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Do we really understand how faecal microbiota transplantation works? Authors' reply

2019; Elsevier BV; Volume: 42; Linguagem: Inglês

10.1016/j.ebiom.2019.03.030

2352-3964

Lito E. Papanicolas, Steve Wesselingh, Geraint B. Rogers,

Inflammatory Bowel Disease

We welcome the comments of Quraishi et al., who highlight the potential of spore-forming bacteria to contribute to the benefit associated with FMT for ulcerative colitis (UC). However, by what mechanism this benefit is conferred is not known. It should be noted that we did not observe a decrease in the abundance of viable spore-forming facultative anaerobes following aerobic processing of stool, as would be predicted if spores (which were not detectable) contributed substantially to their survival in this context. Substantial functional overlap exists between many such species and obligate anaerobes whose viability is significantly reduced by aerobic processing. A recent clinical trial of FMT for UC that employed anaerobic stool processing reported greater efficacy than was observed in prior studies using aerobic processing [[1]Costello S.P. Hughes P.A. Waters O. et al.Effect of fecal microbiota transplantation on 8-week remission in patients with ulcerative colitis: a randomized clinical trial.JAMA. 2019; 321: 156-164Crossref PubMed Scopus (381) Google Scholar]. These findings suggest that the clinical benefit associated with FMT might represent the cumulative effects of multiple bacterial groups, of which spore-forming facultative anaerobes are only one, perhaps acting via multiple mechanistic pathways. In our study, we showed a significant effect of aerobic processing on non-spore forming obligate anaerobes, and in particular, elimination of viable Faecalibacterium prausnitzii and Anaerostipes hadrus from donor material. These species are abundant in healthy donors, and are major contributors to butyrate biosynthesis [[2]Louis P. Young P. Holtrop G. Flint H.J. Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA:acetate CoA-transferase gene.Environ Microbiol. 2010; 12: 304-314Crossref PubMed Scopus (470) Google Scholar], a capacity that has been linked to improved response to FMT [[3]Fuentes S. Rossen N.G. van der Spek M.J. et al.Microbial shifts and signatures of long-term remission in ulcerative colitis after faecal microbiota transplantation.ISME J. 2017; 11: 1877-1889Crossref PubMed Scopus (127) Google Scholar]. In order to maximise the efficacy of this important emerging therapy, we would argue that all potential microbial contributions to benefit must be considered. The ability to define FMT material is essential to understanding and improving treatment. We agree that this is an area where ongoing research is needed. All authors have nothing to declare. Do we really understand how faecal microbiota transplantation works?We read with interest the paper by Papanicolas and colleagues titled 'Bacterial viability in faecal transplants: Which bacteria survive?' [1]. The authors demonstrate a reduction in gut anaerobes following production of FMT in ambient air compared to anaerobic conditions. They conclude that adherence to strict anaerobic stool processing protocols is likely to increase efficacy for FMT. These findings, albeit interesting, have significant limitations and should be interpreted with caution. Full-Text PDF Open AccessBacterial viability in faecal transplants: Which bacteria survive?The practice of preparing material for faecal transplantation in ambient air profoundly affects viable microbial content, disproportionately reducing the abundance of anaerobic commensals and the capacity for biosynthesis of important anti-inflammatory metabolites. Full-Text PDF Open Access