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Bibliography on: Fecal Transplantation

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ESP: PubMed Auto Bibliography 05 Jul 2020 at 01:33 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®)

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RevDate: 2020-07-03

Claytor JD, N El-Nachef (2020)

Fecal microbial transplant for inflammatory bowel disease.

Current opinion in clinical nutrition and metabolic care [Epub ahead of print].

PURPOSE OF REVIEW: The purpose of this brief review is to investigate the current utility of fecal microbial transplantation (FMT) to ameliorate dysbiosis contributing to inflammatory bowel disease pathogenesis.

RECENT FINDINGS: Increasing data from randomized, controlled trials support a role for multiple FMT administrations in the induction of remission and even as a maintenance therapy in mild-to-moderate Ulcerative Colitis. Small series and one small randomized controlled trial among patients with Crohn's Disease and with pouchitis continue to produce conflicting clinical results and microbial profile data on the host and donor levels. It is not clear whether patients with Crohn's disease are more susceptible to disease flare after FMT. Novel FMT delivery systems, including oral, and early-intensity colonoscopic devices, are under investigation.

SUMMARY: The allure of minimizing the risks and cost of long-term immunosuppression via modulation of patient microbiota remains enticing, and the most recent randomized controlled data in ulcerative colitis reveals acceptable clinical remission rates. However, prior to wide adoption of FMT within the inflammatory bowel disease treatment armamentarium, large clinical trials identifying biomarkers of treatment success, ensuring safety across all indications, and cultivating optimized donor and host selection are needed.

RevDate: 2020-07-03

Craven L, Rahman A, Nair Parvathy S, et al (2020)

Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial.

The American journal of gastroenterology, 115(7):1055-1065.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability.

METHODS: Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT.

RESULTS: There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT.

DISCUSSION: FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.

RevDate: 2020-07-03

Khanna S, D Pardi (2020)

Fecal Microbiota Transplantation for Recurrent Clostridioides difficile infection: The COVID-19 Era.

The American journal of gastroenterology, 115(7):971-974.

RevDate: 2020-07-03

Floyd JL, MB Grant (2020)

The Gut-Eye Axis: Lessons Learned from Murine Models.

Ophthalmology and therapy pii:10.1007/s40123-020-00278-2 [Epub ahead of print].

A healthy gut microbiota is essential in maintaining the human body in a homeostatic state by its functions in digestion and immune tolerance. Under states of aberrant microbial composition or function (dysbiosis), the gut microbiota induces systemic inflammation that can lead to the onset of many diseases. In this review, we describe some evidence, largely from rodent studies, that supports the possible role of a dysbiotic gut microbiota in the onset and exacerbation of ocular diseases, primarily diabetic retinopathy, age-related macular degeneration, choroidal neovascularization, and uveitis. Furthermore, we examine several potential therapeutic measures that show promise in restoring the gut microbiota to a eubiotic state, preventing the aforementioned disease pathologies.

RevDate: 2020-07-02

Woodworth MH (2020)

mSphere of Influence: Microbiome-Associated Phenotypes Are Modifiable.

mSphere, 5(4): pii:5/4/e00508-20.

Michael Woodworth focuses on translational microbiome therapeutic research. In this mSphere of Influence article, he reflects on how "Gut microbiomes of Malawian twin pairs discordant for kwashiorkor" by Michelle Smith et al. (M. I. Smith, T. Yatsunenko, M. J. Manary, I. Trehan, et al., Science 339:548-554, 2013, https://doi.org/10.1126/science.1229000) made an impact on him by revealing the causal influence of microbial communities in the development of severe malnutrition.

RevDate: 2020-07-02

Bilinski J, Dziurzynski M, Grzesiowski P, et al (2020)

Multimodal Approach to Assessment of Fecal Microbiota Donors based on Three Complementary Methods.

Journal of clinical medicine, 9(7): pii:jcm9072036.

Methods of stool assessment are mostly focused on next-generation sequencing (NGS) or classical culturing, but only rarely both. We conducted a series of experiments using a multi-method approach to trace the stability of gut microbiota in various donors over time, to find the best method for the proper selection of fecal donors and to find "super-donor" indicators. Ten consecutive stools donated by each of three donors were used for the experiments (30 stools in total). The experiments assessed bacterial viability measured by flow cytometry, stool culturing on different media and in various conditions, and NGS (90 samples in total). There were no statistically significant differences between live and dead cell numbers; however, we found a group of cells classified as not-dead-not-alive, which may be possibly important in selection of "good" donors. Donor C, being a regular stool donor, was characterized by the largest number of cultivable species (64). Cultivable core microbiota (shared by all donors) was composed of only 16 species. ANCOM analysis of NGS data highlighted particular genera to be more abundant in one donor vs. the others. There was a correlation between the not-dead-not-alive group found in flow cytometry and Anaeroplasma found by NGS, and we could distinguish a regular stool donor from the others. In this work, we showed that combining various methods of microbiota assessment gives more information than each method separately.

RevDate: 2020-06-24
CmpDate: 2020-06-24

Daharsh L, Zhang J, Ramer-Tait A, et al (2019)

A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System.

Journal of visualized experiments : JoVE.

Humanized mice (hu-mice) that feature a functional human immune system have fundamentally changed the study of human pathogens and disease. They can be used to model diseases that are otherwise difficult or impossible to study in humans or other animal models. The gut microbiome can have a profound impact on human health and disease. However, the murine gut microbiome is very different than the one found in humans. There is a need for improved pre-clinical hu-mice models that have an engrafted human gut microbiome. Therefore, we created double hu-mice that feature both a human immune system and stable human-like gut microbiome. NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice are one of the best animals for humanization due to their high level of immunodeficiency. However, germ-free NSG mice, and various other important germ-free mice models are not currently commercially available. Further, many research settings do not have access to gnotobiotic facilities, and working under gnotobiotic conditions can often be expensive and time consuming. Importantly, germ-free mice have several immune deficiencies that exist even after the engraftment of microbes. Therefore, we developed a protocol that does not require germ-free animals or gnotobiotic facilities. To generate double hu-mice, NSG mice were treated with radiation prior to surgery to create bone-marrow, liver, thymus-humanized (hu-BLT) mice. The mice were then treated with broad spectrum antibiotics to deplete the pre-existing murine gut microbiome. After antibiotic treatment, the mice were given fecal transplants with healthy human donor samples via oral gavage. Double hu-BLT mice had unique 16S rRNA gene profiles based on the individual human donor sample that was transplanted. Importantly, the transplanted human-like microbiome was stable in the double hu-BLT mice for the duration of the study up to 14.5 weeks post-transplant.

RevDate: 2020-07-02
CmpDate: 2020-07-02

Bajaj JS, Salzman NH, Acharya C, et al (2019)

Fecal Microbial Transplant Capsules Are Safe in Hepatic Encephalopathy: A Phase 1, Randomized, Placebo-Controlled Trial.

Hepatology (Baltimore, Md.), 70(5):1690-1703.

Hepatic encephalopathy (HE) can cause major morbidity despite standard of care (SOC; rifaximin/lactulose). Fecal microbial transplant (FMT) enemas postantibiotics are safe, but the effect of FMT without antibiotics using the capsular route requires investigation. The aim of this work was to determine the safety, tolerability, and impact on mucosal/stool microbiota and brain function in HE after capsular FMT in a randomized, single-blind, placebo-controlled clinical trial in Virginia. Patients with cirrhosis with recurrent HE with MELD (Model for End-Stage Liver Disease) <17 on SOC were randomized 1:1 into receiving 15 FMT capsules versus placebo from a single donor enriched in Lachnospiraceae and Ruminococcaceae. Endoscopies with duodenal and sigmoid biopsies, stool analysis, cognition, serum lipopolysaccharide-binding protein (LBP), and duodenal antimicrobial peptide (AMP) expression at baseline were used. Clinical follow-up with SOC maintenance was performed until 5 months. FMT-assigned patients underwent repeat endoscopies 4 weeks postenrollment. Twenty subjects on lactulose/rifaximin were randomized 1:1. MELD score was similar at baseline (9.6 vs. 10.2) and study end (10.2 vs. 10.5). Six patients in the placebo group required hospitalizations compared to 1 in FMT, which was deemed unrelated to FMT. Infection/HE episodes were similar between groups. Baseline microbial diversity was similar in all tissues between groups. Post-FMT, duodenal mucosal diversity (P = 0.01) increased with higher Ruminococcaceae and Bifidobacteriaceae and lower Streptococcaceae and Veillonellaceae. Reduction in Veillonellaceae were noted post-FMT in sigmoid (P = 0.04) and stool (P = 0.05). Duodenal E-cadherin (P = 0.03) and defensin alpha 5 (P = 0.03) increased whereas interleukin-6 (P = 0.02) and serum LBP (P = 0.009) reduced post-FMT. EncephalApp performance improved post-FMT only (P = 0.02). Conclusion: In this phase 1 study, oral FMT capsules are safe and well tolerated in patients with cirrhosis and recurrent HE. FMT was associated with improved duodenal mucosal diversity, dysbiosis, and AMP expression, reduced LBP, and improved EncephalApp performance. Further studies are needed to prove efficacy.

RevDate: 2020-07-01

Park R, Umar S, A Kasi (2020)

Immunotherapy in Colorectal Cancer: Potential of Fecal Transplant and Microbiota-augmented Clinical Trials.

Current colorectal cancer reports, 16(4):81-88.

Purpose of review: This review summarizes the role of the microbiome in colorectal cancer (CRC) in the setting of immunotherapy and emphasizes the potential of microbiota-influencing strategies with a focus on the use of fecal microbiota transplant (FMT).

Recent findings: Observations from preclinical and clinical studies suggest that the human gut microbiome is implicated in the CRC carcinogenesis and is integral in determining the clinical response and toxicity to immunotherapy. Among the therapeutic methods devised to exploit the microbiome, FMT is the most direct method and is backed by the highest level of evidence of efficacy in nonneoplastic disease settings. Furthermore, a favorable microbiome has the potential to overcome immunotherapy resistance and ameliorate immune-related adverse events (irAEs). To this end, clinical trials are underway to evaluate the potential of FMT and microbiota-augmented methods in the setting of immunotherapy in CRC.

Summary: Evidence from animal studies, retrospective studies, and smaller-scale prospective human studies have led to initiation of a number of microbiota-augmented clinical trials in CRC. Given the intimate relationship between the gut microbiota and the immune system as well as antitumor immune responses, potentiating immunotherapy and managing its toxicity are major areas of research in microbiota-augmented therapies in cancer. Therefore, evaluation of the patient microbiome as a routine part of clinical outcome analysis is warranted in future clinical trials.

RevDate: 2020-07-01

Benech N, H Sokol (2020)

Fecal microbiota transplantation in gastrointestinal disorders: time for precision medicine.

Genome medicine, 12(1):58 pii:10.1186/s13073-020-00757-y.

Fecal microbiota transplantation (FMT) has demonstrated efficacy in treating inflammatory bowel diseases and irritable bowel syndrome in an increasing number of randomized controlled trials. Recently published data gives striking insights into the factors associated with FMT success paving the road for the use of precision medicine in gastrointestinal disorders.

RevDate: 2020-06-30

Meyer DC, Hill SS, Bebinger DM, et al (2020)

Resolution of multiply recurrent and multifocal diverticulitis after fecal microbiota transplantation.

Techniques in coloproctology pii:10.1007/s10151-020-02275-w [Epub ahead of print].

BACKGROUND: The exact pathophysiology of diverticulitis is not well understood and may be multifactorial. Recent studies highlight dysbiosis as a plausible mechanism. FMT is a safe strategy to restore commensal colon microbiota and has proven to be an effective treatment for gastrointestinal dysbiosis such as Clostridium difficile infection (CDI). There have been no studies reporting the treatment of diverticulitis with FMT. Our aim was to describe the novel application of fecal microbiota transplantation (FMT) for the treatment of recurrent diverticulitis.

CASE: We report a case of a 63-year-old woman who had a 13-year history of multiply recurrent and multifocal diverticulitis previously treated with numerous short courses of intravenous and oral antibiotics for acute flares, two segmental colon resections, and suppressive antibiotic therapy for recurrent disease. Secondary to multiple courses of antibiotics , the patient developed CDI. She was treated with a single round of FMT and subsequently stopped all antibiotics at the time of FMT.

RESULTS: In 20 months of follow-up, the patient has had no further recurrence of diverticulitis or CDI.

CONCLUSIONS: FMT could prove to be a novel therapy for refractory diverticulitis but requires further investigation.

RevDate: 2020-06-30

Hazan S (2020)

Rapid improvement in Alzheimer's disease symptoms following fecal microbiota transplantation: a case report.

The Journal of international medical research, 48(6):300060520925930.

Alzheimer's disease (AD), the most common form of dementia, is a leading cause of death and a major cause of morbidity in older people. The disease is characterized by progressive memory loss, cognitive impairment, and the cerebral accumulation of amyloid-β peptide. Given the health and economic impacts of AD, treatments that target the underlying etiology of AD or modify the course of the disease are of significant interest. The gut microbiome has been increasingly implicated in the pathogenesis of several neurological diseases, including multiple sclerosis and Parkinson's disease. Furthermore, emerging evidence has demonstrated that there are alterations in gut microbiome composition in patients with AD, suggesting involvement of the microbiome-gut-brain axis. We present symptom improvement in a patient with AD following fecal microbiota transplantation for a Clostridioides difficile infection.

RevDate: 2020-06-29

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

[A case report of refractory methemoglobinemia after nitrite poisoning treated by fecal microbiota transplantation].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 23(Z1):90-92.

RevDate: 2020-06-29

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

[Application of modified blind nasojejunal tube technique in fecal microbiota transplantation - report of 2267 cases].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 23(Z1):86-89.

RevDate: 2020-06-29

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

[Association between the clinical efficacy of fecal microbiota transplantation in recipients and the choice of donor].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 23(Z1):69-76.

Objective: To examine the association between the clinical efficacy of fecal microbiota transplantation (FMT) in recipients and the choice of donor, and to observe the characteristics of intestinal flora and metabolites among different donors. Methods: A retrospective case-control study was conducted. Donor whose feces was administrated for more than 30 recipients was enrolled. Data of 20 FMT donors and corresponding recipients at Intestinal Microecology Diagnosis and Treatment Center of the Tenth People's Hospital from October 2018 to December 2019 were collected retrospectively. During follow-up, the efficacy of each recipient 8-week after FMT treatment was recorded and analyzed. Based on the efficacy of each donor, the donors were divided into three groups: high efficacy group (effective rate >60%, 10 donors), moderate efficacy group (effective rate 30%-60%, 6 donors) and low efficacy group (effective rate <30%, 4 donors). The structure of the bacterial flora and the content of fecal short-chain fatty acids in each group of donors were detected and compared among groups. Association of the efficacy of each donor group with the morbidity of complications, and association of efficacy of recipients with donors were analyzed. The evaluation indicators of FMT efficacy included objective clinical effectiveness and/or subjective effectiveness. Objective effectiveness indicated clinical cure plus clinical improvement, and subjective effectiveness indicated marked effectiveness plus medium effectiveness through questionnaire during follow-up. Results: A total of 1387 recipients were treated by 20 donors, including 749 cases of chronic constipation, 141 cases of chronic diarrhea, 107 cases of inflammatory bowel disease (IBD), 121 cases of irritable bowel syndrome (IBS), 83 cases of autism, and 186 cases of other diseases, such as radiation bowel injury, intestinal pseudo-obstruction, paralytic intestinal obstruction, functional bloating and allergic diseases. There were 829 cases, 403 cases, and 155 cases in high efficacy group, moderate efficacy group and low efficacy group respectively. Baseline data among 3 groups were not significantly different (all P> 0.05). In comparison of bacterial abundance (operational taxonomic unit, OTU) among different effective donor groups, the high efficacy group was the highest (330.68±57.28), the moderate efficacy group was the second (237.79±41.89), and the low efficacy group was the lowest (160.60±49.61), whose difference was statistically significant (F=16.910, P<0.001). In comparison of bacterial diversity (Shannon index), the high efficacy group and the moderate efficacy group were higher (2.96±0.36 and 2.67±0.54, respectively), and the low efficacy group was lower (2.09±0.55), whose difference was statistically significant (F=5.255, P=0.017). In comparison of butyric acid content among three groups, the high efficacy group had the highest [(59.20±9.00) μmol/g], followed by middle efficacy group [(46.92±9.48) μmol/g], and the low efficacy group had the lowest [(37.23±5.03) μmol/g], whose difference was statistically significant (F=10.383, P=0.001). The differences of acetic acid and propionic acid among three groups were not statistically significant (all P>0.05). A total of 418 cases developed complications (30.1%). Morbidity of complication in low efficacy group, moderate efficacy group and high efficacy group was 40.6% (63/155), 30.0% (121/403) and 28.2% (243/829) respectively, and the difference was statistically significant (χ(2)=9.568, P=0.008). The incidence of diarrhea in low efficacy group, moderate efficacy group and high efficacy group was 7.1% (11/155), 4.0% (16/403) and 2.8% (23/829) respectively, and the difference was statistically significant (χ(2)=7.239, P=0.027). Comparing the incidences of other types of complications, no statistically significant differences were found (all P>0.05). Follow up began 8 weeks after the FMT treatment. The total follow-up rate was 83.6% (1160/1387). The overall effective rate 58.3% (676/1160). Effective rates of various diseases were as follows: chronic constipation 54.3% (328/604), chronic diarrhea 88.5% (115/130), IBD 56.1% (55/98), IBS 55.1% (59/107), autism 61.6% (45/73), and other diseases 50.0% (74/148). Comparing the effective rate of three groups of donors for different diseases, there was no statistically significant difference in chronic diarrhea (P>0.05); there was a positive correlation trend in IBD, IBS and autism, but the differences were not statistically significant (all P>0.05). For chronic constipation and other diseases, high efficacy group had the highest effective rate [65.0% (243/374) and 63.2% (55/87)], followed by moderate efficacy group [49.4% (86/174) and 38.1% (16/42)], and low efficacy group had the lowest [16.1% (9/56) and 15.8% (3/19)], whose differences were significant (all P<0.05). Conclusions: Different donors have different efficacy in different diseases. Chronic constipation, radiation bowel injury, etc. need to choose donors with high efficacy. IBD, IBS and autism may also be related to the effectiveness of donors, while chronic diarrhea is not associated to the donor. The efficiency of the donor is negatively correlated to the morbidity of complications. The abundance and diversity of intestinal flora and the content of butyric acid may affect the efficacy of the donor.

RevDate: 2020-06-29

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

[Effects of fecal microbiota transplantation in different routes on the clinical efficacy of slow transit constipation].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 23(Z1):63-68.

Objective: To evaluate the efficacy and safety of the fecal microbiota transplantation (FMT) in the different route administration for slow transit constipation (STC). Methods: A retrospective cohort study was conducted. The clinical data of 270 STC patients who voluntarily received FMT treatment in the Tenth People's Hospital of Tongji University from May 2018 to May 2019 were collected. Non-relative healthy adult standard donors were applied. The treatment routes of bacterial flora transplantation included nasojejunal tube (nasal enteral tube group, 120 cases), oral enterobacterial capsule treatment (oral capsule group, 120 cases), and colonoscopy infusion (colonoscopy group, 30 cases). The efficacy and safety of treatment among the three groups were compared. Results: Transplanted bacteria of three groups were extracted from 100 g of fresh feces. All the patients successfully completed the transplantation. The waiting time for the nasal enteral tube group, oral capsule group and colonoscopy group was (1.5±0.5) d, (0.4±0.3) d and (3.6±0.8) d respectively; the cost of establishing the transplantation path was (495±20) yuan, (25±10) yuan and (1420±45) yuan respectively, whose differences were statistically significant (F=9.210, P=0.03; F=10.600,P=0.01). The clinical improvement rates at 1 month after FMT treatment in the nasojejunal tube group, oral capsule group and colonoscopy group were 74.2% (89/120), 60.0% (72/120) and 53.3% (16/30) respectively, whose difference was statistically significant (χ(2)=5.990, P<0.05). The clinical improvement rates at 3 months after treatment were 71.1% (69/97), 53.6% (45/84), and 44.0% (11/25) respectively, whose difference was statistically significant (χ(2)=7.620, P<0.05). The incidence of adverse reactions in the colonoscopy group was 76.7% (23/30), which was higher than that in the nasal nasojejunal group (39.2%, 47/120) and oral capsule group (21.7%, 26/120). The most common adverse reactions in the nasojejunal tube group, oral capsule group and colonoscopy group were respiratory discomfort (17.5%, 21/120), nausea and vomiting (10.0%, 12/120), and diarrhea (36.7%, 11/30). During the 3-month follow-up after treatment, no FMT-related adverse reactions were reported. Conclusions: The nasojejunal tube route has stable clinical efficacy and operability, while the oral capsule route has shorter waiting time and less cost. However, the adverse reactions caused by different transplantation methods are different, thus personalized transplantation method should be recommended.

RevDate: 2020-06-29

Lin ZL, Chen QY, Tian HL, et al (2020)

[Effect of fecal bacterial preservation time on the outcomes of fecal microbiota transplantation for slow transit constipation].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 23(Z1):56-62.

Objective: To investigate the effect of different fecal bacterial preservation time on the efficacy and complications of FMT. Methods: A retrospective cohort study was carried out. Clinical data of 483 patients with slow transit constipation undergoing voluntary FMT at Intestinal Microecology Diagnosis and Treatment Center from August 2017 to October 2019 were retrospectively collected. According to the storage time of fecal bacterial samples used in FMT treatment, the cases were divided into fresh bacterial solution (n=29), bacterial solution stored at -80℃ for 1 week (n=187), 1 month (n=121), 3 months (n=89), 6 months (n=38), and 12 months (n=19). The total number of complete bowel movement, Wexner constipation score, gastrointestinal quality of life index (GIQLI), FMT satisfaction score and related adverse reactions were summarized and compared among groups 1 week and 1 month after FMT treatment. Results: There were no statistically significant differences in the baseline data of patients among different bacterial solution storage time (all P>0.05). After 1 month of treatment, the overall frequency of defecation of all the patients was (3.83 ± 1.22) times/week, Wexner constipation score was (6.74 ± 3.56) points, GIQLI score was (108.76 ± 15.38) points, clinical cure rate was 57.8% (279/483). The improvement rate was 66.3% (320/483), and the treatment satisfaction was (3.85 ± 0.93) points. No severe FMT-associated complication and death were observed during treatment and follow-up period. FMT-related adverse events occurred in 115 cases (23.8%), including nausea in 25 cases (5.2%), vomiting in 13 (2.7%), diarrhea in 21 (4.3%), abdominal pain in 16 (3.3%), abdominal distension in 33 (6.8%), sore throat in 56 (11.6%) and fever in 16(3.3%), all of which relieved after symptomatic treatment. There were no statistically significant differences in the number of defecations, Wexner constipation scores, and GIQLI scores before FMT, 1 week and 1 month after FMT treatment among different bacterial solution storage groups (all P>0.05). Differences of clinical cure rate, clinical improvement rate, and treatment satisfaction of patients 1 week and 1 month after treatment were not statistically significant (all P>0.05). Among the groups, differences in the overall complications and types of complications after FMT treatment were not statistically significant (all P>0.05). Conclusions: FMT is safe and effective in the treatment of slow transit constipation. Fresh fecal bacterial samples or fecal bacterial samples frozen at -80℃ for 1 year can be safely applied to FMT for the treatment of slow transit constipation, with stable short-term efficacy and without serious adverse reactions.

RevDate: 2020-06-29

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

[Effect of intestinal preparation on the efficacy and safety of fecal microbiota transplantation treatment].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 23(Z1):48-55.

Objective: To investigate the effect of intestinal preparation on the efficacy and complications of fecal microbiota transplantation (FMT). Methods: A retrospective cohort study was performed. Clinical and follow-up data of 1501 patients who received FMT in the department of Colorectal Disease Specialty, Intestinal Microecology Diagnosis and Treatment Center, the Tenth People's Hospital, Tongji University from February 2018 to June 2019 were collected retrospectively. According to the intestinal preparation before FMT treatment, patients were divided into non-intestinal preparation group (n=216), antibiotic pretreatment group (n=383), intestinal cleansing group (n=267), and antibiotic combined with intestinal cleansing group (n=635). The adverse reactions after FMT treatment and the effective rates at 4-week and 8-week after treatment among the groups were compared. Patients, who repeated FMT treatment in the 3rd month and the 6th month due to reduced efficacy or ineffectiveness were divided into two subgroups: without intestinal preparation group and with intestinal preparation group. The effective rates of the two subgroups were compared. Results: Of the 1501 cases, 588 were male and 913 were female with mean age of (43.3±13.7) years and body mass index of (20.2±2.1) kg/m(2). Transplantation course was (3.3±1.7) weeks. The underlying diseases mainly included constipation (n=564), Crohn's disease (n=157), ulcerative colitis (n=142), irritable bowel syndrome (n=158), recurrent C. difficile infection (CDI) (n=106), autism (n=84), radiation intestinal injury (n=133), radiation enteritis (n=133), and non-CDI chronic diarrhea (n=60); the remaining cases (n=155). Baseline data among the 4 groups were not significantly different (all P>0.05). The overall morbidity of complication was 31.1% (467/1501), including 41 cases of vomiting (2.7%), 91 of nausea (6.1%), 49 of diarrhea (3.3%), 41 of abdominal pain (2.7%), 79 of bloating (5.3%), 72 of throat pain (4.8%), 38 of dizziness (2.5%), 51 of fever (3.4%), 3 of pulmonary infection (0.2%) and 2 of intestinal infection (0.1%). The above symptoms disappeared after symptomatic treatment. There was no statistically significant difference in the incidence of adverse reactions among the 4 groups (P>0.05). After 4-week of FMT treatment, the overall effective rate was 63.5% (902/1420); the effective rate of non-intestinal preparation group, antibiotic pretreatment group, intestinal cleaning group, and antibiotic combined with intestinal cleansing groupwas 57.6% (114/198), 64.2% (231/360), 60.2% (154/265) and 66.5% (403/606), respectively, with no statistically significant difference (χ(2)=6.659, P=0.084). After 8-week of FMT treatment, the overall effective rate was 61.3% (729/1293); the effective rate of non-intestinal preparation group, antibiotic pretreatment group, intestinal cleaning group, and antibiotic combined with intestinal cleansing group was 54.0% (88/163), 62.2% (202/325), 57.4% (132/230) and 64.4% (370/575), respectively, with no statistically significant difference (χ(2)=13.620, P=0.003). The effective rates of antibiotic combined with intestinal cleansing group and antibiotic pretreatment group were obviously higher than that of non-intestinal preparation group (χ(2)=5.789, P=0.016; χ(2)=10.117, P=0.001). Subgroup analysis showed that in the third month, the effective rate at 4-week after treatment was 60.1% (184/306) in the without intestinal preparation group and 61.5% (115/187) in the with intestinal preparation group, whose difference was not significant (χ(2)=0.091, P=0.763); however, in the sixth month, the effective rate at 4-week after treatment was 51.4% (89/173) in the without intestinal preparation group and 61.2% (161/263) in the with intestinal preparationgroup, whose difference was significant (χ(2)=4.229, P=0.040). Conclusions: FMT treatment is safe and effective. The combination of antibiotics and intestinal cleaning can improve overall efficacy of FMT. For patients who need repeated FMT treatment, the combination of antibiotics and intestinal cleaning program within 3 months has no significant effect on the effective rate, but in the sixth month, combinedpreparation is necessary.

RevDate: 2020-06-29

Zhang FM, YF Liu (2020)

[Evidence and decision of the choice of delivery way in washed microbiota transplantation].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 23(Z1):45-47.

Washed microbiota transplantation (WMT) is a new concept and technique of fecal microbiota transplantation. The delivery routes of WMT include oral capsule, nasogastric tube, nasojejunal tube, gastroscopy, colonic transendoscopic enteral tubing, and anal enema. The research results among different indications or different designs based on the same indication are quite different, partially because of the influence of WMT delivery route. In the process of clinical research design and clinical practice, there are four aspects that affect the decision-making of WMT delivery route: safety, efficacy, cost-effectiveness, and patients' willingness. This article focuses on how to integrate the four aspects mentioned above in the decision-making process of choosing proper delivery of WMT for the final goal of mutual satisfaction between doctors and patients.

RevDate: 2020-06-29

Parenteral and Enteral Nutrition Branch of Chinese Medical Association, Enhanced Recovery After Surgery Branch of China International Health Care Promotion and Exchange Association, China Microecological Treatment Innovation Alliance, et al (2020)

[Chinese experts consensus on clinical practice of the selection and establishment of fecal microbiota transplantation delivery routes].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 23(Z1):14-20.

Fecal microbiota transplantation (FMT) has gradually shown application prospects in the treatment of intestinal and extraintestinal diseases. In order to standardized FMT operation, based on the clinical experience of the Tenth People's Hospital Affiliated to Tongji University, combined with domestic and foreign literature, Parenteral and Enteral Nutrition Branch of Chinese Medical Association, Enhanced Recovery after Surgery Branch of China International Health Care Promotion Exchange Association, China Microecological Treatment Innovation Alliance, and Microecology Committee of Shanghai Preventive Medicine Association to formulated the" Chinese experts consensus on clinical practice of the selection and establishment of fecal microbiota transplantation delivery routes". It includes four parts: the selection of delivery route, the methodology of transplantation path establishment, the clinical application, and the monitoring of adverse events.

RevDate: 2020-06-29

Parenteral and Enteral Nutrition Branch of Chinese Medical Association, Enhanced Recovery After Surgery Branch of China International Health Care Promotion and Exchange Association, China Microecological Treatment Innovation Alliance, et al (2020)

[Chinese experts consensus on standardized methodology and clinical application of fecal microbiota transplantation].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 23(Z1):5-13.

Fecal microbiota transplantation (FMT) is to transplant the functional bacteria in the feces of healthy people into the patients' intestines, rebuild the new balance of intestinal flora, and achieve the treatment goals of intestinal and extraintestinal diseases. In the past 10 years, FMT has made a breakthrough in the treatment of intestinal and extraintestinal diseases, which is highly expected to treat difficult diseases. However, due to the complexity of FMT methodology and the lack of a unified standard, there is a high heterogeneity in FMT efficacy among various researches, greatly affected its clinical application. Under the initiative of Parenteral and Enteral Nutrition Branch of Chinese Medical Association, Enhanced Recovery after Surgery Branch of China International Health Care Promotion Exchange Association, China Microecological Treatment Innovation Alliance, and Microecology Committee of Shanghai Preventive Medicine Association, the first expert consensus on standardized methodology and clinical application of FMT was established in China, with a view to improving the efficacy of FMT, reducing the incidence of adverse reactions and promoting the clinical application of FMT.

RevDate: 2020-06-29

Li N (2020)

[Practice and consideration of fecal microbiota transplantation].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 23(Z1):1-4.

As an innovative therapy, FMT has made a breakthrough in the treatment of recurrent Clostridium difficile infection (CDI). With the rapid development of biotechnology, the relationship between intestinal microflora and diseases has been gradually eluciated. Great hope has also been given to FMT in other intestinal and extraintestinal diseases with ineffective traditional treatment. However, as a new therapy method, FMT still has many unknown fields, such as the selection of clinical donors, the preparation of standardized bacterial solution and capsule, the selection of indications, the matching of donor and receptor, and the prevention and treatment of complications. Since 2012, our center has carried out treatment research and practice of FMT, so far with more than 60 000 FMTs for more than 3500 cases. Based on large sample data and experience, this special issue reports and discusses the above topics, and focuses on the establishment and clinical application of standardized methodology of FMT, which will undoubtedly play a positive role in promoting the healthy development of FMT treatment in China.

RevDate: 2020-06-30
CmpDate: 2020-06-30

Mikail M, O'Doherty KC, Poutanen SM, et al (2020)

Ethical implications of recruiting universal stool donors for faecal microbiota transplantation.

The Lancet. Infectious diseases, 20(3):e44-e49.

Faecal microbiota transplantation is an effective therapy for recurrent Clostridioides difficile infection, with potential therapeutic applications in other health conditions. As research uncovers potential associations between the intestinal microbiome and various disease states, stool donor screening has become increasingly stringent, leading to low donor acceptance. Many stool banks have opted to recruit universal stool donors, who are encouraged to donate frequently over a prolonged period and whose stool is used to treat multiple patients. However, various ethical concerns arise when recruiting universal stool donors, which need to be addressed to mitigate harm to donors. In this Personal View, we describe the major ethical issues with universal stool banks across six domains: informed consent, privacy, the imposing of restrictions on autonomy, stewardship of microbiome information, financial incentives, and preventing a sense of obligation. We also suggest several priorities for future research that should be pursued to address these crucial issues and develop more donor-centric stool banks.

RevDate: 2020-06-30
CmpDate: 2020-06-30

Duan Y, Prasad R, Feng D, et al (2019)

Bone Marrow-Derived Cells Restore Functional Integrity of the Gut Epithelial and Vascular Barriers in a Model of Diabetes and ACE2 Deficiency.

Circulation research, 125(11):969-988.

RATIONALE: There is incomplete knowledge of the impact of bone marrow cells on the gut microbiome and gut barrier function.

OBJECTIVE: We postulated that diabetes mellitus and systemic ACE2 (angiotensin-converting enzyme 2) deficiency would synergize to adversely impact both the microbiome and gut barrier function.

METHODS AND RESULTS: Bacterial 16S rRNA sequencing and metatranscriptomic analysis were performed on fecal samples from wild-type, ACE2-/y, Akita (type 1 diabetes mellitus), and ACE2-/y-Akita mice. Gut barrier integrity was assessed by immunofluorescence, and bone marrow cell extravasation into the small intestine was evaluated by flow cytometry. In the ACE2-/y-Akita or Akita mice, the disrupted barrier was associated with reduced levels of myeloid angiogenic cells, but no increase in inflammatory monocytes was observed within the gut parenchyma. Genomic and metatranscriptomic analysis of the microbiome of ACE2-/y-Akita mice demonstrated a marked increase in peptidoglycan-producing bacteria. When compared with control cohorts treated with saline, intraperitoneal administration of myeloid angiogenic cells significantly decreased the microbiome gene expression associated with peptidoglycan biosynthesis and restored epithelial and endothelial gut barrier integrity. Also indicative of diabetic gut barrier dysfunction, increased levels of peptidoglycan and FABP-2 (intestinal fatty acid-binding protein 2) were observed in plasma of human subjects with type 1 diabetes mellitus (n=21) and type 2 diabetes mellitus (n=23) compared with nondiabetic controls (n=23). Using human retinal endothelial cells, we determined that peptidoglycan activates a noncanonical TLR-2 (Toll-like receptor 2) associated MyD88 (myeloid differentiation primary response protein 88)-ARNO (ADP-ribosylation factor nucleotide-binding site opener)-ARF6 (ADP-ribosylation factor 6) signaling cascade, resulting in destabilization of p120-catenin and internalization of VE-cadherin as a mechanism of deleterious impact of peptidoglycan on the endothelium.

CONCLUSIONS: We demonstrate for the first time that the defect in gut barrier function and dysbiosis in ACE2-/y-Akita mice can be favorably impacted by exogenous administration of myeloid angiogenic cells.

RevDate: 2020-06-27

Jiang S, Wang B, Sha T, et al (2020)

Changes in the Intestinal Microbiota in Patients with Stage 5 Chronic Kidney Disease on a Low-Protein Diet and the Effects of Human to Rat Fecal Microbiota Transplantation.

Medical science monitor : international medical journal of experimental and clinical research, 26:e921557 pii:921557.

BACKGROUND Dietary protein restriction is recommended for patients with stage 5 chronic kidney disease (CKD), or end-stage renal disease (ESRD). This study aimed to investigate the changes in the intestinal microbiota due to different dietary regimens in patients with stage 5 CKD and the effects of human to rat fecal microbiota transplantation. MATERIAL AND METHODS Second-generation high-throughput sequencing was used to analyze the amplifiers in the 16S rRNA V4 region in the intestinal microbiota of patients with stage 5 CKD and healthy individuals. The intestinal microbiota of patients with stage 5 CKD in the low-protein group and the healthy individual group was transferred by human to rat fecal microbiota transplantation using Sprague-Dawley rats. Data underwent meta-analysis using Meta-Stat. RESULTS Patients with CKD on a very low-protein diet showed an increase in intestinal Escherichia, Shigella, and Klebsiella, a decrease in Blautia, heat map analysis showed that Christensenellaceae R-7 group rs1 were significantly increased, and MetaStat analysis showed that Bacteroides, Prevotella, and Mitsuokella were significantly increased. Following human to rat fecal microbiota transplantation from patients with stage 5 CKD, the profile of the rat intestinal microbiota became similar to the human donors. The weight of the rats fed a very low-protein diet after fecal microbiota transplantation significantly decreased after six weeks compared with normal rats and rats that received normal fecal microbiota transplantation. CONCLUSIONS Patients with stage 5 CKD on a very low-protein diet showed changes in the intestinal microbiota that could be transferred from humans to rats by fecal microbiota transplantation.

RevDate: 2020-06-26

Zhgun ES, Kislun YV, Kalachniuk TN, et al (2020)

[Evaluation of metabolites levels in feces of patients with inflammatory bowel diseases].

Biomeditsinskaia khimiia, 66(3):233-240.

Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn's disease (CD), are chronic intestinal inflammatory disorders with an unknown etiology. They are characterized by chronic recurrent inflammation of the intestinal mucosa and lead to a significant decrease in the quality of life and death of patients. IBD are associated with suppression of normal intestinal microflora, including a decrease in bacteria, producers of short chain fatty acids (SCFAs), exhibiting anti-inflammatory and protective properties. Among the various methods of intestinal microflora correction, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, is of a particular interest. As a result, a positive therapeutic effect is observed, accompanied by the restoration of the normal intestinal microflora of the patient. A significant drawback of the method is the lack of standardization. Metabolites produced by intestinal microflora, namely SCFAs, allow objective assessment of the functional state of the intestinal microbiota and, consequently, the success of the FMT procedure. Using gas chromatography and nuclear magnetic resonance spectroscopy techniques, we have analyzed concentrations and molar ratios of SCFAs in fecal samples of 60 healthy donors. Results were in good accord when comparing two methods as well as with published data. Analysis of SCFAs in feces of patients with UC (19 patients) and CD (17 patients) revealed a general decrease in the concentration of fatty acids in the experimental groups with significant fluctuations in the values in experimental groups compared to control group of healthy donors. On the limited group of IBD patients (6 patients with UC and 5 patients with CD) concentration of SCFAs before and within 30 days of observation after FMT was determined. It was shown that FMT had a significant impact on the SCFAs levels within 1 month term; tendency to reach characteristics of healthy donors is unambiguously traced for both diseases.

RevDate: 2020-06-26

Li H, Xu H, Li Y, et al (2020)

Alterations of gut microbiota contribute to the progression of unruptured intracranial aneurysms.

Nature communications, 11(1):3218 pii:10.1038/s41467-020-16990-3.

Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Whether changes in gut microbial composition participate in the development of UIAs remains largely unknown. We perform a case-control metagenome-wide association study in two cohorts of Chinese UIA patients and control individuals and mice that receive fecal transplants from human donors. After fecal transplantation, the UIA microbiota is sufficient to induce UIAs in mice. We identify UIA-associated gut microbial species link to changes in circulating taurine. Specifically, the abundance of Hungatella hathewayi is markedly decreased and positively correlated with the circulating taurine concentration in both humans and mice. Consistently, gavage with H. hathewayi normalizes the taurine levels in serum and protects mice against the formation and rupture of intracranial aneurysms. Taurine supplementation also reverses the progression of intracranial aneurysms. Our findings provide insights into a potential role of H. hathewayi-associated taurine depletion as a key factor in the pathogenesis of UIAs.

RevDate: 2020-06-26

Leo S, Lazarevic V, Girard M, et al (2020)

Metagenomic Characterization of Gut Microbiota of Carriers of Extended-Spectrum Beta-Lactamase or Carbapenemase-Producing Enterobacteriaceae Following Treatment with Oral Antibiotics and Fecal Microbiota Transplantation: Results from a Multicenter Randomized Trial.

Microorganisms, 8(6): pii:microorganisms8060941.

Background: The R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) WP3 study was the first multicenter randomized clinical trial systematically investigating fecal microbiota transplantation (FMT) for intestinal decolonization of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Here, we characterized the temporal dynamics of fecal microbiota changes in a sub-cohort of the R-GNOSIS WP3 participants before and after antibiotics/FMT using whole metagenome shotgun sequencing. Methods: We sequenced fecal DNA obtained from 16 ESBL-E/CPE carriers having received oral colistin/neomycin followed by FMT and their corresponding seven donors. Ten treatment-naïve controls from the same trial were included. Fecal samples were collected at baseline (V0), after antibiotics but before FMT (V2) and three times after FMT (V3, V4 and V5). Results: Antibiotic treatment transiently decreased species richness and diversity and increased the abundance of antibiotic resistance determinants (ARDs). Bifidobacterium species, together with butyrate- and propionate-producing species from Lachnospiraceae and Ruminococcaceae families were significantly enriched in post-FMT microbiota of treated carriers. After FMT, the proportion of Enterobacteriaceae was lower compared to baseline but without statistical significance. Conclusions: Combined antibiotic and FMT treatment resulted in enrichment of species that are likely to limit the gut colonization by ESBL-E/CPE.

RevDate: 2020-06-25

Basson AR, Zhou Y, Seo B, et al (2020)

Autologous fecal microbiota transplantation for the treatment of inflammatory bowel disease.

Translational research : the journal of laboratory and clinical medicine pii:S1931-5244(20)30111-0 [Epub ahead of print].

The term autologous fecal microbiota transplantation (a-FMT) refers herein to the use of one's feces during a healthy state for later use to restore gut microbial communities after perturbations. Generally, heterologous fecal microbiota transplantation (h-FMT), where feces from a ``healthy" donor is transplanted into a person with illness, has been used to treat infectious diseases such as recurrent Clostridioides difficile infection (CDI), with cure rates of up to 90%. In humans, due to limited response to medicines, h-FMT has become a hallmark intervention to treat CDI. Extrapolating the benefits from CDI, h-FMT has been attempted in various diseases, including inflammatory bowel disease (IBD), but clinical response has been variable and less effective (ranging between 24% and 50%). Differences in h-FMT clinical response could be because CDI is caused by a Clostridial infection, whereas IBD is a complex, microbiome-driven immunological inflammatory disorder that presents predominantly within the gut wall of genetically-susceptible hosts. FMT response variability could also be due to differences in microbiome composition between donors, recipients, and within individuals, which vary with diet, and environments, across regions. While donor selection has emerged as a key factor in FMT success, the use of heterologous donor stool still places the recipient at risk of exposure to infectious/pathogenic microorganisms. As an implementable solution, herein we review the available literature on a-FMT, and list some considerations on the benefits of a-FMT for IBD.

RevDate: 2020-06-25

Gong Z, Y Wang (2020)

Immune Checkpoint Inhibitor-Mediated Diarrhea and Colitis: A Clinical Review.

JCO oncology practice [Epub ahead of print].

Immune-mediated diarrhea and colitis (IMDC) is among the most common immune-related adverse events in patients with cancer treated with immune checkpoint inhibitors (ICIs). Many factors will affect the risk of IMDC, including the type of ICI used, the type of underlying cancer, and patient characteristics. A recent study showed that preexisting inflammatory bowel disease significantly increases the risk of diarrhea and colitis with ICI treatment. In terms of management, early endoscopic evaluation improves clinical outcome by identifying high-risk patients who will benefit from early add-on immunosuppressants. Inflammatory markers, including fecal lactoferrin and calprotectin, are good screening tools to predict which patients are at risk for colitis. Calprotectin especially is associated with colitis outcome and can be used as a surrogate marker to follow treatment response. Corticosteroids remain the first-line medical treatment of IMDC management, and add-on therapy with vedolizumab or infliximab should be considered in selected patients. Fecal microbiota transplantation may be considered in refractory cases. The decision to resume ICI should be decided by balancing the risk of recurrent IMDC and the likelihood of benefiting from further ICI treatment. There is no clear evidence about whether the use of immunosuppressants will result in a worse cancer outcome. With emerging evidence, our understanding and management strategies are likely to evolve in the future.

RevDate: 2020-06-25

Yan Y, Zhou X, Guo K, et al (2020)

Chlorogenic Acid Protects Against Indomethacin-Induced Inflammation and Mucosa Damage by Decreasing Bacteroides-Derived LPS.

Frontiers in immunology, 11:1125.

Background: Chlorogenic acid (CGA), a natural bioactive polyphenol, exerts anti-inflammatory, antioxidant, and antibacterial effects that support the maintenance of intestinal health. However, the influence of CGA on gut microbiota and their metabolites, as well as its potential effects and mechanism of action in inflammatory bowel disease, remain to be elucidated. Methods: First, an oral gavage was used to administer CGA to indomethacin-treated mice. Then, fecal microbiota transplantation was performed to explore the role of intestinal microbiota in indomethacin-induced inflammation. Results: CGA treatment protected against body weight loss, damage to intestinal morphology and integrity, inflammation, and alteration of microbiota composition in indomethacin-treated mice. Interestingly, CGA failed to inhibit inflammation or protect intestine integrity in mice treated with antibiotics. Notably, mice who had been colonized with intestinal microbiota from CGA-treated or CGA-and-indomethacin-treated mice, through the fecal microbiota transplantation program, were protected from indomethacin-induced inflammation, growth of Bacteroides, and the accumulation of Bacteroides-derived LPS, in congruence with those who had been treated with CGA. Conclusion: The results suggest that CGA may protect intestine integrity and alleviate inflammatory responses, primarily by inhibiting the growth of Bacteroides and the accumulation of Bacteroides-derived LPS, in indomethacin-induced colitis. This newly identified mechanism broadens our knowledge of how CGA exerts protective effects on intestinal inflammation and provides strategies for the prevention of gastrointestinal mucosal damage in patients treated with indomethacin.

RevDate: 2020-06-25

Liang W, Zhao L, Zhang J, et al (2020)

Colonization Potential to Reconstitute a Microbe Community in Pseudo Germ-Free Mice After Fecal Microbe Transplant From Equol Producer.

Frontiers in microbiology, 11:1221.

Human intestinal microbiota plays a crucial role in the conversion of isoflavones into equol. Usually, human microbiota-associated (HMA) animal models are used, since it is difficult to establish the mechanism and causal relationship between equol and microbiota in human studies. Currently, several groups have successfully established HMA animal models that produce equol through germ-free mice or rats; however, the HMA model of producing equol through pseudo germ-free mice has not been established. The objective of this study is to establish an HMA mice model for equol production through pseudo germ-free mice, mimicking the gut microbiota of an adult human equol producer. First, a higher female equol producer was screened as a donor from 15 volunteers. Then, mice were exposed to vancomycin, neomycin sulfate, metronidazole, and ampicillin for 3 weeks to obtain pseudo germ-free mice. Finally, pseudo germ-free mice were inoculated with fecal microbiota of the equol producer for 3 weeks to establish HMA mice of producing equol. The results showed that (i) the ability to produce equol was partially transferred from the donor to the HMA mice. (ii) Most of the original intestinal microbiota of mice were eliminated after broad-spectrum antibiotic administration. (iii) The taxonomy data from HMA mice revealed similar taxa to the donor sample, and the species richness returned to the level close to the donor. (iv) The family Coriobacteriaceae and genera Collinsella were successfully transferred from the donor to HMA mice. In conclusion, the HMA mice model for equol production, based on pseudo germ-free mice, can replace the model established by germ-free mice. The model also provides a basis for studying microbiota during the conversion from isoflavones into equol.

RevDate: 2020-06-24

Inamura K (2020)

Gut microbiota contributes towards immunomodulation against cancer: New frontiers in precision cancer therapeutics.

Seminars in cancer biology pii:S1044-579X(20)30142-5 [Epub ahead of print].

The microbiota influences human health and the development of diverse diseases, including cancer. Microbes can influence tumor initiation and development in either a positive or negative manner. In addition, the composition of the gut microbiota affects the efficacy and toxicity of cancer therapeutics as well as therapeutic resistance. The striking impact of microbiota on oncogenesis and cancer therapy provides compelling evidence to support the notion that manipulating microbial networks represents a promising strategy for treating and preventing cancer. Specific microbes or the microbial ecosystem can be modified via a multiplicity of processes, and therapeutic methods and approaches have been evolving. Microbial manipulation can be applied as an adjunct to traditional cancer therapies such as chemotherapy and immunotherapy. Furthermore, this approach displays great promise as a stand-alone therapy following the failure of standard therapy. Moreover, such strategies may also benefit patients by avoiding the emergence of toxic side effects that result in treatment discontinuation. A better understanding of the host-microbial ecosystem in patients with cancer, together with the development of methodologies for manipulating the microbiome, will help expand the frontiers of precision cancer therapeutics, thereby improving patient care. This review discusses the roles of the microbiota in oncogenesis and cancer therapy, with a focus on efforts to harness the microbiota to fight cancer.

RevDate: 2020-06-24

McQuade JL, Ologun GO, Arora R, et al (2020)

Gut Microbiome Modulation Via Fecal Microbiota Transplant to Augment Immunotherapy in Patients with Melanoma or Other Cancers.

Current oncology reports, 22(7):74 pii:10.1007/s11912-020-00913-y.

PURPOSE OF REVIEW: We review emerging evidence regarding the impact of gut microbes on antitumor immunity, and ongoing efforts to translate this in clinical trials.

RECENT FINDINGS: Pre-clinical models and human cohort studies support a role for gut microbes in modulating overall immunity and immunotherapy response, and numerous trials are now underway exploring strategies to modulate gut microbes to enhance responses to cancer therapy. This includes the use of fecal microbiota transplant (FMT), which is being used to treat patients with Clostridium difficile infection among other non-cancer indications. The use of FMT is now being extended to modulate gut microbes in patients being treated with cancer immunotherapy, with the goal of enhancing responses and/or to ameliorate toxicity. However, significant complexities exist with such an approach and will be discussed herein. Data from ongoing studies of FMT in cancer will provide critical insights for optimization of this approach.

RevDate: 2020-06-24

Giannone G, Ghisoni E, Genta S, et al (2020)

Immuno-Metabolism and Microenvironment in Cancer: Key Players for Immunotherapy.

International journal of molecular sciences, 21(12): pii:ijms21124414.

Immune checkpoint inhibitors (ICIs) have changed therapeutic algorithms in several malignancies, although intrinsic and secondary resistance is still an issue. In this context, the dysregulation of immuno-metabolism plays a leading role both in the tumor microenvironment (TME) and at the host level. In this review, we summarize the most important immune-metabolic factors and how they could be exploited therapeutically. At the cellular level, an increased concentration of extracellular adenosine as well as the depletion of tryptophan and uncontrolled activation of the PI3K/AKT pathway induces an immune-tolerant TME, reducing the response to ICIs. Moreover, aberrant angiogenesis induces a hypoxic environment by recruiting VEGF, Treg cells and immune-suppressive tumor associated macrophages (TAMs). On the other hand, factors such as gender and body mass index seem to affect the response to ICIs, while the microbiome composition (and its alterations) modulates both the response and the development of immune-related adverse events. Exploiting these complex mechanisms is the next goal in immunotherapy. The most successful strategy to date has been the combination of antiangiogenic drugs and ICIs, which prolonged the survival of patients with non-small-cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC), while results from tryptophan pathway inhibition studies are inconclusive. New exciting strategies include targeting the adenosine pathway, TAMs and the microbiota with fecal microbiome transplantation.

RevDate: 2020-06-24
CmpDate: 2020-06-24

Burberry A, Wells MF, Limone F, et al (2020)

C9orf72 suppresses systemic and neural inflammation induced by gut bacteria.

Nature, 582(7810):89-94.

A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia1,2. The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration3-9. The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins5 before its non-canonical translation into neural-toxic dipeptide proteins3,4. The failure of RNA polymerase to read through the mutation also reduces the abundance of the endogenous C9ORF72 gene product, which functions in endolysosomal pathways and suppresses systemic and neural inflammation6-9. Notably, the effects of the repeat expansion act with incomplete penetrance in families with a high prevalence of amyotrophic lateral sclerosis or frontotemporal dementia, indicating that either genetic or environmental factors modify the risk of disease for each individual. Identifying disease modifiers is of considerable translational interest, as it could suggest strategies to diminish the risk of developing amyotrophic lateral sclerosis or frontotemporal dementia, or to slow progression. Here we report that an environment with reduced abundance of immune-stimulating bacteria10,11 protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity. Consistent with C9orf72 functioning to prevent microbiota from inducing a pathological inflammatory response, we found that reducing the microbial burden in mutant mice with broad spectrum antibiotics-as well as transplanting gut microflora from a protective environment-attenuated inflammatory phenotypes, even after their onset. Our studies provide further evidence that the microbial composition of our gut has an important role in brain health and can interact in surprising ways with well-known genetic risk factors for disorders of the nervous system.

RevDate: 2020-06-23

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

5-Fluorouracil induced dysregulation of the microbiome-gut-brain axis manifesting as depressive like behaviors in rats.

Biochimica et biophysica acta. Molecular basis of disease pii:S0925-4439(20)30232-5 [Epub ahead of print].

Disturbances of the gut microbiome have been widely suggested to be associated with 5-fluorouracil (5-Fu) induced digestive pathologies. Furthermore, it has been elucidated that the gut microbiome may play a key role in the pathogenesis of depressive disorders via the microbiota-gut-brain axis. Despite the speculation, there exists no direct evidence proving the causality between disturbances in the gut microbiome induced by 5-Fu and depressive mood dysregulation. Herein, behavioral testing was used to evaluate depressive-like behaviors in 5-Fu treated rats. Subsequently, the gut microbiota and prefrontal cortex (PFC) metabolic were analyzed by 16S rRNA sequencing and 1H nuclear magnetic resonance (1H NMR). To clarify the association between the gut microbiota and their role on depressive-like behaviors caused by 5-Fu, a fecal microbiota transplantation (FMT) experiment was carried out. The results suggested that 5-Fu could significantly alter the diversity and abundance of the gut microbiome, and induce PFC metabolic disorders, as well as depressive behaviors in rats. Transplantation of fecal microbiota from healthy control into 5-Fu treated rats significantly alleviated the PFC metabolic disorder and depressive-like behaviors. In conclusion, this study demonstrated that the gut microbiome was actively involved in the occurrence of 5-Fu induced depressive-like behaviors, and manipulation of specific gut microbiome parameters may serve as a promising novel target for side effects of 5-Fu treatment.

RevDate: 2020-06-23

Bilinski J, Lis K, Tomaszewska A, et al (2020)

Eosinophilic gastroenteritis and graft-versus-host disease induced by transmission of Norovirus with fecal microbiota transplant.

Fecal microbiota transplantation (FMT) was performed to decolonize gastrointestinal tract from antibiotic-resistant bacteria before allogeneic hematopoietic cells transplantation (alloHCT). AlloHCT was complicated by Norovirus gastroenteritis, acute graft-versus-host-disease and eosinophilic pancolitis. Norovirus was identified in samples from FMT material. Symptoms resolved after steroids course and second norovirus-free FMT from another donor.

RevDate: 2020-06-23

Mangioni D, Alagna L, Gori A, et al (2020)

Fecal Microbiota Transplant: keep calm and carry on, learning from experience.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America pii:5861002 [Epub ahead of print].

RevDate: 2020-06-22

Shasthry SM (2020)

Fecal microbiota transplantation in alcohol related liver diseases.

Clinical and molecular hepatology pii:cmh.2020.0057 [Epub ahead of print].

The current standard of care for severe alcoholic hepatitis (SAH) has several limitations in that only up to one-third of patients are eligible for steroid therapy. Additionally, steroids have their own issues: a portion of patients do not respond, while there is doubtful long-term benefit in those who do and a large proportion are ineligible to receive steroids entirely and hence have no definitive options for treatment. As such, there is a large gap between the problem and the available solutions. Alcohol causes dysbiosis and also disrupts gut barrier function, consequently promoting the translocation of microbial lipopolysaccharide into the portal circulation and liver. Therefore, probiotics, prebiotics, antibiotics, or transplantation of gut microbiota are likely to attenuate the dysbiosis-related liver insult. Fecal microbiota transplantation (FMT) is expected to have a role in managing alcoholic liver disease in general and SAH in particular by correcting dysbiosis, the primary insult. Results from mouse studies have suggested beyond doubt that alcohol-related liver injury is transferrable and also treatable by adopting FMT from suitable donors. Initial human trials from our center have affirmed benefits in human subjects with SAH as well, with both improvements in disease severity and as well as the rate of survival. Further studies addressing the head-to-head comparison of steroids and FMT are ongoing. Available preliminary data are promising and FMT and/or gut microbial modulation might become the standard of care in the near future for managing alcohol-related liver diseases, especially alcoholic hepatitis, with greater applicability, improved acceptability, and minimal side effects.

RevDate: 2020-06-23
CmpDate: 2020-06-23

Walter J, Armet AM, Finlay BB, et al (2020)

Establishing or Exaggerating Causality for the Gut Microbiome: Lessons from Human Microbiota-Associated Rodents.

Cell, 180(2):221-232.

Human diseases are increasingly linked with an altered or "dysbiotic" gut microbiota, but whether such changes are causal, consequential, or bystanders to disease is, for the most part, unresolved. Human microbiota-associated (HMA) rodents have become a cornerstone of microbiome science for addressing causal relationships between altered microbiomes and host pathology. In a systematic review, we found that 95% of published studies (36/38) on HMA rodents reported a transfer of pathological phenotypes to recipient animals, and many extrapolated the findings to make causal inferences to human diseases. We posit that this exceedingly high rate of inter-species transferable pathologies is implausible and overstates the role of the gut microbiome in human disease. We advocate for a more rigorous and critical approach for inferring causality to avoid false concepts and prevent unrealistic expectations that may undermine the credibility of microbiome science and delay its translation.

RevDate: 2020-06-23
CmpDate: 2020-06-23

Mishima Y, Oka A, Liu B, et al (2019)

Microbiota maintain colonic homeostasis by activating TLR2/MyD88/PI3K signaling in IL-10-producing regulatory B cells.

The Journal of clinical investigation, 129(9):3702-3716.

Resident microbiota activate regulatory cells that modulate intestinal inflammation and promote and maintain intestinal homeostasis. IL-10 is a key mediator of immune regulatory function. Our studies described the functional importance and mechanisms by which gut microbiota and specific microbial components influenced the development of intestinal IL-10-producing B cells. We used fecal transplant to germ-free (GF) Il10+/EGFP reporter and Il10-/- mice to demonstrate that microbiota from specific pathogen-free mice primarily stimulated IL-10-producing colon-specific B cells and T regulatory-1 cells in ex-GF mice. IL-10 in turn down-regulated microbiota-activated mucosal inflammatory cytokines. TLR2/9 ligands and enteric bacterial lysates preferentially induced IL-10 production and regulatory capacity of intestinal B cells. Analysis of Il10+/EGFP mice crossed with additional gene-deficient strains and B cell co-transfer studies demonstrated that microbiota-induced IL-10-producing intestinal B cells ameliorated chronic T cell-mediated colitis in a TLR2, MyD88 and PI3K-dependent fashion. In vitro studies implicated PI3Kp110δ and AKT downstream signaling. These studies demonstrated that resident enteric bacteria activated intestinal IL-10-producing B cells through TLR2, MyD88 and PI3K pathways. These B cells reduced colonic T cell activation and maintained mucosal homeostasis in response to intestinal microbiota.

RevDate: 2020-06-22

Suraya R, Nagano T, Kobayashi K, et al (2020)

Microbiome as a Target for Cancer Therapy.

Integrative cancer therapies, 19:1534735420920721.

Recently, the microbiome has been gaining traction as a major player regulating various functions that correlate with many pathological conditions, including cancer. The central gut microbiota population has the capability to regulate normal inflammatory, immune, and metabolic functions, and disturbance in the balance of the normal microbiota population can subsequently induce pathological responses that closely relate with the mechanistic development and progression of cancer in various forms and sites. As a disease with major socioeconomic burden partly due to its current therapeutic options, modulating the imbalanced gut microbiota represents a novel option not only as an adjuvant therapy to relieve cancer treatment-related symptoms but also to influence cancer progression itself. In this review, we will discuss how the microbiome, specifically the gut microbiota, could affect cancer pathogenesis and what the effect of gut microbiota-targeting treatment options have on the many aspects of cancer pathologies based on the knowledge of recent years.

RevDate: 2020-06-22
CmpDate: 2020-06-22

Madhusoodanan J (2020)

News Feature: Editing the microbiome.

Proceedings of the National Academy of Sciences of the United States of America, 117(7):3345-3348.

RevDate: 2020-06-22
CmpDate: 2020-06-22

Baron SA, Cassir N, Mékidèche T, et al (2019)

Successful treatment and digestive decolonisation of a patient with osteitis caused by a carbapenemase-producing Klebsiella pneumoniae isolate harbouring both NDM-1 and OXA-48 enzymes.

Journal of global antimicrobial resistance, 18:225-229.

OBJECTIVES: Carbapenem resistance in Klebsiella pneumoniae is an increasing problem worldwide and infections caused by this bacterium can be difficult to treat. This study reported the case of a patient from Romania, who was hospitalised in Bulgaria after an accident trauma. He then came to France for treatment of an osteitis caused by a Klebsiella pneumoniae carrying both blaNDM-1 and blaOXA-48.

METHOD: The resistome of this extremely drug-resistant bacterium was analysed both with phenotypic (large antibiotic susceptibility testing) and genomic methods (genome sequencing). The genetic environment of the two carbapenemases was studied.

RESULTS: Klebsiella pneumoniae ST307 carrying both a blaNDM-1 and blaOXA-48 gene was located on two different plasmids: Inc L/M and IncFII. The patient was successfully treated by a combination of intravenous colistin (9 MUI, then 4.5 MUI bd), intravenous fosfomycin (4g tds) and oral doxycycline (100mg bd) for 3 months. Faecal microbiota transplantation was successfully conducted for stool carriage.

CONCLUSION: The ST307 type is becoming endemic in hospital environments and is frequently associated with carbapenem resistance. Treatment of infection caused by multidrug-resistant bacteria is a clinical challenge, and the use of old antibiotics associated with screening and decolonisation of the reservoirs can be an efficient therapeutic alternative.

RevDate: 2020-06-22
CmpDate: 2020-06-22

Dodiya HB, Kuntz T, Shaik SM, et al (2019)

Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes.

The Journal of experimental medicine, 216(7):1542-1560.

We demonstrated that an antibiotic cocktail (ABX)-perturbed gut microbiome is associated with reduced amyloid-β (Aβ) plaque pathology and astrogliosis in the male amyloid precursor protein (APP)SWE /presenilin 1 (PS1)ΔE9 transgenic model of Aβ amyloidosis. We now show that in an independent, aggressive APPSWE/PS1L166P (APPPS1-21) mouse model of Aβ amyloidosis, an ABX-perturbed gut microbiome is associated with a reduction in Aβ pathology and alterations in microglial morphology, thus establishing the generality of the phenomenon. Most importantly, these latter alterations occur only in brains of male mice, not in the brains of female mice. Furthermore, ABX treatment lead to alterations in levels of selected microglial expressed transcripts indicative of the "M0" homeostatic state in male but not in female mice. Finally, we found that transplants of fecal microbiota from age-matched APPPS1-21 male mice into ABX-treated APPPS1-21 male restores the gut microbiome and partially restores Aβ pathology and microglial morphology, thus demonstrating a causal role of the microbiome in the modulation of Aβ amyloidosis and microglial physiology in mouse models of Aβ amyloidosis.

RevDate: 2020-06-22
CmpDate: 2020-06-22

Ghosh C, Sarkar P, Issa R, et al (2019)

Alternatives to Conventional Antibiotics in the Era of Antimicrobial Resistance.

Trends in microbiology, 27(4):323-338.

As more antibiotics are rendered ineffective by drug-resistant bacteria, focus must be shifted towards alternative therapies for treating infections. Although several alternatives already exist in nature, the challenge is to implement them in clinical use. Advancements within biotechnology, genetic engineering, and synthetic chemistry have opened up new avenues towards the search for therapies that can substitute for antibiotics. This review provides an introduction to the various promising approaches that have been adopted in this regard. Whilst the use of bacteriophages and antibodies has been partly implemented, other promising strategies, such as probiotics, lysins, and antimicrobial peptides, are in various stages of development. Propitious concepts such as genetically modified phages, antibacterial oligonucleotides, and CRISPR-Cas9 are also discussed.

RevDate: 2020-06-20

Wang Y, Ren R, Sun G, et al (2020)

Pilot study of cytokine changes evaluation after fecal microbiota transplantation in patients with ulcerative colitis.

International immunopharmacology, 85:106661 pii:S1567-5769(20)31215-7 [Epub ahead of print].

AIMS: To evaluate the changes of serum cytokines levels after fecal microbiota transplantation (FMT) in patients with active ulcerative colitis (UC) and the correlation with UC disease activity.

METHODS: Patients with active UC who meet the inclusion and exclusion criteria were recruited, and received FMT from a single donor for three times with an interval of 2-3 months. Serum samples were collected before every FMT. Clinical responses to FMT were assessed according to the criteria of Mayo score. 41 serum cytokines, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were quantitatively detected. Changes in serum cytokines levels after FMT and their correlation with CRP, ESR and Mayo scores were investigated.

RESULTS: 16 active UC patients were enrolled, and 14(87.5%) patients achieved clinical response to FMT. Compared with those before FMT, serum concentrations of IL-1Ra, IL-6, IP-10 and ENA-78 decreased significantly after the second FMT (P < 0.05), and serum concentrations of MEC, VCAM-1 and G-CSF decreased significantly after both the first and second FMT (P < 0.05). Serum levels of IL-6, IL-1Ra and VCAM-1 were all significantly positively correlated with CRP and ESR. Serum level of IP-10 was significantly positively correlated with CRP, ESR and Mayo score. Serum level of G-CSF was significantly positively correlated with Mayo score.

CONCLUSIONS: FMT may play a therapeutic role partly through modulating the host immune response. IL-6, IL-1Ra, IP-10, VCAM-1 and G-CSF may be biomarkers to evaluate the effect of FMT on UC.

RevDate: 2020-06-19

Watterson WJ, Tanyeri M, Watson AR, et al (2020)

Droplet-based high-throughput cultivation for accurate screening of antibiotic resistant gut microbes.

eLife, 9: pii:56998 [Epub ahead of print].

Traditional cultivation approaches in microbiology are labor-intensive, low-throughput, and yield biased sampling of environmental microbes due to ecological and evolutionary factors. New strategies are needed for ample representation of rare taxa and slow-growers that are often outcompeted by fast-growers in cultivation experiments. Here we describe a microfluidic platform that anaerobically isolates and cultivates microbial cells in millions of picoliter droplets and automatically sorts them based on colony density to enhance slow-growing organisms. We applied our strategy to a fecal microbiota transplant (FMT) donor stool using multiple growth media, and found significant increase in taxonomic richness and larger representation of rare and clinically relevant taxa among droplet-grown cells compared to conventional plates. Furthermore, screening the FMT donor stool for antibiotic resistance revealed 21 populations that evaded detection in plate-based assessment of antibiotic resistance. Our method improves cultivation-based surveys of diverse microbiomes to gain deeper insights into microbial functioning and lifestyles.

RevDate: 2020-06-19

Allegretti JR, Elliott RJ, Ladha A, et al (2020)

Stool processing speed and storage duration do not impact the clinical effectiveness of fecal microbiota transplantation.

Gut microbes [Epub ahead of print].

RevDate: 2020-06-19

Little R, Wine E, Kamath BM, et al (2020)

Gut microbiome in primary sclerosing cholangitis: A review.

World journal of gastroenterology, 26(21):2768-2780.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by biliary inflammation and stricturing. Exploration of the pathogenesis of PSC in light of its association with inflammatory bowel disease (IBD) and the "gut-liver" axis is an emerging area of interest. A growing number of studies have begun to elucidate the role of the gut microbiota, its metabolites and its influence on host immune responses in the development of PSC and PSC-IBD. Studies of the fecal microbiota have highlighted enriched levels of certain species, including Veillonella, Streptococcus and Enterococcus, among others. A heightened immune response to enteric dysbiosis and bacterial translocation have also been implicated. For example, Klebsiella pneumoniae strains derived from gnotobiotic mice transplanted with PSC-IBD microbiota were found to induce pore formation in human intestinal epithelial cells and enhanced Th17 responses. Gut microbes have additionally been hypothesized to be implicated in PSC pathogenesis through their role in the synthesis of various metabolites, including bile acids (BAs), which function as signaling molecules with important gut and hepatic effects. An expanded knowledge of the gut microbiome as it relates to PSC offers critical insight into the development of microbe-altering therapeutic interventions, such as antibiotics, nutritional interventions and fecal microbial transplantation. Some of these have already shown some preliminary evidence of benefit. Despite exciting progress in the field, much work remains to be done; areas that are particularly lacking include functional characterization of the microbiome and examination of pediatric populations. In this review, we summarize studies that have investigated the microbiome in PSC and PSC-IBD as well as putative mechanisms, including the potential role of metabolites, such as BAs. We then briefly review the evidence for interventions with microbe-altering properties for treating PSC.

RevDate: 2020-06-19
CmpDate: 2020-06-19

Gustot T, R Jalan (2019)

Acute-on-chronic liver failure in patients with alcohol-related liver disease.

Journal of hepatology, 70(2):319-327.

The spectrum of alcohol-related liver diseases (ALD) includes steatosis, steatohepatitis, progressive liver fibrosis, and cirrhosis. Acute-on-chronic liver failure (ACLF) is a recently defined entity that occurs in patients with chronic liver diseases and is characterised by acute decompensation, organ failures and a high risk of short-term mortality. Active alcohol consumption, alcoholic hepatitis and bacterial infections are the most frequent events precipitating the development of ACLF in the context of ALD (ALD-ACLF). The specific management of this entity remains unknown and the place of salvage liver transplantation controversial. This overview details the current knowledge on specific aspects of epidemiology, pathophysiology, prognosis and management of ALD-ACLF.

RevDate: 2020-06-19
CmpDate: 2020-06-19

Singal AK, VH Shah (2019)

Current trials and novel therapeutic targets for alcoholic hepatitis.

Journal of hepatology, 70(2):305-313.

Alcoholic hepatitis is a clinical syndrome in which patients present with acute-on-chronic liver failure and a high risk of short-term mortality. The current treatment of alcoholic hepatitis is suboptimal. Results recently published from the STOPAH study have improved our understanding of how best to design clinical trials for this condition. Although emerging data on liver transplantation for patients with alcoholic hepatitis are encouraging, less than 2% of these patients qualify. Clearly, there is an unmet need for novel treatments to improve the survival of these patients. Changes in the gut microbiota, inflammatory and cytokine signalling, oxidative stress and mitochondrial dysfunction, and abnormalities in the hepatic regenerative capacity alone or in combination contribute to the pathology of alcoholic hepatitis. In this chapter, we will describe the novel therapeutic agents targeting various pathways in the pathophysiology of alcoholic hepatitis. Specifically, we will describe the ongoing clinical trials in which some of these agents are being studied.

RevDate: 2020-06-19
CmpDate: 2020-06-19

Sarin SK, Pande A, B Schnabl (2019)

Microbiome as a therapeutic target in alcohol-related liver disease.

Journal of hepatology, 70(2):260-272.

Alcohol-related liver disease is associated with significant changes in gut microbial composition. The transmissibility of ethanol-induced liver disease has been demonstrated using faecal microbiota transfer in preclinical models. This technique has also led to improved survival in patients with severe alcoholic hepatitis, suggesting that changes in the composition and function of the gut microbiota are causatively linked to alcohol-related liver disease. A major mechanism by which gut microbiota influence the development of alcohol-related liver disease is through a leaky intestinal barrier. This permits translocation of viable bacteria and microbial products to the liver, where they induce and promote inflammation, as well as contribute to hepatocyte death and the fibrotic response. In addition, gut dysbiosis is associated with changes in the metabolic function of the intestinal microbiota, bile acid composition and circulation, immune dysregulation during onset and progression of alcohol-related liver disease. Findings from preclinical and human studies will be used to demonstrate how alcohol causes intestinal pathology and contributes to alcohol-related liver disease and how the latter is self-perpetuating. Additionally, we summarise the effects of untargeted treatment approaches on the gut microbiota, such as diet, probiotics, antibiotics and faecal microbial transplantation in alcohol-related liver disease. We further discuss how targeted approaches can restore intestinal homeostasis and improve alcohol-related liver disease. These approaches are likely to add to the therapeutic options for alcohol-related liver disease independently or in conjunction with steroids.

RevDate: 2020-06-18
CmpDate: 2020-06-18

Taylor VH (2019)

The microbiome and mental health: Hope or hype?.

Journal of psychiatry & neuroscience : JPN, 44(4):219-222.

RevDate: 2020-06-17

Massaro M, Vansia J, S McGill (2020)

Ulcerative Proctitis in a Patient With a History of Fecal Microbiota Transplant for Clostridioides difficile Infection.

ACG case reports journal, 7(4):e00364 pii:ACGCR-19-0747.

Fecal microbiota transplantation (FMT) effectively treats Clostridioides difficile infection and alters the gut microbiota in the long term, but potential adverse effects are poorly understood. We report a man with a family history of ulcerative colitis who developed ulcerative proctitis within a year of FMT.

RevDate: 2020-06-17

Fasanello MK, Robillard KT, Boland PM, et al (2020)

Use of Fecal Microbial Transplantation for Immune Checkpoint Inhibitor Colitis.

ACG case reports journal, 7(4):e00360 pii:ACGCR-19-0376.

Immune checkpoint inhibitors (ICIs) can result in immune-related adverse events which require rapid identification and treatment. Gastrointestinal immune-related adverse events are among the most frequent and severe of these events. ICI colitis can be refractory to current therapies such as corticosteroids and biologic therapy. Fecal microbiota transplantation (FMT) is currently used in cases of recurrent Clostridioides difficile colitis. Many investigations are underway to test the utility of FMT for additional indications, including inflammatory bowel disease (IBD). We present a 71-year-old man with ICI colitis that was nonresponsive to currently defined management options and treated with benefit from FMT.

RevDate: 2020-06-16

Chinna Meyyappan A, Forth E, Wallace CJK, et al (2020)

Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review.

BMC psychiatry, 20(1):299 pii:10.1186/s12888-020-02654-5.

BACKGROUND: The Gut-Brain-Axis is a bidirectional signaling pathway between the gastrointestinal (GI) tract and the brain. The hundreds of trillions of microorganisms populating the gastrointestinal tract are thought to modulate this connection, and have far reaching effects on the immune system, central and autonomic nervous systems, and GI functioning. These interactions Diagnostic and statistical manual of mental disorders have also been linked to various psychiatric illnesses such as depression, anxiety, substance abuse, autism spectrum disorder, and eating disorders. It is hypothesized that techniques aimed at strengthening and repopulating the gut microbiome, such as Fecal Microbiota Transplant (FMT), may be useful in the prevention and treatment of psychiatric illnesses.

METHODS: A systematic search of five databases was conducted using key terms related to FMT and psychiatric illnesses. All results were then evaluated based on specific eligibility criteria.

RESULTS: Twenty-one studies met the eligibility criteria and were analysed for reported changes in mood and behavioural measures indicative of psychiatric wellbeing. The studies included were either entirely clinical (n = 8), preclinical with human donors (n = 9), or entirely preclinical (n = 11). All studies found a decrease in depressive and anxiety-like symptoms and behaviours resulting from the transplantation of healthy microbiota. The inverse was also found, with the transmission of depressive and anxiety-like symptoms and behaviours resulting from the transplantation of microbiota from psychiatrically ill donors to healthy recipients.

CONCLUSION: There appears to be strong evidence for the treatment and transmission of psychiatric illnesses through FMT. Further research with larger sample sizes and stronger scientific design is warranted in order to fully determine the efficacy and safety of this potential treatment. Registered on PROSPERO, IRD: CRD42019126795.

RevDate: 2020-06-15

Wong SH, J Yu (2020)

Proton-pump inhibitor use before fecal microbiota transplant: A wonder drug, a necessary evil, or a needless prescription?.

Journal of gastroenterology and hepatology, 35(6):913-914.

RevDate: 2020-06-14

Uchiyama K, Wakino S, Irie J, et al (2020)

Contribution of uremic dysbiosis to insulin resistance and sarcopenia.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association pii:5857305 [Epub ahead of print].

BACKGROUND: Chronic kidney disease (CKD) leads to insulin resistance (IR) and sarcopenia, which are associated with a high mortality risk in CKD patients; however, their pathophysiologies remain unclear. Recently, alterations in gut microbiota have been reported to be associated with CKD. We aimed to determine whether uremic dysbiosis contributes to CKD-associated IR and sarcopenia.

METHODS: CKD was induced in specific pathogen-free mice via an adenine-containing diet; control animals were fed a normal diet. Fecal microbiota transplantation (FMT) was performed by oral gavage in healthy germ-free mice using cecal bacterial samples obtained from either control mice (control-FMT) or CKD mice (CKD-FMT). Vehicle mice were gavaged with sterile phosphate-buffered saline. Two weeks after inoculation, mice phenotypes, including IR and sarcopenia, were evaluated.

RESULTS: IR and sarcopenia were evident in CKD mice compared with control mice. These features were reproduced in CKD-FMT mice compared with control-FMT and vehicle mice with attenuated insulin-induced signal transduction and mitochondrial dysfunction in skeletal muscles. Intestinal tight junction protein expression and adipocyte sizes were lower in CKD-FMT mice than in control-FMT mice. Furthermore, CKD-FMT mice showed systemic microinflammation, increased concentrations of serum uremic solutes, fecal bacterial fermentation products and elevated lipid content in skeletal muscle. The differences in gut microbiota between CKD and control mice were mostly consistent between CKD-FMT and control-FMT mice.

CONCLUSIONS: Uremic dysbiosis induces IR and sarcopenia, leaky gut and lipodystrophy.

RevDate: 2020-06-14

Liu L, Wang Q, Wu X, et al (2020)

Vancomycin exposure caused opportunistic pathogens bloom in intestinal microbiome by simulator of the human intestinal microbial ecosystem (SHIME).

Environmental pollution (Barking, Essex : 1987), 265(Pt B):114399 pii:S0269-7491(20)30013-0 [Epub ahead of print].

Antibiotics are emerging organic pollutants posing high health risks to humans by causing human intestinal microbial disorders with increasing abundances of opportunistic pathogens, and fecal microbiota transplantation (FMT) has been confirmed to restore the dysbiosis of gut flora in many kinds of intestinal disease. However, to date, few studies have focused on the bloomed opportunistic pathogens associated human disease-related pathways as well as antibiotic resistance genes (ARGs) after vancomycin exposure, and there is limited information on using FMT for restoration of intestinal microbiome affected by antibiotics. Therefore, this study investigated effects of vancomycin on the opportunistic pathogens, human disease-related pathways as well as ARGs in human gut, and the restoration of intestinal microbiome by FMT. Results indicated that vancomycin treatment substantially increased human disease-related pathways and decreased abundances of ARGs. Besides, the bloomed opportunistic pathogens including Achromobacter, Klebsiella, and Pseudomonas, caused by vancomycin exposure, were positively correlated with human disease-related pathways. The microbiota abundance and genes of human disease-related pathways and antibiotic resistance showed a remarkable return towards baseline after FMT, but not for natural recovery. These findings suggest that impacts of vancomycin on human gut are profound and FMT will be a promising strategy in clinical application that can restore the dysbiosis of gut microbiota, which may be valuable for directing future work.

RevDate: 2020-06-12

Li X, He C, Li N, et al (2020)

The interplay between the gut microbiota and NLRP3 activation affects the severity of acute pancreatitis in mice.

Gut microbes [Epub ahead of print].

Early dysbiosis of the gut microbiota is associated with the severity of acute pancreatitis (AP), although the underlying mechanism is unclear. Here, we investigated the role of crosstalk between NLRP3 and the gut microbiota in the development of AP utilizing gut microbiota deficient mice, as well as NLRP3 knockout (KO) mouse models. Pancreatic damage and systemic inflammation were improved in antibiotic-treated (Abx) and germ-free (GF) mice, accompanied by weakened activity of the intestinal NLRP3 inflammasome. Interestingly, fecal microbiota transplantation (FMT) reactivated the intestinal NLRP3 inflammasome and exacerbated the disease in Abx and GF mice. Although the gut barrier in GF and Abx mice was disrupted, gut microbiota deficiency ameliorated the severity of AP, probably due to the reduction in bacterial translocation from the gut to the pancreas. The composition of the gut microbiota was significantly different between NLRP3 KO mice and wild-type (WT) mice at baseline, and there were alterations in response to the induction of AP. While a dramatic shift in the gut microbiota with overgrowth of Escherichia-Shigella was observed in WT mice suffering from AP, there was no significant change in NLRP3 KO mice with or without AP, suggesting that NLRP3 deficiency counteracts AP-induced microbial disturbance. With a strengthened gut barrier and decreased systemic inflammation, NLRP3 KO mice showed less severe AP, as revealed by reduced pancreatic neutrophilic infiltration and necrosis. Taken together, these results identified the bidirectional modulation between the gut microbiota and NLRP3 in the progression of AP, which suggests the interplay of the host and microbiome during AP.

RevDate: 2020-06-12

Biernat MM, Urbaniak-Kujda D, Dybko J, et al (2020)

Fecal microbiota transplantation in the treatment of intestinal steroid-resistant graft-versus-host disease: two case reports and a review of the literature.

The Journal of international medical research, 48(6):300060520925693.

Acute graft-versus-host disease (aGvHD) reduces the efficiency and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, attempts have been made to transplant fecal microbiota from healthy donors to treat intestinal GvHD. This study presented two cases of patients undergoing allo-HSCT who were later selected for fecal microbiota transplantation (FMT). In the first patient, FMT resulted in the complete resolution of symptoms, whereas therapeutic efficacy was not achieved in the second patient. FMT eliminated drug-resistant pathogens, namely very drug-resistant Enterococcus spp., but not multidrug-resistant Acinetobacter baumannii or Candida spp. Further research is needed, particularly on the safety of FMT in patients with intestinal steroid-resistant GvHD and on the distant impact of transplanted microflora on the outcomes of allo-HSCT. FMT appears promising for the treatment of patients with steroid-resistant GvHD.

RevDate: 2020-06-12
CmpDate: 2020-06-12

Fritsch J, MT Abreu (2020)

Candida in IBD: Friend or Foe?.

Cell host & microbe, 27(5):689-691.

In this issue of Cell Host & Microbe, Leonardi et al. demonstrate ulcerative colitis patients with high Candida responded best to fecal microbial transplant (FMT). However, decreased Candida post-treatment was associated with improved disease-suggesting that Candida reductions are associated with less inflammation. Pre-FMT Candida levels may identify FMT responders.

RevDate: 2020-06-11

Pérez-Matute P, Íñiguez M, de Toro M, et al (2020)

Autologous fecal transplantation from a lean state potentiates caloric restriction effects on body weight and adiposity in obese mice.

Scientific reports, 10(1):9388 pii:10.1038/s41598-020-64961-x.

Autologous fecal transplantation (FT-A) emerges as a promising strategy to modulate gut microbiota with minimal side effects since individual´s own feces are transplanted. With the premise of improving obesity and its associated disorders, we investigated if fecal microbiota transplantation (FMT), heterologous and autologous, potentiates the effects of a moderate caloric restriction (CR) in high-fat diet (HFD)-induced obese mice. Mice were randomized into control, HFD, CR (12 weeks on HFD and 6 weeks under CR), FT-H (similar to CR and FMT carried out with feces from controls, weeks 17 & 18), and FT-A (administration of their own feces before developing obesity at weeks 17 & 18). Our study demonstrated that FMT, and, especially, FT-A potentiates the effects of a moderate CR on weight loss and adiposity in the short term, by decreasing feed efficiency and increasing adipose tissue lipolysis. Although FT-A produced a significant increase in bacterial richness/diversity, FMT did not significantly modify gut microbiota composition compared to the CR at phyla and bacteria genera levels, and only significant increases in Bifidobacterium and Blautia genera were observed. These results could suggest that other mechanisms different from bacterial microbiota engraftment participates in these beneficial effects. Thus, FT-A represents a very positive synergetic approach for obese patients that do not respond well to moderate restrictive diets.

RevDate: 2020-06-10

Su X, Zhao Y, Li Y, et al (2020)

Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis.

Clinical science (London, England : 1979) pii:225233 [Epub ahead of print].

BACKGROUND: Previous studies have shown that the gut microbiome is associated with thyroid diseases, including Graves' disease, Hashimoto's disease, thyroid nodules, and thyroid cancer. However, the association between intestinal flora and primary hypothyroidism remains elusive. We aimed to characterize gut microbiome in primary hypothyroidism patients.

METHODS: Fifty-two primary hypothyroidism patients and 40 healthy controls were recruited. The differences in gut microbiota between the two groups were analyzed by 16S rRNA sequencing technology. Fecal microbiota transplantation (FMT) was performed in mice using flora from both groups; changes in thyroid function were then assessed in the mice.

RESULTS: There were significant differences in α and β diversities of gut microbiota between primary hypothyroidism patients and healthy individuals. The random forest analysis indicated that four intestinal bacteria (Veillonella, Paraprevotella, Neisseria, and Rheinheimera) could distinguish untreated primary hypothyroidism patients from healthy individuals with the highest accuracy; this was confirmed by receiver operator characteristic curve analysis. The short chain fatty acid producing ability of the primary hypothyroidism patients' gut was significantly decreased, which resulted in the increased serum lipopolysaccharides (LPS) levels. The FMT showed that mice receiving the transplant from primary hypothyroidism patients displayed decreased total thyroxine levels.

CONCLUSIONS: Our study suggests that primary hypothyroidism causes changes in gut microbiome. In turn, an altered flora can affect thyroid function in mice. These findings could help understand the development of primary hypothyroidism and might be further used to develop potential probiotics to facilitate the adjuvant treatment of this disease.

RevDate: 2020-06-10

Kates AE, Gaulke I, De Wolfe T, et al (2020)

Fecal microbiota transplantation for patients on antibiotic treatment with C. difficile infection history (GRAFT): Study protocol for a phase II, randomized, double-blind, placebo-controlled trial to prevent recurrent C. difficile infections.

Contemporary clinical trials communications, 18:100576 pii:100576.

Recurrent Clostridiodes difficile infections (rCDIs) are a burdensome problem. Patients with a history of CDI that are prescribed antibiotics are at a high risk for recurrence. Fecal microbiota transplantation (FMT) has been shown to be an effective treatment for rCDI, though there is little information on the impact of FMT with antibiotics on the gut microbiome. We are conducting a clinical trial of FMT to prevent rCDI in patients with a history of CDI currently taking antibiotics. Our primary objective is to determine the effect of FMT on the gut microbiome during antibiotic exposure. Our secondary aim is to assess safety and feasibility of using FMT as a prophylaxis for CDI. We plan to enroll 30 patients into a phase II randomized, double-blind, placebo-controlled trial with three arms: (1) 5 FMT capsules per day during antibiotic treatment and for 7 days post antibiotic cessation, (2) a one-time dose of 30 FMT capsules 48-72 h post cessation of antibiotic treatment, or (3) 5 placebo capsules per day during antibiotic treatment and for 7 days post antibiotic treatment. Patients provide stool samples throughout the duration of the study and are cultured C. difficile. Sequencing of the V4 region of the 16S rRNA gene will be carried out to assess the gut microbiota. Results of this study will provide information on the impact of FMT on the gut microbiome as well as the necessary data to examine whether or not prophylactic FMT should be explored further as a way to prevent CDI recurrence.

RevDate: 2020-06-10

Bibbò S, Settanni CR, Porcari S, et al (2020)

Fecal Microbiota Transplantation: Screening and Selection to Choose the Optimal Donor.

Journal of clinical medicine, 9(6): pii:jcm9061757.

In the past decade, fecal microbiota transplantation (FMT) has rapidly spread worldwide in clinical practice as a highly effective treatment option against recurrent Clostridioides difficile infection. Moreover, new evidence also supports a role for FMT in other conditions, such as inflammatory bowel disease, functional gastrointestinal disorders, or metabolic disorders. Recently, some studies have identified specific microbial characteristics associated with clinical improvement after FMT, in different disorders, paving the way for a microbiota-based precision medicine approach. Moreover, donor screening has become increasingly more complex over years, along with standardization of FMT and the increasing number of stool banks. In this narrative review, we discuss most recent evidence on the screening and selection of the stool donor, with reference to recent studies that have identified specific microbiological features for clinical conditions such as Clostridioides difficile infection, irritable bowel syndrome, inflammatory bowel disease, and metabolic disorders.

RevDate: 2020-06-09

Zoll J, Read MR, Heywood SE, et al (2020)

Fecal microbiota transplantation from high caloric-fed donors alters glucose metabolism in recipient mice, independently of adiposity or exercise status.

American journal of physiology. Endocrinology and metabolism [Epub ahead of print].

Studies suggest gut microbiota contributes to the development of obesity and the metabolic syndrome. Exercise alters microbiota composition and diversity and is protective of these maladies. We tested whether the protective metabolic effects of exercise are mediated through fecal components through assessment of body composition and metabolism in recipients of fecal microbiota transplantation (FMT) from exercise-trained (ET) mice fed normal or high energy diets. Donor C57BL/6J mice were fed a chow or high fat, high sucrose (HFHS) diet for 4wk to induce obesity and glucose intolerance. Mice were divided into sedentary (Sed) or ET groups [6wk treadmill-based ET] while maintaining their diets, resulting in four donor groups; chow sedentary (NC-Sed) or ET (NC-ET) and HFHS sedentary (HFHS-Sed) or ET (HFHS-ET). Chow-fed recipient mice were gavaged with feces from the respective donor groups weekly, creating four groups (NC-Sed-R, NC-ET-R, HFHS-Sed-R, HFHS-ET-R) and body composition and metabolism assessed. The HFHS diet led to glucose intolerance and obesity in the donors, while exercise training (ET) restrained adiposity and improved glucose tolerance. No donor group FMT altered recipient body composition. Despite unaltered adiposity, glucose levels were disrupted when challenged in mice receiving feces from HFHS-fed donors, irrespective of donor-ET status, with a decrease in insulin-stimulated glucose clearance into white adipose tissue and large intestine and specific changes in the recipient's microbiota composition. FMT can transmit HFHS-induced disrupted glucose metabolism to recipient mice independently of any change in adiposity. However, the protective metabolic effect of ET on glucose metabolism is not mediated through fecal factors.

RevDate: 2020-06-09

Fong W, Li Q, J Yu (2020)

Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer.

Oncogene pii:10.1038/s41388-020-1341-1 [Epub ahead of print].

Research about the role of gut microbiome in colorectal cancer (CRC) is a newly emerging field of study. Gut microbiota modulation, with the aim to reverse established microbial dysbiosis, is a novel strategy for prevention and treatment of CRC. Different strategies including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT) have been employed. Although these strategies show promising results, mechanistically by correcting microbiota composition, modulating innate immune system, enhancing gut barrier function, preventing pathogen colonization and exerting selective cytotoxicity against tumor cells, it should be noted that they are accompanied by risks and controversies that can potentially introduce clinical complications. During bench-to-bedside translation, evaluation of risk-and-benefit ratio, as well as patient selection, should be carefully performed. In view of the individualized host response to gut microbiome intervention, developing personalized microbiome therapy may be the key to successful clinical treatment.

RevDate: 2020-06-09
CmpDate: 2020-06-09

Lei S, Twitchell EL, Ramesh AK, et al (2019)

Enhanced GII.4 human norovirus infection in gnotobiotic pigs transplanted with a human gut microbiota.

The Journal of general virology, 100(11):1530-1540.

The role of commensal microbiota in enteric viral infections has been explored extensively, but the interaction between human gut microbiota (HGM) and human norovirus (HuNoV) is poorly understood. In this study, we established an HGM-Transplanted gnotobiotic (Gn) pig model of HuNoV infection and disease, using an infant stool as HGM transplant and a HuNoV GII.4/2006b strain for virus inoculation. Compared to germ-free Gn pigs, HuNoV inoculation in HGMT Gn pigs resulted in increased HuNoV shedding, characterized by significantly higher shedding titres on post inoculation day (PID) 3, 4, 6, 8 and 9, and significantly longer mean duration of virus shedding. In addition, virus titres were significantly higher in duodenum and distal ileum of HGMT Gn pigs on PID10, while comparable and transient HuNoV viremia was detected in both groups. 16S rRNA gene sequencing demonstrated that HuNoV infection dramatically altered intestinal microbiota in HGMT Gn pigs at the phylum (Proteobacteria, Firmicutes and Bacteroidetes) and genus (Enterococcus, Bifidobacterium, Clostridium, Ruminococcus, Anaerococcus, Bacteroides and Lactobacillus) levels. In summary, enhanced GII.4 HuNoV infection was observed in the presence of HGM, and host microbiota was susceptible to disruption upon HuNoV infection.

RevDate: 2020-06-08

Bar-Yoseph H, Carasso S, Shklar S, et al (2020)

Oral capsulized Fecal microbiota transplantation for eradication of carbapenemase-producing Enterobacteriaceae colonization with a metagenomic perspective.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America pii:5854737 [Epub ahead of print].

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) infections lead to considerable morbidity and mortality. We assessed the potential of fecal microbiota transplantation (FMT) to eradicate CPE carriage and aimed to explain failure or success through microbiome analyses.

METHODS: In this prospective cohort study, all consenting eligible CPE carriers were treated with oral capsulized FMT for 2 days. The primary outcome was CPE eradication at 1 month, defined by 3 consecutive negative rectal swabs, the last also negative for carbapenemase gene by PCR. Comprehensive metagenomics analysis of the intestinal microbiome of donors and recipients before and after FMT was performed.

RESULTS: Fifteen CPE carriers received FMT, 13 of which completed 2 days of treatment. CPE eradication at 1 month was successful in 9/15 and 9/13, respectively. Bacterial communities showed significant changes in both beta and alpha diversity metrics among participants achieving CPE eradication that were not observed among failures. Post-FMT samples' beta-diversity clustered according to the treatment outcome, both in taxonomy and in function. We observed a significant decrease in beta diversity in participants who received post-FMT antibiotics. Enterobacteriaceae abundance decreased in post-FMT samples of the responders, but increased among failures. Functionally, a clear demarcation between responders (who were similar to the donors) and failures was shown, driven by antimicrobial resistance genes.

CONCLUSION: Our study provides the biological explanation for the effect of FMT against CPE carriage. Decolonization of CPE by FMT is likely mediated by compositional and functional shifts in the microbiome. Thus, FMT might be an efficient strategy for sustained CPE eradication.

RevDate: 2020-06-08

Wang H, Zhou C, Huang J, et al (2020)

The potential therapeutic role of Lactobacillus reuteri for treatment of inflammatory bowel disease.

American journal of translational research, 12(5):1569-1583.

Inflammatory bowel disease (IBD) is a chronic intestinal disease of unknown etiology. However, recent studies have established a pathological role of disordered intestinal microbiota and immune dysregulation. Clinical studies have suggested that the reconstruction of the normal intestinal flora in patients with IBD can reverse the dysbiosis caused by genetic, environmental, dietary, or antibiotic factors to ameliorate the symptoms of IBD. Lactobacillus reuteri is widely present in the intestines of healthy individuals and regulates the intestinal immune system, reducing inflammation through multiple mechanisms. This review summarizes the current knowledge of the role of L. reuteri in maintaining intestinal homeostasis and considers its possible value as a new therapeutic agent for patients with IBD.

RevDate: 2020-06-08

Liu H, HH Wang (2020)

Impact of Microbiota Transplant on Resistome of Gut Microbiota in Gnotobiotic Piglets and Human Subjects.

Frontiers in microbiology, 11:932.

Microbiota transplant is becoming a popular process to restore or initiate "healthy" gut microbiota and immunity. But, the potential risks of the related practices need to be carefully evaluated. This study retrospectively examined the resistomes of donated fecal microbiota for treating intestinal disorders, vaginal microbiota of pregnant women, and infant fecal microbiota from rural and urban communities, as well as the impact of transplants on the fecal resistome of human and animal recipients. Antibiotic resistance (AR) genes were found to be abundant in all donor microbiota. An overall surge of resistomes with higher prevalence and abundance of AR genes was observed in the feces of all transplanted gnotobiotic pigs as well as in the feces of infant subjects, compared to those in donor fecal and maternal vaginal microbiota. Surprisingly, transplants using rural Amish microbiota led to more instead of less AR genes in the fecal microbiota of gnotobiotic pigs than did transplants using urban microbiota. New AR gene subtypes undetected originally also appeared in gnotobiotic pigs, in Crohn's Disease (CD) patients after transplant, and in feces of infant subjects. The data illustrated the key role of the host gastrointestinal tract system in amplifying the ever-increasing AR gene pool, even without antibiotic exposure. The data further suggest that the current approaches of microbiota transplant can introduce significant health risk factor(s) to the recipients, and newborn human and animal hosts with naïve gut microbiota were especially susceptible. Given the illustrated public health risks of microbiota transplant, minimizing massive and unnecessary damages to gut microbiota by oral antibiotics and other gut impacting drugs becomes important. Since eliminating risk factors including AR bacteria and opportunistic pathogens directly from donor microbiota is still difficult to achieve, developing microbial cocktails with defined organisms and functions has further become an urgent need, should microbiota transplantation become necessary.

RevDate: 2020-06-08
CmpDate: 2020-06-08

Dabke K, Hendrick G, S Devkota (2019)

The gut microbiome and metabolic syndrome.

The Journal of clinical investigation, 129(10):4050-4057.

The metabolic syndrome (MetS) is a constellation of risk factors that, if left untreated, will often progress to greater metabolic defects such as type 2 diabetes and nonalcoholic fatty liver disease. While these risk factors have been established for over 40 years, the definition of MetS warrants reconsideration in light of the substantial data that have emerged from studies of the gut microbiome. In this Review we present the existing recent literature that supports the gut microbiome's potential influence on the various risk factors of MetS. The interplay of the intestinal microbiota with host metabolism has been shown to be mediated by a myriad of factors, including a defective gut barrier, bile acid metabolism, antibiotic use, and the pleiotropic effects of microbially produced metabolites. These data show that events that start in the gut, often in response to external cues such as diet and circadian disruption, have far-reaching effects beyond the gut.

RevDate: 2020-06-05

Reygner J, Charrueau C, Delannoy J, et al (2020)

Freeze-dried fecal samples are biologically active after long-lasting storage and suited to fecal microbiota transplantation in a preclinical murine model of Clostridioides difficile infection.

Gut microbes [Epub ahead of print].

Fecal microbiota transplantation is now recommended for treating recurrent forms of Clostridioides difficile infection. Recent studies have reported protocols using capsules of either frozen or freeze-dried stool allowing oral administration in in- and out-patient settings. However, a central question remains the viability, engraftment, and efficacy of the microbiome over time during storage life. This study shows that both the freeze-drying and freezing procedures for fecal samples allowed preserving viability, short-chain fatty acids concentration, and anti-Clostridioides difficile properties of microbiota without significant alteration after storage for 12 months. Fecal transplantation with freeze-dried microbiota allowed engraftment of microbiota leading to clearance of Clostridioides difficile infection in a preclinical murine model with a survival rate of 70% versus 53-60% in mice treated with frozen inocula, and 20% in the untreated group. Moreover, the freeze-dried powder can be used to fill oral hard capsules using a very low amount (0.5%) of glidant excipient, allowing oral formulation. Altogether, this study showed that freeze-dried inocula can be used for the treatment of Clostridioides difficile infection with long-lasting stability of the fecal microbiota. This formulation facilitates biobanking and allows the use of hard capsules, an essential step to simplify patient access to treatment.

RevDate: 2020-06-05

Piekarska A, Panasiuk A, PM Stępień (2020)

Clinical practice guidelines for Clostridioides (Clostridium) difficile infection and fecal microbiota transplant protocol - recommendations of the Polish Society od Epidemiology and Infectious Diseases.

Przeglad epidemiologiczny, 74(1):69-87.

Symptomatic Clostridium difficile infection (CDI) is an acute inflammatory disease of the gastrointestinal tract, manifesting in at least 3 unformed stools within 24 hours. Predicting factors for CDI include contact with medical care (mainly hospitalization), antibiotic therapy in the last 12 weeks, use of proton pump inhibitors (PPI), H2 blockers, cancer chemotherapy, especially in the neutropenia stage, gastrointestinal surgery, advanced age and concomitant chronic diseases (renal failure, liver failure, chronic inflammatory bowel disease - especially ulcerative bowel disease, cancer, HIV infection, cachexia and hypoalbuminaemia) and vitamin D deficiency. Clinical classification distinguishes three types of CDI - mild / moderate, severe, and fulminant. The principles of treatment of the first and subsequent CDI incidents depending on the clinical course are based on oral vancomycin. CDI is recurrent. The basis for treating CDI relapses is vancomycin administered orally at a dose of 4x125 mg for 10 days followed by concomitant vancomycin dose reduction therapy. The use of fecal microbiota transfer (FMT) in the treatment of CDI relapses is considered to be the most effective therapy for recurrent CDI. An indication for FMT is antibiotic-resistant C. difficile infection, regardless of the number of incidents CDI. The panel of tests recommended for a bacterial flora donor is presented in the recommendations.

RevDate: 2020-06-05

Cheung MK, Yue GGL, Chiu PWY, et al (2020)

A Review of the Effects of Natural Compounds, Medicinal Plants, and Mushrooms on the Gut Microbiota in Colitis and Cancer.

Frontiers in pharmacology, 11:744.

The human gastrointestinal tract harbors a diverse array of microorganisms that play fundamental roles in health and disease. Imbalance in the gut microbiota, namely dysbiosis, can lead to various diseases, including cancer and gastrointestinal tract disorders. Approaches to improve gut dysbiosis, such as dietary intervention, intake of probiotics, and fecal microbiota transplantation are emerging strategies to treat these diseases. Various medicinal botanicals have reported anti-cancer and/or anti-inflammatory properties. Preclinical studies have illustrated that some of these natural products are also capable to modulate the gut microbiota, suggesting their use as possible alternative approach to improve gut dysbiosis and thereby assist diseases treatment. In this review article, we have summarized the current knowledge on the effects of natural compounds, medicinal plants, and mushrooms on the gut microbiota in various cancers and colitis in preclinical animal models. Challenges towards the clinical use of these medicinal botanicals as modulators of the gut microbiota in cancer and colitis treatment are also discussed.

RevDate: 2020-06-05

Simpson E, Sanjar F, Wylie D, et al (2020)

Draft Genome Sequences of Two Strains of Bifidobacterium dentium Isolated from a Crude Fecal Extract Used for Fecal Microbiota Transplantation in the Republic of Korea.

Microbiology resource announcements, 9(23): pii:9/23/e00197-20.

We present the draft genome sequences of two Bifidobacterium dentium strains isolated from a fecal extract for fecal microbiota transplantation at a hospital in the Republic of Korea. Phylogenetic and functional analyses were performed to understand the physiological characteristics and functions of Bifidobacterium spp. in the human intestine.

RevDate: 2020-06-05
CmpDate: 2020-06-05

Kuijper EJ, Allegretii J, Hawkey P, et al (2019)

A necessary discussion after transmission of multidrug-resistant organisms through faecal microbiota transplantations.

The Lancet. Infectious diseases, 19(11):1161-1162.

RevDate: 2020-06-05
CmpDate: 2020-06-05

Paik J, Meeker S, Hsu CC, et al (2020)

Validation studies for germ-free Smad3-/- mice as a bio-assay to test the causative role of fecal microbiomes in IBD.

Gut microbes, 11(1):21-31.

While the association between microbiomes and inflammatory bowel disease (IBD) is well known, establishing causal relationships between the two is difficult in humans. Germ-free (GF) mice genetically susceptible to IBD can address this question. Smad3-/- mice with defective transforming growth factor ß signaling are a model of IBD and colon cancer. They develop IBD upon colonization with Helicobacter under specific pathogen-free conditions, suggesting a role of the microbiome in IBD in this model. Thus, we rederived Smad3-/- mice GF to determine the potential of using these mice for testing the causative role of microbiomes in IBD. We found that fecal microbiomes from mice with IBD cause more severe gut inflammation in GF Smad3-/- and wild type mice compared to microbiomes from healthy mice and that Helicobacter induces gut inflammation within the context of other microbiomes but not by itself. Unexpectedly, GF Smad3+/+ and Smad3+/- mice given IBD microbiomes develop IBD despite their lack of disease in SPF conditions upon Helicobacter infection. This was not unique to the background strain of our Smad3 model (129); both wild type C57BL/6 and 129 strains developed IBD upon fecal transfer. However, wild type Swiss Webster stock was not susceptible, indicating that the genetic background of recipient mice influences the severity of IBD following fecal transfer. Our data suggest that the microbiome is an independent risk factor contributing to IBD development, and careful characterization of new GF models is needed to understand potential sources of confounding factors influencing microbiome studies in these mice.

RevDate: 2020-06-04

Assimakopoulos SF, Papadopoulou I, Bantouna D, et al (2020)

Fecal Microbiota Transplantation and Hydrocortisone Ameliorate Intestinal Barrier Dysfunction and Improve Survival in a Rat Model of Cecal Ligation and Puncture-Induced Sepsis.

Shock (Augusta, Ga.) [Epub ahead of print].

INTRODUCTION: Sepsis is a life-threatening syndrome which can progress to multiple organ dysfunction with high mortality. Intestinal barrier failure exerts a central role in the pathophysiological sequence of events that lead from sepsis to multiple organ dysfunction. The present study investigated the role of hydrocortisone (HC) administration and fecal microbiota transplantation (FMT) in several parameters of the gut barrier integrity, immune activation and survival, in a model of polymicrobial sepsis in rats.

METHODS: Forty adults male Wistar rats were randomly divided into four groups: sham (group I), cecal ligation and puncture (CLP) (group II), CLP + HC (2.8 mg/kg, intraperitoneally single dose at 6 hours) (group III) and CLP + FMT at 6 hours (group IV). At 24 h post-CLP, ileal tissues were harvested for histological and immunohistochemical analyses while endotoxin, IL-6 and IL-10 levels in systemic circulation were determined. In a second experiment the same groups were observed for seven days for mortality, with daily administration of hydrocortisone (group III) and FMT (group IV) in surviving rats.

RESULTS: HC administration and FMT significantly reduced mortality of septic rats by 50%. These interventions totally reversed intestinal mucosal atrophy by increasing villous density and mucosal thickness (μm, mean ± SD: Group I: 620 ± 35, Group II: 411 ± 52, Group III: 622 ± 19, Group IV:617 ± 44). HC and FMT reduced the apoptotic body count in intestinal crypts whereas increased the mitotic/apoptotic index. Activated caspase-3 expression in intestinal crypts was significantly reduced by HC or FMT (activated caspase-3 (+) enterocytes/10 crypts, mean ± SD: Group I: 1,6 ± 0,5, Group II: 5,8 ± 2,4, Group III: 3,6 ± 0,9, Group IV:2,3 ± 0,6). Both treatments increased Paneth cell count and decreased intraepithelial CD3(+) T lymphocytes and inflammatory infiltration of lamina propria to control levels. In the sham group almost the total of intestinal epithelial cells expressed occludin (92 ± 8%) and claudin-1 (98 ± 4%) and CLP reduced this expression to 34 ± 12% for occludin and 35 ± 7% for claudin-1. Administration of HC significantly increased occludin (51 ± 17%) and claudin-1 (77 ± 9%) expression. FMT exerted also a significant restoring effect in TJ by increasing occludin (56 ± 15%) and claudin-1 (84 ± 7%) expression. The beneficial effects of these treatments on gut barrier function led to significant reduction of systemic endotoxemia (EU/ml, mean ± SD: Group I: 0,93 ± 0,36, Group II: 2,14 ± 1,74, Group III: 1,48 ± 0,53, Group IV: 1,61 ± 0,58,), while FMT additionally decreased IL-6 and IL-10 levels.

CONCLUSION: Fecal microbiota transplantation and stress dose hydrocortisone administration in septic rats induce a multifactorial improvement of the gut mechanical and immunological barriers, preventing endotoxemia and leading to improved survival.

RevDate: 2020-06-04

Rasmussen TS, Koefoed AK, Jakobsen RR, et al (2020)

Bacteriophage-mediated manipulation of the gut microbiome - promises and presents limitations.

FEMS microbiology reviews pii:5851274 [Epub ahead of print].

Gut microbiome (GM) composition and function are linked to human health and disease, and routes for manipulating the GM have become an area of intense research. Due to its high treatment efficacy, the use of fecal microbiota transplantation (FMT) is generally accepted as a promising experimental treatment for patients suffering from GM imbalances (dysbiosis), e.g. caused by recurrent Clostridioides difficile infections (rCDI). Mounting evidence suggests that bacteriophages (phages) play a key role in successful FMT treatment by restoring the dysbiotic bacterial GM. As a refinement to FMT, removing the bacterial component of donor feces by sterile filtration, also referred to as fecal virome transplantation (FVT), decreases the risk of invasive infections caused by bacteria. However, eukaryotic viruses and prophage-encoded virulence factors remain a safety issue. Recent in vivo studies show how cascading effects are initiated when phage communities are transferred to the gut by e.g. FVT, which leads to changes in the GM composition, host metabolome, and improve host health such as alleviating symptoms of obesity and type-2-diabetes (T2D). In this review, we discuss the promises and limitations of FVT along with the perspectives of using FVT to treat various diseases associated with GM dysbiosis.

RevDate: 2020-06-04

Chinna Meyyappan A, R Milev (2020)

The Safety, Efficacy, and Tolerability of Microbial Ecosystem Therapeutic-2 in People With Major Depression and/or Generalized Anxiety Disorder: Protocol for a Phase 1, Open-Label Study.

JMIR research protocols, 9(6):e17223 pii:v9i6e17223.

BACKGROUND: The bidirectional signaling between the gut microbiota and the brain, known as the gut-brain axis, is being heavily explored in current neuropsychiatric research. Analyses of the human gut microbiota have shown considerable individual variability in bacterial content, which is hypothesized to influence brain function, and potentially mood and anxiety symptoms, through gut-brain axis communication. Preclinical and clinical research examining these effects suggests that fecal microbiota transplant (FMT) may aid in improving the severity of depression and anxiety symptoms by recolonizing the gastrointestinal (GI) tract with healthy bacteria. The microbial ecosystem therapeutic (ie, microbial ecosystem therapeutic-2 [MET-2]) used in this study is an alternative treatment to FMT, which comprises 40 different strains of gut bacteria from a healthy donor.

OBJECTIVE: The primary objective of this study is to assess subjective changes in mood and anxiety symptoms before, during, and after administration of MET-2. The secondary objectives of this study are to assess the changes in metabolic functioning and the level of repopulation of healthy gut bacteria, the safety and tolerability of MET-2, and the effects of early stress on biomarkers of depression/anxiety and the response to treatment.

METHODS: Adults experiencing depressive or anxiety symptoms will be recruited from the Kingston area. These participants will orally consume an encapsulated MET-2 once daily-containing 40 strains of purified and laboratory-grown bacteria from a single healthy donor-for 8 weeks, followed by a 2-week treatment-free follow-up period. Participants will undergo a series of clinical assessments measuring mood, anxiety, and GI symptoms using validated clinical scales and questionnaires. Molecular data will be collected from blood and fecal samples to assess metabolic changes, neurotransmitter levels, inflammatory markers, and the level of engraftment of the fecal samples that may predict outcomes in depression or anxiety.

RESULTS: Given the association between the gut bacteria and the risk factors of depression, we expect to observe an improvement in the severity of depressive and anxiety symptoms following treatment, and we expect that this improvement is mediated by the recolonization of the GI tract with healthy bacteria. The recruitment for this study has been completed, and the data obtained are currently being analyzed.

CONCLUSIONS: This is the first time MET-2 is being tested in psychiatric indications, specifically depression and anxiety. As such, this may be the first study to show the potential effects of microbial therapy in alleviating psychiatric symptoms as well as its safety and tolerability.

DERR1-10.2196/17223.

RevDate: 2020-06-04

Trang-Poisson C, Kerdreux E, Poinas A, et al (2020)

Impact of fecal microbiota transplantation on chronic recurrent pouchitis in ulcerative colitis with ileo-anal anastomosis: study protocol for a prospective, multicenter, double-blind, randomized, controlled trial.

Trials, 21(1):455 pii:10.1186/s13063-020-04330-1.

BACKGROUND: Almost 15% of patients with ulcerative colitis (UC) will require a proctocolectomy with ileal pouch-anal anastomosis (IPAA) as a result of fulminant colitis, dysplasia, cancer, or medical refractory diseases. Around 50% will experience pouchitis, an idiopathic inflammatory condition involving the ileal reservoir, responsible for digestive symptoms, deterioration in quality of life, and disability. Though the majority of initial cases of pouchitis are easily managed with a short course of antibiotics, in about 10% of cases, inflammation of the pouch becomes chronic with very few treatments available. Previous studies have suggested that manipulating the composition of intestinal flora through antibiotics, probiotics, and prebiotics achieved significant results for treating acute episodes of UC-associated pouchitis. However, there is currently no established effective treatment for chronic antibiotic-dependent pouchitis. Fecal microbiota transplantation (FMT) is a novel therapy involving the transfer of normal intestinal flora from a healthy donor to a patient with a medical condition potentially caused by the disrupted homeostasis of intestinal microbiota or dysbiosis.

METHODS: Our project aims to compare the delay of relapse of chronic recurrent pouchitis after FMT versus sham transplantation. Forty-two patients with active recurrent pouchitis after having undergone an IPAA for UC will be enrolled at 12 French centers. The patients who respond to antibiotherapy will be randomized at a ratio of 1:1 to receive either FMT or sham transplantation.

DISCUSSION: On April 30, 2014, the World Health Organization published an alarming report on antibiotic resistance. Finding an alternative medical treatment to antibiotics in order to prevent relapses of pouchitis is therefore becoming increasingly important given the risk posed by multiresistant bacteria. Moreover, if the results of this study are conclusive, FMT, which is less expensive than biologics, could become a routine treatment in the future.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT03524352. Registered on 14 May 2018.

RevDate: 2020-06-03

Gulati M, Singh SK, Corrie L, et al (2020)

Delivery routes for faecal microbiota transplants: Available, anticipated and aspired.

Pharmacological research pii:S1043-6618(20)31262-7 [Epub ahead of print].

Fecal microbiota transplant (FMT) has seen a historic emergence in last decade with its sojourn recently entering into a chequered path, due to a few reports of infection and subsequent mortality. Though FMT has been extensively reported, there is no comprehensive report on the delivery routes available for this non-pharmacological treatment option. Safety, efficacy and cost of FMT not only depend on the quality of contents but also on the delivery route employed. A number of delivery routes are in use for conducting FMT, which include upper gastrointestinal routes (UGI) i.e. nasogastric/nasojejunal tube, endoscopy, oral capsules and lower gastrointestinal routes (LGI) like retention enema, sigmoidoscopy or colonoscopy. Capsules, both conventional as well as colon targeted have been the most commonly used formulations. Surprisingly, the success rates with conventional gastric delivery capsules and colon targeted capsules were found to be quite similar indicating the sufficiency of the inoculum size to withstand the microbial loss in the gastric milieu. Patient compliance, cost effectiveness, comfort of administration, level of invasiveness, patient's hospital admission, risk of aspiration and infections, multiplicity of administration required, recurrence rate are the main factors that seem to influence the choice for route of administration of physicians. The best route for FMT has not been established yet. Extensive studies are required to understand the interplay of route adopted, type of donor, physical nature of sample (fresh or frozen), patient compliance and cost effectiveness to design an approach for the risk free, convenient and cost-effective administration route for FMT.

RevDate: 2020-06-03

Adelman MW, Woodworth MH, Langelier C, et al (2020)

The gut microbiome's role in the development, maintenance, and outcomes of sepsis.

Critical care (London, England), 24(1):278 pii:10.1186/s13054-020-02989-1.

The gut microbiome regulates a number of homeostatic mechanisms in the healthy host including immune function and gut barrier protection. Loss of normal gut microbial structure and function has been associated with diseases as diverse as Clostridioides difficile infection, asthma, and epilepsy. Recent evidence has also demonstrated a link between the gut microbiome and sepsis. In this review, we focus on three key areas of the interaction between the gut microbiome and sepsis. First, prior to sepsis onset, gut microbiome alteration increases sepsis susceptibility through several mechanisms, including (a) allowing for expansion of pathogenic intestinal bacteria, (b) priming the immune system for a robust pro-inflammatory response, and (c) decreasing production of beneficial microbial products such as short-chain fatty acids. Second, once sepsis is established, gut microbiome disruption worsens and increases susceptibility to end-organ dysfunction. Third, there is limited evidence that microbiome-based therapeutics, including probiotics and selective digestive decontamination, may decrease sepsis risk and improve sepsis outcomes in select patient populations, but concerns about safety have limited uptake. Case reports of a different microbiome-based therapy, fecal microbiota transplantation, have shown correlation with gut microbial structure restoration and decreased inflammatory response, but these results require further validation. While much of the evidence linking the gut microbiome and sepsis has been established in pre-clinical studies, clinical evidence is lacking in many areas. To address this, we outline a potential research agenda for further investigating the interaction between the gut microbiome and sepsis.

RevDate: 2020-06-03

Okahara K, Ishikawa D, Nomura K, et al (2020)

Matching between Donors and Ulcerative Colitis Patients Is Important for Long-Term Maintenance after Fecal Microbiota Transplantation.

Journal of clinical medicine, 9(6): pii:jcm9061650.

We previously demonstrated that fresh fecal microbiota transplantation (FMT) following triple antibiotic therapy (amoxicillin, fosfomycin, metronidazole (AFM); A-FMT) resulted in effective colonization of Bacteroidetes species, leading to short-term clinical response in ulcerative colitis (UC). Its long-term efficacy and criteria for donor selection are unknown. Here, we analyzed the long-term efficacy of A-FMT compared to AFM monotherapy (mono-AFM). AFM was administered to patients with mild to severe UC for 2 weeks until 2 days before fresh FMT. Clinical response and efficacy maintenance were defined by the decrease and no exacerbation in clinical activity index. The population for intention-to-treat analysis comprised 92 patients (A-FMT, n = 55; mono-AFM, n = 37). Clinical response was observed at 4 weeks post-treatment (A-FMT, 56.3%; mono-AFM, 48.6%). Maintenance rate of responders at 24 months post-treatment was significantly higher with A-FMT than mono-AFM (p = 0.034). Significant differences in maintenance rate according to the age difference between donors and patients were observed. Additionally, sibling FMT had a significantly higher maintenance rate than parent-child FMT. Microbial analysis of patients who achieved long-term maintenance showed that some exhibited similarity to their donors, particularly Bacteroidetes species. Thus, A-FMT exhibited long-term efficacy. Therefore, matching between donors and UC patients may be helpful in effectively planning the FMT regimen.

RevDate: 2020-06-02

Wang MX, Lin L, Chen YD, et al (2020)

Evodiamine has therapeutic efficacy in ulcerative colitis by increasing Lactobacillus acidophilus levels and acetate production.

Pharmacological research pii:S1043-6618(20)31286-X [Epub ahead of print].

Emerging evidence implicates gut microbiota have an important role in ulcerative colitis (UC). Previous study indicated that Evodiamine (EVO) can alleviate colitis through downregulating inflammatory pathways. However, specific relationship between EVO-treated colitis relief and regulation of gut microbiota is still unclear. Here, our goal was to determine the potential role of gut microbiota in the relief of UC by EVO. By using pathology-related indicators, 16S rRNA sequencing and metabolomics profiling, we assessed the pharmacological effect of EVO on dextran sulfate sodium (DSS)-induced colitis rats as well as on the change of gut microbiota and metabolism. Fecal derived from EVO-treated rats was transplanted into colitis rats to verify the effect of EVO on gut microbiota, and 'driver bacteria' was found and validated by 16S rRNA sequencing, metagenome and qRT-PCR. The effect of Lactobacillus acidophilus (L. acidophilus) was investigated by vivo experiment, microbiota analysis, Short-chain fatty acids (SCFAs) quantification and colon transcriptomics. EVO reduced the susceptibility to DSS-induced destruction of epithelial integrity and severe inflammatory response, and regulated the gut microbiota and metabolites. Fecal Microbiota Transplantation (FMT) alleviated DSS-induced colitis, increased the abundance of L. acidophilus and the level of acetate. Furthermore, gavaged with L. acidophilus reduced pro-inflammatory cytokines, promoted the increase of goblet cells and the secretion of antimicrobial peptides, regulated the ratio of Firmicutes/Bacteroidetes and increased the level of acetate. Our results indicated that EVO mitigation of DSS-induced colitis is associated with increased in L. acidophilus and protective acetate production, which may be a promising strategy for treating UC.

RevDate: 2020-05-25
CmpDate: 2020-05-25

Aroniadis OC, Brandt LJ, Oneto C, et al (2019)

Faecal microbiota transplantation for diarrhoea-predominant irritable bowel syndrome: a double-blind, randomised, placebo-controlled trial.

The lancet. Gastroenterology & hepatology, 4(9):675-685.

BACKGROUND: Faecal microbiota transplantation (FMT) has shown promise in alleviating the symptoms of irritable bowel syndrome (IBS); however, controlled data on this technique are scarce. The aim of this clinical trial was to assess the efficacy of FMT in alleviating diarrhoea-predominant IBS (IBS-D).

METHODS: We did a double-blind, randomised, placebo-controlled crossover trial in patients aged 18-65 years with moderate-to-severe IBS-D defined by an IBS-Symptom Severity Score (IBS-SSS) of more than 175, recruited from three US centres. Patients were randomly assigned (1:1) in blocks of four with a computer-generated randomisation sequence to receive FMT capsules followed by identical-appearing placebo capsules, or placebo capsules followed by FMT capsules. All participants and study team members were masked to randomisation. An independent staff member assigned the treatments according to consecutive numbers. Patients received either 75 FMT capsules (each capsule contained approximately 0·38 g of minimally processed donor stool) or 75 placebo capsules over 3 days (25 capsules per day). All patients crossed over to the alternate treatment at 12 weeks. The primary outcome was difference in IBS-SSS between the groups at 12 weeks. Intention-to-treat analyses were done and all patients who received study drug were included in an adverse events analysis. The trial was terminated during recruitment because results from an interim analysis revealed futility. The study is registered with ClinicalTrials.gov, number NCT02328547.

FINDINGS: From May 28, 2015, to April 21, 2017, 48 patients were randomly assigned to receive FMT first (n=25) or placebo first (n=23). Three participants were lost to follow-up in the FMT group. IBS-SSS did not differ between FMT recipients (mean 221 [SD 105]) and placebo recipients (236 [95]) at 12 weeks (p=0·65), after adjustment for baseline scores. The most common drug-related adverse events included abdominal pain (five [10%] of the 48 participants while receiving FMT capsules vs four [8%] while receiving placebo), nausea (four [8%] vs two [4%]), and exacerbation of diarrhoea (three [6%] vs eight [17%]). One serious adverse event that was unrelated to study drug (acute cholecystitis) was reported in a patient while receiving placebo capsules.

INTERPRETATION: FMT was safe, but did not induce symptom relief at 12 weeks compared with placebo. Additional studies are needed to determine the efficacy of FMT for IBS-D.

FUNDING: National Institutes of Health.

RevDate: 2020-06-01
CmpDate: 2020-06-01

Wang Y, Zhao W, Shi J, et al (2019)

Intestinal microbiota contributes to altered glucose metabolism in simulated microgravity mouse model.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33(9):10140-10151.

Exposure to space environment induces alterations in glucose and lipid metabolism that contribute to muscular atrophy, bone loss, and cardiovascular disorders. Intestinal microbiota is also changed, but its impact on spaceflight-related metabolic disorder is not clear. We investigated the relationship between glucose metabolic changes and gut dysbiosis in a hind limb-unloading (HU) mouse model, a well-accepted ground-based spaceflight analog. Impaired body weight gain, glucose intolerance, and peripheral insulin resistance were found in 2-4-wk HU mice. Reduced abundance of gut Bifidobacterium spp. and Akkermansia muciniphila was observed within 3 d of HU. The ground-based control (Ctrl) mice that were cohoused with HU mice showed similar patterns of dysbiosis and metabolic changes. Compared with the Ctrls, higher levels of plasma LPS-binding protein and altered transcription of Tnfa and glucose metabolism-related genes in the liver were observed in HU mice. The supplementation of Bifidobacterium spp. suppressed endotoxemia and liver inflammation and improved glucose tolerance in HU mice. The results indicate a close relationship between dysbiosis and altered glucose metabolism in the HU model and also emphasize the importance of evaluating intestinal microbiota in astronauts and its effect on glucose metabolism.-Wang, Y., Zhao, W., Shi, J., Wang, J., Hao, J., Pang, X., Huang, X., Chen, X., Li, Y., Jin, R., Ge, Q. Intestinal microbiota contributes to altered glucose metabolism in simulated microgravity mouse model.

RevDate: 2020-06-01
CmpDate: 2020-06-01

Duan Y, Zhong Y, Xiao H, et al (2019)

Gut microbiota mediates the protective effects of dietary β-hydroxy-β-methylbutyrate (HMB) against obesity induced by high-fat diets.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33(9):10019-10033.

Obesity increases the risk of developing insulin resistance and diabetes and is a major public health concern. Our previous study shows that dietary β-hydroxy-β-methylbutyrate (HMB) improves lipid metabolism in a pig model. However, it remains unclear whether HMB blocks obesity through gut microbiota. In this study, we found that HMB reduced body weight, alleviated the whitening of brown adipose tissue, and improved insulin resistance in mice fed a high-fat diet (HFD). High-throughput pyrosequencing of the 16S rRNA demonstrated that HMB administration significantly reversed the gut microbiota dysbiosis in HFD-fed mice, including the diversity of gut microbiota and relative abundances of Bacteroidetes and Firmicutes. Moreover, microbiota transplantation from HMB-treated mice attenuated HFD-induced lipid metabolic disorders. Furthermore, HFD-fed mice showed lower short-chain fatty acids, whereas administration of HMB increased the propionic acid production. Correlation analysis identified a significant correlation between propionic acid production and the relative Bacteroidetes abundance. Sodium propionate treatment also attenuated HFD-induced lipid metabolic disorders. Collectively, our results indicated that HMB might be used as a probiotic agent to reverse HFD-induced obesity, and the potential mechanism was associated with reprogramming gut microbiota and metabolism, especially Bacteroidetes-mediated propionic acid production. In future studies, more efforts should be made to confirm and expand the beneficial effects of HMB to human models.-Duan, Y., Zhong, Y., Xiao, H., Zheng, C., Song, B., Wang, W., Guo, Q., Li, Y., Han, H., Gao, J., Xu, K., Li, T., Yin, Y., Li, F., Yin, J., Kong, X. Gut microbiota mediates the protective effects of dietary β-hydroxy-β-methylbutyrate (HMB) against obesity induced by high-fat diets.

RevDate: 2020-05-31

Lin H, Wang Q, Yuan M, et al (2020)

The prolonged disruption of a single-course amoxicillin on mice gut microbiota and resistome, and recovery by inulin, Bifidobacterium longum and fecal microbiota transplantation.

Environmental pollution (Barking, Essex : 1987), 265(Pt A):114651 pii:S0269-7491(20)30456-5 [Epub ahead of print].

The usages of antibiotics in treating the pathogenic infections could alter the gut microbiome and associated resistome, causing long term adverse impact on human health. In this study, mice were treated with human-simulated regimen 25.0 mg kg-1 of amoxicillin for seven days, and their gut microbiota and resistome were characterized using the 16S rRNA amplicons sequencing and the high-throughput qPCR, respectively. Meanwhile, the flora restorations after individual applications of inulin, Bifidobacterium longum (B. longum), and fecal microbiota transplantation (FMT) were analyzed for up to 35 days. The results revealed the prolonged negative impact of single course AMX exposure on mice gut microbiota and resistome. To be specific, pathobionts of Klebsiella and Escherichia-Shigella were significantly enriched, while prebiotics of Bifidobacterium and Lactobacillus were dramatically depleted. Furthermore, β-lactam resistance genes and efflux resistance genes were obviously enriched after amoxicillin exposure. Compared to B. longum, FMT and inulin were demonstrated to preferably restore the gut microbiota via reconstituting microbial community and stimulating specific prebiotic respectively. Such variation of microbiome caused their distinct alleviations on resistome alteration. Inulin earned the greatest elimination on AMX induced ARG abundance and diversity enrichment. FMT and B. longum caused remove of particular ARGs such as ndm-1, blaPER. Network analysis revealed that most of the ARGs were prone to be harbored by Firmicutes and Proteobacteria. In general, gut resistome shift was partly associated with the changing bacterial community structures and transposase and integron. Taken together, these results demonstrated the profound disruption of gut microbiota and resistome after single-course amoxicillin treatment and different restoration by inulin, B. longum and FMT.

RevDate: 2020-05-29

Kragsnaes MS, Nilsson AC, Kjeldsen J, et al (2020)

How do I establish a stool bank for fecal microbiota transplantation within the blood- and tissue transplant service?.

Transfusion [Epub ahead of print].

Worldwide, there is a rising demand for thoroughly screened, high-quality fecal microbiota transplantation (FMT) products that can be obtained at a reasonable cost. In the light of this evolving therapeutic area of the intestinal microbiota, both private and public stool banks have emerged. However, some of the larger difficulties when establishing stool banks are caused by the absence of or international disagreement on regulation and legislative formalities. In this context, the establishment of a stool bank within a nonprofit blood and tissue transplant service has several advantages. Especially, this setting can ensure that every step of the donation process, laboratory handling, and donor-traceability is in agreement with the current expert guidelines and meets the requirements of the European Union's regulative directives on human cells and tissues. Although safety and documentation are the top priority of the stool bank setup presented here, cost-effectiveness of the production is possible due to a high donor screening success rate and the knowhow, infrastructure, facilities, personnel, and laboratory- and quality-management systems that were already in place. Overall, our experience is that a centralized, nonprofit, blood and tissue transplant service is an ideal and safe facility to run a stool bank of high quality FMT products that are based on stool donations from volunteer, unpaid, healthy, blood donors.

RevDate: 2020-05-29

Jian X, Zhu Y, Ouyang J, et al (2020)

Alterations of gut microbiome accelerate multiple myeloma progression by increasing the relative abundances of nitrogen-recycling bacteria.

Microbiome, 8(1):74 pii:10.1186/s40168-020-00854-5.

BACKGROUND: Gut microbiome alterations are closely related to human health and linked to a variety of diseases. Although great efforts have been made to understand the risk factors for multiple myeloma (MM), little is known about the role of the gut microbiome and alterations of its metabolic functions in the development of MM.

RESULTS: Here, in a cohort of newly diagnosed patients with MM and healthy controls (HCs), significant differences in metagenomic composition were discovered, for the first time, with higher bacterial diversity in MM. Specifically, nitrogen-recycling bacteria such as Klebsiella and Streptococcus were significantly enriched in MM. Also, the bacteria enriched in MM were significantly correlated with the host metabolome, suggesting strong metabolic interactions between microbes and the host. In addition, the MM-enriched bacteria likely result from the regulation of urea nitrogen accumulated during MM progression. Furthermore, by performing fecal microbiota transplantation (FMT) into 5TGM1 mice, we proposed a mechanistic explanation for the interaction between MM-enriched bacteria and MM progression via recycling urea nitrogen. Further experiments validated that Klebsiella pneumoniae promoted MM progression via de novo synthesis of glutamine in mice and that the mice fed with glutamine-deficient diet exhibited slower MM progression.

CONCLUSIONS: Overall, our findings unveil a novel function of the altered gut microbiome in accelerating the malignant progression of MM and open new avenues for novel treatment strategies via manipulation of the intestinal microbiota of MM patients. Video abstract.

RevDate: 2020-05-29

Nance CL, Deniskin R, Diaz VC, et al (2020)

The Role of the Microbiome in Food Allergy: A Review.

Children (Basel, Switzerland), 7(6): pii:children7060050.

Food allergies are common and estimated to affect 8% of children and 11% of adults in the United States. They pose a significant burden-physical, economic and social-to those affected. There is currently no available cure for food allergies. Emerging evidence suggests that the microbiome contributes to the development and manifestations of atopic disease. According to the hygiene hypothesis, children growing up with older siblings have a lower incidence of allergic disease compared with children from smaller families, due to their early exposure to microbes in the home. Research has also demonstrated that certain environmental exposures, such as a farming environment, during early life are associated with a diverse bacterial experience and reduced risk of allergic sensitization. Dysregulation in the homeostatic interaction between the host and the microbiome or gut dysbiosis appears to precede the development of food allergy, and the timing of such dysbiosis is critical. The microbiome affects food tolerance via the secretion of microbial metabolites (e.g., short chain fatty acids) and the expression of microbial cellular components. Understanding the biology of the microbiome and how it interacts with the host to maintain gut homeostasis is helpful in developing smarter therapeutic approaches. There are ongoing trials evaluating the benefits of probiotics and prebiotics, for the prevention and treatment of atopic diseases to correct the dysbiosis. However, the routine use of probiotics as an intervention for preventing allergic disease is not currently recommended. A new approach in microbial intervention is to attempt a more general modification of the gut microbiome, such as with fecal microbiota transplantation. Developing targeted bacterial therapies for food allergy may be promising for both the treatment and prevention of food allergy. Similarly, fecal microbiota transplantation is being explored as a potentially beneficial interventional approach. Overall, targeted bacterial therapies for food allergy may be promising for both the treatment and prevention of food allergy.

RevDate: 2020-05-28

Li M, Li C, Wu X, et al (2020)

Microbiota-driven interleukin-17 production provides immune protection against invasive candidiasis.

Critical care (London, England), 24(1):268 pii:10.1186/s13054-020-02977-5.

BACKGROUND: The intestinal microbiota plays a crucial role in human health, which could affect host immunity and the susceptibility to infectious diseases. However, the role of intestinal microbiota in the immunopathology of invasive candidiasis remains unknown.

METHODS: In this work, an antibiotic cocktail was used to eliminate the intestinal microbiota of conventional-housed (CNV) C57/BL6 mice, and then both antibiotic-treated (ABX) mice and CNV mice were intravenously infected with Candida albicans to investigate their differential responses to infection. Furthermore, fecal microbiota transplantation (FMT) was applied to ABX mice in order to assess its effects on host immunity against invasive candidiasis after restoring the intestinal microbiota, and 16S ribosomal RNA gene sequencing was conducted on fecal samples from both uninfected ABX and CNV group of mice to analyze their microbiomes.

RESULTS: We found that ABX mice displayed significantly increased weight loss, mortality, and organ damage during invasive candidiasis when compared with CNV mice, which could be alleviated by FMT. In addition, the level of IL-17A in ABX mice was significantly lower than that in the CNV group during invasive candidiasis. Treatment with recombinant IL-17A could improve the survival of ABX mice during invasive candidiasis. Besides, the microbial diversity of ABX mice was significantly reduced, and the intestinal microbiota structure of ABX mice was significantly deviated from the CNV mice.

CONCLUSIONS: Our data revealed that intestinal microbiota plays a protective role in invasive candidiasis by enhancing IL-17A production in our model system.

RevDate: 2020-05-27

Abhyankar MM, Ma JZ, Scully KW, et al (2020)

Immune Profiling To Predict Outcome of Clostridioides difficile Infection.

mBio, 11(3): pii:mBio.00905-20.

There is a pressing need for biomarker-based models to predict mortality from and recurrence of Clostridioides difficile infection (CDI). Risk stratification would enable targeted interventions such as fecal microbiota transplant, antitoxin antibodies, and colectomy for those at highest risk. Because severity of CDI is associated with the immune response, we immune profiled patients at the time of diagnosis. The levels of 17 cytokines in plasma were measured in 341 CDI inpatients. The primary outcome of interest was 90-day mortality. Increased tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand 5 (CCL-5), suppression of tumorigenicity 2 receptor (sST-2), IL-8, and IL-15 predicted mortality by univariate analysis. After adjusting for demographics and clinical characteristics, the mortality risk (as indicated by the hazard ratio [HR]) was higher for patients in the top 25th percentile for TNF-α (HR = 8.35, P = 0.005) and IL-8 (HR = 4.45, P = 0.01) and lower for CCL-5 (HR = 0.18, P ≤ 0.008). A logistic regression risk prediction model was developed and had an area under the receiver operating characteristic curve (AUC) of 0.91 for 90-day mortality and 0.77 for 90-day recurrence. While limited by being single site and retrospective, our work resulted in a model with a substantially greater predictive ability than white blood cell count. In conclusion, immune profiling demonstrated differences between patients in their response to CDI, offering the promise for precision medicine individualized treatment.IMPORTANCEClostridioides difficile infection is the most common health care-associated infection in the United States with more than 20% patients experiencing symptomatic recurrence. The complex nature of host-bacterium interactions makes it difficult to predict the course of the disease based solely on clinical parameters. In the present study, we built a robust prediction model using representative plasma biomarkers and clinical parameters for 90-day all-cause mortality. Risk prediction based on immune biomarkers and clinical variables may contribute to treatment selection for patients as well as provide insight into the role of immune system in C. difficile pathogenesis.

RevDate: 2020-05-26

Kaźmierczak-Siedlecka K, Daca A, Fic M, et al (2020)

Therapeutic methods of gut microbiota modification in colorectal cancer management - fecal microbiota transplantation, prebiotics, probiotics, and synbiotics.

Gut microbes [Epub ahead of print].

The link between gut microbiota and the development of colorectal cancer has been investigated. An imbalance in the gut microbiota promotes the progress of colorectal carcinogenesis via multiple mechanisms, including inflammation, activation of carcinogens, and tumorigenic pathways as well as damaging host DNA. Several therapeutic methods are available with which to alter the composition and the activity of gut microbiota, such as administration of prebiotics, probiotics, and synbiotics; these can confer various benefits for colorectal cancer patients. Nowadays, fecal microbiota transplantation is the most modern way of modulating the gut microbiota. Even though data regarding fecal microbiota transplantation in colorectal cancer patients are still rather limited, it has been approved as a clinical method of treatment-recurrent Clostridium difficile infection, which may also occur in these patients. The major benefits of fecal microbiota transplantation include modulation of immunotherapy efficacy, amelioration of bile acid metabolism, and restoration of intestinal microbial diversity. Nonetheless, more studies are needed to assess the long-term effects of fecal microbiota transplantation. In this review, the impact of gut microbiota on the efficiency of anti-cancer therapy and colorectal cancer patients' overall survival is also discussed.

RevDate: 2020-05-26
CmpDate: 2020-05-26

Li J, FB Hu (2019)

Research digest: reshaping the gut microbiota.

The lancet. Diabetes & endocrinology, 7(9):671.

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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.

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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.

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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.

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