Abstract

This study comprehensively evaluated the probiotic properties, safety, genomic characteristics, and protective effects of Lacticaseibacillus rhamnosus Hao9 against chronic low-grade inflammation. Methods included L assays for survival and safety, whole-genome sequencing using Illumina and PacBio platforms, and an in vivo study using mice subjected to 0.2% dextran sulfate sodium (DSS) for 12 weeks. Results indicated that Hao9 exhibits robust acid and bile salt tolerance, moderate aggregation capacity, and a defined antibiotic susceptibility profile without hemolytic activity. Genomic analysis confirmed a safe genetic background lacking virulence factors or mobile resistance elements, while highlighting genes essential for stress adaptation, surface anchoring, and carbohydrate metabolism. In the mouse model, Hao9 intervention significantly mitigated the physiological impact of long-term DSS exposure. It reduced serum lipopolysaccharide, IL-6, and TNF-α levels, alleviated colonic histological damage, and attenuated elevations in liver enzymes. Furthermore, gut microbiota analysis revealed that Hao9 administration partially restored microbial diversity, reshaped community structure by suppressing inflammation-associated taxa, and promoted the recovery of beneficial genera. Overall, L. rhamnosus Hao9 demonstrates a solid safety profile and genome-supported gastrointestinal adaptability. Hao9 administration was associated with improved inflammatory and histological endpoints, lower circulating LPS, and compositional shifts of the gut microbiota, supporting its potential as a candidate probiotic for maintaining intestinal homeostasis.