Commensal segmented filamentous bacteria-derived retinoic acid primes host defense to intestinal infection

Interactions between the microbiota and mammalian host are essential for defense against infection, but the microbial-derived cues that mediate this relationship remain unclear. Here, we find that intestinal epithelial cell (IEC)-associated commensal bacteria, segmented filamentous bacteria (SFB), promote early protection against the pathogen Citrobacter rodentium, independent of CD4+ T cells. SFB induced histone modifications in IECs at sites enriched for retinoic acid receptor motifs, suggesting that SFB may enhance defense through retinoic acid (RA). Consistent with this, inhibiting RA signaling suppressed SFB-induced protection. Intestinal RA levels were elevated in SFB mice, despite the inhibition of mammalian RA production, indicating that SFB directly modulate RA. Interestingly, RA was produced by intestinal bacteria, and the loss of bacterial-intrinsic aldehyde dehydrogenase activity decreased the RA levels and increased infection. These data reveal RA as an unexpected microbiota-derived metabolite that primes innate defense and suggests that pre- and probiotic approaches to elevate RA could prevent or combat infections. [Display omitted] •Commensal segmented filamentous bacteria protect against C. rodentium infection•Commensal bacteria express enzymes that generate retinoic acid in the intestine•Commensal bacterial-derived retinoic acid promotes epithelial defense in the host Interactions with the microbiota alter host defense against pathogens. Woo et al. report that commensal bacteria, including segmented filamentous bacteria, can express aldehyde dehydrogenase (aldh) enzymes, producing retinoic acid in the intestine. Bacterial-derived retinoic acid primes epithelial defense and promotes innate protection against intestinal infection.