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

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. 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 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 <i>Lachnospiraceae</i> 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. Despite an alteration of the intestinal metabolome in SOD1^G93A mice, microbiota data did not show significant changes, underlying the need for further research.