title: Pglyrp-Regulated Gut Microflora Prevotella falsenii, Parabacteroides distasonis and Bacteroides eggerthii Enhance and Alistipes finegoldii Attenuates Colitis in Mice.
abstract: 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.
authors.affiliation: Indiana University School of Medicine-Northwest, Gary, Indiana, United States of America.
authors.forename: Roman
authors.initials: R
authors.lastname: Dziarski
authors.affiliation: Indiana University School of Medicine-Northwest, Gary, Indiana, United States of America.
authors.forename: Shin Yong
authors.initials: SY
authors.lastname: Park
authors.affiliation: Indiana University School of Medicine-Northwest, Gary, Indiana, United States of America.
authors.forename: Des Raj
authors.initials: DR
authors.lastname: Kashyap
authors.affiliation: MR DNA Molecular Research LP, Shallowater, Texas, United States of America.
authors.forename: Scot E
authors.initials: SE
authors.lastname: Dowd
authors.affiliation: Indiana University School of Medicine-Northwest, Gary, Indiana, United States of America.
authors.forename: Dipika
authors.initials: D
authors.lastname: Gupta
mesh_terms: D000818:Animals; D041963:Bacteroidetes / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D016207:Cytokines / Q000172:deficiency / Q000502:physiology; D016264:Dextran Sulfate / Q000633:toxicity; D004198:Disease Susceptibility; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000276:immunology / Q000502:physiology; D007113:Immunity, Innate; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018720:Prevotella / Q000502:physiology*; D019936:Probiotics / Q000627:therapeutic use*; D021521:Ribotyping
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; C113582:Pglyrp1 protein, mouse; C118897:peptidoglycan recognition protein; D016264:Dextran Sulfate