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Disentangle beneficial effects of strain engraftment after fecal microbiota transplantation in subjects with MetSyn.

ABSTRACT: Fecal Microbiota Transplantation (FMT) has emerged as a potential modality for mitigating microbiome-associated diseases. Despite this potential, the precise causal pathways by which specific gut microbiota strains induce remission remain inadequately elucidated. In this study, we aimed to discern the impact of engraftment of donor-infused strains on alterations in plasma metabolites, subsequently contributing to the amelioration of clinical parameters involved in subjects with metabolic syndrome (MetSyn) receiving an FMT. We observed that a higher fraction of donor strains engrafted in the recipient is correlated to a reduction in diastolic blood pressure and found specific strain associations through canonical correlation analysis. Integrating the metabolomics profile shows that engraftment of Collinsella aerofaciens and Fusocatenibacter saccharovorans was related to a reduction in 2-oxoarginine in plasma, which was subsequently correlated to a reduction in diastolic blood pressure. In conclusion, we applied a novel framework to elucidate on the complex and heterogenous FMT intervention, establishing a connection between engrafted microbiota and clinical outcome parameters. Our findings underscore the potential therapeutic efficacy of FMT in ameliorating MetSyn, demonstrating a potential contribution of microbial strain engraftment to the improvement of MetSyn via modulation of circulating metabolites.

SUBMITTER: van der Vossen EWJ

PROVIDER: S-EPMC11340759 | biostudies-literature | 2024 Jan-Dec

REPOSITORIES: biostudies-literature

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Disentangle beneficial effects of strain engraftment after fecal microbiota transplantation in subjects with MetSyn.

van der Vossen Eduard W J EWJ Davids Mark M Voermans Bas B Wortelboer Koen K Hartstra Annick V AV Koopen Annefleur M AM de Groot Pieter P Levin Evgeni E Nieuwdorp Max M

Gut microbes 20240101 1

Fecal Microbiota Transplantation (FMT) has emerged as a potential modality for mitigating microbiome-associated diseases. Despite this potential, the precise causal pathways by which specific gut microbiota strains induce remission remain inadequately elucidated. In this study, we aimed to discern the impact of engraftment of donor-infused strains on alterations in plasma metabolites, subsequently contributing to the amelioration of clinical parameters involved in subjects with metabolic syndrom ...[more]

PMID: 39163526

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Project description:BackgroundDonor selection is an important factor influencing the engraftment and efficacy of fecal microbiota transplantation (FMT) for complex conditions associated with microbial dysbiosis. However, the degree, variation, and stability of strain engraftment have not yet been assessed in the context of multiple donors.MethodsWe conducted a double-blinded randomized control trial of FMT in 87 adolescents with obesity. Participants were randomized to receive multi-donor FMT (capsules containing the fecal microbiota of four sex-matched lean donors) or placebo (saline capsules). Following a bowel cleanse, participants ingested a total of 28 capsules over two consecutive days. Capsules from individual donors and participant stool samples collected at baseline, 6, 12, and 26 weeks post-treatment were analyzed by shotgun metagenomic sequencing allowing us to track bacterial strain engraftment and its functional implications on recipients' gut microbiomes.ResultsMulti-donor FMT sustainably altered the structure and the function of the gut microbiome. In what was effectively a microbiome competition experiment, we discovered that two donor microbiomes (one female, one male) dominated strain engraftment and were characterized by high microbial diversity and a high Prevotella to Bacteroides (P/B) ratio. Engrafted strains led to enterotype-level shifts in community composition and provided genes that altered the metabolic potential of the community. Despite our attempts to standardize FMT dose and origin, FMT recipients varied widely in their engraftment of donor strains.ConclusionOur study provides evidence for the existence of FMT super-donors whose microbiomes are highly effective at engrafting in the recipient gut. Dominant engrafting male and female donor microbiomes harbored diverse microbial species and genes and were characterized by a high P/B ratio. Yet, the high variability of strain engraftment among FMT recipients suggests the host environment also plays a critical role in mediating FMT receptivity.Trial registrationThe Gut Bugs trial was registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12615001351505 ).Trial protocolThe trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174 . Video Abstract.

Project description:Bacterial communities from subjects treated for recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT), using either heterologous donor stool samples or autologous stool samples, were characterized by Illumina next-generation sequencing. As previously reported, the success of heterologous FMT (90%) was superior to that of autologous FMT (43%) (P = 0.019), and post-FMT intestinal bacterial communities differed significantly between treatment arms (P < 0.001). Subjects cured by autologous FMT typically had greater abundances of the Clostridium XIVa clade and Holdemania bacteria prior to treatment, and the relative abundances of these groups increased significantly after FMT compared to heterologous FMT and pre-FMT samples. The typical shift to post-FMT, donor-like assemblages, featuring high relative abundances of genera within the Bacteroidetes and Firmicutes phyla, was not observed in the autologous FMT subjects. Autologous FMT patient bacterial communities were significantly different in composition than those for heterologous FMT patients and donors (P < 0.001). The SourceTracker program, which employs a Bayesian algorithm to determine source contributions to sink communities, showed that patients initially treated by heterologous FMT had significantly higher percentages of engraftment (i.e., similarity to donor communities, mean value of 74%) compared to those who suffered recurrence following autologous FMT (1%) (P ≤ 0.013). The findings of this study suggest that complete donor engraftment may be not necessary if functionally critical taxa are present in subjects following antibiotic therapy. This study provides a detailed characterization of fecal bacterial communities in subjects who participated in a previously published randomized clinical trial to treat recurrent C. difficile infection (rCDI). Bacterial communities were characterized to determine differences between subjects who received fecal bacteria either from healthy donor stool samples or their own stool samples as "placebo" in order to determine which groups of bacteria were most important in achieving a cure. The results of this study suggested that bacteria associated with secondary bile acid metabolism could potentially provide resistance to infection and that complete transfer of healthy donor microorganisms was not necessary to resolve CDI following unsuccessful antibiotic treatment.

Project description:Fecal microbiota transplantation (FMT) has become a common rescue therapy for recurrent Clostridium difficile infection, and encapsulated delivery (cFMT) of healthy donor microbiota shows similar clinical efficacy as more traditional routes of administration. In this study, we characterized long-term patterns of bacterial engraftment in a cohort of 18 patients, who received capsules from one of three donors, up to 409 days post-FMT. Bacterial communities were characterized using Illumina sequencing of the V5-V6 hypervariable regions of the 16S rRNA gene, and engraftment was determined by using the Bayesian algorithm SourceTracker. All patients recovered clinically and were free of C. difficile infection following cFMT. The majority of patients (61%) showed high levels of engraftment after the first week following FMT, which were sustained throughout the year. A small subset, 22%, experienced a decline in donor engraftment after approximately 1 month, and a few patients (17%), two of whom were taking metformin, showed delayed and low levels of donor engraftment. Members of the genera Bacteroides, Parabacteroides, and Faecalibacterium were significantly and positively correlated with donor similarity (ρ = 0.237 to 0.373, P ≤ 0.017). Furthermore, throughout the year, patient fecal communities showed significant separation based on the donor fecal microbiota that they received (P < 0.001). Results of this study, which characterize long-term engraftment following cFMT, suggest that numerical donor similarity is not strictly related to clinical outcome and identify a persistent donor-specific effect on patient fecal microbial communities. Furthermore, results suggest that members of the Bacteroidetes may be important targets to improve engraftment via cFMT.IMPORTANCE Recurrent Clostridium difficile infection (rCDI) is the most common cause of hospital- and community-acquired diarrheal infection associated with antibiotic use. Fecal microbiota transplantation (FMT), a treatment that involves administration of fecal bacteria from a healthy donor to a recipient patient, is a highly effective rescue therapy for rCDI that is increasingly being incorporated into standard clinical practice. Encapsulated, freeze-dried preparations of fecal microbiota, administered orally, offer the simplest and most convenient route of FMT delivery for patients (cFMT). In this study, we evaluated the extent of bacterial engraftment following cFMT and the duration of donor bacterial persistence. All patients studied recovered clinically but showed differing patterns in long-term microbial community similarity to the donor that were associated with members of the bacterial group Bacteroidetes, previously shown to be prominent contributors to rCDI resistance. Results highlight long-lasting, donor-specific effects on recipient patient microbiota and reveal potential bacterial targets to improve cFMT engraftment.

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Disentangle beneficial effects of strain engraftment after fecal microbiota transplantation in subjects with MetSyn.

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Disentangle beneficial effects of strain engraftment after fecal microbiota transplantation in subjects with MetSyn.

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