Abstract
As a complex disease, Multiple Sclerosis (MS)’s etiology is determined by both genetic and environmental factors. In the last decade, the gut microbiome has emerged as an important environmental factor, but its interaction with host genetics is still unknown. In this review, we focus on these dual aspects of MS pathogenesis: we describe the current knowledge on genetic factors related to MS, based on genome-wide association studies, and then illustrate the interactions between the immune system, gut microbiome and central nervous system in MS, summarizing the evidence available from Experimental Autoimmune Encephalomyelitis mouse models and studies in patients. Finally, as the understanding of influence of host genetics on the gut microbiome composition in MS is in its infancy, we explore this issue based on the evidence currently available from other autoimmune diseases that share with MS the interplay of genetic with environmental factors (Inflammatory Bowel Disease, Rheumatoid Arthritis and Systemic Lupus Erythematosus), and discuss avenues for future research.
Highlights
Several studies in mouse models and humans support the idea that host genetic components can regulate gut microbiome composition: twin studies have shown that overall microbiome composition and many individual taxa are heritable
Much effort has been invested, a clear trend indicating a role of the host genetics in the gut microbiome has not been identified, probably due to inconsistencies and unevenness between the studies’ results, low sample sizes and environmental factors [128]
It is widely accepted that the gut microbiota plays a crucial role in the gut–brain axis, controlling Central Nervous System (CNS) diseases, and dysbiosis is present in Multiple Sclerosis (MS) patients; we are very far from the identification of a particular gut microbiome signature in MS
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Pro-inflammatory T helper cells (Th) 1, Th 17 and Th 22 are activated in the periphery following a deficit of regulatory T lymphocytes (T reg), which lose the ability to suppress the autoreactive response [9]. In the later stages of the disease, the inflammatory response is supported by the activation and polarization of microglia, leading to chronic neurodegeneration [1,13,14]. The etiology of MS remains largely unknown, but it is considered a multifactorial disease in which both genetic and environmental factors could influence the immune system development and response in individuals, predisposing them to MS onset [3,4]. How these complex networks of interactions drive disease susceptibility remains to be elucidated
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