A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease

Abstract

The intestinal microbiome may have a critical roll in susceptibility or resistance to immune-mediated diseases. Alterations of the gut microflora after oral antibiotic treatment can regulate encephalomyelitis (EAE), an animal model for human multiple sclerosis (MS). We now show that a zwitterionic capsular polysaccharide A (PSA) of Bacteroides fragilis can protect against central nervous system demyelinating disease. Oral administration with purified PSA protected mice against EAE prophylactic and therapeutically. PSA treatment enhanced CD103 expressing dendritic cells (DCs) that accumulated in the cervical lymph nodes. Exposure of naïve DCs to PSA induced the conversion of naïve CD4(+) T cells into interleukin (IL)-10-producing FoxP3(+)Treg cells. Protection against EAE was completely abrogated in IL-10-deficient mice. Our results show an important role for a molecule from human commensal bacteria in protecting against EAE and suggest the possibility for protection in MS.

The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases

“…102 The role of the components of the microbiota in the pathogenesis of disease using this experimental model has recently been documented by Kasper's group, and the results of this study have been used to propose a novel treatment. 103,104 The gut-brain axis is a bidirectional communication system through which the brain modulates gastrointestinal function and through which the gastrointestinal system is monitored by the brain. Neural and immunological and endocrine mechanisms are involved in this communication.…”

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].…”