The virome in early life and childhood and development of islet autoimmunity and type 1 diabetes: A systematic review and meta-analysis of observational studies

Clare L Faulkner; Yi Xuan Luo; Sonia Isaacs; William D Rawlinson; Maria E Craig; Ki Wook Kim

doi:10.1002/rmv.2209

The virome in early life and childhood and development of islet autoimmunity and type 1 diabetes: A systematic review and meta-analysis of observational studies

Rev Med Virol. 2021 Sep;31(5):1-14. doi: 10.1002/rmv.2209. Epub 2020 Dec 30.

Authors

Clare L Faulkner^{1

2}, Yi Xuan Luo^{1

2}, Sonia Isaacs^{1

2}, William D Rawlinson^{1

2

3

4}, Maria E Craig^{1

2

5

6}, Ki Wook Kim^{1

2}

Affiliations

¹ School of Women's and Children's Health, University of New South Wales Faculty of Medicine, Sydney, New South Wales, Australia.
² Serology and Virology Division, NSW Health Pathology, Virology Research Laboratory, Prince of Wales Hospital, Sydney, New South Wales, Australia.
³ School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
⁴ Faculty of Science, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
⁵ Institute of Endocrinology and Diabetes, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
⁶ Discipline of Child and Adolescent Health, University of Sydney, Sydney, New South Wales, Australia.

Abstract

Viruses are postulated as primary candidate triggers of islet autoimmunity (IA) and type 1 diabetes (T1D), based on considerable epidemiological and experimental evidence. Recent studies have investigated the association between all viruses (the 'virome') and IA/T1D using metagenomic next-generation sequencing (mNGS). Current associations between the early life virome and the development of IA/T1D were analysed in a systematic review and meta-analysis of human observational studies from Medline and EMBASE (published 2000-June 2020), without language restriction. Inclusion criteria were as follows: cohort and case-control studies examining the virome using mNGS in clinical specimens of children ≤18 years who developed IA/T1D. The National Health and Medical Research Council level of evidence scale and Newcastle-Ottawa scale were used for study appraisal. Meta-analysis for exposure to specific viruses was performed using random-effects models, and the strength of association was measured using odds ratios (ORs) and 95% confidence intervals (CIs). Eligible studies (one case-control, nine nested case-control) included 1,425 participants (695 cases, 730 controls) and examined IA (n = 1,023) or T1D (n = 402). Meta-analysis identified small but significant associations between IA and number of stool samples positive for all enteroviruses (OR 1.14, 95% CI 1.00-1.29, p = 0.05; heterogeneity χ² = 1.51, p = 0.68, I² = 0%), consecutive positivity for enteroviruses (1.55, 1.09-2.20, p = 0.01; χ² = 0.19, p = 0.91, I² = 0%) and number of stool samples positive specifically for enterovirus B (1.20, 1.01-1.42, p = 0.04; χ² = 0.03, p = 0.86, I² = 0%). Virome analyses to date have demonstrated associations between enteroviruses and IA that may be clinically significant. However, larger prospective mNGS studies with more frequent sampling and follow-up from pregnancy are required to further elucidate associations between early virus exposure and IA/T1D.

Keywords: childhood; islet autoimmunity; next-generation sequencing; type 1 diabetes; virome.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

MeSH terms

Autoimmunity*
Child
Diabetes Mellitus, Type 1* / genetics
High-Throughput Nucleotide Sequencing
Humans
Infant
Prospective Studies
Virome / genetics*