Functional Restoration of Bacteriomes and Viromes by Fecal Microbiota Transplantation

Fujimoto, Kosuke; Kimura, Yoshinobu; Allegretti, Jessica R.; Yamamoto, Mako; Zhang, Yao-Zhong; Katayama, Kotoe; Tremmel, Georg; Kawaguchi, Yunosuke; Shimohigoshi, Masaki; Hayashi, Tetsuya; Uematsu, Miho; Yamaguchi, Kiyoshi; Furukawa, Yoichi; Akiyama, Yutaka; Yamaguchi, Rui; Crowe, Sheila E.; Ernst, Peter B.; Miyano, Satoru; Kiyono, Hiroshi; Imoto, Seiya; Uematsu, Satoshi

doi:10.1053/j.gastro.2021.02.013

Cited by 52 publications

(39 citation statements)

References 58 publications

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“… 27 Supportive of these data, in a metagenomic study of stool studies collected pre- and post-FMT for rCDI, analysis of gene functions demonstrated that secondary bile acid biosynthesis was one of the pathways most significantly restored by FMT. 64 In totality, these data support the hypothesis that FMT-driven restoration of gut microbial bile acid metabolism is an important mechanism contributing to the efficacy of FMT in treating rCDI.…”

Section: Impact Of CDI Treatments Upon Gut Microbiome–bile Acid Interactionssupporting

confidence: 67%

“… 60 Further experimental work has explored the impact of FMT upon microbial bile acid-metabolizing functionality in both rodent models and patients with rCDI. 27 , 63 , 64 Patients with rCDI had a markedly reduced relative abundance of a broad range of BSH-producing bacteria within their stool microbiome pre-FMT in comparison with post-FMT, as well as in comparison with healthy stool donors. 27 Successful FMT for rCDI rapidly and sustainably restored stool bsh gene copy number and BSH functionality from the very low levels detected pre-FMT up to high levels comparable with those of healthy stool donors, 27 together with at least partial recovery of the bai CD operon of 7-α-dehydroxylase.…”

Section: Impact Of CDI Treatments Upon Gut Microbiome–bile Acid Interactionsmentioning

confidence: 99%

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The contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection

Mullish

Allegretti

2021

Therap Adv Gastroenterol

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Clostridioides difficile infection (CDI) remains a major global cause of gastrointestinal infection, with significant associated morbidity, mortality and impact upon healthcare system resources. Recent antibiotic use is a key risk factor for the condition, with the marked antibiotic-mediated perturbations in gut microbiome diversity and composition that underpin the pathogenesis of CDI being well-recognised. However, only relatively recently has further insight been gained into the specific mechanistic links between these gut microbiome changes and CDI, with alteration of gut microbial metabolites – in particular, bile acid metabolism – being a particular area of focus. A variety of in vitro, ex vivo, animal model and human studies have now demonstrated that loss of gut microbiome members with bile-metabolising capacity (including bile salt hydrolases, and 7-α-dehydroxylase) – with a resulting alteration of the gut bile acid milieu – contributes significantly to the disease process in CDI. More specifically, this microbiome disruption results in the enrichment of primary conjugated bile acids (including taurocholic acid, which promotes the germination of C. difficile spores) and loss of secondary bile acids (which inhibit the growth of C. difficile, and may bind to and limit activity of toxins produced by C. difficile). These bile acid changes are also associated with reduced activity of the farnesoid X receptor pathway, which may exacerbate C. difficile colitis throughout its impact upon gut barrier function and host immune/inflammatory response. Furthermore, a key mechanism of efficacy of faecal microbiota transplant (FMT) in treating recurrent CDI has been shown to be restoration of gut microbiome bile metabolising functionality; ensuring the presence of this functionality among defined microbial communities (and other ‘next generation’ FMT products) designed to treat CDI may be critical to their success.

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Section: Impact Of CDI Treatments Upon Gut Microbiome–bile Acid Interactionssupporting

confidence: 67%

Section: Impact Of CDI Treatments Upon Gut Microbiome–bile Acid Interactionsmentioning

confidence: 99%

The contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection

Mullish

Allegretti

2021

Therap Adv Gastroenterol

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“…This notion becomes even more conceivable when considering that most of the bacteria transferred during the FMT procedure may be dead, and we indeed found in the setting of the metabolic syndrome that responders to an allogenic FMT from a healthy donor maintained a fecal phageome that was more similar to the donor than the non-responders (Manrique et al, 2021). A recent study addressed the development of the microbiome and virome after FMT in patients with recurrent C. difficile infections and showed the concomitant depletion of Proteobacteria and their bacteriophages by the FMT (Fujimoto et al, 2021). Currently, phage-specific transplantations are achieved by performing sterile filtration (Rasmussen et al, 2020).…”

Section: Llmentioning

confidence: 55%

Fecal microbiota transplantation in human metabolic diseases: From a murky past to a bright future?

2021

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Fecal microbiota transplantation (FMT) is gaining considerable traction as a therapeutic approach to influence the course of a plethora of chronic conditions, ranging from metabolic syndrome and malignancies to auto-immune and neurological diseases, and helped to establish the contribution of the gut microbiome to these conditions. Although FMT procedures have yielded important mechanistic insights, their use in clinical practice may be limited due to practical objections in the setting of metabolic diseases. While its applicability is established to treat recurrent Clostridiodes difficile, FMT is emerging in ulcerative colitis and various other diseases. A particularly new insight is that FMTs may not only alter insulin sensitivity but may also alter the course of type 1 diabetes by attenuating underlying auto-immunity. In this review, we will outline the major principles and pitfalls of FMT and where optimization of study design and the procedure itself will further advance the field of cardiometabolic medicine.

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“…Previous research has shown that that functional restoration of bacteriomes and viromes revealed by metagenomic sequencing could be an indicator of successful FMT (Fujimoto et al, 2021). To evaluate the long-term effects of FMT in aged mice with different donors, we performed shotgun metagenomic sequencing of Day-56 fecal samples from each treatment group (SR, FMT-M, and FMT-UM) together with the baseline of 20-month-old mice (matched donors, MD) and 2-month-old mice (unmatched donors, UMD).…”

Section: Long-term Effects Of Fmt On the Gut Metagenome And Colon Genmentioning

confidence: 99%

Establishment and Resilience of Transplanted Gut Microbiota in Aged Mice

Wang

Tang

et al. 2021

Preprint

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Fecal microbiota transplantation (FMT), a procedure in which fecal material is transferred from a donor to a recipient, has been increasingly used as a treatment to restore healthy gut microbiota. There is a substantial difference in the composition of gut microbiota between young and aged hosts, but little is known about whether age matching between the FMT donor and recipient affects microbiota restoration and long-term maintenance. In the present investigation, we aimed to study the establishment and resilience of transplanted gut microbiota in aged recipients. We treated naturally aged mice (20 months old) with a broad-spectrum antibiotic cocktail and monitored the restoration of gut microbiota over 8 weeks. The diversity of gut microbiota in aged mice failed to reach the baseline level via spontaneous recovery; in contrast, FMT from either (age-)matched or unmatched donors facilitated the recovery of gut microbiota diversity. The microbiota transplanted from different donors successfully established in the aged recipients and had long-term effects on the gene expression profiles of the host colon. Finally, we evaluated the long-term maintenance of transplanted microbiota via intentional disruption of gut homeostasis. We found that lack of age matching between FMT donors and recipients may decrease the resilience of transplanted gut microbiota against colonic inflammation. The results from our study systematically examining the effects of FMT on the gut homeostasis of aged hosts suggest that the compatibility between donors and recipients should be taken into account when implementing FMT.

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Functional Restoration of Bacteriomes and Viromes by Fecal Microbiota Transplantation

Cited by 52 publications

References 58 publications

The contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection

The contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection

Fecal microbiota transplantation in human metabolic diseases: From a murky past to a bright future?

Establishment and Resilience of Transplanted Gut Microbiota in Aged Mice

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