Host immunoglobulin G selectively identifies pathobionts in pediatric inflammatory bowel diseases

Heather Armstrong,
Misagh Alipour,
Rosica Valcheva,
Michael Bording-Jorgensen,
Juan Jovel,
Deenaz Zaidi,
Prachi Shah,
Yuefei Lou,
Cory Ebeling,
Andrew L. Mason,
Dawson Lafleur,
Jeremy Jerasi,
Gane K.-S. Wong,
Karen Madsen,
Matthew W. Carroll,
Hien Q. Huynh,
Levinus A. Dieleman and
Eytan WineEmail author

Microbiome20197:1

https://doi.org/10.1186/s40168-018-0604-3

Received: 5 July 2018
Accepted: 25 November 2018
Published: 3 January 2019

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 PseudomonasST29 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.