title: Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn's disease.
abstract: Intestinal microbial dysbiosis is associated with Crohn's disease (CD). However, the mechanisms leading to the chronic mucosal inflammation that characterizes this disease remain unclear. In this report, we use systems-level approaches to study the interactions between the gut microbiota and host in new-onset paediatric patients to evaluate causality and mechanisms of disease. We report an altered host proteome in CD patients indicative of impaired mitochondrial functions. In particular, mitochondrial proteins implicated in H2S detoxification are downregulated, while the relative abundance of H2S microbial producers is increased. Network correlation analysis reveals that Atopobium parvulum controls the central hub of H2S producers. A. parvulum induces pancolitis in colitis-susceptible interleukin-10-deficient mice and this phenotype requires the presence of the intestinal microbiota. Administrating the H2S scavenger bismuth mitigates A. parvulum-induced colitis in vivo. This study reveals that host-microbiota interactions are disturbed in CD and thus provides mechanistic insights into CD pathogenesis.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.|Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.|Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Walid
authors.initials: W
authors.lastname: Mottawea
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.|Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
authors.forename: Cheng-Kang
authors.initials: CK
authors.lastname: Chiang
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida 32611, USA.
authors.forename: Marcus
authors.initials: M
authors.lastname: Mühlbauer
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.|Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Starr
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.|Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
authors.forename: James
authors.initials: J
authors.lastname: Butcher
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.|Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
authors.forename: Turki
authors.initials: T
authors.lastname: Abujamel
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.|Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Deeke
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.|Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
authors.forename: Annette
authors.initials: A
authors.lastname: Brandel
authors.affiliation: Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.|Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Biodiversity Institute of Ontario, Department of Integrative Biology, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
authors.forename: Shadi
authors.initials: S
authors.lastname: Shokralla
authors.affiliation: Biodiversity Institute of Ontario, Department of Integrative Biology, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Hajibabaei
authors.affiliation: Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre and CHEO Research Institute, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8L1.
authors.forename: Ruth
authors.initials: R
authors.lastname: Singleton
authors.affiliation: Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre and CHEO Research Institute, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8L1.|Department of Pediatrics, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.|School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
authors.forename: Eric I
authors.identifier: 0000-0001-8855-3598
authors.initials: EI
authors.lastname: Benchimol
authors.affiliation: Department of Medicine, Department of Infectious Diseases and Pathology, University of Florida, Gainesville, Florida 32611, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Jobin
authors.affiliation: Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre and CHEO Research Institute, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8L1.|Department of Pediatrics, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
authors.forename: David R
authors.initials: DR
authors.lastname: Mack
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.|Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.|Department of Chemistry and Biomolecular Sciences, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
authors.forename: Daniel
authors.initials: D
authors.lastname: Figeys
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.|Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
authors.forename: Alain
authors.initials: A
authors.lastname: Stintzi
mesh_terms: D000293:Adolescent; D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D005856:Germ-Free Life; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010802:Phylogeny
chemical_list: D016753:Interleukin-10