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 App^NL-G-Fmice. 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 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-Fmice. 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-Fmice. Surprisingly, VSL#3 only increased lactate and acetate in brains of App^NL-G-Fmice. No significant differences were observed between vehicle and VSL#3 fed App^NL-G-Fhippocampal immunoreactivities of Aβ, GFAP, Iba-1, and Ki-67. However, hippocampal c-Fos staining increased in VSL#3 fed App^NL-G-Fmice.

Conclusion:

These data demonstrate intestinal dysbiosis in the App^NL-G-Fmouse model of AD. Probiotic VSL#3 feeding altered both serum and brain levels of lactate and acetate in App^NL-G-Fmice correlating with increased expression of the neuronal activity marker, c-Fos.