Bifidobacterium breve B2798 and Its Heat-Killed Cells Alleviate Inflammation in Rats with DSS Model by Modulating Gut Microbiota.

While probiotics are widely recognized for their adjunctive benefits in ulcerative colitis treatment, the therapeutic potential of heat-killed cells remains underexplored. This study directly compared the efficacy of Bifidobacterium breve B2798 probiotics (LB group) and their heat-killed counterparts (DB group) in alleviating dextran sulfate sodium (DSS)-induced colitis in rats. Over a 21-day intervention, both treatments significantly mitigated colitis symptoms, including weight loss, colon damage, and splenomegaly, with heat-killed cells demonstrating superior histological improvement over live probiotics. Serum analysis revealed that both interventions normalized DSS-induced cytokine dysregulation, reducing pro-inflammatory markers and elevating anti-inflammatory. Although α-diversity remained stable, β-diversity analysis indicated distinct gut microbiota restructuring. Heat-killed cells uniquely enriched butyrate-producing Alistipes spp. and Parabacteroides distasonis, while probiotics upregulated Mucispirillum schaedleri and Odoribacter splanchnicus. Metabolomic profiling identified shared elevation of anti-inflammatory metabolites (linoleic acid, isorhamnetin) in both groups, yet heat-killed cells exhibited stronger modulation of metabolic pathways, including TCA cycle activation and pantothenate biosynthesis suppression. Correlation networks highlighted species-specific microbiota-metabolite-cytokine interactions, with Mucispirillum schaedleri and Barnesiella intestinihominis negatively associated with inflammatory markers (MPO, TNF-α). These findings demonstrate that while both live and heat-killed B. breve B2798 alleviate colitis, heat-killed cells exert enhanced regulatory effects on gut microbiota composition, metabolic pathways, and inflammatory responses, offering a safer alternative for inflammatory bowel disease management. Further mechanistic studies are warranted to validate these preclinical insights.