Lactobacillus helveticus alleviates cognitive impairment via microbiota-regulated phosphatidylcholine metabolism

The microbiota-gut-brain axis emerges as a potential therapeutic strategy. In this study, the effect of Lactobacillus helveticus CCFM1096 on alleviation of cognitive impairment and influence on the gut microbiota and metabolites in scopolamine-induced mice were investigated. Our findings indicated that CCFM1096 significantly improved cognitive behavior and brain histopathology in mice, and altered the structure of the gut microbiota and modulated relevant metabolites in cognition impaired mice. In particular, phosphatidylcholine and its metabolites levels were significantly regulated and the expression of genes related to the acetylcholine/Brain-Derived Neurotrophic Factor signaling pathway was significantly up-regulated in hippocampus. Furthermore, phosphatidylcholine and glycerophosphocholine effectively alleviated scopolamine-induced PC12 neuronal cell impairment, increased acetylcholine level and up-regulated the expression of neurotrophic-related genes. In conclusion, CCFM1096, a potential probiotic interfering with cognitive function in mice, attenuated scopolamine-induced cognitive dysfunction in mice via the gut-brain axis and exerted a neuroprotective effect by up-regulating phosphatidylcholine, glycerophosphocholine, and acetylcholine/Brain-Derived Neurotrophic Factor levels.