A next-generation probiotic strain for gut health: Bacteroides cellulosilyticus LYH2 variant with anti-inflammatory and metabolic advantages.

Abstract

BACKGROUND: The rising global incidence of inflammatory bowel disease (IBD) underscores the pressing demand for effective therapeutic approaches. Among promising next-generation probiotics (NGPs), certain Bacteroides species, notably Bacteroides cellulosilyticus, have attracted increasing interests. However, their mechanisms of action remain incompletely elucidated. METHODS: Six Bacteroides strains were isolated from porcine intestine, among which B. cellulosilyticus LYH2 was selected for detailed functional characterisation. Genomic and metabolic profiling were conducted to evaluate its polysaccharide-degrading capacity, short-chain fatty acid (SCFA) production, and antimicrobial metabolite synthesis. In vitro and in vivo studies assessed its dose-dependent effects on pathogen inhibition, macrophage infection, immune modulation, and metabolic safety. A dextran sulphate sodium (DSS)-induced colitis model (male C57BL/6J mice), along with Ffar3-deficient mice, was employed to investigate anti-inflammatory efficacy and underlying mechanisms. FINDINGS: B. cellulosilyticus LYH2 demonstrated broad-spectrum antimicrobial activity, effectively suppressed macrophage infection, and reduced pro-inflammatory gene expression in vitro. Long-term oral administration proved safe in mice and improved metabolic parameters. In DSS-induced colitis, B. cellulosilyticus LYH2 outperformed a reference Bacteroides strain, mesalamine, and Lactobacillus reuteri in mitigating inflammation and restoring colonic goblet cell numbers. Mechanistically, B. cellulosilyticus LYH2 enhanced colonic propionate production, modulated gut microbiota composition, and activated Ffar3 signalling, consequently attenuating M1 macrophage polarisation. Genetic ablation of Ffar3 largely abolished these protective effects. INTERPRETATION: B. cellulosilyticus LYH2 represents a safe and functionally potent NGP that alleviates experimental colitis via propionate-Ffar3 signalling, supporting its therapeutic potential for intestinal inflammatory disorders. FUNDING: This research was supported by grants from National Natural Science Foundation of China (32372900) and Natural Science Foundation of Sichuan Province (2023NSFSC0237).