Mucosal microbial load in Crohn's disease: A potential predictor of response to faecal microbiota transplantation

Abstract

Background: The remission of Crohn's disease (CD) can be accomplished by faecal microbiota transplantation (FMT). However, this procedure has a low success rate, which could be attributed to mis-communication between recipient intestinal mucosa and donor microbiota. Methods: Here we used a human explant tissue model and an in vivo mouse model to examine changes in recipient intestinal mucosa upon contact with a faecal suspension (FS) obtained from a healthy donor. CD patients provided resected inflamed and non-inflamed mucosal tissues, whereas control colonic mucosa samples were collected from colorectal cancer patients. For the models, mucosal microbiome composition and tissue response were evaluated. Findings: We show that cytokine release and tissue damage were significantly greater in inflamed compared to non-inflamed CD tissues. Moreover, mucosal samples harbouring an initial low microbial load presented a shift in composition towards that of the FS, an increase in the relative count of Faecalibacterium prausnitzii, and a higher secretion of anti-inflammatory cytokine IL-10 compared to those with a high microbial load. Interpretation: Our results indicate that FMT during active inflammatory disease can compromise treatment outcome. We recommend the stratification of FMT recipients on the basis of tissue microbial load as a strategy to ensure successful colonization. Funding: This study was supported by grants from the Instituto de Salud Carlos III/FEDER (PI17/00614), the European Commission: (INCOMED-267128) and PERIS (SLT002/16). K.M. is a postdoctoral fellow and S.V. a senior clinical investigator of the Fund for Scientific Research Flanders, Belgium (FWO-Vlaanderen).

Antibiotic-associated dysbiosis affects the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in experimental colitis models

“…We demonstrate that the transfer of an antibiotic-conditioned gut microbiota in colitic animals has an important role for the disease outcome and for the modulation of the inflammatory status, achieved by polarizing the immune response of the FMT recipient and modifying the gut microenvironment. In particular, the colitic recipients transferred with a streptomycin-or vancomycinconditioned microbiota were characterized by blooming of the genera Bacteroides, Parabacteroides, Streptococcus, and unclassified Enterobacteriaceae, all associated with poor outcomes in human clinical studies evaluating FMT efficacy in IBD patients [44][45][46] as well as by the depletion of health-promoting bacteria, i.e., Akkermansia and Bifidobacterium [47,48]. The gut microenvironment associated with these dysbiotic microbial communities showed the specific enrichment of metabolites that are abundant in the mouse gut after antibiotic treatments leading to susceptibility to Clostridioides difficile infections, i.e., gluconic acid [49], or during steatohepatitis, i.e., azelaic acid [50].…”

Faecalibacterium prausnitzii: A Next-Generation Probiotic in Gut Disease Improvement

“…Sarrabayrouse et al investigate changes in recipient intestinal mucosa upon contact with a fecal suspension (FS) obtained from a healthy donor by using a human explant tissue model and an in vivo mouse model. Interestingly, it shows that tissues with a low microbial load and a higher relative abundance of Firmicutes were more susceptible to FMT [76]. ese studies suggest that F. prausnitzii can be a diagnostic and therapeutic candidate for the use of FMT in UC.…”

Organoids and organs-on-chips: Insights into human gut-microbe interactions

“…As explant models normally retain part of their microbiota, the addition of further bacterial species for defined co-cultures is not routinely performed. However, a protocol for eradicating the endogenous microbiota and repopulating human colonic explants with a donor microbial suspension has recently been described (Sarrabayrouse et al, 2020).…”

“…Thus, the secretion of pro-inflammatory cytokines by a DSS-pretreated intestinal layer in response to E. coli and LPS exposure could be measured, as well as the protective effect of a pretreatment with probiotic bacteria (Shin and Kim, 2018). Human organotypic explant cultures were employed to study the prohibitive effects of initial bacterial load on fecal microbial transplant engraftment in the context of IBD (Sarrabayrouse et al, 2020). In this study, the mucosal layer was exposed ex vivo to microbial donor material.…”