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

Abstract

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 study was 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 AppNL–G–F mice. The animals were treated with either vehicle or probiotic (VSL#3) for 8 weeks. Fecal microbiome analysis along with Aβ, GFAP, Iba-1, c-Fos, and Ki-67 immunohisto-chemistry 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 AppNL–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 AppNL–G–F mice. Surprisingly, VSL#3 only increased lactate and acetate in brains of AppNL–G–F mice. No significant differences were observed between vehicle and VSL#3 fed AppNL–G–F hippocampal immunoreactivities of Aβ, GFAP, Iba-1, and Ki-67. However, hippocampal c-Fos staining increased in VSL#3 fed AppNL–G–F mice. Conclusion: These data demonstrate intestinal dysbiosis in the AppNL–G–F mouse model of AD. Probiotic VSL#3 feeding altered both serum and brain levels of lactate and acetate in AppNL–G–F mice correlating with increased expression of the neuronal activity marker, c-Fos.