Abstract

The role of the luxS /autoinducer-2 (AI-2) quorum sensing system in probiotic efficacy is controversial. This study investigated the therapeutic potential of a luxS -deficient mutant (△ luxS ) of Companilactobacillus crustorum MN047 in a dextran sulfate sodium (DSS)-induced colitis mouse model. Unexpectedly, the △ luxS mutant developed a pronounced auto-aggregation phenotype (>90%) and significantly enhanced bile salt tolerance in vitro . Mechanistically, these physical adaptations were driven by the redirection of carbon flux toward exopolysaccharide biosynthesis via the upregulation of specific phosphotransferase systems (PTS). In vivo , these traits translated into superior therapeutic efficacy compared to the wild-type. The mutant effectively alleviated colitis symptoms and restored intestinal barrier integrity. Furthermore, the mutant reshaped the gut microbiota, specifically enriching short-chain fatty acid (SCFA) producers ( Bacteroides and Marinifilaceae), which elevated anti-inflammatory metabolites. These findings indicate that targeted modulation of the LuxS/AI-2 system could be a viable strategy for engineering next-generation probiotics with enhanced physiological resilience.