Gut metabolomic and microbiota analyses in ALS mice reveal specific metabolites despite the absence of significant gut dysbiosis.

Abstract

Objective: Over the past years, interest in the role of gut microbiota in neurodegenerative diseases has emerged. Despite numerous publications over the past decade, both in human and pre-clinical studies, there is no clear consensus on the microbiota's role or involvement in ALS. Few studies on mouse models of ALS highlighted a correlation between specific bacteria species and the prognostic or severity of the disease. Still these results lack reproducibility and remain controverted. In this article we present a study of fecal microbiota in the SOD1^G93A mouse model associated with a metabolomic analysis of cecum content, compared to controls.

Methods: Intestinal metabolomic profile and fecal microbiota were assessed in two cohorts of SOD^G93A mice compared to wildtype controls at the terminal stage of the ALS disease.

Results: Results showed a significant difference in metabolomic profile in SOD1^G93A mice compared to controls but without a marked change in composition and diversity of fecal microbiota. Nevertheless, we observed an increase of Lachnospiraceae family, which are butyrate-producer bacteria, in SOD1^G93A mice. Moreover, some metabolites with significantly different intestinal concentrations are partially produced and linked with intestinal bacteria, such as riboflavin, hippurate, and N-acetylputrescine, leaving us convinced of the interest in looking further into the role of the microbiota in ALS.

Conclusions: Despite an alteration of the intestinal metabolome in SOD1^G93A mice, microbiota data did not show significant changes, underlying the need for further research.