title: Helminth infection promotes colonization resistance via type 2 immunity.
abstract: Increasing incidence of inflammatory bowel diseases, such as Crohn's disease, in developed nations is associated with changes to the microbial environment, such as decreased prevalence of helminth colonization and alterations to the gut microbiota. We find that helminth infection protects mice deficient in the Crohn's disease susceptibility gene Nod2 from intestinal abnormalities by inhibiting colonization by an inflammatory Bacteroides species. Resistance to Bacteroides colonization was dependent on type 2 immunity, which promoted the establishment of a protective microbiota enriched in Clostridiales. Additionally, we show that individuals from helminth-endemic regions harbor a similar protective microbiota and that deworming treatment reduced levels of Clostridiales and increased Bacteroidales. These results support a model of the hygiene hypothesis in which certain individuals are genetically susceptible to the consequences of a changing microbial environment.
authors.affiliation: Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA. Sackler Institute of Graduate Biomedical Sciences, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Deepshika
authors.initials: D
authors.lastname: Ramanan
authors.affiliation: Departments of Microbiology and Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Rowann
authors.initials: R
authors.lastname: Bowcutt
authors.affiliation: Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Soo Ching
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Departments of Microbiology and Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Mei San
authors.initials: MS
authors.lastname: Tang
authors.affiliation: Sackler Institute of Graduate Biomedical Sciences, New York University School of Medicine, New York, NY 10016, USA. Departments of Microbiology and Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Kurtz
authors.affiliation: Department of Pathology, New York University Langone Medical Center, New York, NY 10016, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa 230-0045, Japan. Japan Agency for Medical Research and Development (AMED)-Core Research for Evolutional Science and Technology (CREST), Tokyo 100-0004, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Honda
authors.affiliation: Center for Immunity and Inflammation, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07101, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Gause
authors.affiliation: Departments of Microbiology and Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Blaser
authors.affiliation: Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10003, USA. Courant Institute of Mathematical Sciences, New York University, New York, NY 10012, USA. Simons Center for Data Analysis, Simons Foundation, New York, NY 10011, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bonneau
authors.affiliation: Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. ken.cadwell@med.nyu.edu png.loke@nyumc.org limailian@um.edu.my.
authors.forename: Yvonne A L
authors.initials: YA
authors.lastname: Lim
authors.affiliation: Departments of Microbiology and Medicine, New York University School of Medicine, New York, NY 10016, USA. ken.cadwell@med.nyu.edu png.loke@nyumc.org limailian@um.edu.my.
authors.forename: P'ng
authors.initials: P
authors.lastname: Loke
authors.affiliation: Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA. Departments of Microbiology and Medicine, New York University School of Medicine, New York, NY 10016, USA. ken.cadwell@med.nyu.edu png.loke@nyumc.org limailian@um.edu.my.
authors.forename: Ken
authors.initials: K
authors.lastname: Cadwell
mesh_terms: D000818:Animals; D001439:Bacteroides / Q000276:immunology*; D001442:Bacteroides Infections / Q000276:immunology*; D000068016:Eubacteriales / Q000276:immunology; D003015:Clostridium Infections / Q000276:immunology; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D061148:Hygiene Hypothesis; D007422:Intestines / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology; D051379:Mice; D008817:Mice, Mutant Strains; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D014257:Trichuriasis / Q000276:immunology*; D014258:Trichuris / Q000276:immunology*
chemical_list: D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse