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

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.