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Nat Commun. 2016 Nov 23;7:13419. doi: 10.1038/ncomms13419.

Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn's disease.

Author information

1
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
2
Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
3
Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
4
Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida 32611, USA.
5
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
6
Biodiversity Institute of Ontario, Department of Integrative Biology, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
7
Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre and CHEO Research Institute, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8L1.
8
Department of Pediatrics, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
9
School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
10
Department of Medicine, Department of Infectious Diseases and Pathology, University of Florida, Gainesville, Florida 32611, USA.
11
Department of Chemistry and Biomolecular Sciences, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.

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.

PMID:
27876802
PMCID:
PMC5122959
DOI:
10.1038/ncomms13419
[Indexed for MEDLINE]
Free PMC Article

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