Effects of Probiotic Supplementation on Short Chain Fatty Acids in the App^NL-G-F Mouse Model of Alzheimer’s Disease¹

Article type: Research Article

Authors: Kaur, Harpreet^a | Golovko, Svetlana^a | Golovko, Mikhail Y.^a | Singh, Surjeet^b | Darland, Diane C.^c | Combs, Colin K.^{a; *}

Affiliations: [a] Department of Biomedical Sciences, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, ND, USA | [b] Department of Neuroscience, Canadian Centre for Behavioural Neuroscience (CCBN), University of Lethbridge, Lethbridge, AB, Canada | [c] Department of Biology, University of North Dakota, College of Arts & Sciences, Grand Forks, ND, USA

Correspondence: [*] Correspondence to: Colin K. Combs, PhD, University of North Dakota, School of Medicine and Health Sciences, Department of Biomedical Sciences, 1301 N Columbia Road, Suite W315, Grand Forks, ND58202-9037, USA. Tel.: +1 701 777 4025; E-mail: colin.combs@und.edu.

Note: [1] This article received a correction notice (Erratum) with the reference: 10.3233/JAD-229001, available at https://content.iospress.com/articles/journal-of-alzheimers-disease/jad229001.

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-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 AppNL-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 AppNL-G-Fmice. Surprisingly, VSL#3 only increased lactate and acetate in brains of AppNL-G-Fmice. No significant differences were observed between vehicle and VSL#3 fed AppNL-G-Fhippocampal immunoreactivities of Aβ, GFAP, Iba-1, and Ki-67. However, hippocampal c-Fos staining increased in VSL#3 fed AppNL-G-Fmice. Conclusion:These data demonstrate intestinal dysbiosis in the AppNL-G-Fmouse model of AD. Probiotic VSL#3 feeding altered both serum and brain levels of lactate and acetate in AppNL-G-Fmice correlating with increased expression of the neuronal activity marker, c-Fos.

Keywords: Alzheimer’s disease, butyrate, gliosis, microbiota, plaques, probiotics, short chain fatty acids

DOI: 10.3233/JAD-200436

Journal: Journal of Alzheimer's Disease, vol. 76, no. 3, pp. 1083-1102, 2020