6'-Sialyllactose alleviates loperamide-induced constipation and depressive-like behaviors in mice by modulating gut microbiota and short-chain fatty acids.

Constipation is a common gastrointestinal disorder, which impairs the quality of life. This study investigated the ameliorative effects of 6'-sialyllactose (6'-SL) in a loperamide-induced murine model of constipation and associated depressive-like behaviors. Constipation was induced in mice by loperamide and subsequently treated by administering 6'-SL at doses of 100 or 300 mg per kg body weight for 14 days. The ameliorative effects of 6'-SL were evaluated through defecation-related parameters, histopathological and immunohistochemical analyses of colonic and hippocampal tissues, biochemical assays, behavioral tests, gut microbiota analysis, and short-chain fatty acid (SCFA) levels. The results showed that 6'-SL alleviated loperamide-induced constipation by improving defecation-related parameters, colonic histopathology, gastrointestinal neurotransmitter levels, and AQP3 and SCF/c-Kit levels. Moreover, 6'-SL ameliorated constipation-associated depressive-like behaviors and hippocampal alterations while modulating the gut microbiota composition and increasing the SCFA levels. Spearman's correlation analysis suggested that the alleviation of constipation and depressive-like behaviors may be associated with alterations in the gut microbiota and SCFA levels upon 6'-SL intervention. These results provide a theoretical and practical basis for developing functional foods and biomedical products based on 6'-SL.