Exopolysaccharides of Lactobacillus rhamnosus GG ameliorate Salmonella typhimurium-induced intestinal inflammation via the TLR4/NF-κB/MAPK pathway

J Anim Sci Biotechnol. 2023 Mar 6;14(1):23. doi: 10.1186/s40104-023-00830-7.

Abstract

Background: Salmonella typhimurium (S.T), as an important foodborne bacterial pathogen, can cause diarrhea and gastroenteritis in humans and animals. Numerous studies have confirmed that exopolysaccharides (EPSs) have various biological functions, but the mechanism through which EPSs improve the immunity of animals against the invasion of pathogenic bacteria is unclear. Here, we explored the protective effect of EPSs of Lactobacillus rhamnosus GG (LGG) on the S.T-infected intestine.

Methods: Mice received adequate food and drinking water for one week before the start of the experiment. After 7 d of prefeeding, 2×108 CFU/mL S.T solution and an equivalent volume of saline (control group) were given orally for 1 d. On the fourth day, the mice were treated with 0.5 mg/mL EPSs, 1.0 mg/mL EPSs, 2.0 mg/mL EPSs, or 2.0 mg/mL penicillin for 7 d. Finally, the body and relative organ weight, histological staining, and the levels of antioxidant enzyme activity and inflammatory cytokines were determined.

Results: The S.T-infected mice exhibited symptoms of decreased appetite, somnolence, diarrhea and flagging spirit. Treatment with EPSs and penicillin improved the weight loss of the mice, and the high dose of EPSs showed the best therapeutic effect. EPSs significantly ameliorated S.T-induced ileal injury in mice. High-dose EPSs were more effective than penicillin for alleviating ileal oxidative damage induced by S.T. The mRNA levels of inflammatory cytokines in the ileum of mice showed that the regulatory effects of EPSs on inflammatory cytokines were better than those of penicillin. EPSs could inhibit the expression and activation of key proteins of the TLR4/NF-κB/MAPK pathway and thereby suppress the level of S.T-induced ileal inflammation.

Conclusions: EPSs attenuate S.T-induced immune responses by inhibiting the expression of key proteins in the TLR4/NF-κB/MAPK signaling pathway. Moreover, EPSs could promote bacterial aggregation into clusters, which may be a potential strategy for reducing the bacterial invasion of intestinal epithelial cells.

Keywords: Exopolysaccharides; Lactobacillus rhamnosus; Salmonella typhimurium; TLR4/NF-κB/MAPK.