Lactobacillus sp. alleviates loperamide-induced constipation in mice through redress of gut microbiota and fecal metabolites

Constipation is one of the most common gastrointestinal disorders in the world, with consumption of probiotics being safe and effective means for its treatments eliciting minimal side effects. In this study, physiological and biochemical parameters such as gastrointestinal peristalsis, serum biochemistry, colonic histology, intestinal microbial and metabolites composition of mice were evaluated to explore the possible mechanism of alleviating loperamide-induced constipation treated with Lactobacillus fermentum CCT and L. plantarum YS4. Both two probiotics significantly increased gastrointestinal transport rates and improved constipation to varying degrees (P ​< ​0.05). In addition, thymus development and pro-inflammatory factors such as IL-17 was increased in medium-high dose group of CCT (CM and CH group), (P ​< ​0.05). This was related to the potential activation of innate immune function. 5-Hydroxytryptamine (5-HT) in the colon was significantly increased except in CH group (P ​< ​0.05). Abundance of Desulfovibrio , Bacteroides , Alloprevotella , Lachnoclostridium , Desulfovibrio and Lactobacillus increased in stool samples from the probiotic-treated groups. Both probiotics were effective in reversing the metabolic changes caused by loperamide, especially metabolites related with consumption, such as such as short-chain fatty acids, serotonin, bile acid and methane. Therefore, the probiotics used in this study mitigated loperamide-induced constipation by activating innate immunity, improving intestinal flora and related metabolism. • Lactobacillus spp. alleviate constipation by enhancing GI transit and reversing flora/metabolite abnormalities. • Mechanisms involve flora balance, and improved metabolism with significant correlations. • Gut microbes-metabolites-physiology correlations clarify probiotic therapeutic pathways.