title: Helminth-induced alterations of the gut microbiota exacerbate bacterial colitis.
abstract: Infection with the intestinal helminth parasite Heligmosomoides polygyrus exacerbates the colitis caused by the bacterial enteropathogen Citrobacter rodentium. To clarify the underlying mechanism, we analyzed fecal microbiota composition of control and helminth-infected mice and evaluated the functional role of compositional differences by microbiota transplantation experiments. Our results showed that infection of Balb/c mice with H. polygyrus resulted in significant changes in the composition of the gut microbiota, characterized by a marked increase in the abundance of Bacteroidetes and decreases in Firmicutes and Lactobacillales. Recipients of the gut microbiota from helminth-infected wide-type, but not STAT6-deficient, Balb/c donors had increased fecal pathogen shedding and significant worsening of Citrobacter-induced colitis compared to recipients of microbiota from control donors. Recipients of helminth-altered microbiota also displayed increased regulatory T cells and IL-10 expression. Depletion of CD4+CD25+T cells and neutralization of IL-10 in recipients of helminth-altered microbiota led to reduced stool C. rodentium numbers and attenuated colitis. These results indicate that alteration of the gut microbiota is a significant contributor to the H. polygyrus-induced exacerbation of C. rodentium colitis. The helminth-induced alteration of the microbiota is Th2-dependent and acts by promoting regulatory T cells that suppress protective responses to bacterial enteropathogens.
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: C
authors.initials: C
authors.lastname: Su
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.|Department of Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
authors.forename: L
authors.initials: L
authors.lastname: Su
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.|College of Animal Science, Zhejiang University, Hongzhou, Zhejiang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Long
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.|Research Center for High Altitude Medicine, Qinghai University School of Medicine, Xining, Qinghai, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: W A
authors.initials: WA
authors.lastname: Walker
authors.affiliation: Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Xavier
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Cherayil
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: H N
authors.initials: HN
authors.lastname: Shi
mesh_terms: D000818:Animals; D058491:Bacterial Load; D044082:Citrobacter rodentium / Q000502:physiology*; D003092:Colitis / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology; D003106:Colon / Q000382:microbiology / Q000469:parasitology / Q000473:pathology*; D018450:Disease Progression; D004756:Enterobacteriaceae Infections / Q000276:immunology*; D005243:Feces / Q000382:microbiology; D005260:Female; D056747:Immunomodulation; D016753:Interleukin-10 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D064307:Microbiota / Q000276:immunology*; D009351:Nematospiroides dubius / Q000276:immunology*; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D017206:Strongylida Infections / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D016753:Interleukin-10