The role of gut microbiome and associated metabolome in the regulation of neuroinflammation in multiple sclerosis and its implications in attenuating chronic inflammation in other inflammatory and autoimmune disorders

Abstract

SummaryThe importance of the gut microbiome in the regulation of non-infectious diseases has earned unprecedented interest from biomedical researchers. Widespread use of next-generation sequencing techniques has prepared a foundation for further research by correlating the presence of specific bacterial species with the onset or severity of a disease state, heralding paradigm-shifting results. This review covers the mechanisms through which a dysbiotic gut microbiota contributes to the pathological symptoms in an autoimmune neurodegenerative disorder, multiple sclerosis (MS). Although the central nervous system (CNS) is protected by the bloodbrain barrier (BBB), it is unclear how gut dysbiosis can trigger potential immunological changes in the CNS in the presence of the BBB. This review focuses on the immunoregulatory functionality of microbial metabolites, which can cross the BBB and mediate their effects directly on immune cells within the CNS and/or indirectly through modulating the response of peripheral T cells to stimulate or inhibit pro-inflammatory chemokines and cytokines, which in turn regulate the autoimmune response in the CNS. Although more research is clearly needed to directly link the changes in gut microbiome with neuroinflammation, focusing research on microbiota that produce beneficial metabolites with the ability to attenuate chronic inflammation systemically as well as in the CNS, can offer novel preventive and therapeutic modalities against a wide array of inflammatory and autoimmune diseases.

Lymphocytes T Helper 17 in Multiple Sclerosis: Regulation by Intestinal Microbiota

“…There was a decrease in the anti-inflammatory marker Foxp3. These differential cytokine levels coincided with an upregulation of the AHR, which shows a potential increased susceptibility to both endogenous and microbiota-produced compounds to compete as antagonists/agonists to drive further T cell proliferation towards either an inflammatory or anti-inflammatory phenotype [43,48].…”

Smoking and disability progression in multiple sclerosis

“…Another mechanism by which smoking may affect MS progression is by inducing gastric and intestinal microbiome alterations. The microbiome affects the immune system by regulating the colonic mucosal barrier and intestinal lymphoid tissue, and by inhibiting pathogenic microorganisms and modulating inflammatory responses [22]. Although increasing evidence suggest a critical role of the gut microbiota in MS development and progression, more research is needed to better understand how smoke-induced changes in the gut microbiome affect neuroinflammation.…”

Metabolism and inflammation: implications for traumatic brain injury therapeutics

“…Supplementing microbiota could have indirect effects on inflammation and metabolism. The brain-gut axis is outside the scope of this review, however is recognised in multiple sclerosis [171], and some preliminary studies in TBI [172,173].…”