Bacillus halotolerans attenuates inflammation induced by enterotoxigenic Escherichia coli infection in vivo and in vitro based on its metabolite soyasaponin I regulating the p105-Tpl2-ERK pathway

• Published in: Food & function Vol. 15; no. 12; pp. 6743 - 6758
• Main Authors: Li, Minghan, Zhao, Dongyu, Meng, Jinxin, Pan, Tianxu, Li, Junyi, Guo, Jialin, Huang, Haibin, Wang, Nan, Zhang, Di, Wang, Chunfeng, Yang, Guilian
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 17.06.2024
• Subjects: Antimicrobial activity; Cell permeability; Damage; E coli; Electrical resistivity; Endotoxins; Escherichia coli; Immunoregulation; Inflammation; Inflammatory response; Intestine; Lactic acid; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Metabolites; Oxidative stress; Scientific imaging; Signal transduction; Soyasaponin
• ISSN: 2042-6496; 2042-650X; 2042-650X
• DOI: 10.1039/d4fo01047g

Soyasaponins, recognized for their anti-inflammatory and antioxidant effects, have not yet been fully explored for their role in combating enterotoxigenic (ETEC) infections. Recent findings identified them in small-molecule metabolites of , suggesting their broader biological relevance. This research screened 88 strains of , identifying the strain BH M20221856 as significantly inhibitory against ETEC growth . It also reduced cellular damage and inflammatory response in IPEC-J2 cells. The antimicrobial activity of BH M20221856 was attributed to its small-molecule metabolites rather than secretory proteins. A total of 69 small molecules were identified from the metabolites of BH M20221856 using liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS). Among these, soyasaponin I (SoSa I) represented the largest multiple change in the enrichment analysis of differential metabolites and exhibited potent anti-ETEC effects . It significantly reduced the bacterial load of in mouse intestines, decreased serum endotoxin, D-lactic acid, and oxidative stress levels and alleviated intestinal pathological damage and inflammation. SoSa I enhanced immune regulation by mediating the p105-Tpl2-ERK signaling pathway. Further evaluations using transepithelial electrical resistance (TEER) and cell permeability assays showed that SoSa I alleviated ETEC-induced damage to epithelial barrier function. These results suggest that BH M20221856 and SoSa I may serve as preventative biologics against ETEC infections, providing new insights for developing strategies to prevent and control this disease.