Human gut commensal modulates the host lipidome and delivers anti-inflammatory outer membrane vesicles to suppress colitis in an -deficient mouse model.

Correlative studies have linked human gut microbes to specific health conditions. is one such microbial genus negatively linked to inflammatory bowel disease (IBD). However, the protective role of in IBD is understudied, and the underlying molecular mechanisms remain unknown. In this study, colonization of -deficient mice with DSM 27924 delays colitis development. Colonization does not significantly alter the gut microbiome composition, but instead shifts the host plasma lipidome, increasing phosphatidic acids while decreasing triglycerides. Outer membrane vesicles (OMVs) derived from are detected in the plasma of colonized mice, carrying potentially immunomodulatory metabolites into the host circulatory system. Fractions of OMVs suppress LPS-induced , , and expression in murine macrophages. We detect putative bioactive lipids in the OMVs, including immunomodulatory sulfonolipids (SoLs) in the active fraction, which are also increased in the blood of colonized mice. Treating -deficient mice with purified SoL B, a representative SoL, suppresses colitis development, suggesting its contribution to the anti-inflammatory phenotype observed with colonization. Thus, OMVs represent a potential mechanism for -mediated delay of colitis in -deficient mice via delivery of immunomodulatory lipids and modulation of the host plasma lipidome.