 (SE ± 0.028) to 6.49 (SE ± 0.04) (P < 0.001) after transplant. There was a concomitant 29% increase in gastrointestinal alkali absorption (P < 0.001) 4-weeks after fecal transplant. Slc26a6 expression increased by 90% in the cecum after transplant. Our results suggest that the gut microbiome may impact metabolism, alters urinary chemistry, and thereby may influence USD; the accessibility of the GMB can potentially be leveraged for therapeutic interventions.},
}

Animals
Calcium/urine
Fecal Microbiota Transplantation/*methods
Gastrointestinal Absorption
Gastrointestinal Microbiome
Male
Mice
Mice, Inbred C57BL
Rats
Rats, Zucker
Urinary Calculi/prevention & control/*therapy
Urine/chemistry/microbiology

@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 = {},
number = {},
pages = {},
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 & function},
volume = {},
number = {},
pages = {},
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 = {},
number = {},
pages = {},
doi = {10.5217/ir.2019.00108},
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 {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 ; },
}

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 ; },
}

Animals
Autistic Disorder/*microbiology/therapy
Biodiversity
Fecal Microbiota Transplantation/trends
Gastrointestinal Microbiome/*physiology
*Host Microbial Interactions
Humans
Mice

@article {pmid31898340,
year = {2020},
author = {Li, J and Dubois, W and Thovarai, V and Wu, Z and Feng, X and Peat, T and Zhang, S and Sen, SK and Trinchieri, G and Chen, J and Mock, BA and Young, NS},
title = {Attenuation of immune-mediated bone marrow damage in conventionally housed mice.},
journal = {Molecular carcinogenesis},
volume = {59},
number = {2},
pages = {237-245},
doi = {10.1002/mc.23151},
pmid = {31898340},
issn = {1098-2744},
mesh = {Anemia, Aplastic/immunology/pathology/*therapy ; Animals ; Bone Marrow/*immunology/pathology ; Bone Marrow Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/*immunology ; Hyaluronan Receptors/immunology/metabolism ; Immunologic Memory/immunology ; Lymphocyte Activation/immunology ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Specific Pathogen-Free Organisms ; T-Lymphocytes/*immunology/metabolism/transplantation ; Transplantation Immunology ; Transplantation, Homologous ; },
abstract = {In humans, bone marrow (BM) failure syndromes, both constitutional and acquired, predispose to myeloid malignancies. We have modeled acquired immune aplastic anemia, the paradigmatic disease of these syndromes, in the mouse by infusing lymph node cells from specific pathogen-free (SPF) CD45.1 congenic C57BL/6 (B6) donors into hybrid CByB6F1 recipients housed either in conventional (CVB) or SPF facilities. The severity of BM damage was reduced in CVB recipients; they also had reduced levels of CD44+ CD62L- effector memory T cells, reduced numbers of donor-type CD44+ T cells, and reduced expansion of donor-type CD8 T cells carrying T-cell receptor β-variable regions 07, 11, and 17. Analyses of fecal samples through 16S ribosomal RNA amplicon sequencing revealed greater gut microbial alpha diversity in CVB mice relative to that of SPF mice. Thus, the presence of a broader spectrum of gut microorganisms in CVB-housed CByB6F1 could have primed recipient animal's immune system leading to suppression of allogeneic donor T-cell activation and expansion and attenuation of host BM destruction. These results suggest the potential benefit of diverse gut microbiota in patients receiving BM transplants.},
}

Anemia, Aplastic/immunology/pathology/*therapy
Animals
Bone Marrow/*immunology/pathology
Bone Marrow Transplantation/*methods
Feces/microbiology
Gastrointestinal Microbiome/*immunology
Hyaluronan Receptors/immunology/metabolism
Immunologic Memory/immunology
Lymphocyte Activation/immunology
Mice, Inbred BALB C
Mice, Inbred C57BL
Specific Pathogen-Free Organisms
T-Lymphocytes/*immunology/metabolism/transplantation
Transplantation Immunology
Transplantation, Homologous

@article {pmid31005929,
year = {2019},
author = {Leong, KSW and Jayasinghe, TN and Derraik, JGB and Albert, BB and Chiavaroli, V and Svirskis, DM and Beck, KL and Conlon, CA and Jiang, Y and Schierding, W and Vatanen, T and Holland, DJ and O'Sullivan, JM and Cutfield, WS},
title = {Protocol for the Gut Bugs Trial: a randomised double-blind placebo-controlled trial of gut microbiome transfer for the treatment of obesity in adolescents.},
journal = {BMJ open},
volume = {9},
number = {4},
pages = {e026174},
pmid = {31005929},
issn = {2044-6055},
mesh = {Adolescent ; Adult ; Body Mass Index ; Double-Blind Method ; Dysbiosis/etiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Follow-Up Studies ; *Gastrointestinal Microbiome ; Humans ; Male ; Pediatric Obesity/complications/*therapy ; Quality of Life ; Treatment Outcome ; Young Adult ; },
abstract = {INTRODUCTION: Animal studies showed that germ-free mice inoculated with normal mouse gut bacteria developed obesity, insulin resistance and higher triglyceride levels, despite similar food intake. In humans, an association has been found between obesity and gut microbiome dysbiosis. However, gut microbiome transfer has not been evaluated for the treatment of human obesity. We will examine the effectiveness of gut microbiome transfer using encapsulated material for the treatment of obesity in adolescents.

METHODS AND ANALYSIS: A two-arm, double-blind, placebo-controlled, randomised clinical trial of a single course of gut microbiome transfer will be conducted in 80 obese [body mass index (BMI) ≥30 kg/m2] adolescents (males and females, aged 14-18 years) in Auckland, New Zealand. Healthy lean donors (males and females, aged 18-28 years) will provide fresh stool samples from which bacteria will be isolated and double encapsulated. Participants (recipients) will be randomised at 1:1 to control (placebo) or treatment (gut microbiome transfer), stratified by sex. Recipients will receive 28 capsules over two consecutive mornings (~14 mL of frozen microbial suspension or saline). Clinical assessments will be performed at baseline, 6, 12 and 26 weeks, and will include: anthropometry, blood pressure, fasting metabolic markers, dietary intake, physical activity levels and health-related quality of life. Insulin sensitivity (Matsuda index), gut microbiota population structure characterised by 16S rRNA amplicon sequencing and body composition (using dual-energy X-ray absorptiometry) will be assessed at baseline, 6, 12 and 26 weeks. 24-hour ambulatory blood pressure monitoring will be performed at baseline and at 6 weeks. The primary outcome is BMI SD scores (SDS) at 6 weeks, with BMI SDS at 12 and 26 weeks as secondary outcomes. Other secondary outcomes include insulin sensitivity, adiposity (total body fat percentage) and gut microbial composition at 6, 12 and 26 weeks. Statistical analysis will be performed on the principle of intention to treat.

ETHICS AND DISSEMINATION: Ethics approval was provided by the Northern A Health and Disability Ethics Committee (Ministry of Health, New Zealand; 16/NTA/172). The trial results will be published in peer-reviewed journals and presented at international conferences.

TRIAL REGISTRATION NUMBER: ACTRN12615001351505; Pre-results.},
}

Adolescent
Adult
Body Mass Index
Double-Blind Method
Dysbiosis/etiology/*therapy
Fecal Microbiota Transplantation/*methods
Feces/microbiology
Female
Follow-Up Studies
*Gastrointestinal Microbiome
Humans
Male
Pediatric Obesity/complications/*therapy
Quality of Life
Treatment Outcome
Young Adult

@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 structure and metabolic function of the gut microbiota.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
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 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 pathways linked to host metabolic disease and increased 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. Moreover, 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. We concluded that the RSV-mediated alteration of gut microbiota and related gut metabolites 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},
doi = {10.1038/s41598-020-63214-1},
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 {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 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 ; R01 AI145989/AI/NIAID NIH HHS/United States ; R00 HD087523/HD/NICHD 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.},
}

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

@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 & microbe},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chom.2020.03.006},
pmid = {32298656},
issn = {1934-6069},
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.

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.

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).

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},
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 {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 & 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.},
}

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

@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 = {FAECAL CALPROTECTIN MAY PREDICT NEED OF MULTIPLE MICROBIOTA TRANSPLANTATION 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: Faecal microbiota transplantation (FMT) has proven to be very effective in recurrent Clostridium difficile infection (CDI) when compared to 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.

METHODS: FCC measurement was performed just before first procedure (T0) and two (T1) and five (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.

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 vs 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 to non-responders with a trend towards statistical significance (p=0.07). Correlation at T1 and T2 was not significant.

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 {pmid31850583,
year = {2020},
author = {Quigley, EMM},
title = {Commentary: faecal microbiota transplantation-from home brew to holy grail.},
journal = {Alimentary pharmacology & therapeutics},
volume = {51},
number = {1},
pages = {208-209},
doi = {10.1111/apt.15553},
pmid = {31850583},
issn = {1365-2036},
mesh = {*Clostridium Infections ; Colonoscopy ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; Humans ; Vancomycin ; },
}

*Clostridium Infections
Colonoscopy
*Enterocolitis, Pseudomembranous
Fecal Microbiota Transplantation
Humans
Vancomycin