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 has not been studied and the underlying molecular mechanisms also remain unknown. In this study, colonization of -deficient mice with DSM 27924 delays the development of colitis. Colonization with does not significantly alter the gut microbiome composition during colitis development, but instead shifts the host plasma lipidome, increasing phosphatidic acids while decreasing triglycerides. Outer membrane vesicles (OMVs) derived from are also detected in the plasma of colonized mice, which carry metabolites with immunomodulatory potential into the host circulatory system. We further demonstrate that fractions of OMVs suppress LPS-induced , , and expression in murine macrophages. We detect immunomodulatory sulfonolipids (SoLs) in the active fraction, which are also increased in the blood of -colonized mice; and we identify other putative bioactive lipids in the OMVs. Thus, OMVs represent a potential mechanism for -mediated delay of colitis progression in -deficient mice through the delivery of immunomodulatory lipids, including SoLs, and modulation of the host plasma lipidome.