Abstract

Host immunoglobulin G selectively identifies pathobionts in pediatric inflammatory bowel diseases

Armstrong H1,2, Alipour M1,2, Valcheva R1,3, Bording-Jorgensen M1,4, Jovel J1,3, Zaidi D1,2, Shah P1,2, Lou Y1,3, Ebeling C5, Mason AL1,3, Lafleur D1,2, Jerasi J1,2, Wong GK1,6, Madsen K1,3, Carroll MW2, Huynh HQ2, Dieleman LA1,3, Wine E7,8,9. Microbiome. 2019 Jan 3;7(1):1. doi: 10.1186/s40168-018-0604-3.
 
     

Author information

1 CEGIIR, University of Alberta, Edmonton, AB, T6G 2X8, Canada.

2 Department of Pediatrics, University of Alberta, Edmonton Clinic Health Academy, Room 4-577, 11405 87th Ave, Edmonton, AB, T6G 1C9, Canada.

3 Department of Medicine, University of Alberta, Edmonton, AB, T6G 2G3, Canada.

4 Department of Physiology, University of Alberta, Edmonton, AB, T6G 1C9, Canada.

5 Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, T6G 2G3, Canada.

6 Department of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2G3, Canada.

7 CEGIIR, University of Alberta, Edmonton, AB, T6G 2X8, Canada. wine@ualberta.ca.

8 Department of Pediatrics, University of Alberta, Edmonton Clinic Health Academy, Room 4-577, 11405 87th Ave, Edmonton, AB, T6G 1C9, Canada. wine@ualberta.ca.

9 Department of Physiology, University of Alberta, Edmonton, AB, T6G 1C9, Canada. wine@ualberta.ca.

Abstract

BACKGROUND: Inflammatory bowel diseases (IBD) are a group of complex and multifactorial disorders with unknown etiology. Chronic intestinal inflammation develops against resident intestinal bacteria in genetically susceptible hosts. We hypothesized that host intestinal immunoglobulin (Ig) G can be used to identify bacteria involved in IBD pathogenesis.

RESULTS: IgG-bound and -unbound microorganisms were collected from 32 pediatric terminal ileum aspirate washes during colonoscopy [non-IBD (n = 10), Crohn disease (n = 15), and ulcerative colitis (n = 7)], and composition was assessed using the Illumina MiSeq platform. In vitro analysis of invasive capacity was evaluated by fluorescence in situ hybridization and gentamicin invasion assay; immune activation was measured by qPCR. Despite considerable inter-individual variations, IgG binding favored specific and unique mucosa-associated species in pediatric IBD patients. Burkholderia cepacia, Flavonifractor plautii, and Rumminococcus sp. demonstrated increased IgG binding, while Pseudomonas ST29 demonstrated reduced IgG binding, in IBD. In vitro validation confirmed that B. cepacia, F. plautii, and Rumminococcus display invasive potential while Pseudomonas protogens did not.

CONCLUSION: Using IgG as a marker of pathobionts in larger patient cohorts to identify microbes and elucidate their role in IBD pathogenesis will potentially underpin new strategies to facilitate development of novel, targeted diagnostic, and therapeutic approaches. Interestingly, this method can be used beyond the scope of this manuscript to evaluate altered gut pathobionts in a number of diseases associated with altered microbiota including arthritis, obesity, diabetes mellitus, alcoholic liver disease, cirrhosis, metabolic syndrome, and carcinomas.

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