Abstract
The early stages of life constitute a crucial period for neurodevelopment, during which maternal gut microbiota dysbiosis can impact offspring neurodevelopment via the microbiota-gut-brain axis. This study aimed to examine the ameliorative effects of administering the probiotic Lactobacillus rhamnosus MP108 during pregnancy on neurodevelopmental impairments in offspring induced by a maternal high-fat diet. The findings indicated that the MP108 intervention significantly ameliorated cognitive and behavioral abnormalities in offspring resulting from maternal obesity. Additionally, it restructured the gut microbiota composition in both mothers and offspring, enhancing the prevalence of beneficial bacteria such as Blautia and Alloprevotella. Metabolomic analysis further revealed that MP108 reduced intestinal levels of L-homocystine and methionine while increasing those of L-(+)-arginine, L-(+)-citrulline, and L-tyrosine. Furthermore, MP108 markedly attenuated the aberrant expression of neuroinflammatory and myelin formation-related genes in the hippocampal region of offspring, including cyclooxygenase-2 (Cox2), nuclear factor kappa-B (NF-κB), and myelin basic protein (MBP), thereby restoring their expression levels to normative ranges. This study represents the first evidence that maternal intervention with MP108 during gestation influences gut microbiota composition and metabolite profiles, subsequently reducing neuroinflammation and facilitating neural development. This mechanism effectively alleviates the detrimental effects of a maternal high-fat diet on the neural development of offspring, thereby providing empirical support for the potential application of MP108 in the prevention and amelioration of neurodevelopmental disorders.