Feng Cuijiao, Zhao Yue, He Qiuwen, Yu Jie, Sun Zhihong
Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, National Collection of Microbial Resource for Feed (Inner Mongolia), Inner Mongolia Agricultural University, Hohhot, 010018, Inner Mongolia, China.
Probiotics Antimicrob Proteins. 2025 Sep 5. doi: 10.1007/s12602-025-10648-6.
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.
虽然益生菌在溃疡性结肠炎治疗中的辅助益处已得到广泛认可，但热灭活细胞的治疗潜力仍未得到充分探索。本研究直接比较了短双歧杆菌B2798益生菌（LB组）及其热灭活对应物（DB组）在减轻葡聚糖硫酸钠（DSS）诱导的大鼠结肠炎方面的疗效。在为期21天的干预中，两种治疗均显著减轻了结肠炎症状，包括体重减轻、结肠损伤和脾肿大，热灭活细胞在组织学改善方面优于活益生菌。血清分析表明，两种干预均使DSS诱导的细胞因子失调恢复正常，降低了促炎标志物并提高了抗炎能力。虽然α多样性保持稳定，但β多样性分析表明肠道微生物群发生了明显的重组。热灭活细胞独特地富集了产生丁酸盐的阿利斯杆菌属和多形拟杆菌，而益生菌上调了斯氏黏液螺旋菌和内脏气味杆菌。代谢组学分析确定了两组中抗炎代谢物（亚油酸、异鼠李素）的共同升高，但热灭活细胞对代谢途径的调节作用更强，包括三羧酸循环激活和泛酸生物合成抑制。相关网络突出了物种特异性的微生物群-代谢物-细胞因子相互作用，斯氏黏液螺旋菌和人肠道巴恩斯氏菌与炎症标志物（髓过氧化物酶、肿瘤坏死因子-α）呈负相关。这些发现表明，虽然活的和热灭活的短双歧杆菌B2798都能减轻结肠炎，但热灭活细胞对肠道微生物群组成、代谢途径和炎症反应具有更强的调节作用，为炎症性肠病的管理提供了一种更安全的替代方案。有必要进行进一步的机制研究来验证这些临床前的见解。
