Finding a needle in a haystack: Bacteroides fragilis polysaccharide A as the archetypical symbiosis factor

Abstract

Starting from birth, all animals develop a symbiotic relationship with their resident microorganisms that benefits both the microbe and the host. Recent advances in technology have substantially improved our ability to direct research toward the identification of important microbial species that affect host physiology. The identification of specific commensal molecules from these microbes and their mechanisms of action is still in its early stages. Polysaccharide A (PSA) of Bacteroides fragilis is the archetypical example of a commensal molecule that can modulate the host immune system in health and disease. This zwitterionic polysaccharide has a critical impact on the development of the mammalian immune system and also on the stimulation of interleukin 10-producing CD4 T cells; consequently, PSA confers benefits to the host with regard to experimental autoimmune, inflammatory, and infectious diseases. In this review, we summarize the current understanding of the immunomodulatory effects of B. fragilis PSA and discuss these effects as a novel immunological paradigm. In particular, we discuss recent advances in our understanding of the unique functional mechanisms of this molecule and its therapeutic potential, and we review the recent literature in the field of microbiome research aimed at discovering new commensal products and their immunomodulatory potential.

The Potential of Gut Commensals in Reinforcing Intestinal Barrier Function and Alleviating Inflammation

“…Bacteroides species are adapted to colonize the harsh environment of the intestine with different mechanisms, such as oxygen toleration using cytochrome bd oxidase, metabolizing a variety of diet- and host-derived polysaccharides, and extensive expression of cell surface structures [ 151 ]. One of the most abundant species, Bacteroides fragilis , a Gram-negative obligate anaerobe, exhibits both beneficial and pathogenic actions for the host [ 152 , 153 ]. The health-promoting properties of the species within this genus have been recognized relatively recently with B. fragilis being the best studied representative.…”

Symbionts exploit complex signaling to educate the immune system

“…Bacteroides fragilis is a gram-negative obligate anaerobe inhabiting the lower gastrointestinal tract of humans. B. fragilis confers beneficial immunomodulatory effects on the host immune system through a single molecule, polysaccharide A (PSA), a zwitterionic symbiosis factor that is abundantly expressed in the microbe's capsular complex (3). Documented beneficial effects of B. fragilis PSA include: 1) stimulation of immune system development and balance (4); 2) protection from pathogenic infections (5); 3) induction of host regulatory T cell (Treg) production of IL-10 during inflammation following T cell activation by plasmacytoid dendritic cells (PDCs) (6); 4) IL-10-dependent protection from intestinal inflammatory diseases (7); and 5) protection from systemic immune-mediated diseases, such as experimental autoimmune encephalomyelitis (EAE, the mouse model of multiple sclerosis in humans) (8,9).…”

Hemagglutination byB. fragilisis mediated by capsular polysaccharides and is influenced by host ABO blood type

“…While there is much to learn about the specific roles of the different CPS of B. fragilis, it is clear that they are important to the bacteria as efforts to maintain a strain that completely lacks the CPS repertoire have failed and strains expressing only a single CPS were unable to effectively colonize the host 22 25 . The functional activities of PSA, a CPS that unlike most has a zwitterionic structure, have been extensively studied and include the ability to induce IL-10 expression by regulatory T-cells 30 , to attenuate inflammation in models of Inflammatory Bowel Disease (IBD) , and to cause intraabdominal abscess . PSA also influences the ability of B. fragilis to colonize the intestinal mucosa, as B. fragilis ∆PSA showed a mucus-specific colonization defect in mice 33 .…”