Romboutsia ilealis drives lard diet-induced obesity and gut injury via bile acid imbalance and M1 macrophage polarization

We uncover a critical pathogenic mechanism by which Romboutsia ilealis (R. ilealis) promotes high lard diet-induced obesity through an unconjugated cholic acid (CA)-M1 macrophage regulatory axis. By establishing a lard-fed mouse model, we demonstrated that a lard diet induced pronounced obesity phenotypes and intestinal barrier dysfunction, characterized by a disrupted balance between unconjugated and conjugated bile acids (BAs). 16S rDNA sequencing revealed that a lard diet induced intestinal dysbiosis, with a specific enrichment of R. ilealis. Notably, germ-free mice orally colonized with R. ilealis developed obesity and intestinal injury, even in the absence of a lard diet. Clinically, the abundance of R. ilealis was significantly increased in both obese commercial pigs and obese individuals. Mechanistically, R. ilealis disrupted BA homeostasis and promoted M1 macrophage polarization by increasing the levels of cholic acid (CA). Correspondingly, CA was dramatically elevated in patients with IBD and showed a positive association with colonic M1 macrophages.