• The Role of Gut Microbiome in Multiple Sclerosis Related Autoimmunity and Neuroinflammation ; A Systematic Review
  • Anahita Hashempoor,1,* Zahra Karimi,2
    1. Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
    2. Bushehr university of Medical Sciences, Faculty of Nursing and midwifery


  • Introduction: MS is a neurodegenerative autoimmune disorder in which the tolerance of host immune system breaks down and it invades the myelin sheath surrounding axon terminals leading to chronic neuroinflammation which is mediated by the overabundance of T helper 1 (Th1) and T helper 17 (Th17) T-cell subsets producing pro-inflammatory cytokines and also inactivation of anti- inflammatory T cell subset known as T regulatory cells (Tregs). The etiology of such autoimmunity is still not clear although it has been linked to some genetic and environmental factors. The gut-brain axis is a complex and bidirectional network between gut microbiome and CNS that might be one of the major environmental factors contributing to MS due to growing evidence suggesting its role in triggering autoimmunity. In pursuit of the role of gut microbiome on autoimmunity we designed this systematic review study.
  • Methods: our search was performed by keywords including multiple sclerosis, gut microbiome, microbiota and gut-brain-axis using PubMed, SCOPUS, Science direct and Google Scholar databases up to October 2019. 80 papers were extracted and after considering the inclusion and exclusion criteria and reading the full text 15 papers were selected to be involved in the study.
  • Results: Desulfovibrionaceae are strictly anaerobic bacteria that desulfinate the amino acid “cysteine” which is needed for glutathione production that have antioxidant activity. Elevated levels of Desulfovirbrionaceae has been shown in MS patients causing withdrawal of cysteine and disruption of host defense against reactive oxygen species. Elevated ROS disrupts BBB and leading to chemotaxis of monocytes and phagocytosis of myelin sheath. Bacterial metabolism of tryptophan produce indole based byproducts which can activate Aryl Hydrocarbon Receptor (AHR), a protein presenting on host lymphocytes that have protective role against inflammation and autoimmunity through modulation of the abundance and activation of Treg and Th17 cells. Bacteria metabolizing indigestible carbohydrates produce short chain fatty acids (SCFAs) which can cause epigenetic changes in lymphocyte chromatin resulting in the proliferation of anti-inflammatory Foxp3+ Treg subsets. the gram negative phylum Bacteroidetes and the gram positive phylum Firmicutes which contains the genus Clostridium produce Propionic acid from fermentation of indigestible fibers which is another short chain fatty acid capable of the prevention and relief of symptoms in inflammatory disorders. There are some reports showing that higher levels of omega-3 fatty acids intake to omega-6 fatty acids activates intestinal alkaline phosphatase (IAP) which reduces the abundance of gram negative bacteria (producing LPS) and also inhibits LPS binding efficacy to toll like receptor4 (TLR4) and therefore decrease inflammation. More studies using new technologies such as next generation sequencing(NGS) is needed to characterize the exact content of MS patients gut microbiome to confirm these results.
  • Conclusion: : MS is a neurodegenerative disorder characterized by the autoimmunity against myelin sheath surrounding axons. The etiology of such reaction is unclear. According to the noticeable population of microbes residing in the gut flora and considering their possible role in pathogenesis of many metabolic diseases and neurodegenerative disorder, they might be involved in the initiation of autoimmunity and their metabolic activity may be the missing piece of this puzzle.
  • Keywords: multiple sclerosis, gut microbiome, microbiota, gut-brain-axis