Extracellular vesicles of Bacteroides uniformis induce M1 macrophage polarization and aggravate gut inflammation during weaning

Abstract

Weaning process is commonly associated with gastrointestinal inflammation and dysbiosis of the intestinal microbes. In particular, the impact of gut bacteria and of extracellular vesicles (EV) on the etiology of intestinal inflammation during weaning is not well understand. We have uncovered a potential link between gut inflammation and the corresponding variation of macrophage bacterial sensing and pro-inflammatory polarization during the weaning process of piglet through single-cell transcriptomic analyses. We conducted a comprehensive analysis of bacterial distribution across the gastrointestinal tract and pinpointed Bacteroides uniformis (B. uniformis) enriching in piglets undergoing weaning. Next, we found out that exposure to B. uniformis-derived EVs (BEVs) exacerbated gut inflammation in a murine colitis model while recruiting and polarizing intestinal macrophages towards a pro-inflammatory phenotype. BEVs modulated the function of macrophages cultured in vitro by suppressing the GM-CSF/STAT5/ARG1 pathway, thereby affecting polarization towards an M1-like state. The effects of BEVs were verified both in the macrophage-clearance murine model and by using an adoptive transfer assay. Our findings highlight the involvement of BEVs in facilitating the polarization of pro-inflammatory macrophages and promoting gut inflammation during weaning.