For Fecal Microbiota Transplantation Research Articles

Clostridioides difficile infection promotes gastrointestinal dysfunction in human and mice post-acute phase of the disease

ObjectivesIn the US, Clostridioides difficile (C. difficile) infection (CDI) is the 8th leading cause for hospital readmission and 7th for mortality among all gastrointestinal (GI) disorders. Here, we investigated GI dysfunction post-CDI in human and mice post-acute infection. Materials and methodsFrom March 2020 to July 2021, we reviewed the clinical records of 67 patients referred to the UVA Complicated C. difficile clinic for fecal microbiota transplantation (FMT) eligibility. In vivo, C57BL/6 mice were infected with C. difficile and clinical scores were determined daily. Stool samples from mice were collected to measure the shedding of C. difficile and myeloperoxidase (MPO) levels. On day 21 post-infection, Evans's blue and FITC-70kDa method were performed to evaluate GI motility in mice. ResultsOf the 67 patients evaluated at the C. difficile clinic, 40 patients (59.7%) were confirmed to have CDI, and 22 patients (32.8%) with post-CDI IBS (diarrhea-type, constipation-type, and mixed-type). In infected mice, levels of MPO in stools and clinical score were higher on day 3. On day 21, mice have recovered from body weight loss induced by CDI, and fecal MPO was undetectable. The total GI transit time (TGITT) and FITC-70kDa levels on proximal colon were increased in infected mice (p = 0.002), suggesting a constipation phenotype post-acute phase of CDI. A positive correlation on intestinal inflammation on day 3 and TGITT on day 21 was observed. ConclusionIn conclusion, post-infection intestinal dysfunction occurs in humans and mice post-CDI. Importantly, we have validated in the mouse model that CDI causes abnormal GI transit in the recovery phase of the disease, indicating the potential utility of the model in exploring the underlying mechanisms of post-infectious IBS in humans.

Saccharomyces boulardii alleviates allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner

BackgroundAllergic asthma is a heterogeneous disease and new strategies are needed to prevent or treat this disease. Studies have shown that probiotic interventions are effective in preventing asthma. Here, we investigated the impact of Saccharomyces boulardii (S. boulardii) on ovalbumin (OVA)-induced allergic asthma in mice, as well as the underlying mechanisms. MethodsFirst, we constructed a mouse asthma model using OVA and given S. boulardii intervention. Next, we measured N6-methyladenosine (m6A) levels in lung injury tissues. 16 s rRNA was employed to identify different gut microbiota in fecal samples. The analysis of differential metabolites in feces was performed by non-targeted metabolomics. Pearson correlation coefficient was utilized to analyze correlation between gut microbiota, metabolites and methyltransferase-like 3 (METTL3). Finally, we collected mouse feces treated by OVA and S. boulardii intervention for fecal microbiota transplantation (FMT) and interfered with METTL3. ResultsS. boulardii improved inflammation and oxidative stress and alleviated lung damage in asthmatic mice. In addition, S. boulardii regulated m6A modification levels in asthmatic mice. 16 s rRNA sequencing showed that S. boulardii remodeled gut microbiota homeostasis in asthmatic mice. Non-targeted metabolomics analysis showed S. boulardii restored metabolic homeostasis in asthmatic mice. There was a correlation between gut microbiota, differential metabolites, and METTL3 analyzed by Pearson correlation. Additionally, through FMT and interference of METTL3, we found that gut microbiota mediated the up-regulation of METTL3 by S. boulardii improved inflammation and oxidative stress in asthmatic mice, and alleviated lung injury. ConclusionsS. boulardii alleviated allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner.

Horizontal gene transfer after faecal microbiota transplantation in adolescents with obesity

BackgroundHorizontal gene transfer (HGT) describes the transmission of DNA outside of direct ancestral lineages. The process is best characterised within the bacterial kingdom and can enable the acquisition of genetic traits that support bacterial adaptation to novel niches. The adaptation of bacteria to novel niches has particular relevance for faecal microbiota transplantation (FMT), a therapeutic procedure which aims to resolve gut-related health conditions of individuals, through transplanted gut microbiota from healthy donors.ResultsThree hundred eighty-one stool metagenomic samples from a placebo-controlled FMT trial for obese adolescents (the Gut Bugs Trial) were analysed for HGT, using two complementary methodologies. First, all putative HGT events, including historical HGT signatures, were quantified using the bioinformatics application WAAFLE. Second, metagenomic assembly and gene clustering were used to assess and quantify donor-specific genes transferred to recipients following the intervention. Both methodologies found no difference between the level of putative HGT events in the gut microbiomes of FMT and placebo recipients, post-intervention. HGT events facilitated by engrafted donor species in the FMT recipient gut at 6 weeks post-intervention were identified and characterised. Bacterial strains contributing to this subset of HGT events predominantly belonged to the phylum Bacteroidetes. Engraftment-dependent horizontally transferred genes were retained within recipient microbiomes at 12 and 26 weeks post-intervention.ConclusionOur study suggests that novel microorganisms introduced into the recipient gut following FMT have no impact on the basal rate of HGT within the human gut microbiome. Analyses of further FMT studies are required to assess the generalisability of this conclusion across different FMT study designs and for the treatment of different gut-related conditions.2UrCUamaK1-EwS1Lh8ra1uVideo

A RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF PSYLLIUM FIBER AND FECAL MICROBIOTA TRANSPLANTATION FOR MILD TO MODERATE ULCERATIVE COLITIS

Abstract BACKGROUND Emerging clinical data shows potential for fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), though factors affecting clinical response remain poorly defined. Pre-clinical data suggest the role of dietary fiber in enhancing microbial metabolites to mitigate colitis severity. This study aimed to evaluate the role of the prebiotic psyllium in improving the clinical outcomes of FMT for mild to moderate UC, with the long-term goal of enhancing FMT as a therapeutic strategy for UC. METHODS In a randomized, placebo-controlled clinical trial, 32 participants were screened, and 27 adults with mild to moderate UC were enrolled. Baseline fiber intake was assessed through a food frequency questionnaire. Subjects were randomly assigned to receive FMT alone, FMT with daily fiber (10g of psyllium), or a placebo with or without fiber. The primary endpoint was clinical response by Mayo score at week 8. Secondary endpoints included clinical response by partial Mayo (pMayo) score, endoscopic sub-score, and clinical remission. At week 8, participants underwent crossover treatment with clinical evaluation at week 12. The study ended early due to the manufacturer discontinuing fecal microbiota preparation supply. RESULTS Analysis of primary and secondary endpoints in "FMT alone" and "FMT with fiber" groups revealed no statistically significant differences in clinical response (55.56% alone, N=9 vs. 22.22% fiber, N=9, p=0.1686). Participants with low and high dietary fiber consumption had similar response rates, regardless of supplemental fiber. Consequently, we combined the "FMT" and "no FMT" groups, which showed a significantly higher proportion of subjects achieving clinical response in the FMT group as defined by the partial Mayo score (50.00% FMT group (N=18) and 11.1% in the no FMT group (N=9), p=0.0485). A similar trend was observed for clinical response as defined by the total Mayo score and endoscopic sub-score, where the FMT group outperformed the placebo (38.89% FMT, N=18, vs. 11.11% placebo, N=9, p=0.1362). Among the 9 subjects who received FMT at week 0 and exhibited clinical response defined by pMayo, 77.8% (n=7) maintained their response at week 12. Additionally, 2 patients who initially had no response at week 8 achieved a clinical response by week 12. CONCLUSION The results demonstrate a robust effect of single-dose FMT via colonoscopy in a mild to moderate UC cohort. Given the low cohort size, our results lack the statistical power to reveal the clinical impact of fiber supplementation in FMT. Notably, a substantial proportion of initially responsive FMT recipients maintained their clinical response at week 12, indicating the potential for sustained benefits. Microbiome and metabolomic analyses are currently underway to assess the functional impact of dietary fiber in shaping the effectiveness of FMT for UC.

Gut Microecology May Be Involved in the Pathogenesis of Hashimoto Thyroiditis by Reducing Production of Hydrogen Sulfide.

Hashimoto thyroiditis (HT) is related to intestinal microbiota alteration, but the causal relationship remains unclear. Hydrogen sulfide (H2S) is a microbiota-derived metabolite. We speculated that abnormal intestinal microbiota might limit H2S production capacity, promoting HT pathogenesis. This work aimed to illustrate that the intestinal microbiota plays important roles in HT pathogenesis via microbiota-derived H2S levels. We collected feces from HT patients and healthy donors for fecal microbiota transplantation (FMT). Thirty-six female CBA/J mice were randomly assigned to 4 groups: experimental autoimmune thyroiditis (EAT) group, EAT + Healthy group, EAT + HT group, and EAT + HT + H2S group. 16S ribosomal RNA sequencing was performed to examine gut microbiota alterations and the H2S production pathway. Serum TgAb and H2S levels were assayed by enzyme-linked immunosorbent assay and H2S-selective sensors, respectively. T-cell subpopulations in the spleen were detected by flow cytometry. The gut microbiota was different after FMT among the EAT, EAT + Healthy, and EAT + HT groups. The thyroiditis score assessed by hematoxylin and eosin staining was higher in the EAT + HT group than that in the EAT and EAT + HT + H2S groups. Helper T (Th1) and Th17 cell differentiation ratios were increased in the EAT + HT group compared to the other 3 groups. Serum H2S levels were decreased and the dissimilatory sulfate reduction (DSR) pathway was attenuated in the EAT + HT group compared to the EAT + Healthy group. H2S alleviated thyroiditis severity and related immune disorders, which were aggravated by the FMT from HT patients. The attenuated DSR pathway in the gut microbiota from HT patients might be involved in thyroiditis pathogenesis.

Empagliflozin ameliorates atherosclerosis via regulating the intestinal flora

Background and aimsSodium-glucose cotransporter 2 inhibitor (SGLT2i) has been reported to attenuate atherosclerosis. Further, it has been suggested that intestinal flora influences atherosclerosis progression. Herein we aimed to investigate whether SGLT2i can alleviate atherosclerosis through intestinal flora. MethodsSix-week-old male ApoE−/− mice fed a high-fat diet were gavaged either empagliflozin (SGLT2i group, n = 9) or saline (Ctrl group, n = 6) for 12 weeks. Feces were collected from both groups at the end of the experiment for fecal microbiota transplantation (FMT). Another 12 six-week-old male ApoE−/− mice were fed a high-fat diet and received FMT with feces either from SGLT2i (FMT-SGLT2i group, n = 6) or from Ctrl (FMT-Ctrl group, n = 6) groups. Blood, tissue, and fecal samples were collected for subsequent analyses. ResultsIn comparison with Ctrl group, atherosclerosis was less severe in the SGLT2i group (p < 0.0001), and the richness of probiotic, such as f_Coriobacteriaceae, f_S24-7, f_Lachnospiraceae, and f_Adlercreutzia, was higher in feces. Besides, empagliflozin resulted in a significant reduction in the inflammatory response and altered intestinal flora metabolism. Interestingly, compared with FMT-Ctrl, FMT-SGLT2i also showed a reduction in atherosclerosis and systemic inflammatory response, as well as changes in the component of intestinal flora and pertinent metabolites similar to SGLT2i group. ConclusionsEmpagliflozin seems to mitigate atherosclerosis partly by regulating intestinal microbiota, and this anti-atherosclerotic effect can be transferred through intestinal flora transplantation.

Colonic Transendoscopic Enteral Tubing Is a New Pathway to Microbial Therapy, Colonic Drainage, and Host-Microbiota Interaction Research.

The limitation of traditional delivery methods for fecal microbiota transplantation (FMT) gave birth to colonic transendoscopic enteral tubing (TET) to address the requirement of frequent FMTs. Colonic TET as a novel endoscopic intervention has received increasing attention in practice since 2015 in China. Emerging studies from multiple centers indicate that colonic TET is a promising, safe, and practical delivery method for microbial therapy and administering medication with high patient satisfaction. Intriguingly, colonic TET has been used to rescue endoscopy-related perforations by draining colonic air and fluid through the TET tube. Recent research based on collecting ileocecal samples through a TET tube has contributed to demonstrating community dynamics in the intestine, and it is expected to be a novel delivery of proof-of-concept in host-microbiota interactions and pharmacological research. The present article aims to review the concept and techniques of TET and to explore microbial therapy, colonic drainage, and microbial research based on colonic TET.

The biodiversity dose-response curve translates theory and practice from ecological restoration into research and clinical priorities for fecal microbiota transplantation.

Discoveries of the beneficial effects of gut microbiota have led to efforts to cultivate healthy gut flora to treat disease. The field of ecological restoration specializes on reestablishment of desired species in disturbed ecosystems, which suggests that it may be applicable to microbe restoration in the gut. Common language can lower barriers to interdisciplinary insights. Here I introduce the concept of a "biodiversity dose-response curve" to translate ideas from ecological restoration into research and clinical priorities for fecal microbiota transplantation (FMT). The curve is based on a relationship between ecosystem structure, measured as species diversity found in both nature and gut ecosystems, and ecosystem function, which are the measurable parameters that contribute to ecosystem and human health. I explain why the biodiversity dose-response curve may follow the ecological model of a "rivet-redundancy" relationship, in which the overlap of multiple organisms' functional contributions to a system mask the impact of initial losses of diversity, but, at a certain level of loss, function declines sharply. (Imagine an airplane that flies with a few rivets missing, until it loses enough to fail.) The biodiversity dose-response curve indicates that seemingly healthy individuals may be suboptimal donors; it highlights the importance of recipient diet in FMT success; and it introduces the concept of "passive restoration" into the field of gut medicine. These insights, which may help to explain low success rates of FMT in the treatment of non-Clostridium dificile conditions, are less apparent in the absence of interdisciplinary integration.

S2118 Recurrent Clostridioides difficile Infections Caused by Topical Clindamycin

Introduction: While there are many risk factors for Clostridioides difficile infection (CDI), they are often associated with the use of systemic antibiotics. However, it is possible to acquire this infection after the use of topical antibiotics due to low levels of systemic absorption. Here we describe a case of recurrent CDI after using topical clindamycin. Case Description/Methods: A 56-year-old female with past medical history of acne vulgaris presented to clinic as a referral for recurrent C. difficile infection. The patient began experiencing frequent bouts of diarrhea associated with nausea, vomiting, and abdominal pain. She denied any recent travel, changes in her diet, or use of systemic antibiotics. However, she did report the use of topical clindamycin for facial acne. Stool testing was positive for C. difficile. The decision was made to treat with oral vancomycin for 10 days. However, the patient experienced recurrence of symptoms shortly after finishing treatment. She was eventually treated with multiple courses of pulse-tapered vancomycin. Eventually, the patient was referred for evaluation for fecal microbiota transplantation (FMT). She is now being evaluated for fecal microbiota transplant for recurrent CDI. Discussion: The association between systemic antibiotics and CDI are widely known. However, topical antibiotics are generally not considered to be a risk for CDI. In our case, we have described a patient who developed recurrent CDI in the absence of risk factors aside from the use of topical clindamycin to treat her acne. There have been studies showing that topical clindamycin still has (up to 4-5%) systemic absorption,1 and this may have contributed to this patient’s recurrent CDI. While cases of CDI following the use of topical antibiotics have been reported, literature regarding recurrent infections due to topical antibiotics remain scarce. As in the case of our patient, the absence of other risk factors raises the concern of how much topical antibiotics can be systemically absorbed, and how they may affect the gastrointestinal microbiota. Overall, topical antibiotics are considered relatively safe due to their limited systemic absorption. However, there remains a risk of developing CDI with some of these agents, and alternatives to topical clindamycin should be strongly considered in people at risk for CDI.

Evaluation of an Antibiotic Cocktail for Fecal Microbiota Transplantation in Mouse.

ObjectiveThis study aimed to evaluate the effect of an antibiotic cocktail on gut microbiota and provide a reference for establishing an available mouse model for fecal microbiota transplantation (FMT) of specific microbes.DesignC57BL/6J mice (n = 24) had free access to an antibiotic cocktail containing vancomycin (0.5 g/L), ampicillin (1 g/L), neomycin (1 g/L), and metronidazole (1 g/L) in drinking water for 3 weeks. Fecal microbiota was characterized by 16S rDNA gene sequencing at the beginning, 1st week, and 3rd week, respectively. The mice were then treated with fecal microbiota from normal mice for 1 week to verify the efficiency of FMT.ResultsThe diversity of microbiota including chao1, observed species, phylogenetic diversity (PD) whole tree, and Shannon index were decreased significantly (P < 0.05) after being treated with the antibiotic cocktail for 1 or 3 weeks. The relative abundance of Bacteroidetes, Actinobacteria, and Verrucomicrobia was decreased by 99.94, 92.09, and 100%, respectively, while Firmicutes dominated the microbiota at the phylum level after 3 weeks of treatment. Meanwhile, Lactococcus, a genus belonging to the phylum of Firmicutes dominated the microbiota at the genus level with a relative abundance of 80.63%. Further FMT experiment indicated that the fecal microbiota from the receptor mice had a similar composition to the donor mice after 1 week.ConclusionThe antibiotic cocktail containing vancomycin, ampicillin, neomycin, and metronidazole eliminates microbes belonging to Bacteroidetes, Actinobacteria, and Verrucomicrobia, which can be recovered by FMT in mice.

β-Sitosterol Ameliorates Endometrium Receptivity in PCOS-Like Mice: The Mediation of Gut Microbiota.

Background: Polycystic ovary syndrome (PCOS), one of the most common endocrine diseases in women of childbearing age, has been found to be accompanied by changes in the gut microbiota. The Bu Shen Yang Xue formula (BSYXF) is a traditional Chinese medicine widely used for the treatment of PCOS. This study aimed to investigate whether the protective effects of β-sitosterol, the main active ingredient of BSYXF, on PCOS was mediated by regulating gut microbiota.Methods: The presence of β-sitosterol in BSYXF was detected by liquid chromatography-mass spectrometry. The PCOS-like mouse model was induced by dehydroepiandrosterone. The fecal supernatant of β-sitosterol-treated mice was prepared for fecal microbiota transplantation (FMT). Body weight and wet weight of the uterus and ovary of the mice were recorded for organ index calculation. Hematoxylin and eosin stain was used to assess the endometrial morphology and microenvironment changes. Expression of endometrial receptivity markers cyclooxygenase-2 (COX-2), Integrin ανβ3, leukemia inhibitory factor (LIF), and homeobox A10 (HOXA10) in the endometrium were determined by immunohistochemistry and western blot analysis. Enzyme-linked immunosorbent assay was employed to detect the expression of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), and testosterone (T) in the serum. The diversity of gut microbiota was examined by 16S rDNA gene sequencing.Results: With the treatment of β-sitosterol and β-sitosterol-FMT, the uterine index of PCOS-like mice increased, the ovarian index decreased, levels of COX-2, LH and T decreased, and levels of Integrin ανβ3, LIF, HOXA10, FSH, and P increased. Under β-sitosterol treatment, the structure of the gut microbiota in PCOS-like mice was also changed.Conclusion: β-sitosterol regulates the endometrial receptivity of PCOS and harmonizes the sex hormone balance, which may be related to the changes in the structure and composition of gut microbiota, thus affecting the pathological process of PCOS.

Multi-modality detection of SARS-CoV-2 in faecal donor samples for transplantation and in asymptomatic emergency surgical admissions.

Background: Faecal transplantation is an evidence-based treatment for Clostridioides difficile. Patients infected with SARS-CoV-2 have been shown to shed the virus in stool for up to 33 days, well beyond the average clearance time for upper respiratory tract shedding. We carried out an analytical and clinical validation of reverse-transcriptase quantitative (RT-qPCR) as well as LAMP, LamPORE and droplet digital PCR in the detection of SARS-CoV-2 RNA in stool from donated samples for faecal microbiota transplantation (FMT), spiked samples and asymptomatic inpatients in an acute surgical unit. Methods: Killed SARS-CoV-2 viral lysate and extracted RNA was spiked into donor stool & FMT and a linear dilution series from 10 -1 to 10 -5 and tested via RT-qPCR, LAMP, LamPORE and ddPCR against SARS-CoV-2. Patients admitted to the critical care unit with symptomatic SARS-CoV-2 and sequential asymptomatic patients from acute presentation to an acute surgical unit were also tested. Results: In a linear dilution series, detection of the lowest dilution series was found to be 8 copies per microlitre of sample. Spiked lysate samples down to 10 -2 dilution were detected in FMT samples using RTQPCR, LamPORE and ddPCR and down to 10 -1 with LAMP. In symptomatic patients 5/12 had detectable SARS-CoV-2 in stool via RT-qPCR and 6/12 via LamPORE, and in 1/97 asymptomatic patients via RT-qPCR. Conclusion: RT-qPCR can be detected in FMT donor samples using RT-qPCR, LamPORE and ddPCR to low levels using validated pathways. As previously demonstrated, nearly half of symptomatic and less than one percent of asymptomatic patients had detectable SARS-CoV-2 in stool.

Alternative Diagnoses in Pediatric Fecal Microbiota Transplant Referral Patients.

The incidence of Clostridioides difficile infection (CDI) has been increasing in the United States. About 10-20% recur after initial treatment, with increasing recurrence following subsequent treatment courses. This sequence can lead to recurrent CDI (rCDI), refractory to conventional therapeutics resulting in the most common indication for fecal microbiota transplantation (FMT). FMT is the most effective microbial therapeutic to date and can cure rCDI in 80-90% of cases. There is growing concern, however, for pathogen transmission through FMT, underscoring the importance of careful recipient selection. In adults referred for FMT with a tentative diagnosis of rCDI, alternative diagnoses were recognized in 25% of patients, but such observation in children is lacking. In this single-center retrospective study, alternative diagnoses (eg, constipation/overflow diarrhea, inflammatory bowel disease) were found in 13 (22.4%) of 58 children who were referred for FMT evaluation for rCDI. Of the patients who were diagnosed with rCDI, 16 (27.6%) did not require FMT.

Determinants of community members' willingness to donate stool for faecal microbiota transplantation.

Universal stool banks rely on, but face difficulties recruiting, community volunteers to donate stool for faecal microbiota transplantation (FMT) to effectively treat recurrent Clostridioides difficile. This study sought to identify determinants of community members' willingness to donate stool to guide donor recruitment. 397 Australian residents (52% male, 47% 21-30 years, 63% university educated) completed a survey to gauge willingness to donate stool, bowel habits, information needs, attitudes, barriers, and motives for donation. Most reported regular bowel movements (BMs; 90%), morning BMs (63%), BMs ≤5 minutes duration (67%), and some discomfort doing BMs in public restrooms (69%). Less than half were willing to donate stool in-centre (45% willing) or at home (48%). Important information needs identified by >80% were convenience and travel requirements associated with donation. Main barriers were logistics, capabilities to donate, disgust (e.g., donation process), and discomfort (e.g., privacy). The main motivator was altruism, with compensation secondary. Linear regression models identified less discomfort doing BMs in public restrooms (β = -0.15), understanding benefits to patients (β = 0.15), placing less importance on understanding the donation process (β = -0.13), and positive attitudes (β = 0.56) as determinants of willingness to donate in-centre. Understanding benefits to self (β = 0.11) and patients (β = 0.24), placing less importance on understanding the donation purpose (β = -0.19), and positive attitudes (β = 0.50) determined willingness to donate at home. Stool banks should consider donor's bowel habits, comfort donating in-centre, and information needs early in recruitment; and implement flexible logistics for potential donors who face time constraints and limited access to stool banks.

Eligible blood donors' decisions about donating stool for fecal microbiota transplantation: Does ambivalence play a role?

This cross-sectional study surveyed Australian residents aged 18 years or more who believed themselves eligible to donate blood and met broad criteria for prescreening as a stool donor (eg, healthy, not taking medication). Survey questions assessed attitude, norms, self-efficacy, motives, disgust, ambivalence, and intentions to donate stool. A total of 382 eligible blood donors aged not more than 50 years (mean, 28.71 years; 48% female, 62% "healthy" body mass index) participated. Six percent indicated no ambivalence about donating stool. In regression, significant determinants of ambivalence were less awareness of FMT, lower self-efficacy, motivated by ensuring that stool is available for loved ones, and more disgust about stool donation. Higher ambivalence contributed to decreased donation intention. Self-efficacy and disgust differentiated participants with moderate ambivalence, a group likely responsive to intervention, from those with low or high ambivalence. Ambivalence about donating stool was common among eligible blood donors. BCAs should raise awareness about stool donation and FMT before requesting donation. BCAs may increase cost savings and donor retention by giving clear guidance about donation requirements and implementing processes that build confidence. Early screening of potential donors for ambivalence and disgust will enable BCAs to provide decision support.

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

BACKGROUNDTransendoscopic 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.AIMTo explore the recognition and attitudes of FMT through TET in patients with inflammatory bowel disease (IBD).METHODSAn 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.RESULTSA 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.CONCLUSIONPatients’ 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.

Challenges of Screening Prospective Stool Donors for Fecal Microbiota Transplantation.

Despite high efficacy rates, significant costs and logistical challenges associated with procuring stool from healthy donors for fecal microbiota transplantation (FMT) have presented barriers to broader institutional adoption and limited the availability of this life-saving treatment. Published outcomes for donor screening programs report donor deferral rates between 90% and 96%. Due to the paucity of FMT donor screening data, a secondary analysis on a cohort of previously screened donors (n = 7,968) was conducted to provide a synopsis of the observed trends and rationales for prospective stool donor deferrals. Upon completion of the evaluation, 1.7% of prospective donors (n = 134) qualified for stool donation. Over 50% of donors who completed the online pre-screen were deferred, primarily for a body mass index of 30 kg/m2 or greater (n = 1,516, 37.0%), logistics (n = 841, 20.5%), and travel history (n = 638, 15.5%). Despite pre-screening, 569 donors (72.8%) who completed the in-person clinical assessment were ultimately deferred due primarily to potentially microbiome-mediated diseases (n = 187, 32.9%). A notably small portion of donors (n = 46, 25.6%) were deferred during the laboratory assessment process suggesting the clinical assessment was effective at deferring donors at higher risk for transmissible diseases. Donors lost to follow-up throughout the screening process presented a significant challenge and contributed to a notable (n = 3,117; 39.1%) portion of donor attrition. Findings were used to support recommendations for improving prospective stool donor screening programs and to provide suggestions for future research.

Changes in the gut microbiota caused by ASBTi suppress intrahepatic steatosis and inflammation in a mouse model of non-alcoholic fatty liver disease (NAFLD)

Abstract Although the estimated prevalence of NAFLD is approximately 25%, an effective treatment has not been established. Recently, gut microbiota has been shown to affect the pathogenesis of NAFLD. In this study, the protective effect of Apical Sodium-dependent Bile acid Transporter inhibitor (ASBTi) against NAFLD was investigated in mice fed a high-fat diet for 12 weeks (HFD mice) via changing their gut microbiota. ASBTi mice were mice treated with ASBTi (2.5 μmol/kg/day) during HFD feeding. For fecal microbiota transplantation (FMT), stools were collected from HFD mice and ASBTi mice. Fecal materials obtained from HFD mice and ASBTi mice were transplanted to normal mice, fed HFD for 12 weeks, and designated as HFD-FMT mice and ASBTi-FMT mice, respectively. Microbiota in these groups of mice were analyzed by 16S rRNA gene sequencing. The degrees of hepatic steatosis and inflammation in these mice were determined pathologically. The shannon index of the microbiota from ASBTi mice (3.31±0.19) and ASBTi-FMT mice (3.29±0.18) was significantly high as compared to that from HFD mice (2.90±0.19) and HFD-FMT mice (2.89±0.16). Steatosis and inflammation in the liver of HFD mice and HFD-FMT mice were shown to be pathologically severe and NAFLD Activity Score (NAS) was 7.67±0.58 in HFD mice and 5.67±2.08 in HFD-FMT mice. However, those in the liver of ASBTi mice and ASBTi-FMT mice were improved and NAS was reduced in ASBTi mice (1.67±0.58) and in ASBTi-FMT mice (2.67±0.58). These results suggest that changes in the gut microbiota caused by ASBTi suppress intrahepatic steatosis and inflammation in NAFLD mice. Elobixibat can be expected to prevent fatty liver.

Therapies to modulate gut microbiota: Past, present and future.

The human gut microbiota comprises of a complex and diverse array of microorganisms, and over the years the interaction between human diseases and the gut microbiota has become a subject of growing interest. Disturbed microbial milieu in the gastrointestinal tract is central to the pathogenesis of several diseases including antibiotic-associated diarrhea and Clostridioides difficile infection (CDI). Manipulation of this microbial milieu to restore balance by microbial replacement therapies has proven to be a safe and effective treatment for recurrent CDI. There is considerable heterogeneity in various aspects of stool processing and administration for fecal microbiota transplantation (FMT) across different centers globally, and standardized microbioal replacement therapies offer an attractive alternative. The adverse effects associated with FMT are usually mild. However, there is paucity of data on long term safety of FMT and there is a need for further studies in this regard. With our increasing understanding of the host-microbiome interaction, there is immense potential for microbial replacement therapies to emerge as a treatment option for several diseases. The role of microbioal replacement therapies in diseases other than CDI is being extensively studied in ongoing clinical trials and it may be a potential treatment option for inflammatory bowel disease, irritable bowel syndrome, obesity, multidrug resistant infections, and neuropsychiatric illnesses. Fecal microbiota transplantation for non-CDI disease states should currently be limited only to research settings.

Harnessing the microbiota for therapeutic purposes.

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