6′-Sialyllactose Combined with Bifidobacterium animalis subsp. lactis BB12 Relieves Constipation and Depression-like Behaviors Induced by Loperamide in Mice by Regulating the Gut–Brain Axis

Constipation is a common gastrointestinal disorder, which impairs health and quality of life. This study evaluated the ameliorating effects and underlying mechanism of 6′-sialyllactose (6′-SL) and Bifidobacterium animalis subsp. lactis BB12 (BB12) on loperamide-induced constipation and associated depression-like behaviors. 6′-SL combined with BB12 increased the fecal water content, fecal pellet number, and gastrointestinal transit rate while reducing the time of first black feces. 6′-SL and BB12 modulated secretion of intestinal neurotransmitters, regulated expression of AQP3 and Claudin-1, and modulated expression of key proteins in the SCF/c-Kit pathway. Meanwhile, 6′-SL and BB12 ameliorated depression-like behaviors by inhibiting inflammatory responses and modulating the expression of synaptic plasticity-related proteins in the brain. Moreover, 6′-SL and BB12 regulated the diversity of gut microbiota, enhanced the relative abundance of Bacteroidetes and Akkermansia, and elevated SCFA levels. This study provides a theoretical and practical basis for developing functional foods based on synbiotics containing 6′-SL and BB12.