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Interaction of the Gut Microbiome and Immunity in Multiple Sclerosis: Impact of Diet and Immune Therapy - PubMed

  • ️Sun Jan 01 2023

Review

Interaction of the Gut Microbiome and Immunity in Multiple Sclerosis: Impact of Diet and Immune Therapy

Sudhir Kumar Yadav et al. Int J Mol Sci. 2023.

Abstract

The bidirectional communication between the gut and central nervous system (CNS) through microbiota is known as the microbiota-gut-brain axis. The brain, through the enteric neural innervation and the vagus nerve, influences the gut physiological activities (motility, mucin, and peptide secretion), as well as the development of the mucosal immune system. Conversely, the gut can influence the CNS via intestinal microbiota, its metabolites, and gut-homing immune cells. Growing evidence suggests that gut immunity is critically involved in gut-brain communication during health and diseases, including multiple sclerosis (MS). The gut microbiota can influence the development and function of gut immunity, and conversely, the innate and adaptive mucosal immunity can influence microbiota composition. Gut and systemic immunity, along with gut microbiota, are perturbed in MS. Diet and disease-modifying therapies (DMTs) can affect the composition of the gut microbial community, leading to changes in gut and peripheral immunity, which ultimately affects MS. A high-fat diet is highly associated with gut dysbiosis-mediated inflammation and intestinal permeability, while a high-fiber diet/short-chain fatty acids (SCFAs) can promote the development of Foxp3 Tregs and improvement in intestinal barrier function, which subsequently suppress CNS autoimmunity in the animal model of MS (experimental autoimmune encephalomyelitis or EAE). This review will address the role of gut immunity and its modulation by diet and DMTs via gut microbiota during MS pathophysiology.

Keywords: central nervous system autoimmunity; diet; disease-modifying therapies; gut immunity; gut microbiota; multiple sclerosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1

Role of gut–immune axis in MS pathogenesis. (A) Dysbiotic MS microbiota can promote the differentiation of myelin-specific T cells into Th1/Th17 cells by bystander action and molecular mimicry. (B,C) Myelin-specific Th1/Th17 cells, neutrophiles, and macrophages can cause gut inflammation and increased gut permeability by proinflammatory cytokines. (D) Increased gut permeability leads to the passage of bacterial endotoxins from the gut to periphery including the CNS, which may activate microglia and astrocytes to cause MS onset and/or progression. (E–G) MS gut microbiota is unable to produce sufficient levels of SCFAs, which may further promote intestinal permeability and neuroinflammation. (H) Certain bacterial species produce toxins and promote CNS pathology in MS. (I) Mobilization of IgA+ plasma blast and/or plasma cells from the gut to the CNS can significantly suppress neuroinflammation, and gut dysbiosis may suppress the development of IgA+ B cells in the gut. Schematic diagram was created using

BioRender.com

(accessed on: 13 September 2023).

Figure 2
Figure 2

Mechanisms of gut–immune-axis-mediated effect on the CNS. (A) Microbial metabolites (SCFAs from dietary fibers and tryptophan metabolites) generated from gut microbiota and bacterial endogenous components (LPS and PSA) pass to the circulation due to leaky gut and affect peripheral immunity and glial cells in the CNS. (B) Migration of gut-resident innate and adaptive immune cell populations to the CNS and their cytokines can modulate MS pathogenesis. (C) The gut wall is innervated with both afferent and efferent fibers of the vagus nerve. Efferent nerve fibers carry impulses from the CNS to the gut and affect its physiology. On the other hand, afferent fibers carry impulses from the gut to the CNS. The activity of these fibers can be modulated by the diffusion of bacterial components (like LPS) and metabolites (like SCFAs) or hormonal signals from specialized EECs that are capable of sensing luminal bacterial content. (D) Gut-microbiota-derived LPS and SCFAs modulate the production and release of gut hormones (CCK, ghrelin, Peptide YY, GLP-1, 5-HT) from EECs. Gut hormones potentially suppress Th17 responses and neuroinflammation by attenuating activated microglia. (E) Disease-modifying therapies (DMTs) can affect gut immune cells and epithelial cells to induce changes in gut microbiota, which may contribute toward their therapeutic effects. By promoting anti-inflammatory gut bacteria, DMTs can enhance the development of Tregs or the production of regulatory cytokines in the gut and their circulation, which can suppress CNS autoimmunity. (F) Gut microbiota may modulate the response to DMTs. Schematic diagram was created using

BioRender.com

(accessed on: 13 September 2023).

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References

    1. Rodriguez Murua S., Farez M.F., Quintana F.J. The Immune Response in Multiple Sclerosis. Annu. Rev. Pathol. 2022;17:121–139. doi: 10.1146/annurev-pathol-052920-040318. - DOI - PubMed
    1. Waubant E., Lucas R., Mowry E., Graves J., Olsson T., Alfredsson L., Langer-Gould A. Environmental and genetic risk factors for MS: An integrated review. Ann. Clin. Transl. Neurol. 2019;6:1905–1922. doi: 10.1002/acn3.50862. - DOI - PMC - PubMed
    1. Yadav S.K., Boppana S., Ito N., Mindur J.E., Mathay M.T., Patel A., Dhib-Jalbut S., Ito K. Gut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood. Proc. Natl. Acad. Sci. USA. 2017;114:E9318–E9327. doi: 10.1073/pnas.1615715114. - DOI - PMC - PubMed
    1. McGinley M.P., Goldschmidt C.H., Rae-Grant A.D. Diagnosis and Treatment of Multiple Sclerosis: A Review. JAMA. 2021;325:765–779. doi: 10.1001/jama.2020.26858. - DOI - PubMed
    1. Rutsch A., Kantsjo J.B., Ronchi F. The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology. Front. Immunol. 2020;11:604179. doi: 10.3389/fimmu.2020.604179. - DOI - PMC - PubMed

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