Microbiota-derived metabolism attenuates campylobacteriosis. mouse gut metagenome

The intestinal microbiota represents a complex ecological system implicated in numerous health processes, including immunological responses, metabolic and nutritional functions as well as protection from enteric pathogens such as Clostridium difficile. Campylobacter jejuni (C. jejuni), a prevalent food born bacterial pathogen, exploits the host innate response to elicit colitis. However, the interplay between intestinal microbiota and host susceptibility to C. jejuni infection is unknown. Here we report that introduction of conventionalized microbiota (CONV-Biota) significantly alleviated C. jejuni-induced colitis in germ free (GF) Il10-/- mice, a phenomenon independent of fecal C. jejuni colonization load, but coupled with reduced mTOR activation (p-p70S6K T389). Microbiota manipulation through fecal transplantation showed that anaerobic microbiota (Anaero-Biota) protect against C. jejuni-induced colitis but not aerobic (Aero-Biota) or microaerobic microbiota (Microaero-Biota). Using 16S rDNA sequencing, we found that the bacterial genera Clostridium XI, Bifidobacterium, and Lactobacillus were enriched in mice colonized with protective Anaero-Biota compared to susceptible Aero-Biota mice. HPLC/MS analysis showed that the microbial-derived secondary bile acids sodium deoxycholate (DCA) and ursodeoxycholic acid (UDCA) remained constant in stool of Anaero-Biota mice pre- and post-infection but not in Aero-Biota mice. Supplementation of DCA, but not UDCA or lithocholic acid, reduced C. jejuni-induced colitis in Il10-/- mice. In addition, targeted depletion of secondary bile acid-producing bacteria with clindamycin promoted C. jejuni-induced colitis in SPF Il10-/- mice compared to treatment with the non-specific antibiotic nalidixic acid. Altogether, our findings identify a novel mechanism by which microbiota control susceptibility to C. jejuni infection through secondary bile acid production impacting host response.