Viewport Size Code:
Login | Create New Account


About | Classical Genetics | Timelines | What's New | What's Hot

About | Classical Genetics | Timelines | What's New | What's Hot


Bibliography Options Menu

Hide Abstracts   |   Hide Additional Links
Long bibliographies are displayed in blocks of 100 citations at a time. At the end of each block there is an option to load the next block.

Bibliography on: Fecal Transplantation

The Electronic Scholarly Publishing Project: Providing world-wide, free access to classic scientific papers and other scholarly materials, since 1993.


ESP: PubMed Auto Bibliography 22 Jan 2020 at 01:39 Created: 

Fecal Transplantation

Fecal Transplantion is a procedure in which fecal matter is collected from a tested donor, mixed with a saline or other solution, strained, and placed in a patient, by colonoscopy, endoscopy, sigmoidoscopy, or enema. The theory behind the procedure is that a normal gut microbial ecosystem is required for good health and that sometimes a benefucuial ecosystem can be destroyed, perhaps by antibiotics, allowing other bacteria, specifically Clostridium difficile to over-populate the colon, causing debilitating, sometimes fatal diarrhea. C. diff. is on the rise throughout the world. The CDC reports that approximately 347,000 people in the U.S. alone were diagnosed with this infection in 2012. Of those, at least 14,000 died. Fecal transplant has also had promising results with many other digestive or auto-immune diseases, including Irritable Bowel Syndrome, Crohn's Disease, and Ulcerative Colitis. It has also been used around the world to treat other conditions, although more research in other areas is needed. Fecal transplant was first documented in 4th century China, where the treatment was known as yellow soup.

Created with PubMed® Query: "(fecal OR faecal) (transplant OR transplantation)" OR "fecal microbiota transplant" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

RevDate: 2020-01-21

Barcán L, Ducatenzeiler L, Bangher MDC, et al (2020)

[Intersociety guidelines for diagnosis, treatment and prevention of Clostridioides difficile infections].

Medicina, 80 Suppl 1:1-32.

Clostridioides difficile infections (CDI) are among the leading causes of health care-associated infections. The epidemiology of CDI has undergone major changes in the last decade, showing an increase in incidence, severity, and rate of relapse. These guidelines were developed by specialists from four scientific societies: Sociedad Argentina de Infectología (SADI), Sociedad Argentina de Gastroenterología (SAGE), Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas (SADEBAC) and Asociación de Enfermeras en Control de Infecciones (ADECI). The objective of these intersociety guidelines is to provide national recommendations on CDI diagnosis, treatment and prevention. The methodology used involved the systematic review of the bibliography available up to December 2018, which was performed by six groups formed ad hoc: Epidemiology, Diagnosis, Treatment, Fecal Microbiota Transplantation, Special Populations, and Infection Control. The conclusions were presented and discussed in meetings held by each individual group and plenary meetings. In this document, updated diagnosis algorithms, therapeutic options (including fecal microbiota transplant) for immunocompetent and immunocompromised patients are presented, as well as strategies for the control of C. difficile infection.

RevDate: 2020-01-21

Chen QY, Tian HL, Yang B, et al (2020)

[Diagnosis and treatment of superior mesenteric artery compression syndrome secondary to chronic constipation (Lee's triad syndrome)].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 23(1):44-50.

Objective: To summarize the experience of diagnosis and treatment of superior mesenteric artery compression syndrome (SMACS) secondary to chronic constipation according to the concept of Lee's triad syndrome. Methods: The concept of Lee's triad syndrome: (1) clinical symptoms: triad of constipation, malnutrition, upper gastrointestinal obstruction (vomiting, difficulty in eating); (2) anatomical manifestations: with triple anatomy anomaly of transverse colon sagging, elevated spleen flexure, and mesentery arterial compression; (3) treatment: with triple treatment of enteral nutrition support, chest-knee posture and fecal microbiota transplantation. A descriptive cohort study was performed. According to Lee's triad syndrome criteria, clinical data of 78 patients with superior mesenteric artery compression syndrome secondary to chronic constipation in the Tenth People's Hospital of Tongji University and General Hospital of Eastern Theater Command from June 2004 to November 2018 were prospectively collected, including basic information, symptoms and signs, imaging findings, nutritional indicators, gastrointestinal quality of life index (GIQLI) and Wexner defecation score. The above parameters based on Lee's triad syndrome criteria were followed up and recorded at 1, 3, 6, 12 months after comprehensive treatment. Results: All the patients had Lee's triple symptoms of constipation, malnutrition, upper gastrointestinal obstruction (vomiting, eating difficulties), and triple anatomy anomaly of transverse colon sagging, elevated spleen curvature, and mesentery arterial compression before treatment. After triple treatment of enteral nutrition support, chest-knee posture, and fecal microbiota transplantation, 69 (88.5%) patients had a significant improvement of symptoms, and 9 patients had no significant improvement of symptoms and then eventually received surgery. The 69 cases without operation received follow-up for 12 months. All the patients eventually returned to normal eating, and upper gastrointestinal angiography and superior mesenteric artery imaging showed duodenal compression disappeared. After 1 month, the constipation-related indexes were improved. After 12 months, the number of autonomous defecation per week increased from 1.0±0.8 to 5.0±1.6 (P<0.001). The GIQLI score increased from 52.7±8.5 to 93.2±7.5 (P<0.001), and the Wexner score decreased from 19.1±2.5 to 6.2±2.1 (P<0.001). After 1 month, nutritional indexes were improved gradually. After 12 months, the BMI increased from (17.9±1.8) kg/m(2) to (21.0±1.3) kg/m(2), total protein increased from (65.2±5.7) g/L to (68.3±4.2) g/L, albumin increased from (32.1±5.1) g/L to (40.4±3.0) g/L, prealbumin increased from (163.2±53.7) mg/L to (259.1±45.6) mg/L, fibrinogen increased from (1.9±0.5) g/L to (2.4±0.5) g/L, whose differences were statistically significant (all P<0.001). Upper gastrointestinal angiography and superior mesenteric artery imaging showed duodenal compression were relieved. The angle between superior mesenteric artery and abdominal aorta increased from (17.4±3.8)° to (37.8±5.8)° (t=-22.26, P<0.001). Conclusion: When patients with SMACS secondary to chronic constipation have Lee's triple symptoms and triple anatomy anomaly, the triple combination treatment of enteral nutrition support, chest-knee posture and fecal microbiota transplantation should be applied.

RevDate: 2020-01-21
CmpDate: 2020-01-21

Anonymous (2019)

Faecal quality control.

Nature microbiology, 4(8):1243.

RevDate: 2020-01-20

Chen H, Zhang F, Li R, et al (2020)

Berberine regulates fecal metabolites to ameliorate 5-fluorouracil induced intestinal mucositis through modulating gut microbiota.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 124:109829 pii:S0753-3322(20)30019-6 [Epub ahead of print].

Berberine (BBR) is an isoquinoline alkaloid, which has been used in the treatment of intestinal mucositis. However, BBR on chemotherapy-induced mucositis in cancer patients remains largely unknown. Here, we investigated the effect of BBR on intestinal mucositis induced by 5-fluorouracil (5-Fu) using rat model. We detected the degree of intestinal mucosal damage and inflammatory response in 5-Fu treated rats with or without BBR administration, and investigated the changes of fecal metabolites and gut microbiota using 1H NMR spectroscopy and 16S rRNA. The mechanism was further explored by fecal microbiota transplantation (FMT). Results showed that BBR treated rats displayed less weight loss, lower diarrhea score and longer colon length in 5-Fu treated rats. Meanwhile, BBR treatment significantly increased the expression of Occludin in ileum and decreased the d-lactate content in serum. Moreover, the expression of IL-1β, IL-6 and TNF-α in ileum were suppressed by BBR treatment. The pattern of fecal metabolism changed obviously after treated with 5-Fu, which was reversed by BBR. Importantly, BBR significantly increased the levels of butyrate and glutamine in feces from 5-Fu treated rats. In terms of gut microbiota, BBR enriched the relative abundance of Firmicutes and decreased Proteobacteria at the phylum level. Meanwhile, BBR increased the propotion of unclassified_f_ Porphyromonadaceae, unclassified_f_ Lachnospiraceae, Lactobacillus, unclassified_o_ Clostridiales, Ruminococcus, Prevotella, Clostridium IV, and decreased Escherichia/Shigella at the genera level. Furthermore, principal component analysis (PCA) showed that fecal transplantation led to changes in fecal metabolites. Fecal transplantation from BBR treated rats had low diarrhea score, reduced inflammatory response in ileum, and relieved intestinal mucosal injury, which may be caused by the increased of butyrate level in fecal metabolites. In conclusion, our study provides evidence that BBR regulates fecal metabolites to ameliorate 5-Fu induced intestinal mucositis by modifying gut microbiota.

RevDate: 2020-01-20

Khoruts A, Hoffmann DE, FB Palumbo (2019)

The Impact of Regulatory Policies on the Future of Fecal Microbiota Transplantation.

The Journal of law, medicine & ethics : a journal of the American Society of Law, Medicine & Ethics, 47(4):482-504.

In this article, the authors explore the impact of a potential future regulatory decision by FDA whether or not to continue its enforcement discretion policy allowing physicians to perform, and stool banks to sell, stool product for fecal microbiota transplantation as a treatment for recurrent Clostridium Difficile infection without an Investigative New Drug (IND) application. The paper looks at the Agency's regulatory options in light of the current gut microbiota based products that are in the FDA pipeline for drug approval and the potential impact and repercussions of their approval on FDA action. In laying out FDA's options we consider the implications of market exclusivity and off-label use of newly approved drugs. Ultimately, we explore the potential impact of FDA's decision on patients, research, and innovation.

RevDate: 2020-01-20

DeLong K, Zulfiqar F, Hoffmann DE, et al (2019)

Vaginal Microbiota Transplantation: The Next Frontier.

The Journal of law, medicine & ethics : a journal of the American Society of Law, Medicine & Ethics, 47(4):555-567.

The success of fecal microbiota transplantation (FMT) as a treatment for Clostrioides difficile infection (CDI) has stirred excitement about the potential for microbiota transplantation as a therapy for a wide range of diseases and conditions. In this article, we discuss vaginal microbiota transplantation (VMT) as "the next frontier" in microbiota transplantation and identify the medical, regulatory, and ethical challenges related to this nascent field. We further discuss what we anticipate will be the first context for testing VMT in clinical trials, prevention of the recurrence of a condition referred to as bacterial vaginosis (BV). We also compare clinical aspects of VMT with FMT and comment on how VMT may be similar to or different from FMT in ways that may affect research design and regulatory decisions.

RevDate: 2020-01-20

Murray TS, J Herbst (2019)

The Ethics of Fecal Microbiota Transplant as a Tool for Antimicrobial Stewardship Programs.

The Journal of law, medicine & ethics : a journal of the American Society of Law, Medicine & Ethics, 47(4):541-554.

Multidrug resistant organisms (MDROs) are a public health threat that have reduced the effectiveness of many available antibiotics. Antimicrobial stewardship programs (ASPs) have been tasked with reducing antibiotic use and therefore the emergence of MDROs. While fecal microbiota transplant (FMT) has been proposed as therapy to reduce patient colonization of MDROs, this will require additional evidence to support an expansion of the current clinical indication for FMT. This article discusses the evidence and ethics of the expanded utilization of FMT by ASPs for reasons other than severe recurrent or refractory Clostridioides (formerly Clostridium) difficile infection.

RevDate: 2020-01-20

Scheeler A (2019)

Where Stool is a Drug: International Approaches to Regulating the use of Fecal Microbiota for Transplantation.

The Journal of law, medicine & ethics : a journal of the American Society of Law, Medicine & Ethics, 47(4):524-540.

Regulatory agencies vary widely in their classification of FMT, with significant impact on patient access. This article conducts a global survey of national regulations and collates existing FMT classification statuses, ultimately suggesting that the human cell and tissue product designation best fits FMT's characteristics and that definitional objectives to that classification may be overcome.

RevDate: 2020-01-17

Blanchaert C, Strubbe B, H Peeters (2019)

Fecal microbiota transplantation in ulcerative colitis.

Acta gastro-enterologica Belgica, 82(4):519-528.

BACKGROUND/STUDY AIMS: Fecal microbiota transplantation (FMT), a treatment aiming to restore dysbiosis by transferring stool from a healthy donor into the patient, has cure rates up to 90% in the management of recurrent Clostridium difficile (C. difficile) diarrhea. This paper tries to determine whether FMT is safe and effective in the treatment of ulcerative colitis, and what the potential characteristics could be of a 'super donor'.

METHODS: The PubMed database was searched using the term fecal microbiota transplantation inflammatory bowel disease. Only articles discussing the use of FMT in the treatment of ulcerative colitis were withheld. Finally, 31 original studies (10 case reports, 17 open label trials, 4 randomized controlled trials (RCTs)) and 1 meta-analysis were included.

RESULTS: So far 4 RCTs have investigated the effectiveness of FMT in treating UC. Three RCTs reported a significant difference between FMT and a control group, achieving clinical remission in 24 to 44% of patients (vs. 5 to 20% of patients in control groups). The meta-analysis confirms that significantly more patients in the FMT-group achieve clinical remission in comparison to patients in the control group (p=0,01) : 42,1% vs. 22,6%. The composition of the gut microbiota plays an important role in the success of FMT-treatment.

CONCLUSION: FMT seems to be a promising and safe therapy in the management of UC. Further research, with larger cohorts, will be needed to confirm this and to determine the optimal FMT procedure.

RevDate: 2020-01-19

Oliva A, Aversano L, De Angelis M, et al (2020)

Persistent Systemic Microbial Translocation, Inflammation, and Intestinal Damage During Clostridioides difficile Infection.

Open forum infectious diseases, 7(1):ofz507.

Background: Clostridioides difficile infection (CDI) might be complicated by the development of nosocomial bloodstream infection (n-BSI). Based on the hypothesis that alteration of the normal gut integrity is present during CDI, we evaluated markers of microbial translocation, inflammation, and intestinal damage in patients with CDI.

Methods: Patients with documented CDI were enrolled in the study. For each subject, plasma samples were collected at T0 and T1 (before and after CDI therapy, respectively), and the following markers were evaluated: lipopolysaccharide-binding protein (LPB), EndoCab IgM, interleukin-6, intestinal fatty acid binding protein (I-FABP). Samples from nonhospitalized healthy controls were also included. The study population was divided into BSI+/BSI- and fecal microbiota transplantation (FMT) +/FMT- groups, according to the development of n-BSI and the receipt of FMT, respectively.

Results: Overall, 45 subjects were included; 8 (17.7%) developed primary n-BSI. Markers of microbial translocation and intestinal damage significantly decreased between T0 and T1, however, without reaching values similar to controls (P < .0001). Compared with BSI-, a persistent high level of microbial translocation in the BSI+ group was observed. In the FMT+ group, markers of microbial translocation and inflammation at T1 tended to reach control values.

Conclusions: CDI is associated with high levels of microbial translocation, inflammation, and intestinal damage, which are still present at clinical resolution of CDI. The role of residual mucosal perturbation and persistence of intestinal cell damage in the development of n-BSI following CDI, as well as the possible effect of FMT in the restoration of mucosal integrity, should be further investigated.

RevDate: 2020-01-16

Ho J, Yeoh YK, Barua N, et al (2020)

Systematic review of human gut resistome studies revealed variable definitions and approaches.

Gut microbes [Epub ahead of print].

In this review, we highlight the variations of gut resistome studies, which may preclude comparisons and translational interpretations. Of 22 included studies, a range of 12 to 2000 antibiotic resistance (AR) genes were profiled. Overall, studies defined a healthy gut resistome as subjects who had not taken antibiotics in the last three to 12 months prior to sampling. In studies with de novo assembly, AR genes were identified based on variable nucleotide or amino acid sequence similarities. Different marker genes were used for defining resistance to a given antibiotic class. Validation of phenotypic resistance in the laboratory is frequently lacking. Cryptic resistance, collateral sensitivity and the interaction with repressors or promotors were not investigated. International consensus is needed for selecting marker genes to define resistance to a given antibiotic class in addition to uniformity in phenotypic validation and bioinformatics pipelines.

RevDate: 2020-01-19

Siranosian BA, Tamburini FB, Sherlock G, et al (2020)

Acquisition, transmission and strain diversity of human gut-colonizing crAss-like phages.

Nature communications, 11(1):280.

CrAss-like phages are double-stranded DNA viruses that are prevalent in human gut microbiomes. Here, we analyze gut metagenomic data from mother-infant pairs and patients undergoing fecal microbiota transplantation to evaluate the patterns of acquisition, transmission and strain diversity of crAss-like phages. We find that crAss-like phages are rarely detected at birth but are increasingly prevalent in the infant microbiome after one month of life. We observe nearly identical genomes in 50% of cases where the same crAss-like clade is detected in both the mother and the infant, suggesting vertical transmission. In cases of putative transmission of prototypical crAssphage (p-crAssphage), we find that a subset of strains present in the mother are detected in the infant, and that strain diversity in infants increases with time. Putative tail fiber proteins are enriched for nonsynonymous strain variation compared to other genes, suggesting a potential evolutionary benefit to maintaining strain diversity in specific genes. Finally, we show that p-crAssphage can be acquired through fecal microbiota transplantation.

RevDate: 2020-01-16

Xiang Q, Wu X, Pan Y, et al (2020)

Early-Life Intervention Using Fecal Microbiota Combined with Probiotics Promotes Gut Microbiota Maturation, Regulates Immune System Development, and Alleviates Weaning Stress in Piglets.

International journal of molecular sciences, 21(2): pii:ijms21020503.

Previous studies have suggested that immune system development and weaning stress are closely related to the maturation of gut microbiota. The early-life period is a "window of opportunity" for microbial colonization, which potentially has a critical impact on the development of the immune system. Fecal microbiota transplantation (FMT) and probiotics are often used to regulate gut microbial colonization. This study aims to test whether early intervention with FMT using fecal microbiota from gestation sows combined with Clostridium butyricum and Saccharomyces boulardii (FMT-CS) administration could promote the maturation of gut microbiota and development of immune system in piglets. Piglets were assigned to control (n = 84) and FMT-CS treatment (n = 106), which were treated with placebo and bacterial suspension during the first three days after birth, respectively. By 16S rRNA gene sequencing, we found that FMT-CS increased the α-diversity and reduced the unweighted UniFrac distances of the OTU community. Besides, FMT-CS increased the relative abundance of beneficial bacteria, while decreasing that of opportunistic pathogens. FMT-CS also enhanced the relative abundance of genes related to cofactors and vitamin, energy, and amino acid metabolisms during the early-life period. ELISA analysis revealed that FMT-CS gave rise to the plasma concentrations of IL-23, IL-17, and IL-22, as well as the plasma levels of anti-M.hyo and anti-PCV2 antibodies. Furthermore, the FMT-CS-treated piglets showed decreases in inflammation levels and oxidative stress injury, and improvement of intestinal barrier function after weaning as well. Taken together, our results suggest that early-life intervention with FMT-CS could promote the development of innate and adaptive immune system and vaccine efficacy, and subsequently alleviate weaning stress through promoting the maturation of gut microbiota in piglets.

RevDate: 2020-01-15

Antonelli M, Martin-Loeches I, Dimopoulos G, et al (2020)

Clostridioides difficile (formerly Clostridium difficile) infection in the critically ill: an expert statement.

Intensive care medicine pii:10.1007/s00134-019-05873-x [Epub ahead of print].

Clostridioides difficile (formerly Clostridium difficile) infection (CDI) represents a worrisome condition, often underestimated, with severe clinical presentations, frequently requiring intensive care unit (ICU) admission. The aim of the present expert statement was to give an overview of the management of CDI in critically ill patients, for whom CDI represents a redoubtable problem, in large part related to the use and abuse of antibiotics. The available knowledge about pathophysiology, risk factors, diagnosis and treatment concerning critical care patients affected by CDI has been reviewed, even though most of the existing information come from studies performed outside the ICU and the evidence on several issues in this specific context is scarce. The adoption of potential preventive and therapeutic strategies aimed to stem the phenomenon were discussed, including the faecal microbiota transplantation. This possibility could represent a highly interesting option in critically ill patients, but current evidence is limited and future well designed studies are needed. A special insight on the specific challenges that the ICU physicians may face caring for the critically ill patients with CDI was also proposed.

RevDate: 2020-01-15

Zhang PP, Li LL, Han X, et al (2020)

Fecal microbiota transplantation improves metabolism and gut microbiome composition in db/db mice.

Acta pharmacologica Sinica pii:10.1038/s41401-019-0330-9 [Epub ahead of print].

Fecal microbiota transplantation (FMT) has become an effective strategy to treat metabolic diseases, including type 2 diabetes mellitus (T2DM). We previously reported that the intestinal microbiome had significant difference between individuals with normal glucose tolerance and T2DM in Chinese Kazak ethnic group. In this study, we investigated the effects of transplanted fecal bacteria from Kazaks with normal glucose tolerance (KNGT) in db/db mice. The mice were treated with 0.2 mL of fecal bacteria solution from KNGT daily for 10 weeks. We showed that the fecal bacteria from KNGT successfully colonized in the intestinal tract of db/db mice detected on day 14. In the FMT-treated db/db mice, the levels of fasting blood glucose, postprandial glucose, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol were significantly downregulated, whereas high-density lipoprotein-cholesterol levels were upregulated. In the FMT-treated db/db mice, Desulfovibrio and Clostridium coccoides levels in gut were significantly decreased, but the fecal levels of Akkermansia muciniphila and colon histone deacetylase-3 (HDAC3) protein expression were increased. At 8 weeks, both intestinal target bacteria and HDAC3 were correlated with glycolipid levels; Akkermansia muciniphila level was positively correlated with HDAC3 protein expression (r = +0.620, P = 0.037). Our results suggest that fecal bacteria from KNGT could potentially be used to treat diabetic patients.

RevDate: 2020-01-15

Chang CW, Lee HC, Li LH, et al (2020)

Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer.

International journal of molecular sciences, 21(2): pii:ijms21020386.

FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), a 5-fluorouracil (5-FU)-based chemotherapy regimen, is one of most common therapeutic regimens for colorectal cancer. However, intestinal mucositis is a common adverse effect for which no effective preventive strategies exist. Moreover, the efficacy and the safety of fecal microbiota transplants (FMT) in cancer patients treated with anti-neoplastic agents are still scant. We investigated the effect of FMT on FOLFOX-induced mucosal injury. BALB/c mice implanted with syngeneic CT26 colorectal adenocarcinoma cells were orally administered FMT daily during and two days after five-day injection of FOLFOX regimen for seven days. Administration of FOLFOX significantly induced marked levels of diarrhea and intestinal injury. FMT reduced the severity of diarrhea and intestinal mucositis. Additionally, the number of goblet cells and zonula occludens-1 decreased, while apoptotic and NF-κB-positive cells increased following FOLFOX treatment. The expression of toll-like receptors (TLRs), MyD88, and serum IL-6 were upregulated following FOLFOX treatment. These responses were attenuated following FMT. The disrupted fecal gut microbiota composition was also restored by FMT after FOLFOX treatment. Importantly, FMT did not cause bacteremia and safely alleviated FOLFOX-induced intestinal mucositis in colorectal cancer-bearing mice. The putative mechanism may involve the gut microbiota TLR-MyD88-NF-κB signaling pathway in mice with implanted colorectal carcinoma cells.

RevDate: 2020-01-14

Harris C, Kim PT, Waterhouse D, et al (2020)

Precision medicine and gut dysbiosis.

Healthcare management forum [Epub ahead of print].

Clostridioides difficile Infection (CDI) is a leading cause of healthcare-associated infections in Canada, affecting the gastrointestinal tract which can lead to fever, abdominal pain, and diarrhea. Effective treatment for patients with Recurrent CDI (rCDI) can be achieved by Fecal Microbiota Transplantation (FMT) by introducing the gut micro-organisms of a healthy person (donor) into the bowel of the affected individual. Research has shown that an increase in the specific bacterial phyla post-FMT may be partly responsible for this gut restoration and elimination of disease. Furthermore, in understanding the key bacteria associated with successful FMT, full treatment plans can be developed for the individual needs of the patient by matching an infected individual with a donor possessing ideal microbiota for the specific patient. This development of precision medicine and more systematic adoption of FMT can be the next step toward more rapid resolution of rCDI.

RevDate: 2020-01-13

Ye Z, Wu C, Zhang N, et al (2020)

Altered gut microbiome composition in patients with Vogt-Koyanagi-Harada disease.

Gut microbes [Epub ahead of print].

Background: Vogt-Koyanagi-Harada (VKH) disease is a multisystemic autoimmune disorder characterized by granulomatous panuveitis. Gut microbiome has been considered to play a role in the pathogenesis of this disease but whether the alternation of gut microbiome was involved is unclear. This study was set up to identify abnormalities of gut microbiome composition in VKH disease.Results: Depleted butyrate-producing bacteria, lactate-producing bacteria and methanogens as well as enriched Gram-negative bacteria were identified in the active VKH patients, as well as in VKH patients of Mix enterotype and Bacteroides enterotype. Changes of gut microbiome in the VKH patients were partially restored after an immunosuppressive treatment. The disease susceptibility genotype HLA-DRA was associated with Bacteroides sp.2.1.33B, Paraprevotella clara, Alistipes finegoldii and Eubacterium eligens. A microbial marker profile including 40 disease-associated species was established to differentiate patients from controls. Another microbial marker profile including 37 species was found to be associated with the response to treatment. An animal experiment showed that transfer of gut microbiome from VKH patients could significantly exacerbate disease activity clinically and pathologically in the recipient mice.Conclusion: Our results revealed a distinct gut microbiome signature in VKH patients and showed an exacerbating effect of this gut microbiome on experimental autoimmune uveitis (EAU). We also developed two microbial marker profiles in differentiating VKH patients from healthy controls as well as predicting the effectiveness of treatment.

RevDate: 2020-01-10

Cheng YW, Phelps E, Nemes S, et al (2020)

Fecal Microbiota Transplant Decreases Mortality in Patients with Refractory Severe or Fulminant Clostridioides difficile Infection.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association pii:S1542-3565(20)30002-1 [Epub ahead of print].

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is recommended for recurrent Clostridioides difficile infection (CDI). FMT cures nearly 80% of patients with severe or fulminant CDI (SFCDI) when utilized in a sequential manner. We compared outcomes of hospitalized patients before and after implementation of an FMT program for SFCDI and investigated whether the changes could be directly attributed to the FMT program.

METHODS: We performed a retrospective analysis of characteristics and outcomes of patients hospitalized for SFCDI (430 hospitalizations) at a single center, from January 2009 through December 2016. We performed subgroup analyses of 199 patients with fulminant CDI and 110 patients with refractory SFCDI (no improvement after 5 or more days of maximal anti-CDI antibiotic therapy). We compared CDI-related mortality within 30 days of hospitalization, CDI-related colectomy, length of hospital stay, and readmission to the hospital within 30 days before (2009-2012) vs after (2013-2016) implementation of the inpatient FMT program.

RESULTS: CDI-related mortality and colectomy were lower after implementation of the FMT program. Overall, CDI-related mortality was 10.2% before the FMT program was implemented vs 4.4% after (P=.02). For patients with fulminant CDI, CDI-related mortality was 21.3% before the FMT program was implemented vs 9.1% after (P=.015). For patients with refractory SFCDI, CDI-related mortality was 43.2% before the FMT program vs 12.1% after (P < .001). The FMT program significantly reduced CDI-related colectomy in patients with SFCDI (6.8% before vs 2.7% after; P=.041), in patients with fulminant CDI (15.7% before vs 5.5% after; P=.017), and patients with refractory SFCDI (31.8% vs 7.6%; P = .001). The effect of FMT program implementation on CDI-related mortality remained significant for patients with refractory SFCDI after we accounted for the underlying secular trend (odds ratio, 0.09 for level change; P=.023).

CONCLUSIONS: An FMT program significantly decreased CDI-related mortality among patients hospitalized with refractory SFCDI.

RevDate: 2020-01-13

Zeng SL, Li SZ, Xiao PT, et al (2020)

Citrus polymethoxyflavones attenuate metabolic syndrome by regulating gut microbiome and amino acid metabolism.

Science advances, 6(1):eaax6208.

Metabolic syndrome (MetS) is intricately linked to dysregulation of gut microbiota and host metabolomes. Here, we first find that a purified citrus polymethoxyflavone-rich extract (PMFE) potently ameliorates high-fat diet (HFD)-induced MetS, alleviates gut dysbiosis, and regulates branched-chain amino acid (BCAA) metabolism using 16S rDNA amplicon sequencing and metabolomic profiling. The metabolic protective effects of PMFE are gut microbiota dependent, as demonstrated by antibiotic treatment and fecal microbiome transplantation (FMT). The modulation of gut microbiota altered BCAA levels in the host serum and feces, which were significantly associated with metabolic features and actively responsive to therapeutic interventions with PMFE. Notably, PMFE greatly enriched the commensal bacterium Bacteroides ovatus, and gavage with B. ovatus reduced BCAA concentrations and alleviated MetS in HFD mice. PMFE may be used as a prebiotic agent to attenuate MetS, and target-specific microbial species may have unique therapeutic promise for metabolic diseases.

RevDate: 2020-01-13

Li X, Chu Q, Huang Y, et al (2019)

Consortium of Probiotics Attenuates Colonization of Clostridioides difficile.

Frontiers in microbiology, 10:2871.

Clostridioides difficile infection (CDI) is increasing morbidity and mortality rates globally. Fecal microbiota transplantation (FMT), an effective therapy for eliminating Clostridioides difficile (C. difficile), cannot be used extensive due to a range of challenges. Probiotics thus constitutes a promising alternative therapy. In our study, we evaluated the effect of consortium of probiotics including five Lactobacilli strains and two Bifidobacterium strains on the colonization of toxigenic BI/NAP1/027 C. difficile in a mouse model. The results of 16S rRNA sequencing and targeted metabolomics showed the consortium of probiotics effectively decreased the colonization of C. difficile, changed the α- and β-diversity of the gut microbiota, decreased the primary bile acids, and increased the secondary bile acids. Spearman's correlation showed that some of the OTUs such as Akkermansia, Bacteroides, Blautia et al. were positively correlated with C. difficile numbers and the primary bile acids, and negatively correlated with the secondary bile acids. However, some of the OTUs, such as Butyricicoccus, Ruminococcus, and Rikenellaceae, were negatively correlated with C. difficile copies and the primary bile acids, and positively correlated with the secondary bile acids. In summary, the consortium of probiotics effectively decreases the colonization of C. difficile, probably via alteration of gut microbiota and bile acids. Our probiotics mixture thus offers a promising FMT alternative.

RevDate: 2020-01-10

Zhang T, Lu G, Zhao Z, et al (2020)

Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening.

Protein & cell pii:10.1007/s13238-019-00684-8 [Epub ahead of print].

Fecal microbiota transplantation (FMT) by manual preparation has been applied to treat diseases for thousands of years. However, this method still endures safety risks and challenges the psychological endurance and acceptance of doctors, patients and donors. Population evidence showed the washed microbiota preparation with microfiltration based on an automatic purification system followed by repeated centrifugation plus suspension for three times significantly reduced FMT-related adverse events. This washing preparation makes delivering a precise dose of the enriched microbiota feasible, instead of using the weight of stool. Intraperitoneal injection in mice with the fecal microbiota supernatant obtained after repeated centrifugation plus suspension for three times induced less toxic reaction than that by the first centrifugation following the microfiltration. The toxic reactions that include death, the change in the level of peripheral white blood cells, and the proliferation of germinal center in secondary lymphoid follicles in spleen were noted. The metagenomic next-generation sequencing (NGS) indicated the increasing types and amount of viruses could be washed out during the washing process. Metabolomics analysis indicated metabolites with pro-inflammatory effects in the fecal microbiota supernatant such as leukotriene B4, corticosterone, and prostaglandin G2 could be removed by repeated washing. Near-infrared absorption spectroscopy could be served as a rapid detection method to control the quality of the washing-process. In conclusion, this study for the first time provides evidence linking clinical findings and animal experiments to support that washed microbiota transplantation (WMT) is safer, more precise and more quality-controllable than the crude FMT by manual.

RevDate: 2020-01-17

Zhou A, Tang L, Zeng S, et al (2020)

Gut microbiota: A new piece in understanding hepatocarcinogenesis.

Cancer letters, 474:15-22 pii:S0304-3835(20)30002-1 [Epub ahead of print].

The gut microbiota forms a symbiotic relationship with the host and benefits the body in many critical aspects of life. However, immune system defects, alterations in the gut microbiota and environmental changes can destroy this symbiotic relationship and may lead to diseases, including cancer. Due to the anatomic and functional connection of the gut and liver, increasing studies show the important role of the gut microbiota in the carcinogenesis of hepatocellular carcinoma (HCC). In this manuscript, we review the available evidence and analyze some potential mechanisms of the gut microbiota, including bacterial dysbiosis, lipopolysaccharide (LPS), and genotoxins, in the progression and promotion of HCC. Furthermore, we discuss the possible therapeutic applications of probiotics, chemotherapy modulation, immunotherapy, targeted drugs and fecal microbiota transplantation (FMT) in targeting the gut microbiota.

RevDate: 2020-01-08

Glassner KL, Abraham BP, EMM Quigley (2020)

The microbiome and inflammatory bowel disease.

The Journal of allergy and clinical immunology, 145(1):16-27.

Inflammatory bowel disease (IBD) is a chronic immune-mediated disease affecting the gastrointestinal tract. IBD consists of 2 subtypes: ulcerative colitis and Crohn disease. IBD is thought to develop as a result of interactions between environmental, microbial, and immune-mediated factors in a genetically susceptible host. Of late, the potential role of the microbiome in the development, progression, and treatment of IBD has been a subject of considerable interest and enquiry. Indeed, studies in human subjects have shown that the gut microbiome is different in patients with IBD compared with that in healthy control subjects. Other evidence in support of a fundamental role for the microbiome in patients with IBD includes identification of mutations in genes involved in microbiome-immune interactions among patients with IBD and epidemiologic observations implicating such microbiota-modulating risk factors as antibiotic use, cigarette smoking, levels of sanitation, and diet in the pathogenesis of IBD. Consequently, there has been much interest in the possible benefits of microbiome-modulating interventions, such as probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and gene manipulation in the treatment of IBD. In this review we will discuss the role of the gut microbiome in patients with IBD; our focus will be on human studies.

RevDate: 2020-01-19

Lecronier M, Tashk P, Tamzali Y, et al (2020)

Gut microbiota composition alterations are associated with the onset of diabetes in kidney transplant recipients.

PloS one, 15(1):e0227373.

METHODS: Patients transplanted at our institution provided fecal samples before, and 3-9 months after KT. Fecal bacterial DNA was extracted and 9 bacteria or bacterial groups were quantified by qPCR.

RESULTS: 50 patients (19 controls without diabetes, 15 who developed New Onset Diabetes After Transplantation, NODAT, and 16 with type 2 diabetes before KT) were included. Before KT, Lactobacillus sp. tended to be less frequently detected in controls than in those who would become diabetic following KT (NODAT) and in initially diabetic patients (60%, 87.5%, and 100%, respectively, p = 0.08). The relative abundance of Faecalibacterium prausnitzii was 30 times lower in initially diabetic patients than in controls (p = 0.002). The relative abundance of F. prausnitzii of NODAT patients was statistically indistinguishable from controls and from diabetic patients. The relative abundance of Lactobacillus sp. increased following KT in NODAT and in initially diabetic patients (20-fold, p = 0.06, and 25-fold, p = 0.02, respectively). In contrast, the proportion of Akkermansia muciniphila decreased following KT in NODAT and in initially diabetic patients (2,500-fold, p = 0.04, and 50,000-fold, p<0.0001, respectively). The proportion of Lactobacillus and A. muciniphila did not change in controls between before and after the transplantation. Consequently, after KT the relative abundance of Lactobacillus sp. was 25 times higher (p = 0.07) and the relative abundance of A. muciniphila was 2,000 times lower (p = 0.002) in diabetics than in controls.

CONCLUSION: An alteration of the gut microbiota composition involving Lactobacillus sp., A. muciniphila and F. prausnitzii is associated with the glycemic status in KT recipients, raising the question of their role in the genesis of NODAT.

RevDate: 2020-01-06

Settanni CR, Ianiro G, Franceschi F, et al (2020)

From Regular Catharsis with Castor Oil to Recognizing the Importance of the Intestinal Microbiota.

Digestive diseases (Basel, Switzerland) pii:000505395 [Epub ahead of print].

The need to shed light on the unknown aspects of pathophysiology of common disorders, such as gastrointestinal ones, has led researchers through last decades to study and define the role of microorganisms within the human intestine and their interactions with the host. The progress of technology has permitted the overcoming of culture-based methods to study microbes and paved the way to molecular techniques, which allow the analysis of microbial genome, microbial functions, and metabolism. These progresses opened a window on the world of microbiology and permitted to deepen into the key role played by gut microbiota and dysbiosis in health status and diseases, both gastrointestinal and extraintestinal. So, scientists focused their attention in developing new strategies to restore eubiosis and to manipulate gut microbes by modifying dietary habits, administrating antibiotics, probiotics, and prebiotics and using fecal microbiota transplantation as treatment of gastrointestinal, infectious, cardiovascular, metabolic, immune-mediated, neuro-psychiatric, and oncological disorders. The next challenges will be to elaborate standard protocols with definite outcomes predictors in disease-specific settings.

RevDate: 2020-01-03

Wang Y, Zhang C, Lai J, et al (2020)

Noninvasive PET tracking of post-transplant gut microbiota in living mice.

European journal of nuclear medicine and molecular imaging pii:10.1007/s00259-019-04639-3 [Epub ahead of print].

PURPOSE: The role that gut microbiota plays in determining the efficacy of the anti-tumor effect of immune checkpoint inhibitors is gaining increasing attention, and fecal bacterial transplantation has been recognized as a promising strategy for improving or rescuing the effect of immune checkpoint inhibition. However, techniques for the precise monitoring of in vivo bacterial behaviors after transplantation are limited. In this study, we aimed to use metabolic labeling and subsequent positron emission tomography (PET) imaging to track the in vivo behaviors of gut bacteria that are responsible for the efficacy of anti-PD-1 therapy in living mice.

METHODS: The antitumor effect of anti-PD-1 blockade was tested in a low-response 4T1 syngeneic mouse model with or without fecal transplantation and with or without broad-spectrum antibiotic imipenem treatment. High-throughput sequencing analyses of 16S rRNA gene amplicons in feces of 4T1 tumor-bearing mice pre- and post-anti-PD-1 treatment were performed. The identified bacteria, Bacteroides fragilis (B. fragilis), were labeled with 64Cu and fluorescence dye by the metabolic labeling of N3 followed by click chemistry. In vivo PET and optical imaging of B. fragilis were performed in mice after oral gavage.

RESULTS: The disturbance of gut microbiota reduced the efficacy of anti-PD-1 treatment, and the combination of B. fragilis gavage and PD-1 blockade was beneficial in rescuing the antitumor effect of anti-PD-1 therapy. Metabolic oligosaccharide engineering and biorthogonal click chemistry resulted in successful B. fragilis labeling with 64Cu and fluorescence dye with high in vitro and in vivo stability and no effect on viability. PET imaging successfully detected the in vivo behaviors of B. fragilis after transplantation.

CONCLUSION: PET tracking by metabolic labeling is a powerful, noninvasive tool for the real-time tracking and quantitative imaging of gut microbiota. This strategy is clinically translatable and may also be extended to the PET tracking of other functional cells to guide cell-based adoptive therapies.

RevDate: 2020-01-05

Pierrard J, E Seront (2019)

Impact of the gut microbiome on immune checkpoint inhibitor efficacy-a systematic review.

Current oncology (Toronto, Ont.), 26(6):395-403.

Background: Immune checkpoint inhibitors (icis) are increasingly being used in clinical practice, improving outcomes for cancer patients. Preclinical models showed significant interaction between the gut microbiome (gm) and response to icis. However, that interaction remains unclear in clinical practice.

Methods: We performed a systematic review in medline to determine■ whether antibiotics affect ici efficacy,■ whether baseline gm composition and ici efficacy show any correlations,■ whether baseline gm composition and emergence of immune-related adverse events (iraes) show any correlations, and■ whether gm manipulation can alleviate the iraes.Included publications had to be written in English or French and had to describe a quantifiable link between gm composition or its modification and the response to icis or the occurrence of iraes, or both.

Results: Of 1451 articles published before December 2018, 13 publications met the inclusion criteria. Five full-text articles and two abstracts highlighted a negative effect of antibiotics on ici efficacy. The composition of the gm was associated with ici efficacy in five full-text articles and one abstract, and with iraes in two full-text articles. In 2 cases, fecal microbiota transplantation was reported to reduce immune colitis.

Conclusions: If possible, antibiotics should be avoided before ici treatment because of their negative effect on ici anticancer efficacy. No specific commensal bacterium was associated with ici efficacy, but an intact gm with high bacterial diversity and a good ratio of "responder-associated" bacteria to "non-responder-associated" bacteria seem to be correlated with better patient outcomes. Fecal microbiota transplantation is a promising technique for reducing ici-associated colitis.

RevDate: 2020-01-08

Goloshchapov OV, Olekhnovich EI, Sidorenko SV, et al (2019)

Long-term impact of fecal transplantation in healthy volunteers.

BMC microbiology, 19(1):312.

BACKGROUND: Fecal microbiota transplantation (FMT) has been recently approved by FDA for the treatment of refractory recurrent clostridial colitis (rCDI). Success of FTM in treatment of rCDI led to a number of studies investigating the effectiveness of its application in the other gastrointestinal diseases. However, in the majority of studies the effects of FMT were evaluated on the patients with initially altered microbiota. The aim of our study was to estimate effects of FMT on the gut microbiota composition in healthy volunteers and to monitor its long-term outcomes.

RESULTS: We have performed a combined analysis of three healthy volunteers before and after capsule FMT by evaluating their general condition, adverse clinical effects, changes of basic laboratory parameters, and several immune markers. Intestinal microbiota samples were evaluated by 16S rRNA gene and shotgun sequencing. The data analysis demonstrated profound shift towards the donor microbiota taxonomic composition in all volunteers. Following FMT, all the volunteers exhibited gut colonization with donor gut bacteria and persistence of this effect for almost ∼1 year of observation. Transient changes of immune parameters were consistent with suppression of T-cell cytotoxicity. FMT was well tolerated with mild gastrointestinal adverse events, however, one volunteer developed a systemic inflammatory response syndrome.

CONCLUSIONS: The FMT leads to significant long-term changes of the gut microbiota in healthy volunteers with the shift towards donor microbiota composition and represents a relatively safe procedure to the recipients without long-term adverse events.

RevDate: 2020-01-08

Hantschel J, Weis S, Schäfer KH, et al (2019)

Effect of endometriosis on the fecal bacteriota composition of mice during the acute phase of lesion formation.

PloS one, 14(12):e0226835.

Accumulating evidence indicates that there is an interaction between the gut microbiota and endometriotic lesions. The new formation of these lesions is associated with stem cell recruitment, angiogenesis and inflammation, which may affect the composition of the gut microbiota. To test this hypothesis, we herein induced endometriotic lesions by transplantation of uterine tissue fragments from green fluorescent protein (GFP)+ donor mice into the peritoneal cavity of GFP- C57BL/6 wild-type mice. Sham-transplanted animals served as controls. Fecal pellets of the animals were collected 3 days before as well as 7 and 21 days after the induction of endometriosis to analyze the composition of the gut microbiota by means of 16S ribosomal RNA gene sequencing. The transplantation of uterine tissue fragments resulted in the establishment of endometriotic lesions in all analyzed mice. These lesions exhibited a typical histomorphology with endometrial glands surrounded by a vascularized stroma. Due to their bright GFP signal, they could be easily differentiated from the surrounding GFP- host tissue. Bacterial 16S rRNA genes were successfully PCR-amplified from the DNA extracts of all obtained mice fecal samples. However, no significant effect of endometriosis induction on the composition of the bacterial microbiota was detected with our experimental setup. Our findings allow careful speculation that endometriosis in mice does not induce pronounced dysbiosis during the acute phase of lesion formation.

RevDate: 2019-12-30

Schepper JD, Collins F, Rios-Arce ND, et al (2019)

Involvement of the gut microbiota and barrier function in glucocorticoid induced osteoporosis.

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [Epub ahead of print].

Glucocorticoids (GCs) are potent immune-modulating drugs with significant side effects, including glucocorticoid-induced osteoporosis (GIO). GCs directly induce osteoblast and osteocyte apoptosis but also alter intestinal microbiota composition. While the gut microbiota is known to contribute to the regulation of bone density, its role in GIO has never been examined. To test this, male C57/Bl6J mice were treated 8-weeks with GC (prednisolone, GC-Tx) in the presence or absence of broad-spectrum antibiotic treatment (ABX) to deplete the microbiota. Long-term ABX prevented GC-Tx-induced trabecular bone loss, demonstrating the requirement of gut microbiota for GIO. Treatment of GC-Tx mice with a probiotic (Lactobacillus reuteri, LR) prevented trabecular bone loss. Microbiota analyses indicated that GC-Tx changed the abundance of Verrucomicobiales and Bacteriodales phylums and random forest analyses indicated significant differences in abundance of Porphyromonadaceae and Clostridiales OTUs between groups. Furthermore, transplantation of GC-Tx mouse fecal material into recipient naïve, untreated WT mice caused bone loss, supporting a functional role for microbiota in GIO. We also report that GC caused intestinal barrier breaks, as evidence by increased serum endotoxin level (2.4-fold), that were prevented by LR and ABX treatments. Enhancement of barrier function with a mucus supplement prevented both GC-Tx-induced barrier leakage and trabecular GIO. In bone, treatment with ABX, LR or a mucus supplement reduced GC-Tx-induced osteoblast and osteocyte apoptosis. GC-Tx suppression of Wnt10b in bone was restored by the LR and MDY treatments as well as microbiota depletion. Finally, we identified that bone-specific Wnt10b overexpression prevented GIO. Taken together, our data highlight the previously unappreciated involvement of the gut microbiota and intestinal barrier function in trabecular GIO pathogenesis (including Wnt10b suppression and osteoblast and osteocyte apoptosis) and identify the gut as a novel therapeutic target for preventing GIO. This article is protected by copyright. All rights reserved.

RevDate: 2020-01-02

Wang Y, Zheng F, Liu S, et al (2019)

Research Progress in Fecal Microbiota Transplantation as Treatment for Irritable Bowel Syndrome.

Gastroenterology research and practice, 2019:9759138.

Irritable bowel syndrome is a functional disorder characterized by abdominal pain or discomfort associated with altered bowel habits. Due to the uncertainty of the pathogenesis of IBS and the diversity of its clinical manifestations, IBS cannot be completely cured. Increasing evidence suggests the key role of altered intestinal microbiota in the pathogenesis of IBS. Therefore, attention is being shifted to adjusting the changes in intestinal microbiota to control IBS symptoms. Fecal microbiota transplantation (FMT), antibiotics, probiotics, and synbiotics are currently often employed as treatment for IBS. And FMT is the most significant therapeutic efficacy with the least number of side effects. FMT provides a creative way to restore the abnormal gut microbiome in patients with IBS. But although current clinical studies confirm the effectiveness of FMT in the treatment of IBS, they are short-term studies of small samples, and there is still a lack of large-scale long-term studies. In this paper, we review the intestinal microbiota changes of IBS, the common methods of treating IBS with intestinal microbes, and the research status of FMT for the treatment of IBS. Finally, we put forward some opinions on the future research direction of FMT treatment of IBS.

RevDate: 2019-12-29

Reigadas E, Bouza E, Olmedo M, et al (2019)

Faecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection: Experience with Lyophilized Oral Capsules.

The Journal of hospital infection pii:S0195-6701(19)30543-2 [Epub ahead of print].

BACKGROUND: Faecal microbiota transplantation (FMT) is a highly effective approach for refractory and recurrent Clostridioides difficile infection (CDI). Despite its excellent efficacy, FMT is not yet a routine procedure in most centres. There is very little experience with FMT based on lyophilized capsules, and data from European institutions are lacking. Here, we describe our experience with FMT to treat recurrent CDI using lyophilized oral capsules.

METHODS: We analyzed a prospectively recorded single-center case series of patients with recurrent CDI who underwent FMT between January 2018 and May 2019. The primary outcome was defined as resolution of CDI without recurrences over a 2-month period. Overall resolution was defined as resolution of diarrhea without recurrence of CDI within 2 months after a further cycle of FMT. The FMT process involved oral ingestion of 4-5 lyophilized capsules in a single dose. All stool donors were rigorously screened.

RESULTS: FMT was performed in 32 patients. There were no procedure-related adverse events, and no complications were observed. Primary cure was achieved in 81.3% of patients, and the overall cure rate was 87.5%. FMT via lyophilized capsules was well tolerated. No FMT procedure-related adverse events and no further complications were observed for lyophilized capsule FMT.

CONCLUSIONS: Our initial clinical experience suggests that FMT based on oral lyophilized preparations is a safe, well-tolerated, and highly effective treatment for recurrent CDI. Administration of oral lyophilized capsules seems feasible in hospital routine and will enable FMT to be more widely used.

RevDate: 2019-12-27

Anonymous (2019)

Addendum for: Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection and Other Conditions in Children: A Joint Position Paper From the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Journal of pediatric gastroenterology and nutrition [Epub ahead of print].

RevDate: 2020-01-08
CmpDate: 2019-12-31

Ichikawa M, Sujino T, T Kanai (2019)

[The Relationship between Gut Microbiome, Immune System, and Cancer].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(12):1807-1813.

Various microbes having been living in our intestine and forming the gut microbiome. When dysbiosis which is typically characterized by reduced microbial diversity occurs, many types of diseases are triggered in our bodies. Recently, relationship between gut microbiome and our immune function are discovered gradually. From this view point, the gut microbiome may have an influence on cancer medicine such as development, therapy(immune checkpoint blockade or chemotherapy), and therapeutic toxicity. In real clinical practice, this influence is reported in some cases such as colorectal cancer and other malignancies. In the near future, the approach from gut microbiome may be a clue to improve the existent cancer diagnosis and therapy. In addition, the modulation of gut microbiome in itself, for example fecal microbiota transplant(FMT), probiotics, and limited usage of antibiotics, is expected to be hints for cancer medicine, though this is not yet established and further studies are needed.

RevDate: 2020-01-20

Johnsen PH, Hilpüsch F, Valle PC, et al (2019)

The effect of fecal microbiota transplantation on IBS related quality of life and fatigue in moderate to severe non-constipated irritable bowel: Secondary endpoints of a double blind, randomized, placebo-controlled trial.

EBioMedicine, 51:102562 pii:S2352-3964(19)30772-8 [Epub ahead of print].

BACKGROUND: Severity in irritable bowel syndrome (IBS) is associated to impaired quality of life and fatigue. Fecal microbiota transplantation (FMT) induces significant relief in gastro-intestinal related complaints. The objective was to evaluate the effect of FMT on the secondary endpoints: IBS-related quality of life and fatigue in patients with non-constipated IBS.

METHOD: In this double-blind randomized placebo-controlled, parallel-group, single-center study, we enrolled patients with non-constipated IBS, defined by the ROME 3 criteria. We randomly assigned participants (2:1) in blocks of six to active or placebo FMT. Responder in fatigue and quality of life were defined as a decrease of 20 points in total Fatigue Impact Scale score, and improvement of 14 points in the IBS-quality of life questionnaire, respectively. In a modified-intention-to-treat population, we excluded participants who did not undergo treatment or who were diagnosed with any other disease by pinch biopsies during the treatment procedure.

FINDINGS: Between Jan1, and Oct 30, 2015, we recruited 90 participants and randomly assigned them to active treatment (n = 60) or placebo (n = 30). Three participants did not undergo FMT and four were excluded after diagnosis of microscopic colitis, leaving 83 for final modified intention-to-treat analysis (55 in the active treatment group and 28 in the placebo group). Significant improvement in QoL (Odds ratio (OR) 3,801; confidence interval (CI) = 1,309-11,042 p = 0.011) and fatigue (OR = 4,398; CI = 1,175-16,468 and p = 0,020) was found at six months. Absence of other self reported functional disorders and presence of depression at baseline is suggested to predict a lasting effect of FMT in QoL and fatigue, respectively.

INTERPRETATION: FMT induced significant relief in quality of life and fatigue. Results suggest a lasting effect of FMT in subgroups that should be further investigated in future studies. Funding Helse Nord, Norway and the Norwegian Centre of Rural Medicine, University of Tromsø, Norway.

RevDate: 2020-01-14
CmpDate: 2020-01-14

Wei Y, Li N, Xing H, et al (2019)

Effectiveness of fecal microbiota transplantation for severe diarrhea after drug-induced hypersensitivity syndrome.

Medicine, 98(52):e18476.

The aim of this study was to assess effectiveness of fecal microbiota transplantation (FMT) in treating intestinal failure associated with drug-induced hypersensitivity syndrome (DIHS).A 32-year-old Chinese woman, who developed DIHS-associated multiple organ dysfunction syndrome (MODS) manifesting as combined dysfunction of the intestine, liver, and kidney, was treated with 4 times of FMT at a frequency of once every 6 days. The structure and composition of the patient's fecal microbiota were analyzed by 16S rRNA-based molecular techniques. The clinical outcomes after FMT treatment were assessed by abdominal contrast-enhanced computed tomography (CT), characterization of fecal microbiota, measurement of serum inflammatory markers, and other clinical examinations.After 4 rounds of FMT were administered, the patient showed dramatic improvement in MODS and severe diarrhea with these clinical conditions under control. We consistently observed significant alteration in her gut microbiota, mainly involving considerable enrichment in Firmicutes members and depletion of Proteobacteria opportunistic organisms. Moreover, this reconstituted bacterial community composition correlated with fecal output, T helper cells, and inflammatory markers. Abdominal contrast-enhanced CT scans before and after FMT indicated significant improvement in inflammation and edema within the small intestine and colon of the patient. Notably, after completion of the fourth FMT, the level of inflammation in the intestine and colon had returned to normal. Over 6 months of follow-up, the intestinal mucous remained normal.Our results represent a breakthrough in the clinical management of MODS and suggest new therapeutic avenues to pursue for microbiota-related indications.

RevDate: 2020-01-08

Heimesaat MM, Mrazek K, S Bereswill (2019)

Murine fecal microbiota transplantation lowers gastrointestinal pathogen loads and dampens pro-inflammatory immune responses in Campylobacter jejuni infected secondary abiotic mice.

Scientific reports, 9(1):19797.

Conventional mice are protected from Campylobacter jejuni infection by the murine host-specific gut microbiota composition. We here addressed whether peroral fecal microbiota transplantation (FMT) might be an antibiotics-independent option to lower even high gastrointestinal C. jejuni loads in the infected vertebrate host. To address this, secondary abiotic mice were generated by broad-spectrum antibiotic treatment and perorally infected with C. jejuni by gavage. One week later, mice were stably colonized with more than 109 C. jejuni and subjected to peroral FMT from murine donors on three consecutive days. Two weeks post-intervention, gastrointestinal C. jejuni loads were up to 7.5 orders of magnitude lower following murine FMT versus mock challenge. Remarkably, FMT reversed C. jejuni induced colonic epithelial apoptosis, but enhanced proliferative and regenerative responses in the colon thereby counteracting pathogenic cell damage. Furthermore, FMT dampened both, innate and adaptive immune cell responses in the large intestines upon C. jejuni infection that were accompanied by less C. jejuni-induced colonic nitric oxide secretion. Our study provides strong evidence that novel probiotic formulations developed as alternative option to FMT in severe intestinal inflammatory morbidities including Clostridoides difficile infection might be effective to treat campylobacteriosis and lower pathogen loads in colonized vertebrates including farm animals.

RevDate: 2020-01-09

Ocansey DKW, Wang L, Wang J, et al (2019)

Mesenchymal stem cell-gut microbiota interaction in the repair of inflammatory bowel disease: an enhanced therapeutic effect.

Clinical and translational medicine, 8(1):31.

BACKGROUND: Several investigations affirm that, patients with inflammatory bowel disease (IBD) exhibit dysbiosis characterized by restricted biodiversity and imbalanced bacterial composition intertwined with immune dysregulation. The interaction between stem cells and gut microbiota is a novel and highly promising field that could add up to a better understanding of the gut physiology, as well as therapeutic improvement towards diseases like IBD. Through direct contact or release of products and/or metabolites, gut bacteria regulate gut homeostasis, damage repair, regeneration and differentiation of stem cells. In the same way, mesenchymal stem cells (MSCs) produce similar effects including restoration of gut-microbiome composition. BODY: We reviewed the anti-inflammatory, antimicrobial, pathogenic bacterial clearance, proliferation and tissue remodeling effects of mesenchymal stem cells (MSCs) and fecal microbiota transplantation (FMT) as separate transplants in IBD, and the outcome of the interaction between MSCs and gut microbiota.

CONCLUSION: The two therapies share several points of connection in therapeutics with enhanced functionalities in their interaction with each other. Focused investigations of MSC-gut bacteria interactions could lead to a novel discovery in therapeutics. We also anticipate an improved clinical remission rate in a combined FMT-MSC transplantation approach in IBD than the current single FMT or MSC approach.

RevDate: 2020-01-20

Woldeamlak B, Yirdaw K, B Biadgo (2019)

Role of Gut Microbiota in Type 2 Diabetes Mellitus and Its Complications: Novel Insights and Potential Intervention Strategies.

The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi, 74(6):314-320.

Type 2 diabetes mellitus has become one of the fastest growing public health problems worldwide. The disease is believed to involve a complex process involving genetic susceptibility and environmental factors. The human intestine harbors hundreds of trillions of bacteria, as well as bacteriophage particles, viruses, fungi, and archaea, which constitute a complex and dynamic ecosystem referred to as the gut microbiota. Increasing evidence has indicated changes in the gut microbiota composition or function in type 2 diabetic patients. An analysis of 'dysbiosis' enables the detection of alterations in the specific bacteria, clusters of bacteria, or bacterial functions associated with the occurrence of type 2 diabetes. These bacteria are involved predominantly in the control of inflammation and energy homeostasis. This review attempts to show that the gut microbiota are important factors for the occurrence of type 2 diabetes and are important for the treatment of gut microbiota dysbiosis through bariatric surgery, fecal microbiota transplantation, prebiotics, and probiotics.

RevDate: 2020-01-09

Yan T, Nian T, Liao Z, et al (2019)

Antidepressant effects of a polysaccharide from okra (Abelmoschus esculentus (L) Moench) by anti-inflammation and rebalancing the gut microbiota.

International journal of biological macromolecules, 144:427-440 pii:S0141-8130(19)39679-5 [Epub ahead of print].

The present study aimed to evaluate the antidepressant-like effect of a polysaccharide (OP), which is isolated from okra (Abelmoschus esculentus (L) Moench), in CUMS-induced mice and its possible mechanisms. OPT, FST and TST were employed to examine the anxiety and depressive behavior in CUMS-induced mice and fecal microbiota transplantation (FMT) CUMS-induced mice, while proinflammatory cytokines, TLR4/NF-κB pathway and MAPKs signaling were detected in both CUMS-induced mice and LPS-induced BV2 cells. The results showed that anxiety- and depressive-like behaviors, gut microbiota dysbiosis and changes of SCFAs, and activation of inflammatory reactions in the colon, serum, and hippocampus of CUMS-induced mice, as well as activation of inflammatory reactions in BV2 cells, could be alleviated by the treatment of OP. The mice that were colonized by OP microbiota showed improved anxiety and depressive behaviors and lower inflammatory response. Furthermore, OP inhibited the expression of TLR4, the nuclear translocation of NF-κB and high levels of proinflammatory cytokines, and enhanced the MAPKs signaling, these effects of OP also observed in LPS-induced BV2 cells. Above all, suggested that the potential mechanism of the antidepressant-like effects of OP was closely correlated with the bidirectional communication of microbiota-gut-brain axis via regulation of inflammation response.

RevDate: 2020-01-08

Lara A, C Espadín (2019)

[Considerations should be taken into account to avoid complexities in the transplantation of fecal microbiota.].

Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia, 36(5):674.

RevDate: 2020-01-08

Quera R, Sedano R, Espinoza R, et al (2019)

[Transplantation of fecal matter in octogenarian patients with recurrent Clostridioides difficile infection].

Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia, 36(4):536-540.

Clostridioides (formerly Clostridium) difficile infection has become a major health problem due to the increase in its incidence, severity, and recurrence. In this last scenario, age over 65 has been associated with a more unfavorable evolution. Risk factors such as the presence of altered immunity, comorbidities, malnutrition, polypharmacy, and changes in the intestinal microbiota would explain this higher risk in this group of patients. On the other hand, fecal microbiota transplantation (FMT) is an effective strategy in the treatment of recurrent Clostridioides difficile infection when standard therapy fails. Recently published guidelines suggest that this strategy can be used from the second recurrence. However, few studies have evaluated the results of the FMT in patients over 65 years old, and for our knowledge, there is limited national experience in this group of patients. We present two cases of TMF in octogenarian patients with a recurrent infection due to Clostridioides difficile, with satisfactory recovery at the long term.

RevDate: 2020-01-07

Hoffmann-Vold AM, Fretheim H, Didriksen H, et al (2020)

The potential of fecal microbiota transplantation in systemic sclerosis.

RevDate: 2019-12-30

Liwinski T, E Elinav (2019)

Harnessing the microbiota for therapeutic purposes.

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Epub ahead of print].

The myriads of microorganisms colonizing the human host (microbiome) affect virtually every aspect of its physiology in health and disease. The past decade witnessed unprecedented advances in microbiome research. The field rapidly transitioned from descriptive studies to deep mechanistic insights into host-microbiome interactions. This offers the opportunity for microbiome-targeted therapeutic manipulation. Currently, several strategies of microbiome-targeted interventions are intensively explored. Best evidence from human randomized clinical trials is available for fecal microbiota transplantation (FMT). However, patient eligibility as well as long-term efficacy and safety are not sufficiently defined. Therefore, there is currently no officially approved indication for FMT. Probiotics (live microorganisms) have long been discussed as a means to aid human health but have yielded varying results. Emerging techniques utilizing microbiota-targeted diets, small microbial molecules, recombinant bacteriophages, and precise control of strain abundance recently yielded promising results but require further investigation. The rapid technological progress of "omics" tools spurs advances in personalized medicine. Understanding and integration of interindividual microbiome variability holds potential to promote personalized preventive and therapeutic approaches. Emerging evidence points towards the microbiome as an important player having an impact on transplantation outcomes. Microbiome-targeted interventions have potential to aid against the many challenges faced by transplant recipients.

RevDate: 2019-12-20

Vojvodic A, Peric-Hajzler Z, Matovic D, et al (2019)

Gut Microbiota and the Alteration of Immune Balance in Skin Diseases: From Nutraceuticals to Fecal Transplantation.

Open access Macedonian journal of medical sciences, 7(18):3034-3038.

The P.N.E.I. (Psycho-Neuro-Endocrine-Immunology) approach is represented by the interdisciplinary concept of bidirectional cross-talk between the psycho-neuro-endocrine and immune systems, which can influence the immune response. The well-known Gut-Brain Axis and the Gut-Skin Axis can be merged in a bigger network- the Gut-Brain-Skin Axis, with complex regulation by cytokines, neuro-peptides, neuro-hormones and another messenger (signalling) molecules and maybe the most important modulator of the Gut-Brain-Skin Axis/ the gut microbiota. The role of gut bacterial homeostasis is very important, and the homeostatic imbalance of the immune response may be a relevant etiologic/pathophysiologic factor for extra-intestinal and intestinal inflammatory, allergic and autoimmune diseases. The Low Dose Cytokines Medicine (LDM) is an innovative therapeutic approach. It is based on the most advanced knowledge in molecular biology and low dose pharmacology with the primary outcome. The SKA (Sequential Kinetic Activation) technology, codified and standardised by GUNA S.p.a. -Italy- makes the low doses of signalling molecules able to be active even below the minimum dose classically considered as effective and the significative efficacy of orally administered low-dose signalling molecules is the most representative aspect of LDM. The Physiologic Nutraceuticals and the Low Dose Medicine are two of the most promising approaches for the treatment of skin diseases based on the rebalance of the immune response and the recovery of gut dysbiosis.

RevDate: 2020-01-20

Xu J, Song J, Zhang Y, et al (2019)

Jinzhi protects lipopolysaccharide-treated mice against mortality by repairing intestinal mucosal barrier damage and intestinal microecology.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 123:109749 pii:S0753-3322(19)35371-5 [Epub ahead of print].

OBJECTIVE: Intestinal mucosal barrier damage is an important mechanism for the development of sepsis and multiple organ dysfunction syndrome. At present, there are no satisfactory and effective methods for the protection of the intestinal mucosal barrier. Jinzhi, the first fecal microbiota transplantation worldwide, is often used to treat critically ill patients; however, the specific mechanism involved in this process remains unclear. The aim of this study was to investigate the therapeutic effect and mechanism of Jinzhi intervention on mice with sepsis induced through treatment with lipopolysaccharide (LPS).

METHODS: Mice were intraperitoneally injected with LPS to simulate intestinal mucosal barrier function damage in sepsis; intervention was performed through the oral administration of Jinzhi. The effect of Jinzhi on LPS-induced sepsis was analyzed by comparing the vital signs and survival rate of mice under different treatments. Pathological staining and enzyme-linked immunosorbent assay were used to identify the effects of LPS or treatment with Jinzhi on the intestinal mucosal barrier in mice. The effect of LPS or treatment with Jinzhi on the intestinal flora was analyzed via 16S rRNA gene sequencing of ileal contents.

RESULTS: Immunohistochemistry and enzyme-linked immunosorbent assay showed that treatment with LPS increased levels of inflammatory factors (interleukin-1α, interleukin-6, tumor necrosis factor-α), caspase-3, and caspase-8 in the serum and ileum, and destroyed the tight junction between epithelial cells. Intervention with Jinzhi reduced levels of serum LPS and tumor necrosis factor-α, and repaired the tight junction between epithelial cells. Furthermore, 16S rRNA gene sequencing analysis showed that treatment with Jinzhi improved the diversity and physiological function of the intestinal flora.

CONCLUSIONS: These results suggest that Jinzhi may be a promising option for the treatment of sepsis caused by LPS, and emphasize that Jinzhi exerts a recovery effect on the imbalance of intestinal flora.

RevDate: 2019-12-17

Hu H, Lin A, Kong M, et al (2019)

Intestinal microbiome and NAFLD: molecular insights and therapeutic perspectives.

Journal of gastroenterology pii:10.1007/s00535-019-01649-8 [Epub ahead of print].

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of dysregulated lipid and glucose metabolism, which is often associated with obesity, dyslipidemia and insulin resistance. In view of the high morbidity and health risks of NAFLD, the lack of effective cure has drawn great attention. In recent years, a line of evidence has suggested a close linkage between the intestine and liver diseases such as NAFLD. We summarized the composition and characteristics of intestinal microbes and reviewed molecular insights into the intestinal microbiome in development and progression of NAFLD. Intestinal microbes mainly include bacteria, archaea, viruses and fungi, and the crosstalk between non-bacterial intestinal microbes and human liver diseases should be paid more attention. Intestinal microbiota imbalance may not only increase the intestinal permeability to gut microbes but also lead to liver exposure to harmful substances that promote hepatic lipogenesis and fibrosis. Furthermore, we focused on reviewing the latest "gut-liver axis"-targeting treatment, including the application of antibiotics, probiotics, prebiotics, synbiotics, farnesoid X receptor agonists, bile acid sequestrants, gut-derived hormones, adsorbents and fecal microbiota transplantation for NAFLD. In this review, we also discussed the potential mechanisms of "gut-liver axis" manipulation and efficacy of these therapeutic strategies for NAFLD treatment.

RevDate: 2020-01-11

Herremans KM, Riner AN, Cameron ME, et al (2019)

The Microbiota and Cancer Cachexia.

International journal of molecular sciences, 20(24):.

Cancer cachexia is a multifactorial syndrome defined by weight loss, muscle wasting, and systemic inflammation. It affects the majority of patients with advanced cancer and is associated with poor treatment response, early mortality and decreased quality of life. The microbiota has been implicated in cancer cachexia through pathways of systemic inflammation, gut barrier dysfunction and muscle wasting. The imbalance of the microbiota, known as dysbiosis, has been shown to influence cancer cachexia. Bacteria that play beneficial and detrimental roles in the disease pathogenesis have been identified. The phenotype of cancer cachexia is associated with decreased levels of Lactobacillales and increased levels of Enterobacteriaceae and Parabacteroides. Currently, there are no treatment options that demonstrate increased survival or the quality of life in patients suffering from cancer cachexia. Through the manipulation of beneficial bacteria in the gut microbiota, different treatment options have been explored. Prebiotics and probiotics have been shown to improve outcomes in animal models of cachexia. Expounding on this mechanism, fecal microbiota transplant (FMT) holds promise for a future treatment of cancer cachexia. Further research is necessary to address this detrimental disease process and improve the lives of patients suffering from cancer cachexia.

RevDate: 2019-12-19

Keller JJ, Vehreschild MJ, Hvas CL, et al (2019)

Stool for fecal microbiota transplantation should be classified as a transplant product and not as a drug.

United European gastroenterology journal, 7(10):1408-1410.

RevDate: 2020-01-02

Hong AS, Yu WY, Hong JM, et al (2019)

Proton pump inhibitor in upper gastrointestinal fecal microbiota transplant: A systematic review and analysis.

Journal of gastroenterology and hepatology [Epub ahead of print].

BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) is used in recurrent Clostridioides difficile infections. However, protocols are facility dependent, and one variable is whether pre-procedural proton pump inhibitors (PPIs) are given. In theory, PPIs reduce acidity and protect the transplanted microbiome for the most potent dose. We conducted a systematic review to study the effect of PPIs on FMT delivered by upper gastrointestinal (GI) routes.

METHODS: We searched Pubmed/Medline, Cochrane Library, Embase, Scopus, and Web of Science through December 16, 2018 using variations of keywords "fecal microbiota transplant" and "Clostridium difficile infection." Two authors independently reviewed 4210 results and found 11 qualifying studies with data on upper GI FMT, use of PPIs, and the rate of treatment failure at follow-up.

RESULTS: Of 233 included patients, treatment failure occurred in 20.6% of those with use of PPIs versus 22.6% in the group without (relative risk 0.91; confidence interval 0.56-1.50). Limitations include the lack of studies directly comparing outcomes based on use of PPIs and inability to control for possible confounders such as chronic PPI use, amount of stool transplanted, and pre-FMT antibiotics.

CONCLUSIONS: We did not find evidence supporting a clinically significant benefit from routine use of PPIs in FMT protocol. It is possible that the theoretical benefit from improved survival of transplanted microbiota is offset by negative effects on the microbiome. We suggest that routine use of PPIs in upper GI FMT be reconsidered. Further investigation is needed to optimize protocols for safety and efficacy.

RevDate: 2019-12-12

Ebrahimzadeh Leylabadlo H, Ghotaslou R, Samadi Kafil H, et al (2019)

Non-alcoholic fatty liver diseases: from role of gut microbiota to microbial-based therapies.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology pii:10.1007/s10096-019-03746-1 [Epub ahead of print].

Non-alcoholic fatty liver disease (NAFLD) is the well-known disease of the liver in adults and children throughout the world. The main manifestations related to NAFLD are an unusual storage of lipid in hepatocytes (hepatic steatosis) and progression of inflammation for non-alcoholic steatohepatitis (NASH). NAFLD is described as a multifactorial complication due to the genetic predisposition, metabolic functions, inflammatory, gut microbiota (GM), and environmental factors. The GM dysregulation among these factors is correlated to NAFLD development. In recent decades, advanced microbial profiling methods are continuing to shed light on the nature of the changes in the GM caused by NASH and NAFLD. In the current review, we aim to perform a literature review in different library databases and electronic searches (Science Direct, PubMed, and Google Scholar) which were randomly obtained. This will be done in order to provide an overview of the relation between GM and NAFLD, and the role of prebiotics, probiotics, and fecal microbiota transplantation (FMT), as potential therapeutic challenges for NAFLD.

RevDate: 2019-12-18

Quaranta G, Sanguinetti M, L Masucci (2019)

Fecal Microbiota Transplantation: A Potential Tool for Treatment of Human Female Reproductive Tract Diseases.

Frontiers in immunology, 10:2653.

The gastro-intestinal tract is an extensive organ involved in several activities, with a crucial role in immunity. Billions of commensal and transient microorganisms, known as the gut microbiota, and potential pathogens, which are constantly stimulating intestinal immunity, colonize the intestinal epithelial surface. The gut microbiota may be regarded as analogous to a solid organ with multiple different functions. In the last decade, many studies have demonstrated that intestinal bacteria can be a decisive factor in the health-disease balance of the intestine, and they can also be responsible for illnesses in other locations. For this reason, fecal microbiota transplantation (FMT) represents an important therapeutic option for Clostridium difficile infections and hold promise for different clinical conditions, such as multiple sclerosis, autism, obesity, and other systemic diseases. FMT consists of the infusion of a fecal suspension from a healthy donor to a recipient in order to restore gut flora alterations. Similar to the gut, the female reproductive tract is an example of a very complex biological ecosystem. Recent studies indicate a possible relationship between the gut and female tract microbiota, associating specific intestinal bacteria patterns with genital female diseases, such as polycystic ovary syndrome (PCOS), endometriosis and bacterial vaginosis (BV). FMT could represent a potential innovative treatment option in this field.

RevDate: 2019-12-18

Freitag TL, Hartikainen A, Jouhten H, et al (2019)

Minor Effect of Antibiotic Pre-treatment on the Engraftment of Donor Microbiota in Fecal Transplantation in Mice.

Frontiers in microbiology, 10:2685.

Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI) and is also considered a potential treatment for a wide range of intestinal and systemic diseases. FMT corrects the microbial dysbiosis associated with rCDI, and the engraftment of donor microbiota is likely to play a key role in treatment efficacy. For disease indications other than rCDI, FMT treatment efficacy has been moderate. This may be partly due to stronger resilience of resident host microbiota in patients who do not suffer from rCDI. In rCDI, patients typically have undergone several antibiotic treatments prior to FMT, depleting the microbiota. In this study, we addressed the effect of broad-spectrum antibiotics (Ab) as a pre-treatment to FMT on the engraftment of donor microbiota in recipients. We conducted a pre-clinical study of FMT between two healthy mouse strains, Balb/c as donors and C57BL/6 as recipients, to perform FMT within the same species and to mimic interindividual FMT between human donors and patients. Microbiota composition was assessed with high-throughput 16S rDNA amplicon sequencing. The microbiota of Balb/c and C57BL/6 mice differed significantly, which allowed for the assessment of microbiota transplantation from the donor strain to the recipient. Our results showed that Ab-treatment depleted microbiota in C57BL/6 recipient mice prior to FMT. The diversity of microbiota did not recover spontaneously to baseline levels during 8 weeks after Ab-treatment, but was restored already at 2 weeks in mice receiving FMT. Interestingly, pre-treatment with antibiotics prior to FMT did not increase the overall similarity of the recipient's microbiota to that of the donor's, as compared with mice receiving FMT without Ab-treatment. Pre-treatment with Ab improved the establishment of only a few donor-derived taxa, such as Bifidobacterium, in the recipients, thus having a minor effect on the engraftment of donor microbiota in FMT. In conclusion, pre-treatment with broad-spectrum antibiotics did not improve the overall engraftment of donor microbiota, but did improve the engraftment of specific taxa. These results may inform future therapeutic studies of FMT.

RevDate: 2019-12-10

Tariq R, Disbrow MB, Dibaise JK, et al (2019)

Efficacy of Fecal Microbiota Transplantation for Recurrent C. Difficile Infection in Inflammatory Bowel Disease.

Inflammatory bowel diseases pii:5673067 [Epub ahead of print].

BACKGROUND: Clostridioides difficile infection (CDI) is associated with poor outcomes in inflammatory bowel disease (IBD) patients. Data are scarce on efficacy of fecal microbiota transplant (FMT) for recurrent CDI in IBD patients.

METHODS: We reviewed health records of IBD patients (18 years of age or older) with recurrent CDI who underwent FMT. Outcomes of FMT for CDI were assessed on the basis of symptoms and stool test results.

RESULTS: We included 145 patients (75 women [51.7%]; median age, 46 years). Median IBD duration was 8 (range, 0-47) years, 36.6% had Crohn disease, 61.4% had ulcerative colitis, and 2.1% had indeterminate colitis. Median number of prior CDI episodes was 3 (range, 3-20), and 61.4% had received vancomycin taper. Diarrhea resolved after FMT in 48 patients (33.1%) without further testing. Ninety-five patients (65.5%) underwent CDI testing owing to post-FMT recurrent diarrhea; 29 (20.0%) had positive results. After FMT, 2 patients received empiric treatment of recurrent CDI without symptom resolution, suggesting IBD was the cause of symptoms. The overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1-51) months. Forty-three patients (29.7%) had planned IBD therapy escalation after CDI resolution; none de-escalated or discontinued IBD therapy. Overall, 7.6% had worsening IBD symptoms after FMT that were treated as new IBD flares. No clinical predictors of FMT failure were identified.

CONCLUSIONS: Few patients had new IBD flare after FMT. Fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.

RevDate: 2020-01-08

Chavira A, Belda-Ferre P, Kosciolek T, et al (2019)

The Microbiome and Its Potential for Pharmacology.

Handbook of experimental pharmacology, 260:301-326.

The human microbiota (the microscopic organisms that inhabit us) and microbiome (their genes) hold considerable potential for improving pharmacological practice. Recent advances in multi-"omics" techniques have dramatically improved our understanding of the constituents of the microbiome and their functions. The implications of this research for human health, including microbiome links to obesity, drug metabolism, neurological diseases, cancer, and many other health conditions, have sparked considerable interest in exploiting the microbiome for targeted therapeutics. Links between microbial pathways and disease states further highlight a rich potential for companion diagnostics and precision medicine approaches. For example, the success of fecal microbiota transplantation to treat Clostridium difficile infection has already started to redefine standard of care with a microbiome-directed therapy. In this review we briefly discuss the nature of human microbial ecosystems and with pathologies and biological processes linked to the microbiome. We then review emerging computational metagenomic, metabolomic, and wet lab techniques researchers are using today to learn about the roles host-microbial interactions have with respect to pharmacological purposes and vice versa. Finally, we describe how drugs affect the microbiome, how the microbiome can impact drug response in different people, and the potential of the microbiome itself as a source of new therapeutics.

RevDate: 2019-12-18

Niina A, Kibe R, Suzuki R, et al (2019)

Improvement in Clinical Symptoms and Fecal Microbiome After Fecal Microbiota Transplantation in a Dog with Inflammatory Bowel Disease.

Veterinary medicine (Auckland, N.Z.), 10:197-201.

Purpose: Recently, fecal microbiota transplantation (FMT) has been tested in veterinary medicine as a treatment option for multiple gastrointestinal (GI) diseases, such as inflammatory bowel disease (IBD). However, there are no reports of changes in the microbial diversity of fecal microbiome after treatment with FMT in canine IBD cases. Moreover, little is known about the long-term efficacy and safety of FMT treatment for dogs. Herein, we present a case of canine intractable IBD treated with repeated, long-term FMT.

Patients and methods: The patient was a 10-year-old, neutered, male, 4-kg Toy Poodle with a prolonged history of vomiting and diarrhea. Fecal examination for pathogens was negative. Despite treatment with multiple antibacterial and antidiarrheal agents, the patient showed no improvement. Endoscopic mucus sampling diagnosed a case of lymphocytic-plasmacytic duodenitis, ie, idiopathic IBD. Eventually, we performed periodic, long-term fecal microbiota transplantation of fresh donor feces collected from a 4-year-old, 32.8-kg, neutered male Golden Retriever by rectal enema. Additionally, we performed 16S rRNA sequence analysis, before and after FMT, to evaluate the microbiome diversity.

Results: Fecal microbiome diversity after FMT resembled that of the healthy donor dog's fecal microbiome, before FMT, which led us to conclude that the fecal microbiome in our patient normalized with FMT. Moreover, the clinical symptoms improved remarkably with regard to the changes in the fecal microbiome. Additionally, we noted no observable side effects during FMT treatment.

Conclusion: This report indicates the efficacy and safety of long-term, periodic FMT for a case of canine IBD based on attenuation of clinical symptoms and changes in fecal microbiome diversity. Therefore, FMT could be chosen as a treatment option for IBD in canines in the future.

RevDate: 2019-12-18

Jia Q, Li H, Zhou H, et al (2019)

Role and Effective Therapeutic Target of Gut Microbiota in Heart Failure.

Cardiovascular therapeutics, 2019:5164298.

Although the mechanism of the occurrence and development of heart failure has been continuously explored in the past ten years, the mortality and readmission rate of heart failure is still very high. Modern studies have shown that gut microbiota is associated with a variety of cardiovascular diseases, among which the study of gut microbiota and heart failure attracts particular attention. Therefore, understanding the role of gut microbiota in the occurrence and development of heart failure will help us further understand the pathogenesis of heart failure and provide new ideas for its treatment. This paper introduced intestinal flora and its metabolites, summarized the changes of intestinal flora in patients with heart failure, clarified that intestinal barrier damage and bacterial translocation induced inflammation and immune response aggravated heart failure, and altered intestinal microflora affected various metabolic pathways including trimethylamine/TMAO, SCFA, and Bile acid pathway leads to heart failure. At the same time, regulating intestinal microflora through diet, probiotics, antibiotics, fecal transplantation and microbial enzyme inhibitors has grown up to be a potential treatment for many metabolic disorders.

RevDate: 2019-12-18

Liang W, Huang Y, Tan X, et al (2019)

Alterations Of Glycerophospholipid And Fatty Acyl Metabolism In Multiple Brain Regions Of Schizophrenia Microbiota Recipient Mice.

Neuropsychiatric disease and treatment, 15:3219-3229.

Background: Schizophrenia is a debilitating psychiatric disorder characterized by molecular and anatomical abnormalities of multiple brain regions. Our recent study showed that dysbiosis of the gut microbiota contributes to the onset of schizophrenia-relevant behaviors, but the underlying mechanisms remain largely unknown.

Purpose: This study aimed to investigate how gut microbiota shapes metabolic signatures in multiple brain regions of schizophrenia microbiota recipient mice.

Methods: Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) were used to compare the metabolic signatures in the cortex, cerebellum and striatum of schizophrenia microbiota and healthy microbiota recipient mice. Enrichment analysis was further conducted to uncover the crucial metabolic pathways related to schizophrenia-relevant behaviors.

Results: We found that the metabolic phenotypes of these three regions were substantially different in schizophrenia microbiota recipient mice from those in healthy microbiota recipient mice. In total, we identified 499 differential metabolites that could discriminate the two groups in the three brain regions. These differential metabolites were mainly involved in glycerophospholipid and fatty acyl metabolism. Moreover, we found four of fatty acyl metabolites that were consistently altered in the three brain regions.

Conclusion: Taken together, our study suggests that alterations of glycerophospholipid and fatty acyl metabolism are implicated in the onset of schizophrenia-relevant behaviors, which may provide a new understanding of the etiology of schizophrenia.

RevDate: 2020-01-17

Moron R, Galvez J, Colmenero M, et al (2019)

The Importance of the Microbiome in Critically Ill Patients: Role of Nutrition.

Nutrients, 11(12):.

Critically ill patients have an alteration in the microbiome in which it becomes a disease-promoting pathobiome. It is characterized by lower bacterial diversity, loss of commensal phyla, like Firmicutes and Bacteroidetes, and a domination of pathogens belonging to the Proteobacteria phylum. Although these alterations are multicausal, many of the treatments administered to these patients, like antibiotics, play a significant role. Critically ill patients also have a hyperpermeable gut barrier and dysregulation of the inflammatory response that favor the development of the pathobiome, translocation of pathogens, and facilitate the emergence of sepsis. In order to restore the homeostasis of the microbiome, several nutritional strategies have been evaluated with the aim to improve the management of critically ill patients. Importantly, enteral nutrition has proven to be more efficient in promoting the homeostasis of the gut microbiome compared to parenteral nutrition. Several nutritional therapies, including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation, are currently being used, showing variable results, possibly due to the unevenness of clinical trial conditions and the fact that the beneficial effects of probiotics are specific to particular species or even strains. Thus, it is of great importance to better understand the mechanisms by which nutrition and supplement therapies can heal the microbiome in critically ill patients in order to finally implement them in clinical practice with optimal safety and efficacy.

RevDate: 2020-01-07

Zhang X, Tian H, Chen Q, et al (2019)

Fecal microbiota transplantation: standardization or diversification?.

Science China. Life sciences, 62(12):1714-1716.

RevDate: 2019-12-09

Janket SJ, Ackerson LK, EP Diamandis (2019)

Potential risks in fecal microbiota transplantation.

RevDate: 2019-12-07

Sun Y, Baptista LC, Roberts LM, et al (2019)

The Gut Microbiome as a Therapeutic Target for Cognitive Impairment.

The journals of gerontology. Series A, Biological sciences and medical sciences pii:5666188 [Epub ahead of print].

Declining cognitive functions in older individuals have enormous emotional, clinical and public health consequences. Thus therapeutics for preserving function and keeping older adults living independently are imperative. Aging is associated dysbiosis, defined as a loss of number and diversity in gut microbiota, which has been linked with various aspects of cognitive functions. Therefore, the gut microbiome has the potential to be an important therapeutic target for symptoms of cognitive impairment. In this review, we summarize the current literature regarding the potential for gut-targeted therapeutic strategies for prevention/treatment of the symptoms of cognitive impairment. Specifically, we discuss four primary therapeutic strategies: wild-type and genetically modified probiotics, fecal microbiota transplantation, physical exercise, and high-fiber diets and specifically link these therapies to reducing inflammation. These strategies may hold promise as treatment paradigms symptoms related to cognitive impairment.

RevDate: 2020-01-15

Severyn CJ, Brewster R, TM Andermann (2019)

Microbiota modification in hematology: still at the bench or ready for the bedside?.

Hematology. American Society of Hematology. Education Program, 2019(1):303-314.

Growing evidence suggests that human microbiota likely influence diverse processes including hematopoiesis, chemotherapy metabolism, and efficacy, as well as overall survival in patients with hematologic malignancies and other cancers. Both host genetic susceptibility and host-microbiota interactions may impact cancer risk and response to treatment; however, microbiota have the potential to be uniquely modifiable and accessible targets for treatment. Here, we focus on strategies to modify microbiota composition and function in patients with cancer. First, we evaluate the use of fecal microbiota transplant to restore microbial equilibrium following perturbation by antibiotics and chemotherapy, and as a treatment of complications of hematopoietic stem cell transplantation (HSCT), such as graft-versus-host disease and colonization with multidrug-resistant organisms. We then address the potential use of both probiotics and dietary prebiotic compounds in targeted modulation of the microbiota intended to improve outcomes in hematologic diseases. With each type of therapy, we highlight the role that abnormal, or dysbiotic, microbiota play in disease, treatment efficacy, and toxicity and evaluate their potential promise as emerging strategies for microbiota manipulation in patients with hematologic malignancies and in those undergoing HSCT.

RevDate: 2019-12-28

Mohammed Y, Kootte RS, Kopatz WF, et al (2019)

The intestinal microbiome potentially affects thrombin generation in human subjects.

Journal of thrombosis and haemostasis : JTH [Epub ahead of print].

BACKGROUND: The intestinal microbiome plays a versatile role in the etiology of arterial thrombosis. In venous thrombosis, driven chiefly by plasma coagulation, no such role has yet been established. We hypothesized that the intestinal microbiome composition affects coagulation in humans.

METHODS: We used healthy donor fecal microbiota transplant (FMT) to experimentally change the microbiome composition in metabolic syndrome patients. Thirty-five subjects were randomized in a blinded fashion to healthy donor FMT or autologous FMT as a control in a 2:1 ratio. We measured thrombin generation at baseline and after 6 weeks using automated calibrated thrombinography, and we determined plasma abundance of 32 coagulation related proteins using a targeted mass spectrometry-based quantitative proteomics assay with heavy labeled internal standards.

RESULTS: Healthy donor FMT prolonged the thrombinography lag time (median delta 0.0 versus 0.25 minutes, P = .039). The other thrombinography parameters showed no significant difference. Unsupervised cluster analysis suggested overall downregulation of coagulation related plasma proteins in subject clusters containing predominantly subjects that had a metabolic response to healthy donor FMT. FMT treatment status itself showed no clear clustering pattern with up- or downregulation, however, and proteins did not cluster according to an apparent biological grouping.

DISCUSSION: A single healthy donor FMT tends to modestly suppress the onset thrombin generation in metabolic syndrome patients, representing initial proof-of-principle that the intestinal microbiota composition might affect the coagulation system in humans. The findings merit external validation as a role for intestinal microbiota in coagulation can have clinically important implications.

RevDate: 2019-12-06

Vaughn VM, Greene MT, Ratz D, et al (2019)

Antibiotic stewardship teams and Clostridioides difficile practices in United States hospitals: A national survey in The Joint Commission antibiotic stewardship standard era.

Infection control and hospital epidemiology pii:S0899823X19003131 [Epub ahead of print].

OBJECTIVE: Clostridioides difficile infection (CDI) can be prevented through infection prevention practices and antibiotic stewardship. Diagnostic stewardship (ie, strategies to improve use of microbiological testing) can also improve antibiotic use. However, little is known about the use of such practices in US hospitals, especially after multidisciplinary stewardship programs became a requirement for US hospital accreditation in 2017. Thus, we surveyed US hospitals to assess antibiotic stewardship program composition, practices related to CDI, and diagnostic stewardship.

METHODS: Surveys were mailed to infection preventionists at 900 randomly sampled US hospitals between May and October 2017. Hospitals were surveyed on antibiotic stewardship programs; CDI prevention, treatment, and testing practices; and diagnostic stewardship strategies. Responses were compared by hospital bed size using weighted logistic regression.

RESULTS: Overall, 528 surveys were completed (59% response rate). Almost all (95%) responding hospitals had an antibiotic stewardship program. Smaller hospitals were less likely to have stewardship team members with infectious diseases (ID) training, and only 41% of hospitals met The Joint Commission accreditation standards for multidisciplinary teams. Guideline-recommended CDI prevention practices were common. Smaller hospitals were less likely to use high-tech disinfection devices, fecal microbiota transplantation, or diagnostic stewardship strategies.

CONCLUSIONS: Following changes in accreditation standards, nearly all US hospitals now have an antibiotic stewardship program. However, many hospitals, especially smaller hospitals, appear to struggle with access to ID expertise and with deploying diagnostic stewardship strategies. CDI prevention could be enhanced through diagnostic stewardship and by emphasizing the role of non-ID-trained pharmacists and clinicians in antibiotic stewardship.

RevDate: 2019-12-05

He Y, Li X, Yu H, et al (2019)

The Functional Role of Fecal Microbiota Transplantation on Dextran Sulfate Sodium-Induced Colitis in Mice.

Frontiers in cellular and infection microbiology, 9:393.

Increasingly studies revealed that dysbiosis of gut microbiota plays a pivotal role in the pathogenesis of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) has drawn more and more attention and become an important therapeutic approach. This study aims to examine the facts about the effective components and look into potential mechanisms of FMT. Colitis was induced by 3% (w/v) dextran sulfate sodium (DSS) in drinking water for 7 days. Colitis mice were administered by oral gavage with fecal suspension, fecal supernatant, fecal bacteria, or boiling-killed fecal bacteria from healthy controls and the disease activity index was monitored daily. On the seventh day, mice were euthanized. The length, histological score, parameters related to inflammation, gut barrier functions of the colon, activities of digestive protease and β-glucuronidase in feces were measured. All of the four fecal components showed certain degree of efficacy in DSS-induced colitis, while transplantation of fecal suspension showed the most potent effect as demonstrated by less body weight loss, lower disease activity scores, more expression of tight junction proteins and TRAF6 and IκBα, less expression of TNF-α, IL-1β, IL-10, TLR-4, and MyD88 in gut tissue, as well as restoration of fecal β-glucuronidase and decreases in fecal digestive proteases. These results provide a novel insight into the possible mechanism of FMT and may help to improve and optimize clinical use of FMT.

RevDate: 2019-12-11

Yin A, Luo Y, Chen W, et al (2019)

FAM96A Protects Mice From Dextran Sulfate Sodium (DSS)-Induced Colitis by Preventing Microbial Dysbiosis.

Frontiers in cellular and infection microbiology, 9:381.

Family with sequence similarity 96 member A (FAM96A) is an evolutionarily conserved intracellular protein that is involved in the maturation of the Fe/S protein, iron regulatory protein 1 (IRP1), and the mitochondria-related apoptosis of gastrointestinal stromal tumor cells. In this study, we used a mouse model of chemically induced colitis to investigate the physiological role of FAM96A in intestinal homeostasis and inflammation. At baseline, colons from Fam96a-/- mice exhibited microbial dysbiosis, dysregulated epithelial cell turnover, an increased number of goblet cells, and disordered tight junctions with functional deficits affecting intestinal permeability. After cohousing, the differences between wild-type and Fam96a-/- colons were abrogated, suggesting that FAM96A affects colonic epithelial cells in a microbiota-dependent manner. Fam96a deficiency in mice resulted in increased susceptibility to dextran sulfate sodium (DSS)-induced colitis. Importantly, the colitogenic activity of Fam96a-/- intestinal microbiota was transferable to wild-type littermate mice via fecal microbial transplantation (FMT), leading to exacerbation of DSS-induced colitis. Taken together, our data indicate that FAM96A helps to maintain colonic homeostasis and protect against DSS-induced colitis by preventing gut microbial dysbiosis. This study used gene knockout animals to help to understand the in vivo effects of the Fam96a gene for the first time and provides new evidence regarding host-microbiota interactions.

RevDate: 2019-12-04

Wang Z, Hua W, Li C, et al (2019)

Protective Role of Fecal Microbiota Transplantation on Colitis and Colitis-Associated Colon Cancer in Mice Is Associated With Treg Cells.

Frontiers in microbiology, 10:2498.

Colitis-associated cancer (CAC) is the most serious outcome of inflammatory bowel disease, which has an alteration of commensal intestinal microbiota. However, the role of intestinal microbiota on CAC progression is not well-understood. Fecal microbiota transplantation (FMT) was used for treating murine azoxymethane-dextran sodium sulfate (AOM-DSS) model of CAC. Composition of gut microbiota during FMT treatment was analyzed. RT-PCR and ELISA were used to detect the inflammatory factors, and immunofluorescence was applied to examine the phospho-nuclear factor (NF)-κB p65/p100 and Ki67-positive cells in the colons. In addition, flow cytometry was performed to analyze the immune cell after FMT treatment. Rehabilitation of the intestinal microbiota by FMT restored both the ratio and diversity of microbiota during CAC progression. Remarkably, a favorable morphometric outcome characterized by decreased tumor load and size was observed in CAC mice with FMT treatment. In addition, an anti-inflammatory function of FMT was demonstrated by decreasing pro-inflammatory factors but increasing anti-inflammatory factors through inhibiting canonical NF-κB activity and cellular proliferation in colons of CAC mice. The expression of CD4+CD25+Foxp3+ regulatory T cells (Tregs) was significantly increased after FMT treatment in CAC mice, but not T helper (Th)1/2/17 cells. Our study aids in the understanding of CAC pathogenesis and reveals a previously unrecognized role for FMT in the treatment of CAC through restoring the intestinal microbiota and inducing regulatory T cells.

RevDate: 2020-01-08

Magruder M, Sholi AN, Gong C, et al (2019)

Gut uropathogen abundance is a risk factor for development of bacteriuria and urinary tract infection.

Nature communications, 10(1):5521.

The origin of most bacterial infections in the urinary tract is often presumed to be the gut. Herein, we investigate the relationship between the gut microbiota and future development of bacteriuria and urinary tract infection (UTI). We perform gut microbial profiling using 16S rRNA gene deep sequencing on 510 fecal specimens from 168 kidney transplant recipients and metagenomic sequencing on a subset of fecal specimens and urine supernatant specimens. We report that a 1% relative gut abundance of Escherichia is an independent risk factor for Escherichia bacteriuria and UTI and a 1% relative gut abundance of Enterococcus is an independent risk factor for Enterococcus bacteriuria. Strain analysis establishes a close strain level alignment between species found in the gut and in the urine in the same subjects. Our results support a gut microbiota-UTI axis, suggesting that modulating the gut microbiota may be a potential novel strategy to prevent UTIs.

RevDate: 2020-01-08

Canakis A, Haroon M, HC Weber (2020)

Irritable bowel syndrome and gut microbiota.

Current opinion in endocrinology, diabetes, and obesity, 27(1):28-35.

PURPOSE OF REVIEW: To provide an overview of recent studies exploring the gut microbiota in pathogenesis and treatment of irritable bowel syndrome (IBS).

RECENT FINDINGS: Primary bacterial gut disturbances have been linked to the development and severity of IBS. Dysbiosis, or alteration in the normal intestinal flora, modulates intestinal permeability, inflammation, gut motility and likely quality of life. These biomechanical changes are associated with enteric and central nervous system processing as well. When compared to healthy controls, IBS patients display poor quality of life measures and are at increased risk of depression and anxiety. The severity of psychological and gastrointestinal symptoms in IBS has been linked with a distinct intestinal microbiota signature. Efforts to modulate intestinal dysbiosis in IBS have shown little improvement in large systematic reviews. The low FODMAP diet reduces bacteria, such as Bifidobacterum and Actinobacteria. Although rifaximin improves symptoms, it may only stimulate a transient effect on the gut microbiota. Fecal microbiota transplant does not provide prolonged symptom relief in IBS.

SUMMARY: This review elucidates recent advances in IBS and the gut microbiota. Microbiota changes are one underlying factor in perpetuating global IBS symptoms. The opportunity to exploit this disturbance through treatment modalities requires further investigation.

RevDate: 2020-01-08

Grinspan A (2019)

Fecal Microbiota Transplantation in Inflammatory Bowel Disease Patients With Clostridium difficile Infection.

Gastroenterology & hepatology, 15(9):481-483.

RevDate: 2020-01-08

Liu Y, Wang Y, Ni Y, et al (2020)

Gut Microbiome Fermentation Determines the Efficacy of Exercise for Diabetes Prevention.

Cell metabolism, 31(1):77-91.e5.

Exercise is an effective strategy for diabetes management but is limited by the phenomenon of exercise resistance (i.e., the lack of or the adverse response to exercise on metabolic health). Here, in 39 medication-naive men with prediabetes, we found that exercise-induced alterations in the gut microbiota correlated closely with improvements in glucose homeostasis and insulin sensitivity ( entry NCT03240978). The microbiome of responders exhibited an enhanced capacity for biosynthesis of short-chain fatty acids and catabolism of branched-chain amino acids, whereas those of non-responders were characterized by increased production of metabolically detrimental compounds. Fecal microbial transplantation from responders, but not non-responders, mimicked the effects of exercise on alleviation of insulin resistance in obese mice. Furthermore, a machine-learning algorithm integrating baseline microbial signatures accurately predicted personalized glycemic response to exercise in an additional 30 subjects. These findings raise the possibility of maximizing the benefits of exercise by targeting the gut microbiota.

RevDate: 2020-01-08

Herndon CC, Wang YP, CL Lu (2019)

Targeting the gut microbiota for the treatment of irritable bowel syndrome.

The Kaohsiung journal of medical sciences [Epub ahead of print].

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder that affects an estimated 11% of people across the world. IBS patients are one of the largest subgroups seen in gastroenterology clinics, exhibit a lesser quality of life, and take greater use of the healthcare system. The exact etiology of IBS remains uncertain. Alterations in the gut microbiome may characterize apotential mechanism in the pathogenesis of IBS. This hypothesis is paralleled by rodent models in which manipulation of the gut microbiota leads to disturbed physiological functions along the brain-gut axis. Recent research in IBS treatments has redirected its focus towards gu microbiome based therapeutics. In this review, we discuss potential roles of enteric bacteria in the pathogenesis of IBS and its comorbidities. We then explore the manipulation of the enteric microbiota by prebiotics, probiotics, antibiotics, dietary changes, and fecal microbiota transfer. We also discuss the positive and negative effects of these therapeutics on IBS symptoms.

RevDate: 2020-01-08

Wang W, Zhai S, Xia Y, et al (2019)

Ochratoxin A induces liver inflammation: involvement of intestinal microbiota.

Microbiome, 7(1):151.

BACKGROUND: Ochratoxin A (OTA) is a widespread mycotoxin and induces liver inflammation to human and various species of animals. The intestinal microbiota has critical importance in liver inflammation; however, it remains to know whether intestinal microbiota mediates the liver inflammation induced by OTA. Here, we treated ducklings with oral gavage of OTA (235 μg/kg body weight) for 2 weeks. Then, the microbiota in the cecum and liver were analyzed with 16S rRNA sequencing, and the inflammation in the liver was analyzed. To explore the role of intestinal microbiota in OTA-induced liver inflammation, intestinal microbiota was cleared with antibiotics and fecal microbiota transplantation was conducted.

RESULTS: Here, we find that OTA treatment in ducks altered the intestinal microbiota composition and structure [e.g., increasing the relative abundance of lipopolysaccharides (LPS)-producing Bacteroides], and induced the accumulation of LPS and inflammation in the liver. Intriguingly, in antibiotic-treated ducks, OTA failed to induce these alterations in the liver. Notably, with the fecal microbiota transplantation (FMT) program, in which ducks were colonized with intestinal microbiota from control or OTA-treated ducks, we elucidated the involvement of intestinal microbiota, especially Bacteroides, in liver inflammation induced by OTA.

CONCLUSIONS: These results highlight the role of gut microbiota in OTA-induced liver inflammation and open a new window for novel preventative or therapeutic intervention for mycotoxicosis.

RevDate: 2020-01-08
CmpDate: 2019-12-11

Wang Q, Fu YW, Wang YQ, et al (2019)

[Fecal microbiota transplantation for patients with refractory diarrhea after allogeneic hematopoietic stem cell transplantation].

Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi, 40(10):853-855.

Objective: To explore the availability and safety of fecal microbiota transplantation for patients with refractory diarrhea after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Four acute leukemia patients suffered from refractory diarrhea after allo-HSCT. One of them was refractory intestinal infection, the others were intestinal graft versus host disease. One or two doses of fecal microbiota, 3.4-6.0 U for one dose, were infused via nasal-jejunal tube. The curative effect and side effects were reviewed. Results: Three cases achieved complete remission while 1 was stable disease. The side effects included fever, abdominal pain and diarrhea, which all were Ⅰ grade. Conclusion: Fecal microbiota transplantation was effective and safe for refractory diarrhea after allo-HSCT.

RevDate: 2019-11-29

Lv WJ, Wu XL, Chen WQ, et al (2019)

The Gut Microbiome Modulates the Changes in Liver Metabolism and in Inflammatory Processes in the Brain of Chronic Unpredictable Mild Stress Rats.

Oxidative medicine and cellular longevity, 2019:7902874.

Generally, depression is the result of complex gene-environment interactions. Recent studies have showed that the gut microbiota can affect brain function through the microbiota-gut-brain axis. However, the underlying mechanism of the microbiota and potential influence of depression remain elusive. We aimed to determine how gut microbiome contributes to the process of depression and further influences the host. Chronic unpredictable mild stress (CUMS) is used to establish a depression model. Fecal microbiota transplant (FMT) is applied to illustrate that depression can be transmitted via microbiota, and metabolism of liver analysis is applied to demonstrate further influence to the liver. We also analyzed the astrocyte activation in the brain by immunofluorescence (IF). Here, we show that the structure of the gut microbiome changes markedly after rats undergo CUMS. Notably, we found that the ratio of Lactobacillus to Clostridium can be a vital index for the development of depression. Depression-like behavior can be duplicated through FMT. Moreover, increased zonulin and fatty acid binding protein-2 indicates that gut barrier integrity is broken after FMT. Subsequently, metabolomics shows that liver metabolic disorder occurs and leads to liver coagulative necrosis. In addition, increased inflammatory cytokine expression and higher astrocyte activation indicate an inflammatory process in the brain. These findings suggest that dysbiosis gut microbiome contributes to development of depression and further causes liver metabolic disorders in a way that may be relevant to the Lactobacillus to Clostridium ratio.

RevDate: 2019-12-17

Lee MSL, Ramakrishna B, Moss AC, et al (2019)

Successful treatment of fulminant Clostridioides difficile infection with emergent fecal microbiota transplantation in a patient with acute myeloid leukemia and prolonged, severe neutropenia.

We present a patient with acute myeloid leukemia and prolonged, severe neutropenia who developed fulminant Clostridioides difficile infection refractory to medical therapy and was high-risk for surgical intervention. He was treated with fecal microbiota transplantation (FMT) for life-saving cure. The patient had subsequent clinical improvement, however, developed multidrug-resistant Pseudomonas aeruginosa bacteremia 2 days post-procedure. We describe subsequent investigation of this event that found this bacteremia was not related to the donor stool administered during FMT. This case adds to the literature that FMT could be considered in heavily immunocompromised patients with fulminant Clostridioides difficile infection where maximal medical therapy has been ineffective and surgery may carry an excessively high mortality risk.

RevDate: 2019-11-26

Bowman JA, GH Utter (2019)

Evolving Strategies to Manage Clostridium difficile Colitis.

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract pii:10.1007/s11605-019-04478-5 [Epub ahead of print].

Clostridium difficile infection remains a common nosocomial illness with a significant impact on health care delivery. As molecular phenotyping of this organism has changed our understanding of its transmission and virulence, so too have diagnostic methods and treatment strategies evolved in recent years. The burden of this infection falls predominantly on elderly patients with comorbidities who have recently received antibiotics. Oral or enteral vancomycin is now preferred for first-line antimicrobial treatment across the disease spectrum, including mild-moderate initial cases. Fidaxomicin (a novel macrolide antibiotic), bezlotoxumab (a monoclonal antibody against toxin TcdB), and fecal microbiota transplantation expand the therapeutic armamentarium, particularly for recurrent infection. Operative treatment should be reserved for patients with fulminant infection, and early identification of patients who would benefit from an operation remains a challenge. Less invasive surgical options-such as laparoscopic diverting ileostomy with colonic irrigation-may improve survival and other outcomes relative to total abdominal colectomy and represent an attractive alternative particularly for frail patients.

RevDate: 2020-01-08

Seishima J, Iida N, Kitamura K, et al (2019)

Gut-derived Enterococcus faecium from ulcerative colitis patients promotes colitis in a genetically susceptible mouse host.

Genome biology, 20(1):252.

BACKGROUND: Recent metagenomic analyses have revealed dysbiosis of the gut microbiota of ulcerative colitis (UC) patients. However, the impacts of this dysbiosis are not fully understood, particularly at the strain level.

RESULTS: We perform whole-genome shotgun sequencing of fecal DNA extracts from 13 healthy donors and 16 UC and 8 Crohn's disease (CD) patients. The microbiota of UC and CD patients is taxonomically and functionally divergent from that of healthy donors, with E. faecium being the most differentially abundant species between the two microbial communities. Transplantation of feces from UC or CD patients into Il10-/- mice promotes pathological inflammation and cytokine expression in the mouse colon, although distinct cytokine expression profiles are observed between UC and CD. Unlike isolates derived from healthy donors, E. faecium isolates from the feces of UC patients, along with E. faecium strain ATCC 19434, promotes colitis and colonic cytokine expression. Inflammatory E. faecium strains, including ATCC 19434 and a UC-derived strain, cluster separately from commercially available probiotic strains based on whole-genome shotgun sequencing analysis. The presence of E. faecium in fecal samples is associated with large disease extent and the need for multiple medications in UC patients.

CONCLUSIONS: E. faecium strains derived from UC patients display an inflammatory genotype that causes colitis.

RevDate: 2020-01-08

Albuhairi S, R Rachid (2020)

Novel Therapies for Treatment of Food Allergy.

Immunology and allergy clinics of North America, 40(1):175-186.

Food allergy prevalence has increased over the past 2 decades and is estimated to affect 8% of children and 4% to 10% of adults. There is an unmet need to evaluate new therapeutic modalities that may decrease the risk of food-induced anaphylaxis and improve patients' quality of life. Oral, epicutaneous, and sublingual food immunotherapies have different safety and efficacy profiles, and their long-term outcome and applicability are unclear. Food allergy trials are currently evaluating different biologics (given as monotherapy or adjunct to immunotherapy), modified food proteins, DNA vaccines, and fecal microbiota transplantation.

RevDate: 2020-01-13
CmpDate: 2020-01-13

Chen Y, Zhang L, Hong G, et al (2020)

Probiotic mixtures with aerobic constituent promoted the recovery of multi-barriers in DSS-induced chronic colitis.

Life sciences, 240:117089.

AIMS: Gut microbiota has been closely linked to the mucosal immune and been regarded as a reliable target for intestinal inflammation. This study aimed to explore the therapeutic roles of probiotic mixtures of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis with (quadruple probiotics, P-qua) or without (triple probiotics, P-tri) aerobic Bacillus cereus in colitis, focusing on the multiple barrier functions.

MATERIALS AND METHODS: Chronic colitis was induced by dextran sulfate sodium (DSS) in C57BL/6 mice. The probiotic mixtures P-qua or P-tri was gavage administrated respectively, while fecal microbiota transplantation (FMT) as a positive control. The intestinal inflammation and functions of multiple barriers were assessed, including the mucus barrier, epithelial barrier and endothelial barrier known as gut-vascular barrier (GVB). Altered composition and diversity in gut microbiota were observed via sequencing analysis.

KEY FINDINGS: Both P-qua and P-tri relieved the intestinal inflammation and improved the functions of multiple barriers with increased integrity of mucous layer, enhanced transepithelial electrical resistance, declined epithelial and endothelial permeability to macromolecules in DSS-colitis. Aerobe-contained P-qua revealed a more active role in barrier recovering relative to P-tri, while FMT as a positive control seemed to get better results than pure probiotics. Indeed, P-qua was effective in rebuilding the structure and diversity of gut flora in DSS-colitis, especially increased abundance of Bifidobacterium, Akkermansia, Lactobacillus and Bacteroides.

SIGNIFICANCE: Aerobe-contained P-qua was a powerful adjuvant therapy for chronic colitis, via restoring the intestinal microflora and recovering the multi-barriers in the inflamed gut.

RevDate: 2020-01-08

Cheng H, Guan X, Chen D, et al (2019)

The Th17/Treg Cell Balance: A Gut Microbiota-Modulated Story.

Microorganisms, 7(12): pii:microorganisms7120583.

The intestinal tract of vertebrates is normally colonized with a remarkable number of commensal microorganisms that are collectively referred to as gut microbiota. Gut microbiota has been demonstrated to interact with immune cells and to modulate specific signaling pathways involving both innate and adaptive immune processes. Accumulated evidence suggests that the imbalance of Th17 and Treg cells is associated with the development of many diseases. Herein, we emphatically present recent findings to show how specific gut microbiota organisms and metabolites shape the balance of Th17 and Treg cells. We also discuss the therapeutic potential of fecal microbiota transplantation (FMT) in diseases caused by the imbalance of Th17 and Treg cells.

RevDate: 2019-11-21

Basson AR, Gomez-Nguyen A, Menghini P, et al (2019)

Human Gut Microbiome Transplantation in Ileitis Prone Mice: A Tool for the Functional Characterization of the Microbiota in Inflammatory Bowel Disease Patients.

Inflammatory bowel diseases pii:5637456 [Epub ahead of print].

BACKGROUND: Inflammatory bowel disease (IBD) is a lifelong digestive disease characterized by periods of severe inflammation and remission. To our knowledge, this is the first study showing a variable effect on ileitis severity from human gut microbiota isolated from IBD donors in remission and that of healthy controls in a mouse model of IBD.

METHODS: We conducted a series of single-donor intensive and nonintensive fecal microbiota transplantation (FMT) experiments using feces from IBD patients in remission and healthy non-IBD controls (N = 9 donors) in a mouse model of Crohn's disease (CD)-like ileitis that develops ileitis in germ-free (GF) conditions (SAMP1/YitFC; N = 96 mice).

RESULTS: Engraftment studies demonstrated that the microbiome of IBD in remission could have variable effects on the ileum of CD-prone mice (pro-inflammatory, nonmodulatory, or anti-inflammatory), depending on the human donor. Fecal microbiota transplantation achieved a 95% ± 0.03 genus-level engraftment of human gut taxa in mice, as confirmed at the operational taxonomic unit level. In most donors, microbiome colonization abundance patterns remained consistent over 60 days. Microbiome-based metabolic predictions of GF mice with Crohn's or ileitic-mouse donor microbiota indicate that chronic amino/fatty acid (valine, leucine, isoleucine, histidine; linoleic; P < 1e-15) alterations (and not bacterial virulence markers; P > 0.37) precede severe ileitis in mice, supporting their potential use as predictors/biomarkers in human CD.

CONCLUSION: The gut microbiome of IBD remission patients is not necessarily innocuous. Characterizing the inflammatory potential of each microbiota in IBD patients using mice may help identify the patients' best anti-inflammatory fecal sample for future use as an anti-inflammatory microbial autograft during disease flare-ups.

RevDate: 2019-11-26

Lin DM, Koskella B, Ritz NL, et al (2019)

Transplanting Fecal Virus-Like Particles Reduces High-Fat Diet-Induced Small Intestinal Bacterial Overgrowth in Mice.

Frontiers in cellular and infection microbiology, 9:348.

Fecal microbiota transplantation (FMT) is an effective tool for treating Clostridium difficile infection in the setting of dysbiosis of the intestinal microbiome. FMT for other forms of human disorders linked to dysbiosis have been less effective. The fecal microbiota contains a high density of virus-like particles (VLP), up to 90% of which are bacteriophages, thought to have a role in regulating gut bacterial populations. We hypothesized that transplantation of the phage-containing fecal VLP fraction may reduce bacterial density in the dysbiotic setting of small intestinal bacterial overgrowth (SIBO). In an experiment using fecal transplantation, we compared the effect of the fecal VLP fraction (bacteria removed) against "Whole" FMT (bacteria intact) on the ileal microbiome. Recipients were either treated with a 30-day high-fat diet (HFD) as a model of dysbiosis to induce SIBO or were on a standard diet (SD). We observed that transplantation of fecal VLPs from donors on a HFD was sufficient to alter the ileal microbiota, but the effect was dependent on diet of the recipient. In recipients on a HFD, ileal bacterial density was reduced. In recipients on a SD, the ileal microbiome transitioned toward the composition associated with a HFD. In both recipient groups, transplantation of fecal VLP fraction alone produced the same outcome as whole FMT. Neither treatment altered expression of antimicrobial peptides. These findings demonstrated a potential role of VLPs, likely phages, for modifying the gut microbiome during dysbiosis.

RevDate: 2020-01-19

Cheng YW, M Fischer (2019)

Treatment of Severe and Fulminnant Clostridioides difficile Infection.

Current treatment options in gastroenterology, 17(4):524-533.

PURPOSE OF REVIEW: This article will review current management strategies for severe and fulminant Clostridioides difficile infection (CDI).

RECENT FINDINGS: Clostridioides difficile is the most common nosocomial cause of infectious diarrhea. With the rise of hypervirulent strains of CDI, almost 8% of patients hospitalized with CDI are afflicted with severe CDI (SCDI) or fulminant CDI (FCDI). A significant proportion of these patients do not respond to recommended anti-CDI antibiotic therapy such as oral vancomycin and fidaxomicin. Current recommendations suggest that patients with refractory CDI should proceed to colectomy or diverting loop ileostomy with colonic lavage. However, both of these surgical interventions result in high rates of post-surgical mortality approaching 30%. Fecal microbiota transplantation (FMT) is a promising therapy that is recommended in recurrent CDI. Recent studies have found that FMT can safely produce cure rates between 70 and 90% in patients with SCDI and FCDI, while significantly decreasing rates of CDI-related mortality and colectomy. A patient population likely to benefit the most from FMT is elderly patients due to their increased risk for CDI, treatment failure, and high comorbidity burden that may preclude surgical intervention. FMT should be considered in patients with SCDI or FCDI particularly when traditional anti-CDI antibiotics are ineffective.

RevDate: 2020-01-08

Fu A, Mo Q, Wu Y, et al (2019)

Protective effect of Bacillus amyloliquefaciens against Salmonella via polarizing macrophages to M1 phenotype directly and to M2 depended on microbiota.

Food & function, 10(12):7653-7666.

Bacillus amyloliquefaciens SC06 (BaSC06), a potential probiotic, plays a positive role in animal growth performance and immune function. The aim of the present study was to investigate the protective effect of BaSC06 against Salmonella infection and its association with macrophage polarization. C57BL/6 mice were fed with or without a BaSC06-containing diet before Salmonella enterica Typhimurium (ST) challenge. Results showed that BaSC06 had a protective effect against ST inoculation and induced both M1 and M2 macrophage polarization in the cecum. An in vitro co-culture model demonstrated that BaSC06 promoted M1 polarization directly, and thus increased the phagocytosis and bactericidal activity against ST. In addition, adoptive transfer of bone marrow-derived macrophages (BMDMs) stimulated by BaSC06 significantly decreased the counts of ST in the spleen. Furthermore, 16S rRNA-based analysis of cecal content showed that BaSC06 significantly increased the proportion of Verrucomicrobia and decreased Bacterodetes. Transplantation of the fecal microbiota from BaSC06-treated animals promoted M2 macrophage polarization in the cecum and significantly relieved inflammation caused by ST. In conclusion, BaSC06 polarized macrophages to the M1 type directly resulting in excellent bactericidal activity. Meanwhile, the microbiota modified by BaSC06 can induce M2 polarization which ameliorates the inflammation caused by ST.

RevDate: 2019-11-21
CmpDate: 2019-11-21

Schulte LA, Schäfer A, Steding K, et al (2019)

[Acceptance of fecal microbiota transfer among patients with chronic inflammatory bowel diseases in a highly specialized outpatient department: a questionnaire-based survey].

Zeitschrift fur Gastroenterologie, 57(11):1291-1297.

Recently, research in the treatment of inflammatory bowel diseases has become increasingly focused on fecal microbiota transfer (FMT) due to increasing evidence of its possible benefits. Still, there are doubts about this method, because there is contradicting evidence regarding its effectiveness and the possible side effects are not well known. Furthermore, the majority of patients are not open to this procedure. We performed a questionnaire-based survey amongst 302 patients with an inflammatory bowel disease that received treatment in our specialized outpatient clinic to determine the factors relevant for acceptance or rejection of fecal microbiota transfer as a possible treatment for Crohn's disease or ulcerative colitis. Our data supports the hypothesis that a lack of information about FMT is a key factor for hypothetical acceptance of this method (68 % of pre-informed participants vs. 30 % of not pre-informed participants would accept FMT as treatment, p < 0.001), and, therefore, it highlights patient education as a possible intervention to improve acceptance. The main concern regarding FMT was possible transmission of infections (ranked first by 98 participants). The most accepted method to perform FMT was application via oral capsule (44 % of participants).

RevDate: 2019-12-18

Krajicek E, Bohm M, Sagi S, et al (2019)

Fulminant Clostridium difficile Infection Cured by Fecal Microbiota Transplantation in a Bone Marrow Transplant Recipient With Critical Neutropenia.

ACG case reports journal, 6(8):e00198.

Clostridium difficile infection is the most prevalent health care-associated infection. Treatment relies on antimicrobial therapy with mounting evidence supporting fecal microbiota transplant (FMT) in refractory cases. Cohort studies have documented the safety of FMT in immunocompromised patients. However, the safety of FMT in patients with critically low (<500/μL) absolute neutrophil count is unknown. Currently, in severely immunocompromised bone marrow or solid organ transplant recipients, FMT is delayed until normalization of absolute neutrophil count. We present a patient with absolute neutropenia in whom sequential FMTs were safely and successfully administered, resulting in cure of fulminant C. difficile infection.

RevDate: 2019-11-15

Terveer EM, van Gool T, Ooijevaar RE, et al (2019)

Human transmission of Blastocystis by Fecal Microbiota Transplantation without development of gastrointestinal symptoms in recipients.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America pii:5625875 [Epub ahead of print].

BACKGROUND: Patients with multiple recurrent Clostridioides difficile infections (rCDI) are treated with fecal microbiota transplantation (FMT) provided by healthy donors. Blastocystis colonization of donors is considered an exclusion criterion, whereas its pathogenicity is still under debate.

METHODS: The introduction of molecular screening for Blastocystis sp. at our stool bank identified two donors with prior negative microscopy but positive PCR. Potential transmission of Blastocystis sp. to patients was assessed on 16 fecal patient samples, pre- and post-FMT, by PCR and subtype (ST) analysis. In addition, clinical outcome for treatment of rCDI (n=31), as well as development of gastrointestinal symptoms was assessed.

RESULTS: One donor carried Blastocystis ST1, the other contained ST3. All patients tested Blastocystis negative prior to FMT. With a median of 20.5 days after FMT, 8 of 16 (50%) patients developed intestinal colonization with Blastocystis, with identical ST-sequences as their respective donors. Blastocystis containing fecal suspensions were used to treat 31 rCDI patients, with a FMT success rate of 84%. This success rate was not statistically different from patients transferred with Blastocystis sp. negative donor feces (93%, 76/82). Patients transferred with Blastocystis sp. positive donor feces did not report any significant difference in bowel complaints in the first week, after 3 weeks and the months following FMT.

CONCLUSIONS: We demonstrated the first transmission of Blastocystis ST1 and ST3 from donor to patients by FMT. This did not result in gastrointestinal symptomatology or have any significant effect on rCDI treatment outcome.

RevDate: 2020-01-08

Fukui H (2019)

Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far?.

Diseases (Basel, Switzerland), 7(4): pii:diseases7040058.

Accumulating evidence supports that gut dysbiosis may relate to various liver diseases. Alcoholics with high intestinal permeability had a decrease in the abundance of Ruminnococcus. Intestinal dysmotility, increased gastric pH, and altered immune responses in addition to environmental and genetic factors are likely to cause alcohol-associated gut microbial changes. Alcohol-induced dysbiosis may be associated with gut barrier dysfunction, as microbiota and their products modulate barrier function by affecting epithelial pro-inflammatory responses and mucosal repair functions. High levels of plasma endotoxin are detected in alcoholics, in moderate fatty liver to advanced cirrhosis. Decreased abundance of Faecalibacterium prausnitzii, an anti-inflammatory commensal, stimulating IL-10 secretion and inhibiting IL-12 and interferon-γ expression. Proteobacteria, Enterobacteriaceae, and Escherichia were reported to be increased in NAFLD (nonalcoholic fatty liver disease) patients. Increased abundance of fecal Escherichia to elevated blood alcohol levels in these patients and gut microbiota enriched in alcohol-producing bacteria produce more alcohol (alcohol hypothesis). Some undetermined pathological sequences related to gut dysbiosis may facilitate energy-producing and proinflammatory conditions for the progression of NAFLD. A shortage of autochthonous non-pathogenic bacteria and an overgrowth of potentially pathogenic bacteria are common findings in cirrhotic patients. The ratio of the amounts of beneficial autochthonous taxa (Lachnospiraceae + Ruminococaceae + Veillonellaceae + Clostridiales Incertae Sedis XIV) to those of potentially pathogenic taxa (Enterobacteriaceae + Bacteroidaceae) was low in those with early death and organ failure. Cirrhotic patients with decreased microbial diversity before liver transplantation were more likely to develop post-transplant infections and cognitive impairment related to residual dysbiosis. Patients with PSC had marked reduction of bacterial diversity. Enterococcus and Lactobacillus were increased in PSC patients (without liver cirrhosis.) Treatment-naive PBC patients were associated with altered composition and function of gut microbiota, as well as a lower level of diversity. As serum anti-gp210 antibody has been considered as an index of disease progression, relatively lower species richness and lower abundance of Faecalibacterium spp. in gp210-positive patients are interesting. The dysbiosis-induced altered bacterial metabolites such as a hepatocarcinogenesis promotor DCA, together with a leaky gut and bacterial translocation. Gut protective Akkermansia and butyrate-producing genera were decreased, while genera producing-lipopolysaccharide were increased in early hepatocellular carcinoma (HCC) patients.

RevDate: 2020-01-08

Severyn CJ, Brewster R, TM Andermann (2019)

Microbiota modification in hematology: still at the bench or ready for the bedside?.

Blood advances, 3(21):3461-3472.

Growing evidence suggests that human microbiota likely influence diverse processes including hematopoiesis, chemotherapy metabolism, and efficacy, as well as overall survival in patients with hematologic malignancies and other cancers. Both host genetic susceptibility and host-microbiota interactions may impact cancer risk and response to treatment; however, microbiota have the potential to be uniquely modifiable and accessible targets for treatment. Here, we focus on strategies to modify microbiota composition and function in patients with cancer. First, we evaluate the use of fecal microbiota transplant to restore microbial equilibrium following perturbation by antibiotics and chemotherapy, and as a treatment of complications of hematopoietic stem cell transplantation (HSCT), such as graft-versus-host disease and colonization with multidrug-resistant organisms. We then address the potential use of both probiotics and dietary prebiotic compounds in targeted modulation of the microbiota intended to improve outcomes in hematologic diseases. With each type of therapy, we highlight the role that abnormal, or dysbiotic, microbiota play in disease, treatment efficacy, and toxicity and evaluate their potential promise as emerging strategies for microbiota manipulation in patients with hematologic malignancies and in those undergoing HSCT.

RevDate: 2019-11-10

Hadjivasilis A, Tsioutis C, Michalinos A, et al (2019)

New insights into irritable bowel syndrome: from pathophysiology to treatment.

Annals of gastroenterology, 32(6):554-564.

Irritable bowel syndrome (IBS) is the most common reason to visit a gastroenterologist. IBS was believed to be a functional disease, but many possible pathophysiologic mechanisms can now explain the symptoms. IBS patients are classified into subtypes according to their predominant bowel habit, based on the Rome IV criteria. These include diarrhea-predominant and constipation-predominant IBS, as well as the mixed type, a combination of the two. Usually, IBS treatment is based on the predominant symptoms, with many options for each subtype. A new promising treatment option, fecal microbiota transplantation, seems to have beneficial effects on IBS. However, treating the pathophysiological causative agent responsible for the symptoms is an emerging approach. Therefore, before the appropriate therapeutic option is chosen for treating IBS, a clinical evaluation of its pathophysiology should be performed.

RevDate: 2020-01-08

Alhifany AA, Almutairi AR, Almangour TA, et al (2019)

Comparing the efficacy and safety of faecal microbiota transplantation with bezlotoxumab in reducing the risk of recurrent Clostridium difficile infections: a systematic review and Bayesian network meta-analysis of randomised controlled trials.

BMJ open, 9(11):e031145.

OBJECTIVES: The risk of recurrent Clostridium difficile infections (RCDIs) is high when treated with standard antibiotics therapy (SAT) alone. It is suggested that the addition of faecal microbiota transplantation (FMT) or bezlotoxumab after SAT reduces the risk of RCDI. In the absence of head-to-head randomised controlled trials (RCTs), this review attempts to compare the efficacy and safety of bezlotoxumab with FMT in reducing the risk of RCDI in hospitalised patients.

DESIGN: A systematic review and Bayesian network meta-analysis.

DATA SOURCE: A comprehensive search from inception to 30 February 2019 was conducted in four databases (Medline/PubMed, Embase, Scopus,

ELIGIBILITY CRITERIA: RCTs reporting the resolution of diarrhoea associated with RCDI without relapse for at least 60 days after the end of treatments as the primary outcome.

DATA EXTRACTION AND SYNTHESIS: We extracted author, year of publication, study design and binomial data that represented the resolution of diarrhoea or adverse events of monoclonal antibodies and FMT infusion. Random-effects models were used for resolution rate of RCDI and adverse events. The Cochrane Risk of Bias tool was used to assess the quality of included RCTs.

RESULTS: Out of 1003 articles identified, seven RCTs involving 3043 patients contributed to the review. No difference was reported between single or multiple infusions of FMT and bezlotoxumab in resolving RCDI, (OR 1.53, 95% credible interval (CrI) 0.39 to 5.16) and (OR 2.86, 95% CrI 1.29 to 6.57), respectively. Patients treated with SAT alone or bezlotoxumab with SAT showed significantly lower rates of diarrhoea than FMT (OR 0, 95% CrI 0 to 0.09) and (OR 0, 95% CrI 0 to 0.19), respectively. There was no difference in terms of other adverse events.

CONCLUSIONS: This is the first network meta-analysis that has compared the recently Food and Drug Administration-approved monoclonal antibody bezlotoxumab with FMT for resolving RCDI. The quality of the included RCTs was variable. The findings of this study suggested no difference between single or multiple infusions of FMT and bezlotoxumab. However, FMT was associated with a higher rate of non-serious diarrhoea as opposed to SAT used alone or in combination with bezlotoxumab.

RevDate: 2020-01-08

Kang XX, Yan J, Huang F, et al (2019)

On the mechanism of antibiotic resistance and fecal microbiota transplantation.

Mathematical biosciences and engineering : MBE, 16(6):7057-7084.

Antibiotic resistance is a growing threat to human health and is caused by mainly the overuse of antibiotics in clinical medicine. Clinically, drug resistance emerges after a series of antibiotic treatments, implying that each treatment changes the intestinal flora composition and the accumulations of these changes induce the resistance. But mathematically, this cumulative effect cannot be achieved by a general population model, because the system will return to its pre-treatment state (an isolated steady state) after each cure. Based on the fact that sensitive bacteria and resistant bacteria are similar in most respects except their reactions to antibiotics, we developed a mathematical model with a specific phase-space structure: instead of isolated points, the steady states of this system compose one-dimensional manifolds (line segments). This structure explains the fundamental mechanism of antibiotic resistance: after antibiotic treatment, the system cannot return to the pretreatment healthy steady state but rather slightly moves along the manifold to a different steady state. Each use of antibiotics can change the ratio of resistant to susceptible pathogens in the host. The change the ratio can persist and accumulate, and finally promotes the emergence of antimicrobial resistance. We also assessed key factors (such as pathogen composition, the amount and composition of beneficial bacteria, medication duration and bactericidal rates of drugs) influencing the development of drug resistance. In addition, we clarified how fecal microbiota transplantation affects the treatment of antibiotic-resistant infections. The effect is essentially a transfer towards the healthy state in the phase space. Finally, based on the mechanisms revealed by the mathematical models, we suggested some strategies to delay or prevent the emergence of drug resistance. These findings not only provide a solid theoretical basis for the treatment of antimicrobial resistance, but also inspire clues to the phenomenon of drug resistance.

RevDate: 2020-01-05

Manca C, Boubertakh B, Leblanc N, et al (2020)

Germ-free mice exhibit profound gut microbiota-dependent alterations of intestinal endocannabinoidome signaling.

Journal of lipid research, 61(1):70-85.

The gut microbiota is a unique ecosystem of microorganisms interacting with the host through several biochemical mechanisms. The endocannabinoidome (eCBome), a complex signaling system including the endocannabinoid system, approximately 50 receptors and metabolic enzymes, and more than 20 lipid mediators with important physiopathologic functions, modulates gastrointestinal tract function and may mediate host cell-microbe communications there. Germ-free (GF) mice, which lack an intestinal microbiome and so differ drastically from conventionally raised (CR) mice, offer a unique opportunity to explore the eCBome in a microbe-free model and in the presence of a reintroduced functional gut microbiome through fecal microbiota transplant (FMT). We aimed to gain direct evidence for a link between the microbiome and eCBome systems by investigating eCBome alterations in the gut in GF mice before and after FMT. Basal eCBome gene expression and lipid profiles were measured in various segments of the intestine of GF and CR mice at juvenile and adult ages using targeted quantitative PCR transcriptomics and LC-MS/MS lipidomics. GF mice exhibited age-dependent modifications in intestinal eCBome gene expression and lipid mediator levels. FMT from CR donor mice to age-matched GF male mice reversed several of these alterations, particularly in the ileum and jejunum, after only 1 week, demonstrating that the gut microbiome directly impacts the host eCBome and providing a cause-effect relationship between the presence or absence of intestinal microbes and eCBome signaling. These results open the way to new studies investigating the mechanisms through which intestinal microorganisms exploit eCBome signaling to exert some of their physiopathologic functions.

RevDate: 2019-12-04

Kumar V, M Fischer (2020)

Expert opinion on fecal microbiota transplantation for the treatment of Clostridioides difficile infection and beyond.

Expert opinion on biological therapy, 20(1):73-81.

Introduction: Fecal microbiota transplantation (FMT) is a procedure involving transfer of stool from a healthy donor into the intestinal tract of a diseased recipient to restore intestinal microbial composition and functionality. FMT's tremendous success in recurrent and refractory Clostridioides difficile infection (CDI) catalyzed gut microbiota research and opened the door to microbiome-based therapy for various gastrointestinal and other disorders.Areas covered: We used PubMed search engine to identify significant publications in the field of CDI and FMT. Here we present an overview of the current literature on FMT's use for recurrent, non-severe, severe, and fulminant CDI and on promising future application.Expert opinion: FMT as the best tool for treatment of antibiotic-refractory CDI has gained immense popularity over the last decade. The future of gut microbiota-based therapy should include oral formulations that contain well-described ingredients in effective doses, clear mechanism of action, and excellent safety profile.

RevDate: 2019-11-29

Wu M, Li P, An Y, et al (2019)

Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota.

Pharmacological research, 150:104489.

Phloretin, extracted from the pericarp and velamen of apples or pears, is a dihydrochalcone flavonoid with anti-bacterial and anti-inflammatory activities. It has been reported that phloretin has anti-inflammatory effects in ulcerative colitis (UC) mice. However, the role of the gut microbiota in the phloretin anti-UC process remains unclear. In this study, we observed that the anti-UC effect of phloretin was affected by co-housing, probably because of the transmissible nature of the gut micobiota. Through fecal micobiota transplantation (FMT), the effects of the gut microbiota on the anti-UC of phloretin were further confirmed. UC was induced in mice by administrating 3% dextran sulfate sodium (DSS) in drinking water for 7 days. Phloretin (60 mg/kg) was administered by gavage every day during the experiment. Fecal microbes (109 CFU/mL) from phloretin-treated UC mice were administered by gavage to non-phloretin-treated UC mice for 7 days. The results showed that FMT, like phloretin, ameliorated UC by improving disease symptoms and colon inflammation, balancing inflammatory cytokines, maintaining intestinal barrier integrity, restoring systemic immune function, inhibiting NF-κB and NLRP3 inflammasome activation and ameliorating the oxidant stress. Both FMT and phloretin treatment increased the levels of Bacteroidetes, Alistipes and Lactobacillus and decreased those of Firmicutes, Oscillibacter and Ruminiclostridium_6. Correlation analysis between gut microbes and micro-environmental factors revealed that Alistipes abundance was negatively correlated with DAI, pathological score, and TNF-α, IL-6 and IL-1β levels, and Alistipes was more abundant in phloretin or FMT treated UC mice. Oscillibacter abundance was significantly positively correlated with IL-6 and IL-1β levels and pathological score, and Oscillibacter was increased in UC mice. Furthermore, network analysis of the dominant genera revealed that Alistipes abundance was negatively related to Oscillibacter abundance. In conclusion, this study suggests that the anti-UC effects of phloretin are achieved through regulation of the gut microbiota and phloretin has the potential to be developed as a promising agent for the treatment of UC.

RevDate: 2020-01-08

Singh H, Ross L, Smith H, et al (2019)

Oral fecal microbiota transplant for recurrent Clostridium difficile in pediatric autoimmune enteropathy.

European journal of gastroenterology & hepatology, 31(12):1602-1603.

RevDate: 2019-11-04

Ianiro G, Murri R, Sciumè GD, et al (2019)

Incidence of Bloodstream Infections, Length of Hospital Stay, and Survival in Patients With Recurrent Clostridioides difficile Infection Treated With Fecal Microbiota Transplantation or Antibiotics: A Prospective Cohort Study.

Annals of internal medicine pii:2754174 [Epub ahead of print].

Background: Clostridioides difficile infection (CDI) is a risk factor for bloodstream infection (BSI). Fecal microbiota transplantation (FMT) is more effective than antibiotics in treating recurrent CDI, but its efficacy in preventing CDI-related BSI is uncertain.

Objective: To assess incidence of primary BSI in patients with recurrent CDI treated with FMT versus antibiotics.

Design: Prospective cohort study. Patients treated with FMT and those treated with antibiotics were matched on propensity score.

Setting: Single academic medical center.

Patients: 290 inpatients with recurrent CDI (57 patients per treatment in matched cohort).

Intervention: FMT or antibiotics.

Measurements: The primary outcome was primary BSI within 90 days. Secondary outcomes were length of hospitalization and overall survival (OS) at 90 days.

Results: Of the 290 patients, 109 were treated with FMT and 181 received antibiotics. Five patients in the FMT group and 40 in the antibiotic group developed BSI. Because of differences in the patients treated with FMT versus antibiotics in many baseline characteristics, including number of recurrences and CDI severity, comparative analyses were limited to the matched cohort. Risk for BSI was 23 percentage points (95% CI, 10 to 35 percentage points) lower in the FMT group; the FMT group also had 14 fewer days of hospitalization (CI, 9 to 20 fewer days) and a 32-percentage point increase in OS (CI, 16 to 47 percentage points) compared with the antibiotic group.

Limitation: Nonrandomized study with potential for unmeasured or residual confounding; limited generalizability of the propensity score-matched cohort.

Conclusion: In a propensity score-matched cohort, patients with recurrent CDI treated with FMT were less likely to develop primary BSI.

Primary Funding Source: None.


ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

Electronic Scholarly Publishing
961 Red Tail Lane
Bellingham, WA 98226

E-mail: RJR8222 @

Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin (and even a collection of poetry — Chicago Poems by Carl Sandburg).


ESP now offers a much improved and expanded collection of timelines, designed to give the user choice over subject matter and dates.


Biographical information about many key scientists.

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are now being automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 07 JUL 2018 )