Abstract
The symbiotic relationship between animals and their resident microorganisms has profound effects on host immunity. The human microbiota comprises bacteria that reside in the gastrointestinal tract and are involved in a range of inflammatory and autoimmune diseases. The gut microbiota’s immunomodulatory effects extend to extraintestinal tissues, including the central nervous system (CNS). Specific symbiotic antigens responsible for inducing immunoregulation have been isolated from different bacterial species. Polysaccharide A (PSA) of Bacteroides fragilis is an archetypical molecule for host-microbiota interactions. Studies have shown that PSA has beneficial effects in experimental disease models, including experimental autoimmune encephalomyelitis (EAE), the most widely used animal model for multiple sclerosis (MS). Furthermore, in vitro stimulation with PSA promotes an immunomodulatory phenotype in human T cells isolated from healthy and MS donors. In this review, we discuss the current understanding of the interactions between gut microbiota and the host in the context of CNS inflammatory demyelination, the immunomodulatory roles of gut symbionts. More specifically, we also discuss the immunomodulatory effects of B. fragilis PSA in the gut-brain axis and its therapeutic potential in MS. Elucidation of the molecular mechanisms responsible for the microbiota’s impact on host physiology offers tremendous promise for discovering new therapies.
Highlights
Mammals have co-evolved with eons of resident microorganisms that play an integral role in regulating the host immunity [1]
We propose that polysaccharide A (PSA) produced by B. fragilis is an identified symbiont factor model for immunomodulation
Multiple Sclerosis (MS) is an immune-mediated debilitating disease initiated by the immune system attacking the neuron protecting myelin sheet, which results in inflammation, chronic demyelination, axonal degeneration, and loss of brain volume [67, 68]
Summary
Mammals have co-evolved with eons of resident microorganisms that play an integral role in regulating the host immunity [1]. These microorganisms live in a complex community called microbiota, which is dominated by bacteria and includes archaea, fungi, and viruses [2]. PSA mediates gut homeostasis by directing cellular and physical development of the immune system [10], stimulating Tregs [11] via plasmacytoid dendritic cells (PDCs) [12], and protecting animals from experimental diseases like colitis [11, 12], asthma [13], or pulmonary inflammation [14], and experimental autoimmune encephalomyelitis (EAE) [15,16,17]. Our review will summarize how PSA regulates immune responses in MS/EAE and discusses PSA’s therapeutic potential
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
