Microbial Dysbiosis and Lack of SCFAs Production on the Gut of Patients With Multiple Sclerosis in a Spanish Cohort

Abstract

Multiple Sclerosis (MS) is a heterogeneous disease on its clinic and evolution, on which the myelin sheath of the axons is attacked by the own immune system. The origin of MS is still unknown; however, genetic, epigenetic and environmental factors seem to be implicated in its development. In the last years, much effort has been made to describe the gut microbiota dysbiosis of MS patients. Nevertheless, differences in geographical location, diets and lifestyles have made this goal difficult to achieve; therefore, the role of the bacterial dysbiosis in the MS is unclear. The microbiota produces thousands of biologically active substances among which are notable the Short Chain Fatty Acids (SCFAs) excretion. These metabolites are the main mediators of the interaction with the immune and neuroendocrine systems; in consequence, their analysis in the MS could be of great interest. The aim of this study is to determine the microbial dysbiosis and its SCFAs production in a Spanish cohort of MS patients. The gut microbiota of the Spanish cohort of MS patients is characterized by an increment in members of the phylum Proteobacteria, especially marked on those patients that are not receiving any disease modifying treatment. Regarding SCFAs production, a lack in total SCFAs excretion and an altered profile of SCFAs in MS patients, (characterized by a decrease of butyric acid production) could be observed. This alteration is more evident when patients with an Expanded Disability Status Scale (EDSS) score higher than 1 were considered, also presenting a significative reduction of caproic acid and an increase of acetic acid excretion. The abundance of Proteobacteria and acetate and the low excretion of total SCFAs, especially butyrate, are common characteristics of MS patients and, besides, both are associated with a worse prognosis of the disease. Funding Statement: This work was supported by the Spanish Network of Multiple Sclerosis (REEM) under the grant (BIOD19- 021). Declaration of Interests: The authors report no conflict of interest. Ethics Approval Statement: The local ethical committee approved this trial with the reference 09/157.