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

Zwitterionic capsular polysaccharides (ZPSs) 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 ZPSs to interact with the host as well as those with potential probiotic properties. [Display omitted] •Genomic screen identifies bacteria with ability to produce zwitterionic polysaccharides•Predicted bacteria display anti-inflammatory immune modulation in human cell assays•Putative ZPS-producer Bacteroides cellulosilyticus protected mice from colitis•ZPS-producing bacteria may have therapeutic potential Identifying anti-inflammatory host-associated bacteria can reveal strategies to combat inflammatory disease. Neff et al. conduct a genomic screen to identify bacteria with the capability to produce capsular zwitterionic polysaccharides (ZPSs). These ZPS-producing bacteria induce increased levels of anti-inflammatory IL-10 and Tregs and prevent experimental colitis in mice.