Low mucosal microbial load favors fecal microbiota colonization and anti-inflammatory response

Background: Recent findings of non-randomized clinical trials of fecal microbiota transplantation (FMT) in Crohn's disease (CD) showed low efficiency rate. Our aim was to study the crosstalk between recipient intestinal mucosa and donor microbiota, using an explant tissue model to examine changes in the mucosal microbiome community, immune responses and tissue structure upon contact with a fecal suspension obtained from a healthy donor (HD-FS).Results: We adapted an explant tissue model to examine changes in the mucosal microbiome community, immune responses, and tissue structure upon contact with a fecal suspension. The fecal suspension was obtained from 1 healthy donor (healthy donor fecal suspension, HD-FS). We cultured explant tissues from 24 patients (12 with CD and 12 without inflammatory bowel diseases [controls]) collected from patients who underwent ileocolectomy or colectomy. The fecal suspension (1x109 microbes) was applied to the explants, which were analyzed by histology, flow cytometry, and ELISAs to measure cytokines; microbiota were characterized by 16s DNA sequence analysis (n = 141), and microbes were quantified by real-time PCR analysis of 16S rRNA. We validated our findings using biopsies from 26 patients with CD.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. Tissues 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 compared to those with a high microbial load.Conclusions: Our results indicate that the use of FMT for CD patients with active disease may compromise its outcome and support the stratification of FMT recipients on the basis of tissue microbial load as a strategy to ensure successful colonization.