Bifidobacterium animalis subsp. lactis BL-99 with fructo-oligosaccharide alleviates constipation in mice by modulating gut microbiota

AbstractConstipation, a widespread gastrointestinal condition, significantly impairs life quality and health. Recent advancements in modulating gut microbiota through prebiotics, probiotics, and synbiotics have unveiled new therapeutic possibilities. In this study, metagenomic and non-target metabolomics techniques were used to evaluate the effects of Bifidobacterium animalis subsp. lactis BL-99 (BL-99), fructooligosaccharide (FOS), and a synbiotic combination of BL-99 and FOS (BL-99+FOS) on constipated mice. Mice were divided into six groups, including control, loperamide-induced constipated model, BL-99, FOS, BL-99+FOS, and positive control (POS) groups. Our results showed that BL-99, FOS, and BL-99+FOS each alleviated constipation, with the synbiotic showing significant efficacy in first black stool defecation time and gastrointestinal transit rate (P < 0.05). Additionally, significant increased in serum 5-HT and IL-10 were observed in the BL-99+FOS group, alongside an increased relative abundance of Lachnospiraceae_NK4A136_group, Blautia, and Clostridium sensu stricto 1, while significantly reducing the relative abundance of Alistipes and Bacteroides. These changes facilitated alterations in bile acid (BA) and short-chain fatty acids (SCFAs) metabolism. And these changes were closely associated with the expression of genes related to the 5-HT pathway and the modulation of serum inflammatory factors. This study provides a theoretical basis for synbiotic to improve constipation by regulating the gut microbiota and metabolites.

【摘要】便秘是一种高发的胃肠道疾病，会严重损害患者的生活质量与健康水平。近年来，通过益生元（prebiotics）、益生菌（probiotics）及合生素（synbiotics）调控肠道菌群的研究进展，为便秘治疗提供了全新的潜在方案。本研究采用宏基因组学与非靶向代谢组学技术，评估了动物双歧杆菌乳亚种BL-99（Bifidobacterium animalis subsp. lactis BL-99，简称BL-99）、低聚果糖（fructooligosaccharide，FOS）以及二者的合生素组合BL-99+FOS对便秘小鼠的干预效果。实验将小鼠分为6组：空白对照组、洛哌丁胺（loperamide）诱导的便秘模型组、BL-99干预组、FOS干预组、BL-99+FOS合生素干预组以及阳性对照组（POS）。研究结果显示，BL-99、FOS以及BL-99+FOS均能缓解小鼠便秘症状，其中合生素组合在首次黑便排出时间与胃肠道推进率方面展现出显著干预效果（P < 0.05）。此外，BL-99+FOS组小鼠的血清5-羟色胺（5-HT）与白细胞介素10（IL-10）水平显著升高；同时，该组小鼠肠道菌群中毛螺菌科NK4A136群（Lachnospiraceae_NK4A136_group）、布劳特氏菌属（Blautia）以及梭菌属1群（Clostridium sensu stricto 1）的相对丰度显著上升，而别样杆菌属（Alistipes）与拟杆菌属（Bacteroides）的相对丰度显著降低。上述菌群与代谢水平的改变，可调控胆汁酸（bile acid，BA）与短链脂肪酸（short-chain fatty acids，SCFAs）的代谢过程。这些代谢与菌群变化与5-HT通路相关基因的表达，以及血清炎症因子的调控密切相关。本研究为合生素通过调控肠道菌群与代谢产物改善便秘提供了理论依据。