Abstract：
Weaning process is commonly associated with gastrointestinal inflammation and dysbiosis of the intestinal microbes. In particular, the impact of gut bacteria and extracellular vesicles on the etiology of intestinal inflammation during weaning is not well understood. 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 piglets through single-cell transcriptomic analyses. We conducted a comprehensive analysis of bacterial distribution across the gastrointestinal tract and pinpointed Bacteroides uniformis enriching in piglets undergoing weaning. Next, we found out that exposure to B. uniformis-derived extracellular vesicles (BEVs) exacerbated gut inflammation in a murine colitis model while recruiting and polarizing intestinal macrophages toward a pro-inflammatory phenotype. BEVs modulated the function of macrophages cultured in vitro by suppressing the granulocyte-macrophage colony-stimulating factor/signal transducer and activator of transcription 5/arginase 1 pathway, thereby affecting polarization toward 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.
摘要：
断奶过程通常与胃肠道炎症和肠道微生物菌群失调有关。特别是,肠道细菌和细胞外囊泡（EV）对断奶期间肠道炎症病因的影响尚不清楚。通过单细胞转录组学分析，我们发现了仔猪断奶过程中肠道炎症与巨噬细胞细菌感知和促炎极化的相应变化之间的潜在联系。我们对整个胃肠道的细菌分布进行了全面分析，并精确地确定了拟杆菌（B.shiformis）在断奶仔猪中富集。接下来,我们发现,在小鼠结肠炎模型中,暴露于异形芽孢杆菌衍生的EV(BEV)会加剧肠道炎症,同时使肠道巨噬细胞向促炎表型募集和分化.BEV通过抑制GM-CSF/STAT5/ARG1通路调节体外培养的巨噬细胞的功能，从而影响朝向M1样状态的极化。在巨噬细胞清除鼠模型中以及通过使用过继转移测定来验证BEV的作用。我们的发现强调了BEV参与促进促炎巨噬细胞的极化和促进断奶期间的肠道炎症。
