Mucosal microbial load: a potential predictor of response to fecal microbiota transplantation in human explant and murine models

Low remission rates have been reported on fecal microbiota transplantation in particular in Crohn's disease (CD). Our aim was to study the mechanism leading to mis-communication between recipient intestinal mucosa and donor microbiota.Using an explant tissue model, we examined changes in the mucosal microbiome community, immune responses and tissue structure upon contact with a fecal suspension obtained from a selected healthy donor (HD-FS).We showed that histological damage to the mucosal barrier was dependent on the concentration of microorganisms present in the HD-FS. Cytokine release and tissue damage were significantly greater in inflamed CD tissues compared to control and non-inflamed CD tissues. Mucosal samples harboring an initial low microbial load showed a shift in composition towards that of the HD-FS, a significant increase in the relative count of Faecalibacterium Prausnitzii, and a higher anti-inflammatory immune response (P < 0.05) compared to those with a high microbial load. Our findings were validated in an in vivo mouse model.Our results indicate that the use of FMT for patients with active disease may compromise its outcome. Furthermore, they support the possible stratification of FMT recipients on the basis of tissue microbial load as a strategy to ensure successful colonization.