Multiple sclerosis occurrence with gut microbial metabolites and sex hormones

Multiple sclerosis (MS) is a chronic immune and neurodegenerative condition that affects the central nervous system (CNS). Multiple factors, both genetic (including the HLA gene locus) and environmental (Epstein-Barr virus, low vitamin D levels), may contribute to MS development. Growing evidence supports the importance of the gut-brain axis and hormones in disease pathogenesis and progression. This review focuses on identifying the role of specific gut microbial products (short-chain fatty acids, tryptophan derivatives, bile acids, and polyamines) in this process and how they affect the immune system, blood-brain barrier (BBB), and glial cells. The review will also describe key differences between female and male patients with MS, including the higher prevalence in females and the tendency toward a progressive course in males. Estrogens, progesterone, and androgens have immunomodulatory, neuroprotective, and remyelinating activities, and this review will describe their impact on multiple sclerosis based on preclinical and clinical findings from pregnancy, menopause, and hormone replacement therapy. This paper discusses the intersection of these ideas through the "microgenderome" concept, which describes how hormones influence gut microbiota composition and how the microbiota, in turn, modulates hormone metabolism and levels.