Effects of Probiotic Supplementation on Short Chain Fatty Acids in the AppNL-G-F Mouse Model of Alzheimer's Disease

Background: The intestinal microbiota and its metabolites, particularly short-chain fatty acids (SCFAs), have been implicated in immune function, host metabolism, and even behavior. Objective: This studywas performed to investigate whether probiotic administration influences levels of intestinal microbiota and their metabolites in a fashion that may attenuate brain changes in a mouse model of Alzheimer's disease (AD). Methods: C57BL/6 wild-type (WT) mice were compared to App(NL-G-F) mice. The animals were treated with either vehicle or probiotic (VSL#3) for 8 weeks. Fecal microbiome analysis along with A beta, GFAP, Iba-1, c-Fos, and Ki-67 immunohistochemistry was done. SCFAs were analyzed in serum and brains using UPLC-MS/MS. Results: Probiotic (VSL#3) supplementation for 2 months resulted in altered microbiota in both WT and App(NL-G-F) mice. An increase in serum SCFAs acetate, butyrate, and lactate were found in both genotypes following VSL#3 treatment. Propionate and isobutyrate were only increased in App(NL-G-F) mice. Surprisingly, VSL#3 only increased lactate and acetate in brains of App(NL-G-F) mice. No significant differences were observed between vehicle and VSL#3 fed App(NL-G-F) hippocampal immunoreactivities of A beta, GFAP, Iba-1, and Ki-67. However, hippocampal c-Fos staining increased in VSL#3 fed App(NL-G-F) mice. Conclusion: These data demonstrate intestinal dysbiosis in the App(NL-G-F) mouse model of AD. Probiotic VSL#3 feeding altered both serum and brain levels of lactate and acetate in App(NL-G-F) mice correlating with increased expression of the neuronal activity marker, c-Fos.