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Related Experiment Video

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Perturbed Microbiota/Immune Homeostasis in Multiple Sclerosis.

Delphine Sterlin1, Martin Larsen1, Jehane Fadlallah1

  • 1From the Sorbonne Université (D.S., M.L., J.F., C.P., M.V., G.A., K.D., G.G.), Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), AP-HP Hôpital Pitié-Salpêtrière, France; Université Paris-Saclay (C.J., P.L.), INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France; Hôpital Ophtalmologique Adolphe de Rothschild (J.A., O.G., R.D.), Département de Neurologie, Paris, France; and Sorbonne Université (S.V., E.M., C.L., C.P.), Département de Neurologie, AP-HP Hôpital Pitié-Salpêtrière, Paris, France.

Neurology(R) Neuroimmunology & Neuroinflammation
|May 12, 2021
PubMed
Summary

Multiple sclerosis (MS) patients exhibit reduced gut IgA responses and increased systemic IgG responses to gut microbes, indicating a breakdown in immune tolerance. This suggests dysregulated gut microbiota contribute to MS immune system alterations.

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Area of Science:

  • Immunology
  • Microbiology
  • Neurology

Background:

  • Gut microbial dysbiosis is suspected to influence immunity and multiple sclerosis (MS) progression.
  • Host-microbiota interactions play a crucial role in immune system regulation.

Purpose of the Study:

  • To investigate deregulated microbiota-induced systemic immune responses in MS patients.
  • To identify specific antibody responses to gut microbiota in individuals with MS and clinically isolated syndromes (CIS).

Main Methods:

  • Compared gut microbiota composition and diversity using 16S rRNA sequencing.
  • Quantified gut and systemic commensal-specific antibody responses (IgG and IgA) using bacterial flow cytometry assays.
  • Analyzed antibody responses in healthy controls (n=32), MS patients (n=30), and CIS individuals (n=15).

Main Results:

  • Significantly reduced commensal-specific gut IgA responses were observed in MS patients, correlated with disease severity.
  • Increased serum IgG responses to IgA-unbound bacteria were found in MS and CIS patients compared to controls.
  • Gut microbiota composition and diversity differed between controls and MS patients.

Conclusions:

  • MS is associated with perturbed gut and systemic microbiota-immune homeostasis.
  • Defective IgA responses in MS may lead to a breakdown of systemic tolerance to gut microbiota.
  • This breakdown enhances systemic IgG immunity against gut commensals, potentially contributing to early MS pathogenesis.