Working Paper Article Version 1 This version is not peer-reviewed

A Metabologenomic Approach Reveals Alterations in the Gut Microbiota of a Mouse model of Alzheimer’s Disease

Version 1 : Received: 5 October 2021 / Approved: 6 October 2021 / Online: 6 October 2021 (12:21:28 CEST)

How to cite: Favero, F.; Barberis, E.; Gagliardi, M.; Espinoza, S.; Contu, L.; Gunstincich, S.; Boccafoschi, F.; Borsotti, C.; Lim, D.; Rubino, V.; Mignone, F.; Pasolli, E.; Manfredi, M.; Zucchelli, S.; Corà, D.; Corazzari, M. A Metabologenomic Approach Reveals Alterations in the Gut Microbiota of a Mouse model of Alzheimer’s Disease. Preprints 2021, 2021100105 Favero, F.; Barberis, E.; Gagliardi, M.; Espinoza, S.; Contu, L.; Gunstincich, S.; Boccafoschi, F.; Borsotti, C.; Lim, D.; Rubino, V.; Mignone, F.; Pasolli, E.; Manfredi, M.; Zucchelli, S.; Corà, D.; Corazzari, M. A Metabologenomic Approach Reveals Alterations in the Gut Microbiota of a Mouse model of Alzheimer’s Disease. Preprints 2021, 2021100105

Abstract

The key role played by host-microbiota interactions on human health, disease onset and progression, and on host response to treatments has increasingly emerged in the latest decades. Indeed, dysbiosis has been associated to several human diseases such as obesity, diabetes, cancer and also neurodegenerative diseases, such as Parkinson, Huntington and Alzheimer’s disease (AD), although whether causative, consequence or merely an epiphenomenon is still under investigation. In the present study, we performed a metabologenomic analysis of stool samples from a mouse model of AD, the 3xTgAD. We found a significant change in the microbiota of AD mice compared to WT, with a longitudinal divergence of the F/B ratio. Moreover, AD mice showed a significant decrease of some amino acids, while data integration revealed a dysregulated production of desaminotyrosine (DAT) and dihydro-3-coumaric acid. Collectively, our data suggest that intestinal microbiota could influence the onset and/or progression of AD, also indicating that a dysbiosis can occur prior to significant symptoms, evidenced by early SCFA alterations, compatible with gut inflammation. Therefore, rebalancing the gut dysbiosis might represent a valuable therapeutic approach to treat AD patients.

Keywords

Alzheimer’s Disease; Microbiota; Metabologenomics; Metabolomics; Metagenomics

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