Gut microbiota-derived ursodeoxycholic acid alleviates low birth weight-induced colonic inflammation by enhancing M2 macrophage polarization

• DOI: 10.1186/s40168-022-01458-x
• Publication Date: 2023-01-31T08:03:00Z
• Authors: Yu Pi; Yujun Wu; Xiangyu Zhang; Dongdong Lu; Dandan Han; Jiangchao Zhao; Xiaojiao Zheng; Shiyi Zhang; Hao Ye; Shuai Lian; Yu Bai; Zhenyu Wang; Shiyu Tao; Dongjiao Ni; Xinhua Zou; Wei Jia; Guolong Zhang; Defa Li; Junjun Wang
• Keywords: Ursodeoxycholic acid; Dysbiosis; Deoxycholic acid

Low birth weight (LBW) is associated with intestinal inflammation and dysbiosis after birth. However, the underlying mechanism remains largely unknown.In present study, we aimed to investigate metabolism, therapeutic potential, mechanisms of action bile acids (BAs) in LBW-induced a piglet model.The fecal microbiome BA profile between LBW normal (NBW) neonatal piglets were compared. Fecal microbiota transplantation (FMT) was employed further confirm linkage microbial metabolism inflammation. The potential ursodeoxycholic acid (UDCA), highly differentially abundant NBW piglets, alleviating colonic evaluated both an LBW-FMT mice model, DSS-induced colitis mouse model. cellular molecular by which UDCA suppresses also investigated DSS-treated macrophage cell line. Microbiomes analyzed using 16S ribosomal RNA sequencing. profiles measured targeted metabolomics. Levels farnesoid X receptor (FXR) knocked down J774A.1 cells small interfering RNAs.We show significant difference animals Transplantation antibiotic-treated leads Importantly, oral administration UDCA, major diminished tract markedly alleviates model inducing M2 polarization. Mechanistically, reduces inflammatory cytokine production engaging FXR while suppressing NF-κB activation macrophages.These findings establish causal relationship LBW-associated abnormalities dysbiosis, suggesting that restoring health postnatal maldevelopment infants may be achieved targeting metabolism. Video Abstract.