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25 Sep 2020 at 01:43
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Bibliography on: Fecal Transplantation


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Fecal Transplantation

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

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

Citations The Papers (from PubMed®)


RevDate: 2020-09-24

Wang L, An J, Song S, et al (2020)

Electroacupuncture preserves intestinal barrier integrity through modulating the gut microbiota in DSS-induced chronic colitis.

Life sciences pii:S0024-3205(20)31226-1 [Epub ahead of print].

AIMS: Electroacupuncture (EA) at ST36 has been verified to ameliorate experimental acute colitis. However, the effect of EA on chronic colitis and its mechanism has not yet been explored. This study aimed to assess the protective effect of EA against chronic colitis and the related mechanisms.

MAIN METHODS: Chronic colitis was induced by dextran sulfate sodium (DSS) in C57BL/6 mice, and EA was applied throughout the entire experiment. Colonic inflammation and intestinal barrier integrity were evaluated. Alterations in the gut microbiota were analyzed by 16S rRNA gene sequencing. The fecal microbiota transplantation (FMT) experiment was used to further confirm the effect of the gut microbiota on the barrier protective effect of EA. The potential molecular mechanisms were explored by western blotting.

KEY FINDINGS: (1) EA lowered the disease activity index (DAI) and histological scores, decreased the levels of TNFα, IL1β, IL6 and iNOS, and increased the IL10 level in DSS-induced chronic colitis. (2) EA upregulated the protein expression of ZO-1, Occludin, E-Cadherin and mucin2 (MUC2), reduced the apoptosis and proliferation of intestinal epithelial cells (IECs) and intestinal permeability. (3) EA enhanced the gut microbiota diversity and restored the community structure. (4) Both the low-frequency EA (LEA) FMT and high-frequency EA (HEA) FMT maintained the intestinal barrier integrity. (5) EA promoted activation of the mitogen activated protein kinase (MAPK) signaling pathway.

SIGNIFICANCE: EA can relieve chronic experimental colitis, and this effect may depend on activation of the MAPK signaling pathway through modulation of the gut microbiota to preserve the intestinal barrier.

RevDate: 2020-09-24

Ross CN, KR Reveles (2020)

Feasibility of fecal microbiota transplantation via oral gavage to safely alter gut microbiome composition in marmosets.

American journal of primatology [Epub ahead of print].

Disruption of microbial communities within human hosts has been associated with infection, obesity, cognitive decline, cancer risk and frailty, suggesting that microbiome-targeted therapies may be an option for improving healthspan and lifespan. The objectives of this study were to determine the feasibility of delivering fecal microbiota transplants (FMTs) to marmosets via oral gavage and to evaluate if alteration of the gut microbiome post-FMT could be achieved. This was a prospective study of marmosets housed at the Barshop Institute for Longevity and Aging Studies in San Antonio, Texas. Eligible animals included healthy young adult males (age 2-5 years) with no recent medication use. Stool from two donors was combined and administered in 0.5 ml doses to five young recipients once weekly for 3 weeks. Safety outcomes and alterations in the gut microbiome composition via 16S ribosomal RNA sequencing were compared at baseline and monthly up to 6 months post-FMT. Overall, significant differences in the percent relative abundance was seen in FMT recipients at the phylum and family levels from baseline to 1 month and baseline to 6 months post-FMT. In permutational multivariate analysis of variance analyses, treatment status (donor vs. recipient) (p = .056) and time course (p = .019) predicted β diversity (p = .056). The FMT recipients did not experience any negative health outcomes over the course of the treatment. FMT via oral gavage was safe to administer to young adult marmosets. The marmoset microbiome may be altered by FMT; however, progressive changes in the microbiome are strongly driven by the host and its baseline microbiome composition.

RevDate: 2020-09-24

Bonfili L, Cecarini V, Gogoi O, et al (2020)

Microbiota modulation as preventative and therapeutic approach in Alzheimer's disease.

The FEBS journal [Epub ahead of print].

The gut microbiota coevolves with its host, and numerous factors like diet, lifestyle, drug intake and geographical location continuously modify its composition, deeply influencing host health. Recent studies demonstrated that gut dysbiosis can alter normal brain function through the so-called gut-brain axis, a bidirectional communication network between the central nervous system and the gastrointestinal tract, thus playing a key role in the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD). In this perspective, in the constant search for novel treatments in AD, the rational modulation of gut microbiota composition could represent a promising approach to prevent or delay AD onset or to counteract its progression. Preclinical and human studies on microbiota modulation through oral bacteriotherapy and fecal transplantation showed anti-inflammatory and antioxidant effects, upregulation of plasma concentration of neuroprotective hormones, restoration of impaired proteolytic pathways, amelioration of energy homeostasis with consequent decrease of AD molecular hallmarks and improvement of behavioural and cognitive performances. In this review, we dissect the role of gut microbiota in AD and highlight recent advances in the development of new multi-target strategies for microbiota modulation to be used as possible preventative and therapeutic approaches in AD.

RevDate: 2020-09-23

Cold F, Kousgaard SJ, Halkjaer SI, et al (2020)

Fecal Microbiota Transplantation in the Treatment of Chronic Pouchitis: A Systematic Review.

Microorganisms, 8(9): pii:microorganisms8091433.

The objective was to evaluate available literature on treatment of chronic pouchitis with fecal microbiota transplantation (FMT) focusing on clinical outcomes, safety, and different approaches to FMT preparation and delivery. A systematic review of electronic databases was conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials Library from inception through April 2020. Human studies of all study types reporting results of FMT to treat chronic pouchitis were included. Nine studies, reporting FMT treatment of 69 patients with chronic pouchitis were found eligible for the review. Most studies were case series and cohort studies rated as having fair to poor quality due to high risk of bias and small sample size. Only one randomized controlled trial was included, finding no beneficial effect of FMT. In total clinical response after FMT was reported in 14 (31.8%) out of 44 evaluated patients at various timepoints after FMT, and clinical remission in ten (22.7%) patients. Only minor self-limiting adverse events were reported. FMT varied greatly regarding preparation, length of treatment, and route of delivery. The effects of FMT on symptoms of chronic pouchitis are not established, though some studies show promising results. Future controlled well-designed studies are warranted.

RevDate: 2020-09-23
CmpDate: 2020-09-23

Arita S, K Inagaki-Ohara (2019)

High-fat-diet-induced modulations of leptin signaling and gastric microbiota drive precancerous lesions in the stomach.

Nutrition (Burbank, Los Angeles County, Calif.), 67-68:110556.

OBJECTIVES: Obesity is a risk factor for malignancy in various tissues, and has been associated with gut microbiota alterations. However, the link between obesity-associated microbiota and gastric pathogenesis has not been clarified. We demonstrated that high-fat-diet (HFD) feeding causes intestinal metaplasia, which are precancerous lesions of the stomach, with augmented gastric leptin signaling. The aim of this study was to investigate the precise role of leptin signaling in the altered microbiota composition and pathogenesis in the stomach during diet-induced obesity.

METHODS: Male C57 BL/6 J, leptin receptor (Lepr)-mutated db/db, and gastrointestinal epithelium-specific Lepr conditional knockout (T3 b-Lepr cKO) mice were fed a HFD or control diet. Gastrointestinal microbiota was analyzed by 16 S rRNA gene sequences and quantitative polymerase chain reaction. Transplantation of gastric microbiota of HFD-fed mice was performed to evaluate metaplasia onset in recipient mice.

RESULTS: One week of HFD caused severe microbial dysbiosis in the stomach. The microbiota changes were accompanied by increased gastric leptin, leading to the consequent development of intestinal metaplasia. Transplantation of gastric microbiota from HFD-fed mice induced intestinal metaplasia in recipient mice; however, only a limited effect on pathogenesis was noted. HFD-fed db/db mice did not show a decrease in microbial abundance. Moreover, T3 b-Lepr cKO mice failed spontaneous obesity, and suppressed decreased abundance of gastric microbiota and occurrence of intestinal metaplasia during HFD feeding similar to db/db mice.

CONCLUSIONS: Gastric leptin signaling modulates the gastric microbiota community and regulates the pathogenesis in the gastric mucosa.

RevDate: 2020-09-22

Mao D, Jiang Q, Sun Y, et al (2020)

Treatment of intestinal graft-versus-host disease with unrelated donor fecal microbiota transplantation capsules: A case report.

Medicine, 99(38):e22129.

INTRODUCTION: Fecal microbiota transplantation (FMT), administering fecal suspensions via a nasoduodenal tube, has achieved a promising effect in the treatment of intestinal graft-versus-host disease (GvHD) in some pilot studies. In this study, oral FMT capsules from unrelated donor were used for the first time in the treatment of intestinal GvHD. Patient concerns: A 31-year-old male who was diagnosed as "myelodysplastic syndromes with excess blasts II" (intermediate risk 2 of international prognostic scoring system) received human leukocyte antigen -matched sibling donor allogeneic hematopoietic stem cell transplantation. The patient developed diarrhea, vomiting, and bloody stool on 28 days after transplantation.

DIAGNOSIS: Intestinal acute GvHD was diagnosed clinically with histological confirmation by colonoscopy and pathological biopsy.

INTERVENTIONS: This patient was treated with first cycle of oral FMT capsules after failure to initial treatment of methylprednisolone (2 mg/kg/d) combined with recombinant human tumor necrosis factor-α receptorII: IgG Fc fusion protein (25 mg, biw). The symptoms of intestinal GvHD were relieved but recurred 11 days later. Second cycle of oral FMT capsules was carried out.

OUTCOMES: After 2 cycles of fecal bacteria transplantation, intestinal GvHD was gradually controlled and did not recur again during the 2-month follow-up. The diversity and structure of the intestinal flora after FMT was closer to that of healthy donors than that before.

CONCLUSION: Our case showed oral FMT capsules could be used as a treatment option for corticosteroid refractory intestinal GvHD. Further studies are warranted to assess the clinical efficacy and safety of oral FMT capsules in the treatment of intestinal GvHD.

RATIONALE: Fecal microbiota transplantation (FMT), administering fecal suspensions via a nasoduodenal tube, has achieved a promising effect in the treatment of intestinal graft-versus-host disease (GvHD) in some pilot studies. In this study, oral FMT capsules from unrelated donor were used for the first time in the treatment of intestinal GvHD.

PATIENT CONCERNS: A 31-year-old male who was diagnosed as "myelodysplastic syndromes with excess blasts II" (intermediate risk 2 of international prognostic scoring system) received human leukocyte antigen -matched sibling donor allogeneic hematopoietic stem cell transplantation. The patient developed diarrhea, vomiting, and bloody stool on 28 days after transplantation.

DIAGNOSES: Intestinal acute GvHD was diagnosed clinically with histological confirmation by colonoscopy and pathological biopsy.

INTERVENTIONS: This patient was treated with first cycle of oral FMT capsules after failure to initial treatment of methylprednisolone (2 mg/kg/d) combined with recombinant human tumor necrosis factor-a receptorII: IgG Fc fusion protein (25 mg, biw). The symptoms of intestinal GvHD were relieved but recurred 11 days later. Second cycle of oral FMT capsules was carried out.

OUTCOMES: After 2 cycles of fecal bacteria transplantation, intestinal GvHD was gradually controlled and did not recur again during the 2-month follow-up. The diversity and structure of the intestinal flora after FMT was closer to that of healthy donors than that before.

CONCLUSION: Our case showed oral FMT capsules could be used as a treatment option for corticosteroid refractory intestinal GvHD. Further studies are warranted to assess the clinical efficacy and safety of oral FMT capsules in the treatment of intestinal GvHD.

LESSONS: There is still a possibility of recurrence after the treatment of GvHD with capsule fecal microbiota transplantation. How to optimize the dosage and treatment course of fecal microbiota capsule administration needs further exploration.

RevDate: 2020-09-21

Li Q, Ding X, Liu K, et al (2020)

Fecal Microbiota Transplantation for Ulcerative Colitis: The Optimum Timing and Gut Microbiota as Predictors for Long-Term Clinical Outcomes.

Clinical and translational gastroenterology, 11(8):e00224.

INTRODUCTION: The previous researches aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for ulcerative colitis (UC) in a short-term observation. The present study aimed to explore the optimum timing of FMT for maintaining the long-term clinical benefits and to target the gut microbiota that may help to predict the long-term success or failure of FMT in UC.

METHODS: Two hundred two patients with UC were recruited from November 2012 to September 2018. The primary endpoint of this study was the maintaining time of the first and second courses of FMT. Relapse was defined as partial Mayo score ≥2 after achieving clinical remission and an increase of partial Mayo score ≥1 after achieving clinical response. The stool samples were analyzed by 16S rRNA gene sequencing.

RESULTS: The median maintaining time of the efficacy was 120 days (IQR, 45-180) and 182.5 days (IQR, 105-311.25) from the first course and second course of FMT, respectively. No FMT-related serious adverse events were observed. The differences of the relative abundance in Eggerthella, Lactobacillus, and Ruminococcus between pre-FMT and 5 days post-FMT were remarkably correlated with the long-term clinical remission (P < 0.05).

DISCUSSION: This study demonstrated that patients with UC should undergo the second course of FMT within 4 months after the first course of FMT for maintaining the long-term clinical benefits. The short-term alterations of microbiota after FMT may be conducive to predicting the long-term efficacy of FMT in UC (see Visual Abstract, Supplementary Digital Content, http://links.lww.com/CTG/A363).

RevDate: 2020-09-21

Ianiro G, Segal JP, Mullish BH, et al (2020)

Fecal microbiota transplantation in gastrointestinal and extraintestinal disorders.

Future microbiology, 15:1173-1183.

Fecal microbiota transplantation (FMT) is the infusion of feces from a healthy donor into the gut of a recipient to treat a dysbiosis-related disease. FMT has been proven to be a safe and effective treatment for Clostridioides difficile infection, but increasing evidence supports the role of FMT in other gastrointestinal and extraintestinal diseases. The aim of this review is to paint the landscape of current evidence of FMT in different fields of application (including irritable bowel syndrome, inflammatory bowel disease, liver disorders, decolonization of multidrug-resistant bacteria, metabolic disorders and neurological disorders), as well as to discuss the current regulatory scenario of FMT, and hypothesize future directions of FMT.

RevDate: 2020-09-21

Zhong M, Sun Y, Wang HG, et al (2020)

Awareness and attitude of fecal microbiota transplantation through transendoscopic enteral tubing among inflammatory bowel disease patients.

World journal of clinical cases, 8(17):3786-3796.

BACKGROUND: Transendoscopic enteral tubing (TET) has been used in China as a novel delivery route for fecal microbiota transplantation (FMT) into the whole colon with a high degree of patient satisfaction among adults.

AIM: To explore the recognition and attitudes of FMT through TET in patients with inflammatory bowel disease (IBD).

METHODS: An anonymous questionnaire, evaluating their awareness and attitudes toward FMT and TET was distributed among IBD patients in two provinces of Eastern and Southwestern China. Question formats included single-choice questions, multiple-choice questions and sorting questions. Patients who had not undergone FMT were mainly investigated for their cognition and acceptance of FMT and TET. Patients who had experience of FMT, the way they underwent FMT and acceptance of TET were the main interest. Then all the patients were asked whether they would recommend FMT and TET. This study also analyzed the preference of FMT delivery in IBD patients and the patient-related factors associated with it.

RESULTS: A total of 620 eligible questionnaires were included in the analysis. The survey showed that 44.6% (228/511) of patients did not know that FMT is a therapeutic option in IBD, and 80.6% (412/511) of them did not know the concept of TET. More than half (63.2%, 323/511) of the participants stated that they would agree to undergo FMT through TET. Of the patients who underwent FMT via TET [62.4% (68/109)], the majority [95.6% (65/68)] of them were satisfied with TET. Patients who had undergone FMT and TET were more likely to recommend FMT than patients who had not (94.5% vs 86.3%, P = 0.018 and 98.5% vs 87.8%, P = 0.017). Patients' choice for the delivery way of FMT would be affected by the type of disease and whether the patient had the experience of FMT. When compared to patients without experience of FMT, Crohn's disease and ulcerative colitis patients who had experience of FMT preferred mid-gut TET (P < 0.001) and colonic TET (P < 0.001), respectively.

CONCLUSION: Patients' experience of FMT through TET lead them to maintain a positive attitude towards FMT. The present findings highlighted the significance of patient education on FMT and TET.

RevDate: 2020-09-18

Caldeira LF, Borba HH, Tonin FS, et al (2020)

Fecal microbiota transplantation in inflammatory bowel disease patients: A systematic review and meta-analysis.

PloS one, 15(9):e0238910 pii:PONE-D-19-35050.

OBJECTIVES: Current evidence on fecal microbiota transplantation for inflammatory bowel disease is inconclusive. We conducted a systematic review to gather evidence on the efficacy and safety of fecal microbiota transplantation for inflammatory bowel disease.

METHODS: Systematic searches were conducted in PubMed, Scopus, and Web of Science. Clinical remission was considered as the primary endpoint. Pairwise meta-analyses were performed for the randomized controlled studies (Mantel Haenszel, random effects model). Proportion meta-analyses, accounting for weighted pooled rates reported in the interventional studies, were conducted using the mixed effects model. Subgroup analyses considering the type of stool, donor type, and disease subtype were also performed. Cumulative meta-analyses to assess further needs of evidence were conducted.

RESULTS: Sixty studies were included, from which 36 could be synthesized in the quantitative analyses. Pairwise meta-analyses of six controlled trials showed significant differences in favor of fecal microbiota transplantation compared with placebo (clinical remission: RR 1.70 [95% CI 1.12, 2.56]; clinical response: RR 1.68 [95% CI 1.04, 2.72]). An overall clinical remission of 37%, overall clinical response of 54%, and a prevalence of 29% of adverse events were found for the interventional studies. Frozen fecal material and universal donors were related to better efficacy outcomes. In addition, Crohn's disease patients seemed to benefit more from the procedure.

CONCLUSIONS: The comparative analyses demonstrated that frozen fecal material from universal donors may be related to a higher rate of clinical remission, especially for Crohn's disease.

RevDate: 2020-09-18

El-Salhy M, Valeur J, Hausken T, et al (2020)

Changes in fecal short-chain fatty acids following fecal microbiota transplantation in patients with irritable bowel syndrome.

Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society [Epub ahead of print].

BACKGROUND: Short-chain fatty acids (SCFAs) may play a role in the pathophysiology of irritable bowel syndrome (IBS). This study analyzed fecal SCFAs after performing fecal microbiota transplantation (FMT) in the IBS patients who were included in our previous study of the efficacy of FMT.

METHODS: This study included 142 of the 164 IBS patients who participated in our previous study. They were belonging to three groups: placebo (own feces), 30-g (superdonor feces), and 60-g (superdonor feces) FMT. The patients completed the IBS Severity Scoring System (IBS-SSS) Birmingham IBS Symptom, Fatigue Assessment Scale (FAS), the IBS Quality of Life (IBS-QoL) and Short-Form Nepean Dyspepsia Index (SF-NDI) questionnaires and delivered fecal samples at the baseline and 1 month after FMT. The SCFA levels were determined by vacuum distillation followed by gas chromatography.

KEY RESULTS: The fecal butyric acid level was significantly increased after FMT in both the 30-g and 60-g groups (both P ≤ 0.001). In the 60-g group, the levels of total SCFAs and isobutyric, isovaleric, and valeric acids increased after FMT. Butyric acid levels in the responders in both the 30-g and 60-g FMT groups were significantly inversely correlated with IBS-SSS and FAS scores (P = 0.001, r = -0.3 and P = 0.0001. r=- 0.3, respectively). There were no differences in the SCFA levels in the placebo group after FMT.

CONCLUSION AND INFERENCES: FMT increases the fecal SCFA levels in IBS patients. The increase in the butyric acid level is inversely correlated with symptoms in IBS patients following FMT, suggesting that SCFAs might play a role in the pathophysiology of IBS. www.clini​caltr​ials.gov (NCT03822299).

RevDate: 2020-09-18

Xie Z, Jiang H, Liu W, et al (2020)

The triterpenoid sapogenin (2α-OH-Protopanoxadiol) ameliorates metabolic syndrome via the intestinal FXR/GLP-1 axis through gut microbiota remodelling.

Cell death & disease, 11(9):770 pii:10.1038/s41419-020-02974-0.

Gypenosides, extracts of Gynostemma yixingense, have been traditionally prescribed to improve metabolic syndrome in Asian folk and local traditional medicine hospitals. However, the mechanism of its action remains unclarified. In this work, our results indicated that chronic administration of 2α-OH-protopanoxadiol (GP2), a metabolite of gypenosides in vivo, protected mice from high-fat diet-induced obesity and improved glucose tolerance by improving intestinal L-cell function. Mechanistically, GP2 treatment inhibited the enzymatic activity of bile salt hydrolase and modulated the proportions of the gut microbiota, which led to an increase in the accumulation of tauro-β-muricholic acid (TβMCA) in the intestine. TβMCA induced GLP-1 production and secretion by reducing the transcriptional activity of nuclear receptor farnesoid X receptor (FXR). Transplantation of GP2-remodelled fecal microbiota into antibiotic-treated mice also increased the intestinal TβMCA content and improved intestinal L-cell function. These findings demonstrate that GP2 ameliorates metabolic syndrome at least partly through the intestinal FXR/GLP-1 axis via gut microbiota remodelling and also suggest that GP2 may serve as a promising oral therapeutic agent for metabolic syndrome.

RevDate: 2020-09-18

Stebel R, Vojtilová L, P Husa (2020)

Clostridium difficile Infection: an update on treatment and prevention.

Vnitrni lekarstvi, 66(2):58-62.

Disruption of the colonic microflora is one of the most significant adverse effects of antibiotic (ATB) therapy. Excessive multiplication of toxigenic Clostridioides difficile strains is responsible for about 20 % of cases of post-antibiotic diarrhoea. The global trend of Clostridium colitis incidence, severity, mortality and in particular therapeutic failure keeps rising. At the Department of Infectious Diseases we work on long-term monitoring of the most important colitis-associated risk factors and evaluation of individual therapeutic and preventive procedures (selective ATB therapy, faecal bacteriotherapy). A diligent analysis of risk factors and knowledge of pathogenesis are a prerequisite to practical implementation of effective and rational precautions to curb spreading of this illness. In the future, we anticipate increased use of fecal microbiota transplant, improvements in faecal transplant administration, wider use of probiotics and selective ATBs and further introduction of passive and active immunization into practice.

RevDate: 2020-09-17

Masetti R, Zama D, Leardini D, et al (2020)

The gut microbiome in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.

Pediatric blood & cancer [Epub ahead of print].

The gut microbiome (GM) has been associated with different clinical outcomes in the context of allogeneic hematopoietic stem cell transplantation (HSCT). Large multicenter cohort studies in adults have found significant correlations with overall survival, relapse, and incidence of complications. Moreover, GM is already a promising target for therapeutic interventions. However, few data are available in children, a population presenting unique features and challenges. During childhood, the GM evolves rapidly with large structural fluctuations, alongside with the maturation of the immune system. Furthermore, the HSCT procedure presents significant differences in children. These considerations underline the importance of a specific focus on the pediatric setting, and the role of GM and its age-dependent trajectory in influencing the immunity reconstitution and clinical outcomes. This review provides a comprehensive overview of the available evidence in the field of GM and pediatric HSCT, highlighting age-specific issues and discussing GM-based therapeutic approaches.

RevDate: 2020-09-17
CmpDate: 2020-09-17

Ianiro G, Rossi E, Thomas AM, et al (2020)

Faecal microbiota transplantation for the treatment of diarrhoea induced by tyrosine-kinase inhibitors in patients with metastatic renal cell carcinoma.

Nature communications, 11(1):4333.

Diarrhoea is one of the most burdensome and common adverse events of chemotherapeutics, and has no standardised therapy to date. Increasing evidence suggests that the gut microbiome can influence the development of chemotherapy-induced diarrhoea. Here we report findings from a randomised clinical trial of faecal microbiota transplantation (FMT) to treat diarrhoea induced by tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (ClinicalTrials.gov number: NCT04040712). The primary outcome is the resolution of diarrhoea four weeks after the end of treatments. Twenty patients are randomised to receive FMT from healthy donors or placebo FMT (vehicle only). Donor FMT is more effective than placebo FMT in treating TKI-induced diarrhoea, and a successful engraftment is observed in subjects receiving donor faeces. No serious adverse events are observed in both treatment arms. The trial meets pre-specified endpoints. Our findings suggest that the therapeutic manipulation of gut microbiota may become a promising treatment option to manage TKI-dependent diarrhoea.

RevDate: 2020-09-15

Ebell MH (2020)

Fecal Microbiota Transplant Effective for Irritable Bowel Syndrome.

American family physician, 102(6):377.

RevDate: 2020-09-16

Wu J, Wei Z, Cheng P, et al (2020)

Rhein modulates host purine metabolism in intestine through gut microbiota and ameliorates experimental colitis.

Theranostics, 10(23):10665-10679.

Background: Gut microbiota, which plays a crucial role in inflammatory bowel diseases (IBD), might have therapeutic benefits for ulcerative colitis or Crohn's disease. Targeting gut microbiota represents a new treatment strategy for IBD patients. Rhein is one of the main components of rhubarb and exhibits poor oral bioavailability but still exerts anti-inflammatory effects in some diseases. Therefore, we investigated the effect of rhein on colitis and studied its possible mechanisms. Methods: The chronic mouse colitis model was induced by four rounds of 2% dextran sulfate sodium (DSS) treatment. The mice were treated with 50 mg/kg and 100 mg/kg rhein daily, body weight, colon length, histological score, inflammatory cytokines in serum or intestine, and fecal lipocalin 2 concentration were determined. Th17 cell, Th1 cell and Th2 cell infiltration in the mesenteric lymph node were analyzed by flow cytometry. Metabolic profiles were collected by non-targeted metabolomics and key metabolic pathways were identified using MetaboAnalyst 4.0. We also assessed intestinal barrier permeability and performed 16s rDNA sequencing. Lactobacillus sp. was cultured, and fecal microbiota transplantation (FMT) was employed to evaluate the contribution of gut microbiota. Results: Rhein could significantly alleviate DSS-induced chronic colitis. Uric acid was identified as a crucial modulator of colitis and rhein treatment led to decreased uric acid levels. We determined that rhein changed purine metabolism indirectly, while the probiotic Lactobacillus was involved in the regulation of host metabolism. Uric acid resulted in a worsened intestinal barrier, which could be rescued by rhein. We further confirmed that rhein-treated gut microbiota was sufficient to relieve DSS-induced colitis by FMT. Conclusion: We showed that rhein could modulate gut microbiota, which indirectly changed purine metabolism in the intestine and subsequently alleviated colitis. Our study has identified a new approach to the clinical treatment of colitis.

RevDate: 2020-09-14

Jeney SES, Lane F, Oliver A, et al (2020)

Fecal Microbiota Transplantation for the Treatment of Refractory Recurrent Urinary Tract Infection.

Obstetrics and gynecology [Epub ahead of print].

RevDate: 2020-09-14

Liu Y, Qin S, Feng Y, et al (2020)

Perturbations of gut microbiota in gestational diabetes mellitus patients induce hyperglycemia in germ-free mice.

Journal of developmental origins of health and disease pii:S2040174420000768 [Epub ahead of print].

Shifts in the maternal gut microbiota have been implicated in the development of gestational diabetes mellitus (GDM). Understanding the interaction between gut microbiota and host glucose metabolism will provide a new target of prediction and treatment. In this nested case-control study, we aimed to investigate the causal effects of gut microbiota from GDM patients on the glucose metabolism of germ-free (GF) mice. Stool and peripheral blood samples, as well as clinical information, were collected from 45 GDM patients and 45 healthy controls (matched by age and prepregnancy body mass index (BMI)) in the first and second trimester. Gut microbiota profiles were explored by next-generation sequencing of the 16S rRNA gene, and inflammatory factors in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Fecal samples from GDM and non-GDM donors were transferred to GF mice. The gut microbiota of women with GDM showed reduced richness, specifically decreased Bacteroides and Akkermansia, as well as increased Faecalibacterium. The relative abundance of Akkermansia was negatively associated with blood glucose levels, and the relative abundance of Faecalibacterium was positively related to inflammatory factor concentrations. The transfer of fecal microbiota from GDM and non-GDM donors to GF mice resulted in different gut microbiota colonization patterns, and hyperglycemia was induced in mice that received GDM donor microbiota. These results suggested that the shifting pattern of gut microbiota in GDM patients contributed to disease pathogenesis.

RevDate: 2020-09-14

Lin Z, Iqbal Z, Ortiz JF, et al (2020)

Fecal Microbiota Transplantation in Recurrent Clostridium Difficile Infection: Is it Superior to Other Conventional Methods?.

Cureus, 12(8):e9653.

Clostridium difficile (C. difficile) is a gram-positive species of spore-forming bacteria. C. difficile infection (CDI) is one of the most common hospital-acquired infections in the United States, mainly caused by the use of recent antibiotics that leads to intestinal dysbiosis. Recurrent C. difficile infection (rCDI) often occurs after the successful treatment of CDI. Approximately, 30% of patients experience a clinical recurrence of prior symptoms within eight weeks of antibiotic cessation. This present literature review covers the current pathophysiology of CDI, risk factors for infection, diagnostic methods, several treatment modalities, and the potential use of fecal microbial transplant (FMT) for patients with multiple recurrent CDIs. Recent studies have focused on FMT, with an efficacy rate of nearly 90% in multiple recurrent CDI settings. Despite its efficacy, it is not commonly used as first-line treatment. More studies are needed to establish this therapy as the first option in patients with rCDI.

RevDate: 2020-09-14

Kreft L, Hoffmann C, C Ohnmacht (2020)

Therapeutic Potential of the Intestinal Microbiota for Immunomodulation of Food Allergies.

Frontiers in immunology, 11:1853.

Food allergy is an atopic disease that is caused by the immune system targeting harmless food antigens that can result in life-threatening anaphylaxis. As humans and microbes have co-evolved, inevitably commensal microbes have a tremendous impact on our health. As such, the gut with its enormous microbial richness reflects a highly tolerogenic environment at steady state, in which immune cells are educated to react in a well-calibrated manner to food and microbial antigens. Recent evidence indicates that the susceptibility to food allergy is critically linked to microbial dysbiosis and can be transmitted by microbial transfer from humans to mice. Experimental work and epidemiological studies further point toward a critical time window in early childhood during which the immune system is imprinted by microbial colonization. Particularly, Foxp3-expressing regulatory T cells turn out to be key players, acting as rheostats for controlling the magnitude of food allergic reactions. An increasing number of bacterial metabolites has recently been shown to regulate directly or indirectly the differentiation of peripherally induced Tregs, most of which co-express the RAR-related orphan receptor gamma t (RORγt). Genetic ablation provided additional direct evidence for the importance of RORγt+ Tregs in food allergy. Future strategies for the stratification of food allergic patients with the aim to manipulate the intestinal microbiota by means of fecal transplantation efforts, pre- or probiotic regimens or for boosting oral immunotherapy may improve diagnosis and therapy. In this review some of the key underlying mechanisms are summarized and future directions for potential microbial therapy are explored.

RevDate: 2020-09-13

Zhang L, Zhou W, Zhan L, et al (2020)

Fecal microbiota transplantation alters the susceptibility of obese rats to type 2 diabetes mellitus.

Aging, 12: pii:103756 [Epub ahead of print].

Obesity is one of the susceptibility factors for type 2 diabetes (T2DM), both of which could accelerate the aging of the body and bring many hazards. A causal relationship is present between intestinal microbiota and body metabolism, but how the microbiota play a role in the progression of obesity to T2DM has not been elucidated. In this study, we transplanted healthy or obese-T2DM intestinal microbiota to ZDF and LZ rats, and used 16S rRNA and targeted metabonomics to evaluate the directional effect of the microbiota on the susceptibility of obese rats to T2DM. The glycolipid metabolism phenotype could be changed bidirectionally in obese rats instead of in lean ones. One possible mechanism is that the microbiota and metabolites alter the structure of the intestinal tract, and improve insulin and leptin resistance through JAK2 / IRS / Akt pathway. It is worth noting that 7 genera, such as Lactobacillus, Clostridium and Roche, can regulate 15 metabolites, such as 3-indolpropionic acid, acetic acid and docosahexaenoic acid, and have a significant improvement on glycolipid metabolism phenotype. Attention to intestinal homeostasis may be the key to controlling obesity and preventing T2DM.

RevDate: 2020-09-13

Seong H, Lee SK, Cheon JH, et al (2020)

Fecal Microbiota Transplantation for multidrug-resistant organism: Efficacy and Response prediction.

The Journal of infection pii:S0163-4453(20)30597-1 [Epub ahead of print].

OBJECTIVES: The increasing prevalence of multidrug-resistant microorganisms (MDRO) is increasing the frequency of poor clinical outcomes, prolonging hospitalizations, and raising healthcare costs. This study evaluated the eradication efficacy of fecal microbiota transplantation (FMT) and identified microbial and functional biomarkers of MDRO decolonization.

METHODS: Fecal solution obtained from healthy unrelated donors was infused in the participants' guts which had been colonized with carbapenemase-producing enterobacteriacea (CPE), vancomycin-resistant enterococci (VRE), or both CPE and VRE. Fecal samples from recipients were collected and microbiome changes before and after FMT were assessed.

RESULTS: Twenty-four (68.6%) out of 35 patients were decolonized within one year of receiving FMT. Multivariate analysis showed that FMT (FMT: hazard ratio (HR) = 5.343, 95% confidence interval (CI) = 1.877-15.212, p = 0.002) and MDRO types (CPE: HR = 11.146, 95% CI = 2.420-51.340, p = 0.002; CPE/VRE: HR = 2.948, 95% CI = 1.200-7.246, p = 0.018; VRE served as the reference) were significant independent factors associated with time to decolonization. Microbiota analysis showed higher richness and biodiversity before FMT resulted in VRE decolonization. The species Clostridium ramosum and the genuses Anaerostipes and Eisenbergiella could serve as taxonomic biomarkers and K02017 could serve as a functional biomarker for VRE clearance.

CONCLUSION: FMT is an effective way to decolonize MDRO and its effectiveness may be predicted by microbiome analysis.

RevDate: 2020-09-12

Apartsin K, V Smirnova (2020)

Convalescent fecal microbiota transplantation as a possible treatment for COVID-19.

RevDate: 2020-09-10

Vicente Dueñas C, Janssen S, Oldenburg M, et al (2020)

An intact gut microbiome protects genetically predisposed mice against leukemia.

Blood pii:463729 [Epub ahead of print].

The majority of childhood leukemias are precursor B cell-acute lymphoblastic leukemias (pB-ALL) caused by a combination of prenatal genetic predispositions and oncogenic events occurring after birth. Although genetic predispositions are frequent in children (>1-5%), fewer than 1% of genetically predisposed carriers will develop pB-ALL. While infectious stimuli are believed to play a major role in leukemogenesis, the critical determinants are not well defined. Here, employing murine models of pB-ALL, we show that microbiome disturbances incurred by antibiotic treatment early in life were sufficient to induce leukemia in genetically predisposed mice even in the absence of infectious stimuli and independent of T-cells. Using V4 and full-length 16S rRNA sequencing of a series of fecal samples, we found that genetic predisposition to pB-ALL (Pax5 heterozygosity or ETV6-RUNX1 fusion) shaped a distinct gut microbiome. Machine learning accurately (96.8%) predicted genetic predisposition using 40 of 3,983 amplicon sequence variants (ASVs) as proxies for bacterial species. Transplantation of either wild type (WT) or Pax5+/- hematopoietic bone marrow cells into WT recipient mice revealed that the microbiome is shaped and determined in a donor-genotype-specific manner. Gas chromatography-mass spectrometric (GC-MS) analyses of sera from WT and Pax5+/- mice demonstrated the presence of a genotype-specific distinct metabolomic profile. Taken together, our data indicate that it is a lack of commensal microbiota rather than the presence of specific bacteria that promotes leukemia in genetically predisposed mice. Future large-scale longitudinal studies are required to determine whether targeted microbiome modification in children predisposed to pB-ALL could become a successful prevention strategy.

RevDate: 2020-09-10

Dutta D, Jafri F, Stuhr D, et al (2020)

A contemporary review of Clostridioides difficile infections in patients with hematologic diseases.

Journal of internal medicine [Epub ahead of print].

Clostridioides (Clostridium) difficile (C. difficile) infection is one of the most common cause of increased morbidity and mortality. Approximately 500,000 C. difficile infections (CDIs) occur each year in the United States and they result in more than 29,000 deaths. Patients with hematologic diseases are at a higher risk for this infection due to frequent hospitalization and exposure to treatment-associated risk factors. While several currently available antimicrobial agents offer resolution, recurrence of infection remains a major concern. Recent advancement in deciphering C. difficile virulence mechanisms and identification of its allies in contributing to the infection has led to the development of alternative treatment strategies. Here, we will provide a contemporary discussion of how major risk factors in hematologic diseases such as immunosuppression, chemoradiation, use of antibiotic, proton pump inhibitor, and opioid, and deficiency in butyrate and antimicrobial peptides contribute to C. difficile infection. Next, we will highlight different approaches to control and mitigate this infection such as antibiotic stewardship and fecal microbiota transplantation. Finally, we will explore several emerging treatments such as use of pre- and probiotics, immunotherapy, and microbiome-sparing agents.

RevDate: 2020-09-10

Chen M, Liu X, Zhang Y, et al (2020)

Efficacy and Safety of Fecal Microbiota Transplantation by washed preparation in Patients with Moderate to Severe Active Ulcerative Colitis.

Journal of digestive diseases [Epub ahead of print].

AIM: The role of fecal microbiota transplantation (FMT) for severe ulcerative colitis (UC) is unclear. This study aimed to evaluate the short-term efficacy and safety of FMT by washed preparation for moderate to severe active UC.

METHODS: An open-label, prospective trial was conducted in an inflammatory bowel disease (IBD) tertiary referral center from April 2016 to March 2018. Patients with moderate to severe UC were randomly assigned to undergo FMT three times on day1, day3 and day5 by nasojejunal tube (NJT) or transendoscopic enteral tubing (TET). The primary endpoint was clinical response at week 2 post-FMT. The secondary endpoints were clinical and endoscopic remission at week 12 post-FMT, safety and disease progression.

RESULTS: Nine patients were included. 77.8% (7/9) of the patients achieved clinical response at week 2. 55.6% (5/9) and 33.3% (3/9) achieved clinical remission and endoscopic remission at week 12, respectively. 11.1% (1/9) switched to anti-TNFα therapy and 11.1% (1/9) underwent colectomy. FMT was delivered through NJT in 44.4% (4/9) of the patients, while TET was used in 55.6% (5/9). The clinical outcomes were not significantly different based on the delivery route (p>0.05). Adverse events, which were all mild and self-limited, were observed in 33.3% (3/9) of the patients.

CONCLUSIONS: FMT by washed preparation appears to be a safe and effective adjunct therapy for patients with moderate to severe UC in a short-term follow-up. The efficacy was not significantly different between the FMT delivery routes (NJT or TET). Further randomized controlled studies are needed to confirm these findings. This article is protected by copyright. All rights reserved.

RevDate: 2020-09-10

Park JC, SH Im (2020)

Of men in mice: the development and application of a humanized gnotobiotic mouse model for microbiome therapeutics.

Experimental & molecular medicine pii:10.1038/s12276-020-0473-2 [Epub ahead of print].

Considerable evidence points to the critical role of the gut microbiota in physiology and disease. The administration of live microbes as a therapeutic modality is increasingly being considered. However, key questions such as how to identify candidate microorganisms and which preclinical models are relevant to recapitulate human microbiota remain largely unanswered. The establishment of a humanized gnotobiotic mouse model through the fecal microbiota transplantation of human feces into germ-free mice provides an innovative and powerful tool to mimic the human microbial system. However, numerous considerations are required in designing such a model, as various elements, ranging from the factors pertaining to human donors to the mouse genetic background, affect how microbes colonize the gut. Thus, it is critical to match the murine context to that of human donors to provide a continuous and faithful progression of human flora in mice. This is of even greater importance when the need for accuracy and reproducibility across global research groups are taken into account. Here, we review the key factors that affect the formulation of a humanized mouse model representative of the human gut flora and propose several approaches as to how researchers can effectively design such models for clinical relevance.

RevDate: 2020-09-10

Roussin L, Prince N, Perez-Pardo P, et al (2020)

Role of the Gut Microbiota in the Pathophysiology of Autism Spectrum Disorder: Clinical and Preclinical Evidence.

Microorganisms, 8(9): pii:microorganisms8091369.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 160 people in the world. Although there is a strong genetic heritability to ASD, it is now accepted that environmental factors can play a role in its onset. As the prevalence of gastrointestinal (GI) symptoms is four-times higher in ASD patients, the potential implication of the gut microbiota in this disorder is being increasingly studied. A disturbed microbiota composition has been demonstrated in ASD patients, accompanied by altered production of bacterial metabolites. Clinical studies as well as preclinical studies conducted in rodents have started to investigate the physiological functions that gut microbiota might disturb and thus underlie the pathophysiology of ASD. The first data support an involvement of the immune system and tryptophan metabolism, both in the gut and central nervous system. In addition, a few clinical studies and a larger number of preclinical studies found that modulation of the microbiota through antibiotic and probiotic treatments, or fecal microbiota transplantation, could improve behavior. Although the understanding of the role of the gut microbiota in the physiopathology of ASD is only in its early stages, the data gathered in this review highlight that this role should be taken in consideration.

RevDate: 2020-09-09

Cheung MK, Yue GGL, Tsui KY, et al (2020)

Discovery of an interplay between the gut microbiota and esophageal squamous cell carcinoma in mice.

American journal of cancer research, 10(8):2409-2427.

Esophageal squamous cell carcinoma (ESCC) is the main type of esophageal cancer (EC) worldwide, causing half a million deaths each year. Recent evidence has demonstrated the role of the gut microbiota in health and disease. However, our current understanding of the gut microbiome in EC remains scarce. Here, we characterized the gut and esophageal microbiome in a metastatic mouse model of ESCC and examined the functional roles of the gut microbiota in EC development in fecal microbiota transplantation (FMT) experiments. Nude mice intraperitoneally xenografted with human EC-109 cells showed significant alterations in the overall structure, but not alpha diversity, of the gut and esophageal microbiome as compared to naïve control mice. Xenograft of EC cells depleted the order Pasteurellales in the gut microbiome, and enriched multiple predicted metabolic pathways, including those involved in carbohydrate and lipid metabolism, in the esophageal microbiome. FMT of stool from healthy mice to antibiotic-treated xenograft-bearing mice significantly attenuated liver metastasis, suggesting a protective role of the commensal gut microbiota in EC. Moreover, we showed that combination chemotherapy with cisplatin and 5-fluorouracil, and the anti-EC medicinal herb Andrographis paniculata (AP) differentially affected the gut and esophageal microbiome in EC. FMT experiment revealed a reduced anti-metastatic efficacy of AP on liver metastasis in antibiotic-treated xenograft-bearing mice, suggesting a role of the commensal gut microbiota in the anti-metastatic efficacy of the herb. In conclusion, our findings reveal for the first time an interplay between the gut microbiota and EC and provide insights into the treatment strategies for EC.

RevDate: 2020-09-09

Lozupone M, D'Urso F, Piccininni C, et al (2020)

The relationship between epigenetics and microbiota in neuropsychiatric diseases.

Epigenomics [Epub ahead of print].

Microbiota might be considered as a pool for environmental epigenetic factors. Evidence is accumulating that environmental exposures - including microbes, diet, drugs - play a role in the pathogenesis of many neuropsychiatric disorders. Underlying mechanisms are complex, involving the sensitive interplay of genetics with epigenetics, neuroinflammation and the innate immune system. Modifications of microbiota affect neurogenesis and the maturation of microglia, influencing social behavior, stress-related responses and fear learning mechanisms. The excitatory neurons in the medial prefrontal cortex appear to play a key role. The mechanisms through which antibiotics administration may modulate microbiota and, therefore, behavior and neuropsychiatric disorders, may be influenced by several variables such as pre-existing gastrointestinal inflammation, the baseline microbiota composition, diet and stress perception. Probiotics, individualized diet, antibiotics and fecal transplantation could positively modulate the effects of epigenetic factors on neuropsychiatric disorders.

RevDate: 2020-09-09

Wang SC, Chen YC, Chen SJ, et al (2020)

Alcohol Addiction, Gut Microbiota, and Alcoholism Treatment: A Review.

International journal of molecular sciences, 21(17): pii:ijms21176413.

Alcohol addiction is a leading risk factor for personal death and disability. In 2016, alcohol use caused 2.2% of female deaths and 6.8% of male deaths, and disability-adjusted life years (DALYs) were 2.3% in female and 8.9% in male. Individuals with alcohol use disorder are at high risk of anxiety, depression, impaired cognition performance, and illicit drug use and are comorbid with liver disease, such as alcoholic hepatitis and liver cirrhosis, which is a major cause of personal death and disability worldwide. Psychological interventions, such as cognitive behavior therapy and motivational interviewing, as well as medical treatments, such as disulfiram, naltrexone, acamprosate, and nalmefene, are used for the treatment of alcohol addiction in Europe and the United States. However, the effect of current interventions is limited, and the need for additional interventions is substantial. Alcohol use impairs the intestinal barrier and causes changes to the intestinal permeability as well as the gut microbiota composition. Emerging studies have tried to reveal the role of the gut-brain axis among individuals with alcohol use disorder with or without alcohol liver disease. Bacterial products penetrate the impaired intestinal barrier and cause central inflammation; changes to the gut microbiota impair enterohepatic circulation of bile acids; alcohol abuse causes shortage of vital nutrients such as thiamine. Several studies have suggested that probiotics, through either oral administration or fecal microbiota transplantation, increased intestinal levels of potentially beneficial bacteria such as bifidobacteria and lactobacilli, improving the levels of liver-associated enzymes in patients with mild alcoholic hepatitis, and demonstrating beneficial psychotropic effects on anxiety and depression. In addition to medications for alcohol addiction, gene editing therapy such as clustered regularly interspaced short palindromic repeats (CRISPRs) may be another potential research target. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are associated with ADH and ALDH genes, are major enzymes involved in alcohol metabolism, and gene editing approaches may have the potential to directly modify specific genes to treat alcoholism caused by genetic defects. Further research is needed to study the effect of the combined treatment for alcohol addiction.

RevDate: 2020-09-08

Galan-Ros J, Ramos-Arenas V, P Conesa-Zamora (2020)

Predictive values of colon microbiota in the treatment response to colorectal cancer.

Pharmacogenomics [Epub ahead of print].

The crosstalk between the colon mucosa and the microbiota represents a complex and delicate equilibrium. Gastrointestinal diseases such as inflammatory bowel disease and colorectal cancer (CRC) are associated with a state of altered microbiota composition known as dysbiosis, which seems to play a causative role in some of these illnesses. Recent reports have shown that the colorectal microbiome is responsible for the response and safety to treatments against CRC, especially immunotherapy, hence opening the possibility to use bacteria as a predictive marker and also as a therapeutic agent. The review objective is to summarize updated reports about the the implication of the colorectal microbiome in the development of CRC, in treatment response and its potential as a therapeutic approach.

RevDate: 2020-09-07

Martinez-Gili L, McDonald JAK, Liu Z, et al (2020)

Understanding the mechanisms of efficacy of fecal microbiota transplant in treating recurrent Clostridioides difficile infection and beyond: the contribution of gut microbial-derived metabolites.

Gut microbes, 12(1):1810531.

Fecal microbiota transplant (FMT) is a highly-effective therapy for recurrent Clostridioides difficile infection (rCDI), and shows promise for certain non-CDI indications. However, at present, its mechanisms of efficacy have remained poorly understood. Recent studies by our laboratory have noted the particular key importance of restoration of gut microbe-metabolite interactions in the ability of FMT to treat rCDI, including the impact of FMT upon short chain fatty acid (SCFAs) and bile acid metabolism. This includes a significant impact of these metabolites upon the life cycle of C. difficile directly, along with potential postulated additional benefits, including effects upon host immune response. In this Addendum, we first present an overview of these recent advancements in this field, and then describe additional novel data from our laboratory on the impact of FMT for rCDI upon several gut microbial-derived metabolites which had not previously been implicated as being of relevance.

RevDate: 2020-09-03

Dawoodbhoy FM, Patel BK, Patel K, et al (2020)

Gut Microbiota Dysbiosis as a Target for Improved Post-Surgical Outcomes and Improved Patient Care. A Review of Current Literature.

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

Critical illness results in significant changes in the human gut microbiota, leading to the breakdown of the intestinal barrier function, which plays a role in the pathogenesis of multiple organ dysfunction. Patients with sepsis/acute respiratory distress syndrome (ARDS) have a profoundly distorted intestinal microbiota rhythm, which plays a considerable role in the development of gut-derived infections and intestinal dysbiosis. Despite recent medical developments, post-surgical complications are associated with a high morbidity and mortality rate. Bacterial translocation (BT), which is the movement of bacteria and bacterial products across the intestinal barrier, was shown to be a mechanism behind sepsis. Current research is focusing on a solution by addressing significant factors that contribute to intestinal dysbiosis, which subsequently leads to multiple organ failure and, thus, mortality. It may, however, be challenging to manipulate the microbiota in critically ill patients for enhanced therapeutic gain. Probiotic manipulation is advantageous for maintaining the gut-barrier defense and for modulating the immune response. Based on available published research, this review aims to address the application of potential strategies in the intensive care unit (ICU), supplemented with current therapeutics by the administration of probiotics, prebiotics, and fecal microbiota transplant, to reduce post-surgical complications of sepsis/ARDS in critically ill patients.

RevDate: 2020-09-04
CmpDate: 2020-09-04

Kundu P, Lee HU, Garcia-Perez I, et al (2019)

Neurogenesis and prolongevity signaling in young germ-free mice transplanted with the gut microbiota of old mice.

Science translational medicine, 11(518):.

The gut microbiota evolves as the host ages, yet the effects of these microbial changes on host physiology and energy homeostasis are poorly understood. To investigate these potential effects, we transplanted the gut microbiota of old or young mice into young germ-free recipient mice. Both groups showed similar weight gain and skeletal muscle mass, but germ-free mice receiving a gut microbiota transplant from old donor mice unexpectedly showed increased neurogenesis in the hippocampus of the brain and increased intestinal growth. Metagenomic analysis revealed age-sensitive enrichment in butyrate-producing microbes in young germ-free mice transplanted with the gut microbiota of old donor mice. The higher concentration of gut microbiota-derived butyrate in these young transplanted mice was associated with an increase in the pleiotropic and prolongevity hormone fibroblast growth factor 21 (FGF21). An increase in FGF21 correlated with increased AMPK and SIRT-1 activation and reduced mTOR signaling. Young germ-free mice treated with exogenous sodium butyrate recapitulated the prolongevity phenotype observed in young germ-free mice receiving a gut microbiota transplant from old donor mice. These results suggest that gut microbiota transplants from aged hosts conferred beneficial effects in responsive young recipients.

RevDate: 2020-09-03
CmpDate: 2020-09-03

Newman KM, BP Vaughn (2019)

Efficacy of intestinal microbiota transplantation in ulcerative colitis: a review of current literature and knowledge.

Minerva gastroenterologica e dietologica, 65(4):268-279.

Inflammatory bowel disease (IBD) results in chronic inflammation in the intestine and is thought to arise from an abnormal immune response to host commensal bacteria. The current treatment paradigm for IBD is focused on suppression of the immune system. However, intestinal microbiota transplant (IMT) may present an avenue to treat IBD by altering the target of inflammation without necessitating immune suppression. Presently, reports of the greatest success with IMT in IBD have been with ulcerative colitis (UC). Four randomized controlled trials have evaluated the efficacy of IMT in UC and reported a pooled rate of combined clinical and endoscopic remission of 28% (95% CI: 4-10). For clinical remission alone, the pooled rate was as high as 42% with a number needed to treat of 5 (95% CI: 3-17). While promising, many questions remain which include elucidating the optimal microbiota enrichment, exacting donor profiling, and identifying the optimal IMT route and frequency. Longer follow-up is needed to determine the ability to achieve stable engraftment for maintenance of remission as well as safety of IMT therapeutics. This review will critically appraise the current literature for IMT in UC and identify key knowledge gaps.

RevDate: 2020-07-28
CmpDate: 2020-07-28

Revolinski SL, LS Munoz-Price (2019)

Clostridium difficile in Immunocompromised Hosts: A Review of Epidemiology, Risk Factors, Treatment, and Prevention.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 68(12):2144-2153.

Clostridium difficile is a significant pathogen in healthcare today, impacting both hospitalized and community-based patients. Immunocompromised patients experience a high incidence of C. difficile infection, ranging from 6% to 33% in the hematology-oncology population and up to 23% among lung transplant recipients, and have a rate of 7.1-8.3 cases per 1000 patient-years in patients with human immunodeficiency virus (HIV). Recurrence of C. difficile infections among immunocompromised patients is also high, with rates up to 40% in both the hematology-oncology population and solid organ transplant recipients. This higher incidence of C. difficile infection and recurrence is believed to be secondary to frequent antimicrobial use, suppressed immune function, increased exposure to healthcare settings, and higher prevalence of C. difficile colonization. This review summarizes published data describing the epidemiology, risk factors for acquisition and infection, treatment, and prevention of C. difficile in hematology-oncology, solid organ transplant, and HIV-infected patients.

RevDate: 2020-09-03

Yue B, Yu ZL, Lv C, et al (2020)

Regulation of the intestinal microbiota: An emerging therapeutic strategy for inflammatory bowel disease.

World journal of gastroenterology, 26(30):4378-4393.

The rapid development of metagenomics, metabolomics, and metatranscriptomics provides novel insights into the intestinal microbiota factors linked to inflammatory bowel disease (IBD). Multiple microorganisms play a role in intestinal health; these include bacteria, fungi, and viruses that exist in a dynamic balance to maintain mucosal homeostasis. Perturbations in the intestinal microbiota disrupt mucosal homeostasis and are closely related to IBD in humans and colitis in mice. Therefore, preventing or correcting the imbalance of microbiota may serve as a novel prevention or treatment strategy for IBD. We review the most recent evidence for direct or indirect interventions targeting intestinal microbiota for treatment of IBD in order to overcome the current limitations of IBD therapies and shed light on personalized treatment options.

RevDate: 2020-09-02

Xue LJ, Yang XZ, Tong Q, et al (2020)

Fecal microbiota transplantation therapy for Parkinson's disease: A preliminary study.

Medicine, 99(35):e22035.

Imbalances in the gut microbiota mediate the progression of neurodegenerative diseases such as Parkinson's disease (PD). Fecal microbiota transplantation (FMT) is currently being explored as a potential therapy for PD. The objective of this study was to assess the efficacy and safety of FMT on PD. Fifteen PD patients were included, 10 of them received FMT via colonoscopy (colonic FMT group) and 5 received FMT via nasal-jejunal tube (nasointestinal FMT group). The score of PSQI, HAMD, HAMA, PDQ-39, NMSQ and UPDRS-III significantly decreased after FMT treatment (all P < .05). Colonic FMT group showed significant improvement and longer maintenance of efficacy compared with nasointestinal FMT (P = .002). Two patients achieved self-satisfying outcomes that last for more than 24 months. However, nasointestinal FMT group had no significant therapeutic effect, although UPDRS-III score slightly reduced. There were no patients were satisfied with nasointestinal FMT for more than 3 months. Among 15 PD patients, there were 5 cases had adverse events (AEs), including diarrhea (2 cases), abdominal pain (2 cases) and flatulence (1 case). These AEs were mild and self-limiting. We conclude that FMT can relieve the motor and non-motor symptoms with acceptable safety in PD. Compared with nasointestinal FMT, colonic FMT seems better and preferable.

RevDate: 2020-08-31

Marcondes Ávila PR, Fiorot M, Michels M, et al (2020)

Effects of microbiota transplantation and the role of the vagus nerve in gut-brain axis in animals subjected to chronic mild stress.

Journal of affective disorders, 277:410-416 pii:S0165-0327(20)32609-4 [Epub ahead of print].

INTRODUCTION: Currently, there is a growing emphasis on the study of intestinal signaling as an influencer in the pathophysiology of neuropsychiatric diseases, and the gut-brain axis is recognized as a communication route through endocrine, immune, and neural pathways (vagus nerve). Studies have shown that diets that modify the microbiota can reduce stress-related behavior and hypothalamic-pituitary-adrenal axis activation. Investigators have used fecal microbiota transplantation (FMT) approaches to demonstrate that stress-related microbiota composition plays a causal role in behavioral changes.

AIM: We hypothesized that FMT may present immunomodulatory, biochemical, endocrine, cognitive, and behavioral benefits in stress situations and that these changes can be mediated via the vagus nerve.

METHODS: Animals were subjected to a chronic mild stress (CMS) protocol. In one experiment, animals were divided into five groups: control, control + FMT, control + FMT + CMS, CMS + saline, and CMS + FMT. The animals received FMT, and behavioral tests were performed; cytokine and carbonyl levels were measured. In a second experiment, animals were submitted to vagotomy and divided into two groups: CMS + FMT and CMS + vagotomy + FMT.

RESULTS: Animals submitted to the CMS protocol or that received FMT from stressed animals showed behavioral changes and changes in neuroactive substances (increased IL-6 and TNF-α levels and carbonyl proteins). The FMT of healthy donors improved the analyzed parameters. In addition, vagotomy influenced beneficial FMT results, confirmed by behavioral testing and protein carbonyl in the hippocampus.

CONCLUSION: Manipulation of the microbiota reversed the behavioral and biochemical changes induced by the CMS protocol, and the vagus nerve influenced the gut-brain axis response.

RevDate: 2020-08-31

Magruder M, Edusei E, Zhang L, et al (2020)

Gut commensal microbiota and decreased risk for Enterobacteriaceae bacteriuria and urinary tract infection.

Gut microbes, 12(1):1805281.

Urinary tract infection (UTI) is a common complication in kidney transplant recipients and can lead to significant morbidity and mortality. Recent evidence supports a role for the gut as a source for UTIs but little is known about the relationship between gut commensal bacteria and UTI development. We hypothesized that the abundance of gut commensal bacteria is associated with a lower risk of developing bacteriuria and UTIs. We performed gut microbiome profiling using 16S rRNA gene sequencing of the V4-V5 hypervariable region on 510 fecal specimens in 168 kidney transplant recipients. Fifty-one kidney transplant recipients (30%) developed Enterobacteriaceae bacteriuria within the first 6 months after transplantation (Enterobacteriaceae Bacteriuria Group) and 117 did not (No Enterobacteriaceae Bacteriuria Group). The relative abundances of Faecalibacterium and Romboutsia were significantly higher in the fecal specimens from the No Enterobacteriaceae Bacteriuria Group than those from the Enterobacteriaceae Bacteriuria Group (Adjusted P value<.01). The combined relative abundance of Faecalibacterium and Romboutsia was inversely correlated with the relative abundance of Enterobacteriaceae (r = -0.13, P = .003). In a multivariable Cox Regression, a top tercile cutoff of the combined relative abundance of Faecalibacterium and Romboutsia of ≥13.7% was independently associated with a decreased risk for Enterobacteriaceae bacteriuria (hazard ratio 0.3, P = .02) and Enterobacteriaceae UTI (hazard ratio 0.4, P = .09). In conclusion, we identify bacterial taxa associated with decreased risk for Enterobacteriaceae bacteriuria and Enterobacteriaceae UTI in kidney transplant recipients, which supports future studies on modulating the gut microbiota as a novel treatment for preventing UTIs.

RevDate: 2020-08-31

Raghu Subramanian C, Talluri S, Khan SU, et al (2020)

Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in Patients With Multiple Comorbidities: Long-Term Safety and Efficacy Results From a Tertiary Care Community Hospital.

Gastroenterology research, 13(4):138-145.

Background: Cure rates of Clostridium difficile infection (CDI) with fecal microbiota transplant (FMT) have been promising. However, there is debate regarding success of FMT in patients with comorbidities.

Methods: Electronic chart review was done to collect data on patients who underwent FMT from January 2015 to August 2017. Charts were analyzed in November 2018 with a median follow-up of 25.4 months (interquartile range 20 - 31 months).

Results: Twenty patients underwent FMT. The primary success rate at our institution was 90% and overall success rate was 100%. Six patients (43%) had FMT failure (two early and four late).

Conclusions: This case series is a description of our center's initial experience with FMT for treatment of recurrent CDI. Our high success rate reiterates the efficacy and safety of FMT in this population including patients with comorbidities.

RevDate: 2020-08-31

Kwak S, Choi J, Hink T, et al (2020)

Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial.

Microbiome, 8(1):125 pii:10.1186/s40168-020-00907-9.

BACKGROUND: Intestinal microbiota restoration can be achieved by complementing a subject's perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another emerging application of interest is reducing antibiotic-resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome.

RESULTS: All patients exhibited significant recovery of gut microbiome diversity and a decrease of ARG relative abundance during the first 7 days post-treatment. However, the microbiome and resistome shifts toward average configurations from unperturbed individuals were more significant and longer-lasting in RBX2660 recipients compared to placebo. We quantified microbiome and resistome modification by RBX2660 using a novel "transplantation index" metric. We identified taxonomic and metabolic features distinguishing the baseline microbiome of non-transplanted patients and taxa specifically enriched during the process of transplantation. We elucidated the correlation between resistome and taxonomic transplantations and post-treatment dynamics of patient-specific and RBX2660-specific ARGs. Whole genome sequencing of AROs cultured from RBX2660 product and patient samples indicate ARO eradication in patients via RBX2660 administration, but also, to a lesser extent, introduction of RBX2660-derived AROs.

CONCLUSIONS: Through shotgun metagenomic sequencing, we elucidated the effects of RBX2660 in the microbiome and resistome. Antibiotic discontinuation alone resulted in significant recovery of gut microbial diversity and reduced ARG relative abundance, but RBX2660 administration more rapidly and completely changed the composition of patients' microbiome, resistome, and ARO colonization by transplanting RBX2660 microbiota into the recipients. Although ARGs and AROs were transmitted through RBX2660, the resistome post-RBX2660 more closely resembled that of the administered product-a proxy for the donor-than an antibiotic perturbed state.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299570 . Registered 19 November 2014 Video Abstract.

RevDate: 2020-08-31
CmpDate: 2020-08-31

Toral M, Robles-Vera I, de la Visitación N, et al (2019)

Role of the immune system in vascular function and blood pressure control induced by faecal microbiota transplantation in rats.

Acta physiologica (Oxford, England), 227(1):e13285.

AIM: High blood pressure (BP) is associated with gut microbiota dysbiosis. The aim of this study was to investigate whether changes in gut microbiota induced by exchanging the gut microbiota between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) alter the gut-immune system interaction inducing changes in vascular function and BP.

METHODS: Twenty-week-old recipient WKY and SHR were orally gavaged with donor faecal contents from WKY or SHR. In additional experiments, we used a design to determine whether blockade of B7-dependent costimulation with CTLA4-Ig or blockade of IL-17 with IL-17-neutralizing antibody could prevent hypertension caused by faecal microbiota transplantation (FMT) from SHR to WKY.

RESULTS: Correlation analyses identified the bacterial abundance of Turicibacter and S24-7_g that, respectively, positively and negatively correlated with systolic BP. FMT from WKY rats to SHR rats reduced basal systolic BP, restored the imbalance between Th17/Treg in mesenteric lymph nodes (MLNs) and aorta, and improved endothelial dysfunction and vascular oxidative status found in SHR transplanted with SHR faeces. FMT from SHR to WKY increased CD80 and CD86 mRNA levels and T cells activation in MLNs, circulating T cells, aortic T cell infiltration, impaired endothelial function and increased basal SBP. These effects were abolished by blockade of B7-dependent costimulation with CTLA4-Ig. IL-17a neutralizing antibody reduced SBP and improved endothelial dysfunction induced by FMT from SHR to WKY.

CONCLUSION: Gut microbiota is an important factor involved in the control of BP, as a consequence of its effect in T-cell activation in gut immune system and vascular T-cells accumulation.

RevDate: 2020-08-29

Zhang F, Zhang X, Yu J, et al (2020)

The gut microbiota confers the lipid-lowering effect of bitter melon (Momordica charantia L.) In high-fat diet (HFD)-Induced hyperlipidemic mice.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 131:110667 pii:S0753-3322(20)30860-X [Epub ahead of print].

The bitter melon (Momordica charantia) is a medical food with well-documented hypoglycemic and anti-hyperlipidemic activities. Previous studies showed that the M. charantia fruit (MC) could modulate the gut microbiota, but whether this modulation is essential for MC's pharmacological effects is largely unknown. Here, we assessed the causality of gut microbes in MC-elicited anti-hyperlipidemic effects for the first time. Oral administration of MC significantly prevented hyperlipidemia, but this amelioration substantially diminished when co-treated with antibiotics. Transplantation of gut flora from MC-treated donor mice also significantly decreased serum lipids. The microbiological analysis revealed that MC moderately increased diversity and shifted the overall structure of gut microbiota. It selectively enhanced the relative abundance of short-chain fatty acid (SCFAs)-producing genera and increased fecal SCFAs content. These results demonstrate that M. charantia fruit (MC) may exert an anti-hyperlipidemic effect through modulating gut microbes and increasing SCFAs production.

RevDate: 2020-08-29

Rinott E, Youngster I, Meir AY, et al (2020)

Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain.

Gastroenterology pii:S0016-5085(20)35111-8 [Epub ahead of print].

BACKGROUND & AIMS: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight loss phase.

METHODS: In the DIRECT-PLUS weight loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to (1)healthy dietary guidelines, (2)Mediterranean diet, and (3)green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both iso-caloric Mediterranean groups consumed 28g/day walnuts (+440mg/d polyphenols provided). The green-Mediterranean dieters further consumed green tea (3-4 cups/day) and a Wolffia-globosa (Mankai strain;100g/day) green shake (+800mg/day polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight regain phase (months 6-14). Secondary outcomes were gastrointestinal symptoms, waist-circumference, glycemic status and changes in the gut microbiome, as measured by metagenomic sequencing and 16s-rRNA. We validated the results in a parallel in-vivo study of mice specifically fed with Mankai, as compared to control chow diet.

RESULTS: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules over the transplantation period. No aFMT-related adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6-14 (aFMT, 30.4% vs. placebo, 40.6%;P=.28), aFMT significantly attenuated weight regain in the green-Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P=.02), but not in the dietary guidelines (P=.57) or Mediterranean diet (P=.64) groups (P for the interaction=.03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89cm vs placebo, 5.05cm;P=.01) and insulin rebound (aFMT, 1.46±3.6μIU/ml vs placebo, 1.64±4.7μIU/ml;P=.04) in the green Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction=.04 and .03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight loss phase, and to prompt preservation of weight loss-associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) following the aFMT. In mice, Mankai-modulated aFMT in the weight loss phase, compared with control diet aFMT, significantly prevented weight regain, and resulted in better glucose tolerance, during a high-fat-diet induced regain phase (P<.05 for all).

CONCLUSIONS: Autologous FMT, collected during the weight loss phase and administrated in the regain phase, might preserve weight loss and glycemic control and is associated with specific microbiome signatures. High-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure. (ClinicalTrials.gov number, NCT03020186).

RevDate: 2020-08-29

Kong L, Lloyd-Price J, Vatanen T, et al (2020)

Linking strain engraftment in fecal microbiota transplantation with maintenance of remission in Crohn's disease.

Gastroenterology pii:S0016-5085(20)35116-7 [Epub ahead of print].

BACKGROUND AND AIMS: Crohn's Disease (CD) is a chronic gastrointestinal disease resulting from the dysfunctional interplay between genetic susceptibility, the immune system and commensal intestinal microbiota. Emerging evidence suggests that treatment by suppression of the immune response and replacement of the microbiota through Fecal Microbiota Transplantation (FMT) is a promising approach for the treatment of CD.

METHODS: We obtained stool metagenomes from CD patients in remission and assessed gut microbiome composition before and after FMT at the species and strain levels. Longitudinal follow-up evaluation allowed us to identify the gain, loss, and strain replacement of specific species, and link these events to the maintenance of remission in CD.

RESULTS: We find that FMT had a significant long-term effect on patient microbial compositions, though this was primarily driven by the engraftment of donor species which remained at low abundance. 38% of FMT-driven changes were strain replacements, emphasizing the importance of detailed profiling methods such as metagenomics. Several instances of long-term coexistence between donor and patient strains were also observed. Engraftment of some Actinobacteria, and engraftment or loss of Proteobacteria, were related to better disease outcomes in CD patients who received FMT, while transmission of Bacteroidetes was deleterious.

CONCLUSION: Our results suggest clades that may be beneficial to transmit/eliminate through FMT, and thus provide criteria that may help identify personalized FMT donors to more effectively maintain remission in CD patients. The framework established here creates a foundation for future studies centered around the application of FMT and defined microbial communities as a therapeutic approach for treating CD.

RevDate: 2020-08-28

Wang Y, Liu F, Zhang G, et al (2020)

Gut microbiome alterations and its link to corticosteroid resistance in immune thrombocytopenia.

Science China. Life sciences pii:10.1007/s11427-020-1788-2 [Epub ahead of print].

Quantitative metagenomic studies have linked the gut microbiota to autoimmune disorders. Here, we performed deep shotgun metagenomic sequencing of fecal samples from 99 immune thrombocytopenia (ITP) patients and 52 healthy controls. Dysbiosis in the gut microbiome of ITP was detected phylogenetically and functionally, and classifier based on species markers distinguished individuals with ITP from healthy controls. In particular, the abundance of Ruminococcus gnavus, Bifidobacterium longum and Akkermansia muciniphila was markedly increased in treatment-naïve ITP patients, and the alterations of microbial species were correlated with clinical indices. Functionally, the secondary bile acid biosynthesis and flagellar assembly were depleted in the gut microbiota of ITP, which may contribute to the onset of ITP by affecting the immune system. Furthermore, we found that corticosteroid treatment affected the gut microbiome of ITP. Compared with corticosteroid-sensitive ITP patients, we identified that the corticosteroid-resistant ITP patients displayed a distinct gut microbiome, which was different from that of the treatment-naïve ITP patients. Together, we provided support for the critical role of gut microbiota in the development of ITP and established a foundation for further research characterizing gut microbiota in relation to corticosteroid resistance of ITP.

RevDate: 2020-08-28
CmpDate: 2020-08-28

Fremin BJ, Sberro H, AS Bhatt (2020)

MetaRibo-Seq measures translation in microbiomes.

Nature communications, 11(1):3268.

No method exists to measure large-scale translation of genes in uncultured organisms in microbiomes. To overcome this limitation, we develop MetaRibo-Seq, a method for simultaneous ribosome profiling of tens to hundreds of organisms in microbiome samples. MetaRibo-Seq was benchmarked against gold-standard Ribo-Seq in a mock microbial community and applied to five different human fecal samples. Unlike RNA-Seq, Ribo-Seq signal of a predicted gene suggests it encodes a translated protein. We demonstrate two applications of this technique: First, MetaRibo-Seq identifies small genes, whose identification until now has been challenging. For example, MetaRibo-Seq identifies 2,091 translated, previously unannotated small protein families from five fecal samples, more than doubling the number of small proteins predicted to exist in this niche. Second, the combined application of RNA-Seq and MetaRibo-Seq identifies differences in the translation of transcripts. In summary, MetaRibo-Seq enables comprehensive translational profiling in microbiomes and identifies previously unannotated small proteins.

RevDate: 2020-08-28
CmpDate: 2020-08-28

Carlucci C, Jones CS, Oliphant K, et al (2019)

Effects of defined gut microbial ecosystem components on virulence determinants of Clostridioides difficile.

Scientific reports, 9(1):885.

Many cases of Clostridioides difficile infection (CDI) are poorly responsive to standard antibiotic treatment strategies, and often patients suffer from recurrent infections characterized by severe diarrhea. Our group previously reported the successful cure of two patients with recurrent CDI using a standardized stool-derived microbial ecosystem therapeutic (MET-1). Using an in vitro model of the distal gut to support bacterial communities, we characterized the metabolite profiles of two defined microbial ecosystems derived from healthy donor stool (DEC58, and a subset community, MET-1), as well as an ecosystem representative of a dysbiotic state (ciprofloxacin-treated DEC58). The growth and virulence determinants of two C. difficile strains were then assessed in response to components derived from the ecosystems. CD186 (ribotype 027) and CD973 (ribotype 078) growth was decreased upon treatment with DEC58 metabolites compared to ciprofloxacin-treated DEC58 metabolites. Furthermore, CD186 TcdA and TcdB secretion was increased following treatment with ciprofloxacin-treated DEC58 spent medium compared to DEC58 spent medium alone. The net metabolic output of C. difficile was also modulated in response to spent media from defined microbial ecosystems, although several metabolite levels were divergent across the two strains examined. Further investigation of these antagonistic properties will guide the development of microbiota-based therapeutics for CDI.

RevDate: 2020-08-27

Ouyang J, Isnard S, Lin J, et al (2020)

Treating From the Inside Out: Relevance of Fecal Microbiota Transplantation to Counteract Gut Damage in GVHD and HIV Infection.

Frontiers in medicine, 7:421.

The gastrointestinal (GI) tract is a complex and well-balanced milieu of anatomic and immunological barriers. The epithelial surface of the GI tract is colonized by trillions of microorganisms, known as the gut microbiota, which is considered an "organ" with distinctive endocrine and immunoregulatory functions. Dysregulation of the gut microbiota composition, termed dysbiosis, has been associated with epithelial damage and translocation of microbial products into the circulating blood. Dysbiosis, increased gut permeability and chronic inflammation play a major role on the clinical outcome of inflammatory bowel diseases, graft-vs.-host disease (GVHD) and HIV infection. In this review, we focus on GVHD and HIV infection, conditions sharing gut immune damage leading to dysbiosis. The degree of dysbiosis and level of epithelial gut damage predict poor clinical outcome in both conditions. Emerging interventions are therefore warranted to promote gut microbiota homeostasis and improve intestinal barrier function. Interventions such as anti-inflammatory medications, and probiotics have toxicity and/or limited transitory effects, justifying innovative approaches. Fecal microbiota transplantation (FMT) is one such approach where fecal microorganisms are transferred from healthy donors into the GI tract of the recipient to restore microbiota composition in patients with Clostridium difficile-induced colitis or inflammatory bowel diseases. Preliminary findings point toward a beneficial effect of FMT to improve GVHD and HIV-related outcomes through the engraftment of beneficial donor bacteria, notably those producing anti-inflammatory metabolites. Herein, we critically review the potential for FMT in alleviating dysbiosis and gut damage in patients with GVHD or HIV-infection. Understanding the underlying mechanism by which FMT restores gut function will pave the way toward novel scalable and targeted interventions.

RevDate: 2020-08-27

Sehgal R, Bedi O, N Trehanpati (2020)

Role of Microbiota in Pathogenesis and Management of Viral Hepatitis.

Frontiers in cellular and infection microbiology, 10:341.

Hepatitis is a condition that can be self-limiting or can progress to fibrosis (scarring), cirrhosis, or liver cancer. These days, gut microbiota becomes an important part of our immune system, which is important for disease progression or recovery. Translocation of gut microbial and metabolic products causes intestinal inflammation by modulating immune cells leading to impairment of the primary barrier. But there are limited studies discussing pathogenesis and management of hepatitis with gut microbiota. In this review, we have discussed the role of gut microbiota in pathogenesis and management of various hepatitis, especially hepatitis B and C. We have discussed the role of bacterial products, LPS-TLR4 pathway, and unmethylated CpG DNA, which ultimately affects downstream NF-kB signaling in hepatitis. Finally, we have discussed the role of fecal microbiota transplantation in the management of hepatitis.

RevDate: 2020-08-27

Barberio B, Massimi D, Bonfante L, et al (2020)

Fecal microbiota transplantation for norovirus infection: a clinical and microbiological success.

Therapeutic advances in gastroenterology, 13:1756284820934589 pii:10.1177_1756284820934589.

RevDate: 2020-08-27

Sfera A, Osorio C, Diaz EL, et al (2020)

The Other Obesity Epidemic-Of Drugs and Bugs.

Frontiers in endocrinology, 11:488.

Chronic psychiatric patients with schizophrenia and related disorders are frequently treatment-resistant and may require higher doses of psychotropic drugs to remain stable. Prolonged exposure to these agents increases the risk of weight gain and cardiometabolic disorders, leading to poorer outcomes and higher medical cost. It is well-established that obesity has reached epidemic proportions throughout the world, however it is less known that its rates are two to three times higher in mentally ill patients compared to the general population. Psychotropic drugs have emerged as a major cause of weight gain, pointing to an urgent need for novel interventions to attenuate this unintended consequence. Recently, the gut microbial community has been linked to psychotropic drugs-induced obesity as these agents were found to possess antimicrobial properties and trigger intestinal dysbiosis, depleting Bacteroidetes phylum. Since germ-free animals exposed to psychotropics have not demonstrated weight gain, altered commensal flora composition is believed to be necessary and sufficient to induce dysmetabolism. Conversely, not only do psychotropics disrupt the composition of gut microbiota but the later alter the metabolism of the former. Here we review the role of gut bacterial community in psychotropic drugs metabolism and dysbiosis. We discuss potential biomarkers reflecting the status of Bacteroidetes phylum and take a closer look at nutritional interventions, fecal microbiota transplantation, and transcranial magnetic stimulation, strategies that may lower obesity rates in chronic psychiatric patients.

RevDate: 2020-08-26

Li L, Wang Q, Gao Y, et al (2020)

Colistin and amoxicillin combinatorial exposure alters the human intestinal microbiota and antibiotic resistome in the simulated human intestinal microbiota.

The Science of the total environment, 750:141415 pii:S0048-9697(20)34944-5 [Epub ahead of print].

Antibiotics treatment could cause the dysbiosis of human intestinal microbiota and antibiotic resistome. Fecal microbiota transplantation (FMT) has been an efficacious treatment to restore the dysbiosis of intestinal microbiota in a variety of intestinal diseases. However, to data, the effect of the combinatorial antibiotic treatment on microbiota, antibiotic resistome and the FMT for restoration affected by combinatorial antibiotic exposure in the human intestinal microbiota remain unclear. In this study, we systematically investigated the effect of the colistin and amoxicillin combinatorial exposure in the simulator of the human intestinal microbial ecosystem (SHIME) and found that this combinatorial exposure significantly altered (p < 0.05) the human intestinal microbiota and antibiotic resistome. The shift of bacterial community and antibiotic resistome could incompletely recovery to baseline by FMT treatment after combinatorial antibiotic exposure. Additionally, the variance of antibiotic resistome was dominantly driven by the bacterial community (41.18%-68.03%) after the combinatorial antibiotic exposure. Overall, this study first to investigate the influence of the colistin and amoxicillin combinatorial exposure on the intestinal microbiota and antibiotic resistome, and assess the FMT recovery in the simulated human intestinal microbiota, which may potentially provide a correct administration of antibiotics and application of FMT in the clinic.

RevDate: 2020-08-26

Zhang W, KW Jiang (2020)

[Role of gut microbiota in carcinogenesis and treatment for colorectal cancer].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 23(5):516-520.

Colorectal cancer is one of the most common malignant tumors of digestive tract. There are a large number of microorganisms in the digestive tract. Under normal physiological conditions, intestinal microorganisms can help with digestion and absorption, resist pathogen invasion and regulate the proliferation of intestinal mucosal cells. However, intestinal microflora imbalance will affect the intestinal microenvironment and intestinal cell function, and is closely related to the incidence and progression of colorectal cancer. Firstly, this paper introduces the changes of intestinal flora in patients with colorectal cancer, and then summarizes the mode of intestinal flora participating in the occurrence of colorectal cancer from the macro level. Then, we elaborate the involvement of intestinal flora in colorectal cancer from the aspects of cytokine-dependent chronic inflammation, DNA damage of intestinal epithelial cells, carcinogenic metabolites of intestinal flora and cellular enzymes, and changes of intestinal immune system. The pathogenesis of colorectal cancer provides a reference for further study of the pathogenesis of colorectal cancer. Finally, from the perspective of intestinal flora and colorectal cancer treatment, we analyze the significance of probiotics and bacterial flora transplantation for the treatment of colorectal cancer, and provide some new treatment ideas and methods that may be useful for the treatment of colorectal cancer.

RevDate: 2020-08-26

Zhang XY, Chen QY, Li N, et al (2020)

[Indication selection and clinical application strategies of fecal microbiota transplantation].

Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 23(5):509-515.

Fecal microbiota transplant (FMT) has become an effective method for the treatment of recurrent C. difficile infection. In addition, it has shown certain effects in other diseases inside and outside the intestine. A large number of clinical trials have been carried out. However, there is still lack of uniform standard for strategies of FMT. In this paper, we discussed the current hot and controversial issues of FMT from the aspects of indication, donor screening, fecal suspension quality control, methodology, follow-up and efficacy judgment, treatment of adverse reaction and ethical supervision based on our team's clinical experience.

RevDate: 2020-08-25

Collins M, M DeWitt (2020)

Fecal microbiota transplantation in the treatment of Crohn disease.

JAAPA : official journal of the American Academy of Physician Assistants, 33(9):34-37.

Fecal microbiota transplantation (FMT) is an alternative treatment option with minimal risk for patients with Crohn disease. This article explains FMT and how it effectively targets the gut microbiota changes associated with the pathogenesis of Crohn disease.

RevDate: 2020-08-25

Kelly CR, Laine LA, GD Wu (2020)


RevDate: 2020-08-25

Song DS (2020)

[Medical Treatment of Alcoholic Liver Disease].

The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi, 76(2):65-70.

Alcoholic liver disease is a major cause of liver disease that results in significant morbidity and mortality in Korea. Abstinence is the most important strategy to prevent disease progression. Corticosteroids improve the one-month survival in patients with severe alcoholic hepatitis, but it was not effective on long-term survival. An N-acetylcysteine treatment combined with corticosteroids may provide a short-term survival benefit than corticosteroids alone. Pentoxifylline is unlikely to affect short-term survival. Hence, studies on new therapies, such as granulocyte colony-stimulating factor and fecal microbiota transplantation, are ongoing. This paper briefly reviews the current knowledge of the medical treatment of alcoholic liver disease.

RevDate: 2020-08-25

Yoon H, Shim HI, Seol M, et al (2020)

Factors Related to Outcomes of Fecal Microbiota Transplantation in Patients with Clostridioides difficile Infection.

Gut and liver pii:gnl20135 [Epub ahead of print].

Background/Aims: The aim of this study was to evaluate factors related to outcomes of fecal microbiota transplantation (FMT) in patients with Clostridioides difficile infection (CDI) and viability of frozen stock for FMT.

Methods: Clinical data of patients who had received FMT for CDI were prospectively collected. Next-generation 16S rRNA gene sequencing of bacteria was performed from donors' and recipients' stool. Colony-forming units (CFUs) of cultures from frozen stock solutions for FMT were measured at 0, 4, 8, 12, 24, 48 weeks after preparation of the solutions.

Results: In total, 25 FMT procedures were performed in 20 cases (14 fresh and 11 frozen FMT). Forty-five percent of cases involved fulminant CDI. The overall success rate was 55% after the 1st FMT and 75% after the 2nd FMT. The success rate was significantly higher in partially treated CDI than in refractory CDI (100% vs 71.4%; p=0.001). In successful cases only, the decrease in alpha-diversity in the recipient stool microbiomes was recovered after FMT to a level similar to that in donor stools. There was a significant difference in the microbiome composition in pre-FMT recipients' stool between successful and failed cases (p=0.001). The CFUs of frozen solution for FMT did not decrease for 48 weeks in both aerobic and anaerobic cultures.

Conclusions: FMT is highly effective in partially treated CDI but not in refractory CDI. The microbiome differs between failed and successful cases. Frozen stock for FMT is viable up to 48 weeks.

RevDate: 2020-08-25
CmpDate: 2020-08-25

Lahtinen P, Jalanka J, Hartikainen A, et al (2020)

Letter: faecal microbiota transplantation for irritable bowel syndrome. Authors' reply.

Alimentary pharmacology & therapeutics, 52(3):557-558.

RevDate: 2020-08-25
CmpDate: 2020-08-25

Segal JP, Mullish BH, Quraishi MN, et al (2020)

Letter: faecal microbiota transplantation for IBS.

Alimentary pharmacology & therapeutics, 52(3):556-557.

RevDate: 2020-08-25
CmpDate: 2020-08-25

Ostojic SM (2020)

Letter: balancing gut hydrogen as a proxy for bacteriotherapy benefits in irritable bowel syndrome.

Alimentary pharmacology & therapeutics, 51(12):1451-1452.

RevDate: 2020-08-24

Zhan J, Ma X, Liu D, et al (2020)

Gut microbiome alterations induced by tributyltin exposure are associated with increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice.

Environmental pollution (Barking, Essex : 1987), 266(Pt 3):115276 pii:S0269-7491(20)35964-9 [Epub ahead of print].

Tributyltin (TBT), an organotin compound once widely used in agriculture and industry, has been reported to induce obesity and endocrine disruption. Gut microbiota has a strong connection with the host's physiology. Nevertheless, the influences of TBT exposure on gut microbiota and whether TBT-influenced gut microbiota is related to TBT-induced toxicity remain unclear. To fill these gaps, ICR (CD-1) mice were respectively exposed to TBT at NOEL (L-TBT) and tenfold NOEL (H-TBT) daily by gavage for 8 weeks in the current study. The results showed that TBT exposure significantly increased body weight as well as epididymal fat, and led to adipocyte hypertrophy, dyslipidemia and impaired glucose and insulin homeostasis in mice. Additionally, TBT exposure significantly decreased the levels of T4, T3 and testosterone in serum. Also of note, TBT exposure changed gut microbiota composition mainly by decreasing Bacteroidetes and increasing Firmicutes proportions. To confirm the role of gut microbiota in TBT-induced overweight and hormonal disorders, fecal microbiota transplantation was performed and the mice receiving gut microbiota from H-TBT mice had similar phenotypes with their donor mice including significant body weight and epididymal fat gain, glucose and insulin dysbiosis and hormonal disorders. These results suggested that gut microbiome altered by TBT exposure was involved in the TBT-induced increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice, providing significant evidence and a novel perspective for better understanding the mechanism by which TBT induces toxicity.

RevDate: 2020-08-24

Badran M, Khalyfa A, Ericsson A, et al (2020)

Fecal microbiota transplantation from mice exposed to chronic intermittent hypoxia elicits sleep disturbances in naïve mice.

Experimental neurology pii:S0014-4886(20)30270-3 [Epub ahead of print].

Obstructive sleep apnea (OSA) is a chronic prevalent condition characterized by intermittent hypoxia (IH) and sleep fragmentation (SF). Evidence suggests that OSA can alter the gut microbiome (GM) diversity and composition that may then promote the occurrence of some of the OSA-associated morbidities. However, it is unclear whether perturbations in the GM caused by IH can elicit sleep disturbances that underlie the increased sleep propensity that occurs in IH-exposed mice. To evaluate this issue, we exposed C57Bl/6 J mice to IH or room air (RA) for 6 weeks, and fecal matter was collected and frozen. C57Bl/6 J naïve mice were then randomly assigned to a fecal microbiota transfer (FMT) protocol for 3 weeks with either IH or RA fecal slur, and their GM was then analyzed using 16 s rRNA sequencing. In addition, FMT recipients underwent sleep recordings using piezoelectric approaches for 3 consecutive days. As anticipated, FMT-IH and FMT-RA mice showed different taxonomic profiles that corresponded to previous effects of IH on GM. Furthermore, FMT-IH mice exhibited increased sleep duration and the frequency of longer sleep bouts during the dark cycle, suggesting increased sleepiness (p < 0.0001 vs. FMT-RA mice). Thus, alterations of GM diversity induced by IH exposures can elicit sleep disturbances in the absence of concurrent IH, suggesting that sleep disturbances can be mediated, at least in part, by IH-induced alterations in GM.

RevDate: 2020-08-24

Li K, Wei S, Hu L, et al (2020)

Protection of Fecal Microbiota Transplantation in a Mouse Model of Multiple Sclerosis.

Mediators of inflammation, 2020:2058272.

Given the growing evidence of a link between gut microbiota (GM) dysbiosis and multiple sclerosis (MS), fecal microbiota transplantation (FMT), aimed at rebuilding GM, has been proposed as a new therapeutic approach to MS treatment. To evaluate the viability of FMT for MS treatment and its impact on MS pathology, we tested FMT in mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We provide evidence that FMT can rectify altered GM to some extent with a therapeutic effect on EAE. We also found that FMT led to reduced activation of microglia and astrocytes and conferred protection on the blood-brain barrier (BBB), myelin, and axons in EAE. Taken together, our data suggest that FMT, as a GM-based therapy, has the potential to be an effective treatment for MS.

RevDate: 2020-08-24

Zou J, Zhao X, Shi Z, et al (2020)

Critical role of innate immunity to flagellin in absence of adaptive immunity.

The Journal of infectious diseases pii:5896377 [Epub ahead of print].

BACKGROUND: Bacterial flagellin is a major target of innate and adaptive immunity, both of which can promote and/or compensate for deficiencies in each other's function.

AIM/METHODS: To investigate the role of innate immune detection of flagellin irrespective of adaptive immunity, we examined the consequences of loss of toll-like receptor 5 (T5) and/or Nod-like receptor 4 (N4) upon a Rag1-deficient background.

RESULTS: Mice lacking TLR5 and Rag1 (T5/Rag-DKO) exhibited frequent lethal Pasteurellaceae-containing abscesses that prevented breeding of these mice. Mice lacking TLR5, NLRC4, and Rag1 (T5/N4/Rag-TKO) also resulted in sporadic lethal abdominal abscesses caused by similar Pasteurellaceae. In the absence of such infections, relative to Rag1-KO, T5/N4/Rag-TKO mice exhibited microbiota encroachment, low-grade inflammation, microbiota dysbiosis, and, moreover were highly prone to Citrobacter infection and developed severe colitis when adoptively transferred with colitogenic T-cells. Relative proneness of T5/N4/Rag-TKO mice to T-cell colitis was ablated by antibiotics while fecal microbiota transplant from T5/N4/Rag-TKO mice to WT mice transferred proneness to Citrobacter infection, indicating that dysbiosis in T5/N4/Rag-TKO mice contributed to these phenotypes.

CONCLUSIONS: These results demonstrate a critical role for innate immune detection of flagellin, especially in the intestinal tract and particularly in hosts deficient in adaptive immunity.

RevDate: 2020-08-24
CmpDate: 2020-08-24

Anonymous (2019)

Microbiota Manipulated to Enhance Immunity.

Cancer discovery, 9(7):822.

Oncologists are testing fecal transplants and other microbiome-based products in combination with checkpoint inhibitors in an effort to increase and enhance responses. However, questions remain about how the microbes affect host immunity and which preparations of bacteria are optimal.

RevDate: 2020-08-21

Chen H, Chen Z, Shen L, et al (2020)

Fecal microbiota transplantation from patients with autoimmune encephalitis modulates Th17 response and relevant behaviors in mice.

Cell death discovery, 6:75 pii:309.

The significance of the microbiota-gut-brain axis has been increasingly recognized as a major modulator of autoimmunity. Here, we aim to characterize the gut microbiota of a large cohort of treatment-naïve anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis patients relative to that of healthy controls (HCs). Relative to HCs, anti-NMDAR encephalitis patients had a decreased microbiome alpha-diversity index, marked disturbances of gut microbial composition and intestinal permeability damage. Disturbed microbiota in anti-NMDAR encephalitis patients might be linked with different clinical characteristics. Imputed KEGG analysis revealed perturbations of functional modules in the gut microbiomes of anti-NMDAR encephalitis. Compared to HCs, microbiota-depleted mice receiving fecal microbiota transplantation (FMT) from anti-NMDAR encephalitis patients had hypersensitivity and cognitive impairment. Furthermore, anti-NMDAR encephalitis FMT mice showed altered T cells in the spleen and small intestine lamina propria with an increased Th17 cells. Overall, this study first suggests that the anti-NMDAR encephalitis microbiome itself can influence neurologic, Th17 response and behavioral function. The gut microbiota is a potential therapeutic target for anti-NMDAR encephalitis.

RevDate: 2020-08-21

Ghouri YA, Tahan V, B Shen (2020)

Secondary causes of inflammatory bowel diseases.

World journal of gastroenterology, 26(28):3998-4017.

Inflammatory bowel diseases (IBD), conventionally consist of Crohn's disease (CD) and ulcerative colitis. They occur in individuals with high risk genotype for the disease in the setting of appropriate environmental factors. The pathogenesis of IBD involves a dysregulated autoimmune response to gut dysbiosis, which in turn is triggered due to exposure to various inciting environmental factors. But there is no clearly defined etiology of IBD and this type of disease is termed as "idiopathic IBD", "classic IBD", or "primary IBD". We reviewed the current medical literature and found that certain etiological factors may be responsible for the development of IBD or IBD-like conditions, and we consider this form of de novo IBD as "secondary IBD". Currently known factors that are potentially responsible for giving rise to secondary IBD are medications; bowel altering surgeries and transplantation of organs, stem cells or fecal microbiome. Medications associated with the development of secondary IBD include; immunomodulators, anti-tumor necrosis factor alpha agents, anti-interleukin agents, interferons, immune stimulating agents and checkpoint inhibitors. Colectomy can in some cases give rise to de novo CD, pouchitis of the ileal pouch, or postcolectomy enteritis syndrome. After solid organ transplantation or hematopoietic stem cell transplantation, the recipient may develop de novo IBD or IBD flare. Fecal microbiota transplantation has been widely used to treat patients suffering from recurrent Clostridium difficile infection but can also causes IBD flares.

RevDate: 2020-08-21

Li Y, Luo ZY, Hu YY, et al (2020)

The gut microbiota regulates autism-like behavior by mediating vitamin B6 homeostasis in EphB6-deficient mice.

Microbiome, 8(1):120 pii:10.1186/s40168-020-00884-z.

BACKGROUND: Autism spectrum disorder (ASD) is a developmental disorder, and the effective pharmacological treatments for the core autistic symptoms are currently limited. Increasing evidence, particularly that from clinical studies on ASD patients, suggests a functional link between the gut microbiota and the development of ASD. However, the mechanisms linking the gut microbiota with brain dysfunctions (gut-brain axis) in ASD have not yet been full elucidated. Due to its genetic mutations and downregulated expression in patients with ASD, EPHB6, which also plays important roles in gut homeostasis, is generally considered a candidate gene for ASD. Nonetheless, the role and mechanism of EPHB6 in regulating the gut microbiota and the development of ASD are unclear.

RESULTS: Here, we found that the deletion of EphB6 induced autism-like behavior and disturbed the gut microbiota in mice. More importantly, transplantation of the fecal microbiota from EphB6-deficient mice resulted in autism-like behavior in antibiotic-treated C57BL/6J mice, and transplantation of the fecal microbiota from wild-type mice ameliorated the autism-like behavior in EphB6-deficient mice. At the metabolic level, the disturbed gut microbiota in EphB6-deficient mice led to vitamin B6 and dopamine defects. At the cellular level, the excitation/inhibition (E/I) balance in the medial prefrontal cortex was regulated by gut microbiota-mediated vitamin B6 in EphB6-deficient mice.

CONCLUSIONS: Our study uncovers a key role for the gut microbiota in the regulation of autism-like social behavior by vitamin B6, dopamine, and the E/I balance in EphB6-deficient mice, and these findings suggest new strategies for understanding and treating ASD. Video abstract.

RevDate: 2020-08-20

Britton GJ, Contijoch EJ, Spindler MP, et al (2020)

Defined microbiota transplant restores Th17/RORγt+ regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas.

Proceedings of the National Academy of Sciences of the United States of America pii:1922189117 [Epub ahead of print].

The building evidence for the contribution of microbiota to human disease has spurred an effort to develop therapies that target the gut microbiota. This is particularly evident in inflammatory bowel diseases (IBDs), where clinical trials of fecal microbiota transplantation have shown some efficacy. To aid the development of novel microbiota-targeted therapies and to better understand the biology underpinning such treatments, we have used gnotobiotic mice to model microbiota manipulations in the context of microbiotas from humans with inflammatory bowel disease. Mice colonized with IBD donor-derived microbiotas exhibit a stereotypical set of phenotypes, characterized by abundant mucosal Th17 cells, a deficit in the tolerogenic RORγt+ regulatory T (Treg) cell subset, and susceptibility to disease in colitis models. Transplanting healthy donor-derived microbiotas into mice colonized with human IBD microbiotas led to induction of RORγt+ Treg cells, which was associated with an increase in the density of the microbiotas following transplant. Microbiota transplant reduced gut Th17 cells in mice colonized with a microbiota from a donor with Crohn's disease. By culturing strains from this microbiota and screening them in vivo, we identified a specific strain that potently induces Th17 cells. Microbiota transplants reduced the relative abundance of this strain in the gut microbiota, which was correlated with a reduction in Th17 cells and protection from colitis.

RevDate: 2020-08-20

Zhang L, S Roy (2020)

Opioid Modulation of the Gut-Brain Axis in Opioid-Associated Comorbidities.

Cold Spring Harbor perspectives in medicine pii:cshperspect.a040485 [Epub ahead of print].

Growing evidence from animal and human studies show that opioids have a major impact on the composition and function of gut microbiota. This leads to disruption in gut permeability and altered microbial metabolites, driving both systemic and neuroinflammation, which in turn impacts central nervous system (CNS) homeostasis. Tolerance and dependence are the major comorbidities associated with prolonged opioid use. Inflammatory mediators and signaling pathways have been implicated in both opioid tolerance and dependence. We provide evidence that targeting the gut microbiome during opioid use through prebiotics, probiotics, antibiotics, and fecal microbial transplantation holds the greatest promise for novel treatments for opioid abuse. Basic research and clinical trials are required to examine what is more efficacious to yield new insights into the role of the gut-brain axis in opioid abuse.

RevDate: 2020-08-19

Yu Z, Shi Z, Zheng Z, et al (2020)

DEHP induce cholesterol imbalance via disturbing bile acid metabolism by altering the composition of gut microbiota in rats.

Chemosphere, 263:127959 pii:S0045-6535(20)32154-8 [Epub ahead of print].

Di(2-ethylhexyl) phthalate (DEHP) is one of the most widespread environmental contaminants worldwide because of its massive production, extensive use in common products, and liability to leach from products. This study investigated the mechanisms of DEHP mediated alteration of lipid metabolism. Rats were treated with 0.5 mg kg-1 d-1 of DEHP for 23 weeks. Results showed that the treatment induced cholesterol imbalance. Further fecal transplantation experiments corroborated the involvement of gut microbiota in DEHP-induced cholesterol imbalance. In addition, 16S rRNA gene sequencing analysis of cecal contents showed that DEHP disrupted the gut microbiota diversity in rats and increased the ratio of Firmicutes to Bacteroidetes. Further cecal metabolomic analyses, bile salt hydrolase enzyme activity, and gene expression examination revealed that chronic DEHP exposure generated a bile acid profile in the gut that is a more potent activator of farnesoid X receptor (FXR). The activation of FXR in the gut induced the expression of fibroblast growth factor 15, which subsequently suppressed cytochrome P450 family 7 subfamily A member 1 in the liver and bile acid synthesis. These results suggest that DEHP might induce cholesterol imbalance by regulating bile acid metabolism via the remodeling of the gut microbiota.

RevDate: 2020-08-19

Stephen-Victor E, Crestani E, TA Chatila (2020)

Dietary and Microbial Determinants in Food Allergy.

Immunity, 53(2):277-289.

The steep rise in food allergy (FA) has evoked environmental factors involved in disease pathogenesis, including the gut microbiota, diet, and their metabolites. Early introduction of solid foods synchronizes with the "weaning reaction," a time during which the microbiota imprints durable oral tolerance. Recent work has shown that children with FA manifest an early onset dysbiosis with the loss of Clostridiales species, which promotes the differentiation of ROR-γt+ regulatory T cells to suppress FA. This process can be reversed in pre-clinical mouse models by targeted bacteriotherapy. Here, we review the dominant tolerance mechanisms enforced by the microbiota to suppress FA and discuss therapeutic intervention strategies that act to recapitulate the early life window of opportunity in stemming the FA epidemic.

RevDate: 2020-08-18

Olesen SW, Y Gerardin (2020)

Re-evaluating the evidence for fecal microbiota transplantation "super-donors" in inflammatory bowel disease.

Journal of Crohn's & colitis pii:5893677 [Epub ahead of print].

BACKGROUND: Fecal microbiota transplantation (FMT) is a recommended treatment for recurrent Clostridioides difficile infection, and there is promise that FMT may be effective for conditions like inflammatory bowel disease (IBD). Previous FMT clinical trials have considered the possibility of a "donor effect", that is, that FMT material from different donors has different clinical efficacies.

AIM & METHODS: Here we re-evaluate evidence for donor effects in published FMT clinical trials for IBD.

RESULTS: In 10 of 12 published studies, no statistically significant donor effect was detected when rigorously re-evaluating the original analyses. One study had statistically significant separation of microbiota composition of pools of donor stool when stratified by patient outcome. One study reported a significant effect but did not have underlying data available for re-evaluation. When quantifying the uncertainty on the magnitude of the donor effect, confidence intervals were large, including both zero donor effect and very substantial donor effects.

CONCLUSION: Although we found very little evidence for donor effects, the existing data also cannot rule out the possibility that donor effects are clinically important. Large clinical trials prospectively designed to detect donor effects are likely necessary to determine if donor effects are clinically relevant for IBD.

RevDate: 2020-08-18
CmpDate: 2020-08-18

Cho JM, Pardi DS, S Khanna (2020)

Update on Treatment of Clostridioides difficile Infection.

Mayo Clinic proceedings, 95(4):758-769.

Clostridioides difficile infection (CDI) is the leading cause of health care-associated infections in the United States. The increasing incidence and recurrence rates of CDI together with its associated morbidity and mortality are great concerns. Newer treatment methods, such as narrow-spectrum antibiotics, monoclonal antibodies, and microbial replacement therapies, are being developed and implemented. We searched PubMed to identify published literature from 2010 to 2018 using the following keywords: Clostridium difficile, treatment, and therapy. Cited references were also used to identify relevant literature. This review focuses on the current standard of therapy and emerging therapies for CDI and summarizes the updated guidelines on treatment of CDI.

RevDate: 2020-08-18
CmpDate: 2020-08-18

Holster S, Hooiveld GJ, Repsilber D, et al (2019)

Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome.

Biomolecules, 9(10):.

Faecal microbiota transfer (FMT) consists of the introduction of new microbial communities into the intestine of a patient, with the aim of restoring a disturbed gut microbiota. Even though it is used as a potential treatment for various diseases, it is unknown how the host mucosa responds to FMT. This study aims to investigate the colonic mucosa gene expression response to allogenic (from a donor) or autologous (own) FMT in patients with irritable bowel syndrome (IBS). In a recently conducted randomised, double-blinded, controlled clinical study, 17 IBS patients were treated with FMT by colonoscopy. RNA was isolated from colonic biopsies collected by sigmoidoscopy at baseline, as well as two weeks and eight weeks after FMT. In patients treated with allogenic FMT, predominantly immune response-related gene sets were induced, with the strongest response two weeks after the FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected. Furthermore, several microbiota genera showed correlations with immune-related gene sets, with different correlations found after allogenic compared to autologous FMT. This study shows that the microbe-host response is influenced by FMT on the mucosal gene expression level, and that there are clear differences in response to allogenic compared to autologous FMT.

RevDate: 2020-08-17

Vandekerckhove E, Janssens F, Tate D, et al (2020)

Treatment of Gut Fermentation Syndrome With Fecal Microbiota Transplantation.

RevDate: 2020-08-17

van Lier YF, Davids M, Haverkate NJE, et al (2020)

Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients.

Science translational medicine, 12(556):.

Disruption of the intestinal microbiota occurs frequently in allogeneic hematopoietic cell transplantation (allo-HCT) recipients and predisposes them to development of graft-versus-host disease (GvHD). In a prospective, single-center, single-arm study, we investigated the effect of donor fecal microbiota transplantation (FMT) on symptoms of steroid-refractory or steroid-dependent, acute or late-onset acute intestinal GvHD in 15 individuals who had undergone allo-HCT. Study participants received a fecal suspension from an unrelated healthy donor via nasoduodenal infusion. Donor FMT was well tolerated, and infection-related adverse events did not seem to be related to the FMT procedure. In 10 of 15 study participants, a complete clinical response was observed within 1 month after FMT, without additional interventions to alleviate GvHD symptoms. This response was accompanied by an increase in gut microbial α-diversity, a partial engraftment of donor bacterial species, and increased abundance of butyrate-producing bacteria, including Clostridiales and Blautia species. In 6 of the 10 responding donor FMT recipients, immunosuppressant drug therapy was successfully tapered. Durable remission of steroid-refractory or steroid-dependent GvHD after donor FMT was associated with improved survival at 24 weeks after donor FMT. This study highlights the potential of donor FMT as a treatment for steroid-refractory or steroid-dependent GvHD, but larger clinical trials are needed to confirm the safety and efficacy of this procedure.

RevDate: 2020-08-17

Wang S, Ishima T, Zhang J, et al (2020)

Ingestion of Lactobacillus intestinalis and Lactobacillus reuteri causes depression- and anhedonia-like phenotypes in antibiotic-treated mice via the vagus nerve.

Journal of neuroinflammation, 17(1):241 pii:10.1186/s12974-020-01916-z.

BACKGROUND: The brain-gut-microbiota axis plays a role in the pathogenesis of stress-related disorders such as depression. In this study, we examined the effects of fecal microbiota transplantation (FMT) in mice with antibiotic-treated microbiota depletion.

METHODS: The fecal microbiota was obtained from mice subjected to chronic social defeat stress (CSDS) and control (no CSDS) mice. FMT from these two groups was performed to antibiotic-treated mice. 16S rRNA analysis was performed to examine the composition of gut microbiota. Furthermore, the effects of subdiaphragmatic vagotomy in depression-like phenotypes after ingestion of microbes were examined.

RESULTS: The ingestion of fecal microbiota from CSDS-susceptible mice resulted in an anhedonia-like phenotype, higher plasma levels of interleukin-6 (IL-6), and decreased expression of synaptic proteins in the prefrontal cortex (PFC) in antibiotic-treated mice but not in water-treated mice. 16S rRNA analysis suggested that two microbes (Lactobacillus intestinalis and Lactobacillus reuteri) may be responsible for the anhedonia-like phenotype in antibiotic-treated mice after FMT. Ingestion of these two microbes for 14 days led to depression- and anhedonia-like phenotypes, higher plasma IL-6 levels, and decreased expression of synaptic proteins in the PFC of antibiotic-treated mice. Interestingly, subdiaphragmatic vagotomy significantly blocked the development of behavioral abnormalities, elevation of plasma IL-6 levels, and downregulation of synaptic proteins in the PFC after ingestion of these two microbes.

CONCLUSIONS: These findings suggest that microbiota depletion using an antibiotic cocktail is essential for the development of FMT-induced behavioral changes and that the vagus nerve plays a key role in behavioral abnormalities in antibiotic-treated mice after the ingestion of L. intestinalis and L. reuteri. Therefore, it is likely that the brain-gut-microbiota axis participates in the pathogenesis of depression via the vagus nerve.

RevDate: 2020-08-14
CmpDate: 2020-08-14

Kc D, Sumner R, S Lippmann (2020)

Gut microbiota and health.

Postgraduate medicine, 132(3):274.

RevDate: 2020-08-13

Su X, Yin X, Liu Y, et al (2020)

Gut dysbiosis contributes to the imbalance of Treg and Th17 cells in Graves' disease patients by propionic acid.

The Journal of clinical endocrinology and metabolism pii:5891790 [Epub ahead of print].

BACKGROUND: Graves' disease (GD) is a typical organ-specific autoimmune disease. Intestinal flora plays pivotal roles in immune homeostasis and autoimmune disease development. However, the association and mechanism between intestinal flora and GD remain elusive.

OBJECTIVE: To investigate the association and mechanism between intestinal flora and GD.

METHODS: We recruited 58 initially untreated GD patients and 63 healthy individuals in the study. The composition and metabolic characteristics of the intestinal flora in GD patients and the causal relationship between intestinal flora and GD pathogenesis were assessed using 16S rRNA gene sequencing, targeted/untargeted metabolomics, and fecal microbiota transplantation (FMT).

RESULTS: The composition, metabolism and inter-relationships of the intestinal flora were also changed, particularly the significantly reduced short-chain fatty acid (SCFA) producing bacteria and SCFAs. YCH46 strain of Bacteroides fragilis could produce propionic acid and increase Treg cell numbers while decrease Th17 cell numbers. Transplanting the intestinal flora of GD patients significantly increased GD incidence in GD mouse model. Additionally, three intestinal bacteria genera (Bacteroides, Alistipes, Prevotella) could distinguish GD patients from healthy individuals with 85% accuracy.

CONCLUSIONS: Gut dysbiosis contributes to Treg/Th17 imbalance through the pathway regulated by propionic acid and promotes the occurrence of GD together with other pathogenic factors. Bacteroides, Alistipes and Prevotella have great potential to serve as adjunct markers for GD diagnosis. This study provided valuable clues for improving immune dysfunction of GD patients using B. fragilis and illuminated the prospects of microecological therapy for GD as an adjunct treatment.

RevDate: 2020-08-10

Zhang Q, Lu Q, Y Luo (2020)

Fecal Microbiota Transplantation and Detection of Prevalence of IgA-Coated Bacteria in the Gut.

Journal of visualized experiments : JoVE.

Gut microbiota exert pleiotropic roles in human health and disease. Fecal microbiota transplantation (FMT) is an effective method to investigate the biological function of intestinal bacteria as a whole or at the species level. Several different FMT methods have been published. Here, we present an FMT protocol that successfully depletes gut microbiota in a matter of days, followed by transplantation of fecal microbiota from fresh or frozen donor intestinal contents to conventional mice. Real time-PCR is applied to test the efficacy of bacterial depletion. Sequencing of the 16S ribosomal RNA (rRNA) is then applied to test the relative abundance and identity of gut microbiota in recipient mice. We also present a flow cytometry-based detection method of immunoglobulin A (IgA)-coated bacteria in the gut.

RevDate: 2020-08-10

Sood A, Singh A, Mahajan R, et al (2020)

Clinical Predictors of response to Faecal Microbiota Transplantation in patients with active ulcerative colitis.

Journal of Crohn's & colitis pii:5890140 [Epub ahead of print].

BACKGROUND: Fecal Microbiota Transplantation (FMT) has been shown to be effective for induction of remission in patients with active ulcerative colitis (UC). At present, clinical factors impacting the response to FMT in UC remain unclear.

METHODS: Patients with active UC treated with multisession FMT via colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22, were analysed. Response to FMT was defined as achievement of corticosteroid free clinical remission at week 30. Patient and disease characteristics were evaluated to determine the predictors of response to FMT.

RESULTS: Out of 140 patients with active UC treated with FMT, 93 patients [mean age 34.96±11.27 years, 62.36% males (n=58), mean Mayo clinic score 8.07±2.00] who completed the multi-session FMT protocol were analysed. Fifty-seven (61.29%) patients achieved clinical remission. Younger age (OR for age 0.93, 95% CI 0.89-0.97, p=0.001), moderate (Mayo clinic score 6-9) disease severity (OR 3.01, 95% CI 1.12 to 8.06, p=0.025) and endoscopic Mayo score 2 (OR 5.55, 95% CI 2.18-14.06, p<0.001) were significant predictors of remission on univariate analysis. Younger age, disease extent E2 and endoscopic mayo score 2 (OR 0.925, 95% CI 0.88-0.97, p=0.002; OR 2.89, 95% CI 1.01-8.25, p=0.04 and OR 8.43, 95% CI 2.38-29.84, p=0.001, respectively) were associated with clinical remission on multivariate logistic regression. A mathematical model (nomogram) was developed for estimating the probability of remission with FMT protocol.

CONCLUSION: Younger age, disease extent E2, and endoscopic mayo score 2 significantly predict achievement of clinical remission with FMT in active UC. The prediction model can help in selecting individuals for FMT. Validation in larger cohorts is needed.

RevDate: 2020-08-09

He Y, Xu R, Wang W, et al (2020)

Probiotics, prebiotics, antibiotic, Chinese herbal medicine, and fecal microbiota transplantation in irritable bowel syndrome: Protocol for a systematic review and network meta-analysis.

Medicine, 99(32):e21502.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disease, with a high global incidence, which seriously influences the quality of life and work efficiency of patients. Extensive research showed that IBS is related to changes in the intestinal microenvironment. The novel treatment strategy targeting the gut microbiota is being actively implemented. Probiotics, antibiotics, prebiotics, fecal microbiota transplantation, and Chinese Herbal Medicine have been proven to be effective in the treatment of IBS, and all have an impact on the intestinal flora of patients. However, these 5 treatments have their own pros and cons and have not been systematically evaluated and compared. Therefore, this study will indirectly compare the safety and effectiveness of these 5 methods in the treatment of IBS through network meta-analysis.

METHODS: The following databases including Embase, Pubmed, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, WHO International Clinical Trials Registry Platform and ClinicalTrials.gov will be retrieved from inception to June 2020 without language restrictions. Literature selection, data extraction, and bias analysis will be done by 2 researchers. The primary outcome is global symptoms improvement. The secondary outcomes will include individual IBS symptom scores, emotional response, and adverse events. The conventional pair-wise meta-analysis will be performed using Stata V.14.0 and be pooled using a random-effects model. We will use WinBUGS V.1.4.3 (Cambridge, United Kingdom) with a Bayesian hierarchical random-effects model to conduct the network meta-analysis.

RESULTS: This study will provide systematic reviews and indirect network comparison results about treatments of IBS.

CONCLUSIONS: This study will systematically evaluate and compare 5 intestinal flora-related therapies for IBS and to provide an evidence-based medical decision-making basis for clinicians.


RevDate: 2020-08-08

Tan GSE, Tay HL, Tan SH, et al (2020)

Gut Microbiota Modulation: Implications for Infection Control and Antimicrobial Stewardship.

Advances in therapy pii:10.1007/s12325-020-01458-z [Epub ahead of print].

The human microbiome comprises a complex ecosystem of microbial communities that exist within the human body, the largest and most diverse of which are found within the human intestine. It has been increasingly implicated in human health and diseases, demonstrably playing a critical role in influencing host immune response, protection against pathogen overgrowth, biosynthesis, and metabolism. As our understanding of the links between the gut microbiota with host immunity and infectious diseases deepens, there is a greater need to incorporate methods of modulating it as a means of therapy or infection prevention in daily clinical practice. Traditional antimicrobial stewardship principles have been evaluated to assess their impact on the gut microbiota diversity and the consequent repercussions, taking into consideration antibiotic pharmacokinetic and pharmacodynamic properties. Novel strategies of selective digestive decontamination and fecal microbiota transplantation to regulate the gut microbiota have also been tested in different conditions with variable results. This review seeks to provide an overview of the available literature on the modulation of the gut microbiota and its implications for infection control and antimicrobial stewardship. With increased understanding, gut microbiota profiling through metataxonomic analysis may provide further insight into modulating microbial communities in the context of infection prevention and control.

RevDate: 2020-08-08

Yang CQ, Guo XS, Ji-Li , et al (2020)

Rifaximin Improves Visceral Hyperalgesia via TRPV1 by Modulating Intestinal Flora in the Water Avoidance Stressed Rat.

Gastroenterology research and practice, 2020:4078681.

Background: Rifaximin is effective in relieving pain symptoms with IBS patients, although the mechanisms were not clear. The aims of the research were to investigate whether the visceral hyperalgesia was alleviated by rifaximin via TRPV1 channel in rats.

Methods: Rats were subjected to water avoidance stress (WAS) and were pretreated with rifaximin by oral gavage. The visceromotor response to colorectal distension was measured. The changes of TRPV1 in peripheral and central neurons of rats were detected by immunofluorescence, western blot method, and RT-PCR. Bacterial 16S ribosomal DNA in ileal contents was assessed using the Illumina MiSeq platform. The effect of intestinal flora on TRPV1 channel was observed by fecal microbiota transplantation (FMT) methods.

Results: Rifaximin could relieve the visceral hyperalgesia and reduce the TRPV1 expression of neurons and ileum mucosa in rats induced by WAS. The reduced relative abundance of intestinal flora induced by WAS could be partly prevented by rifaximin. The electromyographical activities and immunoreactivity of TRPV1 in rats could be changed after FMT.

Conclusions: Rifaximin could improve visceral hyperalgesia via TRPV1 channels of peripheral and central neurons by modulating intestinal flora in rats.

RevDate: 2020-08-08

Alagna L, Palomba E, Mangioni D, et al (2020)

Multidrug-Resistant Gram-Negative Bacteria Decolonization in Immunocompromised Patients: A Focus on Fecal Microbiota Transplantation.

International journal of molecular sciences, 21(16): pii:ijms21165619.

Antimicrobial resistance is an important issue for global health; in immunocompromised patients, such as solid organ and hematological transplant recipients, it poses an even bigger threat. Colonization by multidrug-resistant (MDR) bacteria was acknowledged as a strong risk factor to subsequent infections, especially in individuals with a compromised immune system. A growing pile of studies has linked the imbalance caused by the dominance of certain taxa populating the gut, also known as intestinal microbiota dysbiosis, to an increased risk of MDR bacteria colonization. Several attempts were proposed to modulate the gut microbiota. Particularly, fecal microbiota transplantation (FMT) was successfully applied to treat conditions like Clostridioides difficile infection and other diseases linked to gut microbiota dysbiosis. In this review we aimed to provide a look at the data gathered so far on FMT, focusing on its possible role in treating MDR colonization in the setting of immunocompromised patients and analyzing its efficacy and safety.

RevDate: 2020-08-08

Arias N, Arboleya S, Allison J, et al (2020)

The Relationship between Choline Bioavailability from Diet, Intestinal Microbiota Composition, and Its Modulation of Human Diseases.

Nutrients, 12(8): pii:nu12082340.

Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which, upon absorption by the host is converted into trimethylamine-N-oxide (TMAO) in the liver. A high accumulation of both components is related to cardiovascular disease, inflammatory bowel disease, non-alcoholic fatty liver disease, and chronic kidney disease. However, the relationship between the microbiota production of these components and its impact on these diseases still remains unknown. In this review, we will address which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., the genotype) and diet affect TMA production, and the colonization of these microbes and the reversal of dysbiosis as a therapy for these diseases.

RevDate: 2020-08-08

Witkowski M, Weeks TL, SL Hazen (2020)

Gut Microbiota and Cardiovascular Disease.

Circulation research, 127(4):553-570.

Fecal microbial community changes are associated with numerous disease states, including cardiovascular disease (CVD). However, such data are merely associative. A causal contribution for gut microbiota in CVD has been further supported by a multitude of more direct experimental evidence. Indeed, gut microbiota transplantation studies, specific gut microbiota-dependent pathways, and downstream metabolites have all been shown to influence host metabolism and CVD, sometimes through specific identified host receptors. Multiple metaorganismal pathways (involving both microbe and host) both impact CVD in animal models and show striking clinical associations in human studies. For example, trimethylamine N-oxide and, more recently, phenylacetylglutamine are gut microbiota-dependent metabolites whose blood levels are associated with incident CVD risks in large-scale clinical studies. Importantly, a causal link to CVD for these and other specific gut microbial metabolites/pathways has been shown through numerous mechanistic animal model studies. Phenylacetylglutamine, for example, was recently shown to promote adverse cardiovascular phenotypes in the host via interaction with multiple ARs (adrenergic receptors)-a class of key receptors that regulate cardiovascular homeostasis. In this review, we summarize recent advances of microbiome research in CVD and related cardiometabolic phenotypes that have helped to move the field forward from associative to causative results. We focus on microbiota and metaorganismal compounds/pathways, with specific attention paid to short-chain fatty acids, secondary bile acids, trimethylamine N-oxide, and phenylacetylglutamine. We also discuss novel therapeutic strategies for directly targeting the gut microbiome to improve cardiovascular outcomes.

RevDate: 2020-08-07

Jouhten H, Ronkainen A, Aakko J, et al (2020)

Cultivation and Genomics Prove Long-Term Colonization of Donor's Bifidobacteria in Recurrent Clostridioides difficile Patients Treated With Fecal Microbiota Transplantation.

Frontiers in microbiology, 11:1663.

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) and it's also considered for treating other indications. Metagenomic studies have indicated that commensal donor bacteria may colonize FMT recipients, but cultivation has not been employed to verify strain-level colonization. We combined molecular profiling of Bifidobacterium populations with cultivation, molecular typing, and whole genome sequencing (WGS) to isolate and identify strains that were transferred from donors to recipients. Several Bifidobacterium strains from two donors were recovered from 13 recipients during the 1-year follow-up period after FMT. The strain identities were confirmed by WGS and comparative genomics. Our results show that specific donor-derived bifidobacteria can colonize rCDI patients for at least 1 year, and thus FMT may have long-term consequences for the recipient's microbiota and health. Conceptually, we demonstrate that FMT trials combined with microbial profiling can be used as a platform for discovering and isolating commensal strains with proven colonization capacity for potential therapeutic use.

RevDate: 2020-08-06

Mańkowska-Wierzbicka D, Stelmach-Mardas M, Gabryel M, et al (2020)

The Effectiveness of Multi-Session FMT Treatment in Active Ulcerative Colitis Patients: A Pilot Study.

Biomedicines, 8(8): pii:biomedicines8080268.

The modification of the microbiome through fecal microbiota transplantation (FMT) is becoming a very promising therapeutic option for inflammatory bowel disease (IBD) patients. Our pilot study aimed to assess the effectiveness of multi-session FMT treatment in active ulcerative colitis (UC) patients. Ten patients with UC were treated with multi-session FMT (200 mL) from healthy donors, via colonoscopy/gastroscopy. Patients were evaluated as follows: at baseline, at week 7, and after 6 months, routine blood tests (including C reactive protein (CRP) and calprotectin) were performed. 16S rRNA gene (V3V4) sequencing was used for metagenomic analysis. The severity of UC was classified based on the Truelove-Witts index. The assessment of microbial diversity showed significant differences between recipients and healthy donors. FMT contributed to long-term, significant clinical and biochemical improvement. Metagenomic analysis revealed an increase in the amount of Lactobacillaceaea, Micrococcaceae, Prevotellaceae, and TM7 phylumsp.oral clone EW055 during FMT, whereas Staphylococcaceae and Bacillaceae declined significantly. A positive increase in the proportion of the genera Bifidobacterium, Lactobacillus, Rothia, Streptococcus, and Veillonella and a decrease in Bacillus, Bacteroides, and Staphylococcus were observed based on the correlation between calprotectin and Bacillus and Staphylococcus; ferritin and Lactobacillus, Veillonella, and Bifidobacterium abundance was indicated. A positive change in the abundance of Firmicutes was observed during FMT and after 6 months. The application of multi-session FMT led to the restoration of recipients' microbiota and resulted in the remission of patients with active UC.

RevDate: 2020-08-06

Holmes A, Finger C, Morales-Scheihing D, et al (2020)


Translational research : the journal of laboratory and clinical medicine pii:S1931-5244(20)30180-8 [Epub ahead of print].

The gut microbiota is a complex ecosystem of bacteria, fungi, and viruses that acts as a critical regulator in microbial, metabolic, and immune responses in the host organism. Imbalances in the gut microbiota, termed "dysbiosis", often induce aberrant immune responses, which in turn disrupt the local and systemic homeostasis of the host. Emerging evidence has highlighted the importance of gut microbiota in intestinal diseases, and more recently, in age-related central nervous systems diseases, e.g., stroke and Alzheimer's disease. It is now generally recognized that gut microbiota significantly influences host behaviors and modulates the interaction between microbiota, gut, and brain, via the "microbiota-gut-brain axis". Several approaches have been utilized to reduce age-related dysbiosis in experimental models and in clinical studies. These include strategies to manipulate the microbiome via fecal microbiota transplantation, administration of prebiotics and probiotics, and dietary interventions. In this review, we explore both clinical and pre-clinical therapies for treating age-related dysbiosis.

RevDate: 2020-08-06

Bernardazzi C, Xu H, Tong H, et al (2020)

An indisputable role of NHE8 in mucosal protection.

American journal of physiology. Gastrointestinal and liver physiology [Epub ahead of print].

The loss of the intestinal Na+/H+ exchanger isoform 8 (NHE8) results in an ulcerative colitis-like condition with reduction of mucin production and dysbiosis, indicating that NHE8 plays an important role in intestinal mucosal protection. The aim of this study was to investigate the potential rebalance of the altered microbiota community of NHE8-deficient mice via fecal microbiota transplantation (FMT) and feeding probiotic VSL#3. We also aimed to stimulate mucin production by sodium butyrate administration via enema. Data from 16S rRNA sequencing showed that loss of NHE8 contributes to colonic microbial dysbiosis with reduction of butyrate-producing bacteria. FMT increased bacterial adhesion in the colon in NHE8KO mice. PAS stain and qPCR showed no changes in mucin production during FMT. In mice treated with probiotic VSL#3, a reduction of Lactobacillus and SFB in NHE8KO mouse colon was detected, and an increase in goblet cell theca were observed. In NHE8KO mice receiving sodium butyrate (NaB), 1mM NaB stimulated Muc2 expression without changing goblet cell theca, but 10mM NaB induced a significant reduction of goblet cell theca without altering Muc2 expression. Furthermore, 5mM and 10mM NaB treated HT29-MTX cells displayed increased apoptosis, while 0.5mM NaB stimulated Muc2 gene expression. These data showed that loss of NHE8 leads to dysbiosis with reduction of butyrate-producing bacteria, and FMT and VSL#3 failed to rebalance the microbiota in NHE8KO mice. Therefore, FMT, VSL#3, and NaB are not able to restore mucin production in the absence of NHE8 in the intestine.

RevDate: 2020-08-05

Mohammed A, Alghetaa H, Zhou J, et al (2020)

Protective Effects of Δ9-Tetrahydrocannabinol Against Enterotoxin-induced Acute Respiratory Distress Syndrome is Mediated by Modulation of Microbiota.

British journal of pharmacology [Epub ahead of print].

BACKGROUND: Staphylococcal enterotoxin-B (SEB) is one of the most potent bacterial superantigens that exerts profound toxic effects by inducing cytokine storm. When SEB is inhaled, it can cause Acute Respiratory Distress Syndrome (ARDS), which is often fatal and currently there are no effective treatment modalities.

EXPERIMENTAL APPROACH: We used mouse model of SEB-mediated ARDS to test the efficacy of Δ9-tetrahydrocannabinol (THC). These mice were monitored for lung inflammation, alterations in gut and lung microbiota and production of short-chain fatty acids (SCFA). Gene dysregulation of lung epithelial cells was studied by transcriptome arrays. Fecal microbiota transplantation (FMT) was performed to confirm the role of microbiota in suppressing ARDS.

KEY RESULTS: While SEB triggered ARDS and 100% mortality in mice, THC protected the mice from fatality effects. Pyrosequencing analysis revealed that THC caused significant and similar alterations in microbiota in the lungs and gut of mice exposed to SEB. THC significantly increased the abundance of beneficial bacterial species, Ruminococcus gnavus, but decreased pathogenic microbiota, Akkermansia muciniphila. FMT confirmed that THC-mediated reversal of microbial dysbiosis played crucial role in attenuation of SEB-mediated ARDS. THC treatment also led to increase in SCFA, of which propionic acid was found to inhibit the inflammatory response. Transcriptome array showed that THC up-regulated several genes like lysozyme-1&2, β-defensin-2, claudin, zonula-1, occludin-1, Mucin2 and Muc5b while downregulating β-defensin-1.

CONCLUSIONS: Current study demonstrates for the first time that THC attenuates SEB-mediated ARDS and toxicity by altering the microbiota in the lungs and the gut as well as promoting anti-microbial and anti-inflammatory pathways.

RevDate: 2020-08-05

Perillo F, Amoroso C, Strati F, et al (2020)

Gut Microbiota Manipulation as a Tool for Colorectal Cancer Management: Recent Advances in Its Use for Therapeutic Purposes.

International journal of molecular sciences, 21(15): pii:ijms21155389.

Colorectal cancer (CRC) is a multifaceted disease influenced by both environmental and genetic factors. A large body of literature has demonstrated the role of gut microbes in promoting inflammatory responses, creating a suitable microenvironment for the development of skewed interactions between the host and the gut microbiota and cancer initiation. Even if surgery is the primary therapeutic strategy, patients with advanced disease or cancer recurrence after surgery remain difficult to cure. Therefore, the gut microbiota has been proposed as a novel therapeutic target in light of recent promising data in which it seems to modulate the response to cancer immunotherapy. The use of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics, and fecal microbiota transplantation, is therefore considered to support current therapies in CRC management. In this review, we will discuss the importance of host-microbe interactions in CRC and how promoting homeostatic immune responses through microbe-targeted therapies may be useful in preventing/treating CRC development.

RevDate: 2020-08-04

Bajaj JS, Gavis EA, Fagan A, et al (2020)

A Randomized Clinical Trial of Fecal Microbiota Transplant for Alcohol Use Disorder.

Hepatology (Baltimore, Md.) [Epub ahead of print].

BACKGROUND & AIMS: Alcohol use disorder (AUD) is associated with microbial alterations that worsen with cirrhosis. Fecal microbiota transplant (FMT) could be a promising approach.

APPROACH & RESULTS: In this phase 1, double-blind, randomized clinical trial, AUD-related cirrhosis patients with problem drinking (AUDIT-10>8) were randomized 1:1 into receiving one placebo or FMT enema from a donor enriched in Lachnospiraceae and Ruminococcaceae. 6-month safety was the primary outcome. Alcohol craving questionnaire, alcohol consumption (urinary ethylglucuronide/creatinine, Etg), quality of life (QOL), cognition, serum IL-6 and lipopolysaccharide-binding protein (LBP), plasma/stool short-chain fatty acids (SCFA) and stool microbiota were tested at baseline and day 15. A 6-month follow-up with serious adverse events (SAE) analysis was performed. 20 patients with AUD-related cirrhosis [65±6.4 years, all men, MELD 8.9±2.7] with similar demographics, cirrhosis and AUD severity were included. Craving reduced significantly in 90% of FMT versus 30% in placebo at day15(p=0.02) with lower urinary Etg (p=0.03), improved cognition and psychosocial QOL. There was reduction in serum IL-6 and LBP and increased butyrate/isobutyrate compared to baseline in FMT but not placebo. Microbial diversity increased with higher Ruminococcaceae and other SCFA producing taxa post-FMT but not placebo, which were linked with SCFA levels. At 6 months, patients with any SAEs (8 vs 2, p=0.02), AUD-related SAEs (7 vs 1, p=0.02) and SAEs/patient [median(IQR),1.5(1.25) vs 0(0.25) in FMT,p=0.02] were higher in placebo versus FMT.

CONCLUSIONS: This phase 1 trial shows that FMT is safe and associated with short-term reduction in alcohol craving and consumption with favorable microbial changes versus placebo in patients with alcohol-related cirrhosis with alcohol misuse. There was also a reduction in AUD-related events over 6 months in patients assigned to FMT.


RJR Experience and Expertise


Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.


Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.


Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.


Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.


While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.


Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.


Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.


Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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E-mail: RJR8222@gmail.com

Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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RJR Picks from Around the Web (updated 11 MAY 2018 )