Diverse Intestinal Bacteria Contain Putative Zwitterionic Capsular Polysaccharides with Anti-inflammatory Properties

Abstract

Summary Zwitterionic capsular polysaccharides (ZPS) are bacterial products that modulate T cells, including inducing anti-inflammatory IL-10-secreting T regulatory cells (Tregs). However, only a few diverse bacteria are known to modulate the host immune system via ZPS. We present a genomic screen for bacteria encoding ZPS molecules. We identify diverse host-associated bacteria, including commensals and pathogens with known anti-inflammatory properties, with the capacity to produce ZPSs. Human mononuclear cells stimulated with lysates from putative ZPS-producing bacteria induce significantly greater IL-10 production and higher proportions of Tregs than lysates from non ZPS-encoding relatives or a commensal strain of Bacteroides cellulosilyticus in which a putative ZPS biosynthetic operon was genetically disrupted. Similarly, wild-type B. cellulosilyticus DSM 14838, but not a close relative lacking a putative ZPS, attenuated experimental colitis in mice. Collectively, this screen identifies bacterial strains that may use ZPS to interact with the host as well as those with potential probiotic properties.

Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis

“…Intriguingly, a recent study showed that zwitterionic capsular polysaccharides derived from various commensal gut bacteria produce anti-inflammatory effects by inducing regulatory T cells 50. Our observations that P. goldsteinii treatment induces expression of IL-10 (figure 7H) and helps maintain intestinal integrity (figure 7G,I,J) support the possibility that the bacterium may preserve intestinal homeostasis and improve gut barrier functions in vivo.…”

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“…Fermentation of dietary fibers by Clostridia clusters IV, XIVa and XVIII produces short-chain fatty acids (SCFA), particularly butyrate, which exert significant anti-inflammatory functions, promote peripheral T reg cell generation, and are key nutrients for colonocytes 103–106 . Moreover, subtypes of B. fragilis and certain other intestinal bacteria produce capsular polysaccharide A (PSA), which provides immunoprotection through induction of IL-10-producing T reg cells, and administration of B. fragilis or even PSA alone corrected immune defects in germ-free mice and had protective effects in models of colitis 107,108 . Further, the intestinal tissues of IBD patients often show downregulation of the aryl hydrocarbon receptor (AHR), which, in response to bacteria-derived indole metabolites, induces production of IL-22 by group 3 innate lymphoid cells (ILC3) 109 .…”

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“…2b). A recent study has identified additional gut commensals that produce zwitterionic capsular polysaccharides, including a strain of Bacteroides cellulosilyticus , with similar anti-inflammatory properties to PSA 114 .…”