Central Nervous System Demyelinating Disease Protection by the Human Commensal Bacteroides fragilis Depends on Polysaccharide A Expression

Abstract

Material

The Microbiome and Neurologic Disease: Past and Future of a 2-Way Interaction

“…Although genetic susceptibility is a factor that may determine disease, other risk factors are also necessary, in particular, environmental triggers such as those associated with known risk factors. We, among other investigators, explored the effects of the gut microbiota in experimental autoimmune encephalomyelitis (EAE) models of MS and proposed the idea that the composition of the gut microbiota is relevant for the balance of the proinflammatory and anti-inflammatory cell subpopulations that result in disease induction or protection [9][10][11][12][13][14][15][16][17]. This special issue covers the most recent literature on the experimental models and the clinical evidence for changes in the gut microbiota observed in patients with MS. Tremlett and Waubant [18] explore the microbiota of pediatric MS cases.…”

Reciprocity in Microbiome and Immune System Interactions and its Implications in Disease and Health

“…In an experimental setting, colonization of mice with Bacleroides fragilis leads to protection from colitis development due to PSA-mediated expansion of IL-10 producing regulatory T cells and suppression of IL-17 producing cells 181. Capsular polysaccharide A (PSA) of Bacleroides fragilis can also protect against central nervous system demyelinating disease, EAE, by induction of IL-10 producing regulatory T cells [12,13]. These immunomodulatory features have also been reported for the other commensal bacterial species [1,14].…”

“…A probiotic mixture of lactobacilli also induces regulatory T cells that leads to protection from EAE [99]. Oral treatment with purified PSA antigen derived from human commensal microbiota, Bacteroides fregilis protects mice against EAE by enhancing CD103 + dendritic cells for induction of regulatory T cells in the gut, mesenteric, and cervical lymphoid nodes [12,13]. Similar to a NOD mouse model, administration of mycobacyterial adjuvant has a protective role in an EAE model [100].…”

CD4+ T cells from multiple sclerosis patients respond to a commensal‐derived antigen

“…The human gut commensal B. fragilis has been shown to have a beneficial effect in the mouse model of MS that is dependent on the expression of PSA 9. Similarly, purified PSA can significantly reduce disease severity when orally administered either prophylactically or therapeutically using IL‐10‐dependent mechanisms 12…”

“…The ability of gut microbes to modulate neuroimmune activity has been well documented. In the mouse model of MS (experimental autoimmune encephalomyelitis; EAE), segmented filamentous bacteria promote the development of disease, while Bacteroides fragilis has anti‐inflammatory properties 7, 8, 9. In humans, Clostridium perfringens has been associated with the onset of neuromyelitis optica spectrum disorder, an MS‐like disease 10…”