Microbiota, IgA and Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a neuroinflammatory disease characterized by immune cell infiltration in the central nervous system and destruction of myelin sheaths. Alterations of gut bacteria abundances are present in MS patients. In mouse models of neuroinflammation, depletion of microbiota results in amelioration of symptoms, and gavage with MS patient microbiota exacerbates the disease and inflammation via Th17 cells. On the other hand, depletion of B cells using anti-CD20 is an efficient therapy in MS, and growing evidence shows an important deleterious role of B cells in MS pathology. However, the failure of TACI-Ig treatment in MS highlighted the potential regulatory role of plasma cells. The mechanism was recently demonstrated involving IgA+ plasma cells, specific for gut microbiota and producing IL-10. IgA-coated bacteria in MS patient gut exhibit also modifications. We will focus our review on IgA interactions with gut microbiota and IgA+ B cells in MS. These recent data emphasize new pathways of neuroinflammation regulation in MS.

Orchestrating the fecal microbiota transplantation: Current technological advancements and potential biomedical application

“…Recently, the efficacy of FMT has been observed in changing not only the gut microbiome composition but also the host metabolome and epigenome of immune cells ( 14 ). Several case reports and animal models have also revealed the probable therapeutic effects of FMT in patients with severe multiple sclerosis ( 15 ), autism ( 16 ), multidrug-resistant (MDR) infections ( 17 ), and multiple organ dysfunction in critical patients ( 18 ). Furthermore, the studies also demonstrated the positive effects of immunotherapy on melanoma with FMT in an animal model and clinical trial ( 19 , 20 ).…”

Advantages and limitations of experimental autoimmune encephalomyelitis in breaking down the role of the gut microbiome in multiple sclerosis

“…Furthermore, EAE studies have revealed that several gut bacteria can influence the immune system. For example, microbiota can influence populations of Tregs, Bregs, and IgA+ plasma cell populations (Ochoa-Repáraz et al, 2010a;Opazo et al, 2018;Pröbstel et al, 2020;Boussamet et al, 2022). Specific microbiota, such as Erysipelotrichaceae and segmented filamentous bacteria, have the ability to stimulate T helper (Th) 17 responses (Cryan et al, 2020;Miyauchi et al, 2020), including production of Il17a, Csf2 [encoding granulocyte macrophage colony-stimulating factor (GM-CSF) and Il23r], which are known to be inflammatory in EAE and MS. On the other hand, Prevotella has been found to induce Tregs in mesenteric lymph nodes and the spleen and to suppress Th1 and Th17 cells in EAE mice (Mangalam et al, 2017).…”