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Dysbiosis is a hallmark of inflammatory bowel disease (IBD), but it is unclear which specific intestinal bacteria predispose to and which protect from IBD and how they are regulated. Peptidoglycan recognition proteins ( Pglyrps ) are antibacterial, participate in maintaining intestinal microflora, and modulate inflammatory responses. Mice deficient in any one of the four  Pglyrp  genes are more sensitive to dextran sulfate sodium (DSS)-induced colitis, and stools from  Pglyrp -deficient mice transferred to wild type (WT) germ-free mice predispose them to much more severe colitis than stools from WT mice. However, the identities of these  Pglyrp -regulated bacteria that predispose  Pglyrp -deficient mice to colitis or protect WT mice from colitis are not known. Here we identified significant changes in β-diversity of stool bacteria in  Pglyrp -deficient mice compared with WT mice. The most consistent changes in microbiome in all  Pglyrp -deficient mice were in  Bacteroidales , from which we selected four species, two with increased abundance ( Prevotella falsenii  and  Parabacteroides distasonis ) and two with decreased abundance ( Bacteroides eggerthii  and  Alistipes finegoldii ). We then gavaged WT mice with stock type strains of these species to test the hypothesis that they predispose to or protect from DSS-induced colitis.  P .  falsenii ,  P .  distasonis , and  B .  eggerthii  all enhanced DSS-induced colitis in both WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora. By contrast,  A .  finegoldii  (which is the most abundant species in WT mice) attenuated DSS-induced colitis both in WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora, similar to the colitis protective effect of the entire normal microflora. These results identify  P .  falsenii ,  P .  distasonis , and  B .  eggerthii  as colitis-promoting species and  A .  finegoldii  as colitis-protective species.

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Pglyrp-Regulated Gut Microflora Prevotella falsenii, Parabacteroides distasonis and Bacteroides eggerthii Enhance and Alistipes finegoldii Attenuates Colitis in Mice