Distinct gut virome profile of pregnant women with type 1 diabetes in the ENDIA study

BACKGROUND: The importance of gut bacteria in human physiology, immune regulation and disease pathogenesis is well established. In contrast, the composition and dynamics of the gut virome (the viral component of the microbiome) remain largely unknown in adults including pregnant women. Viruses are implicated as potential triggers and/or accelerants of many diseases including type 1 diabetes (T1D), and to date, no study has comprehensively examined the gut virome during pregnancy, and how it may be altered by T1D.

METHODS: Comprehensive virome capture sequencing (VirCapSeq-VERT) was used to characterise the gut virome of 61 pregnant women (35 with T1D and 26 without) longitudinally followed in the Environmental Determinants of Islet Autoimmunity (ENDIA) - an Australian prospective cohort study of children at risk of T1D (> 1 first-degree relative with T1D) followed from pregnancy. Women were recruited between 2012-2016. Fecal samples (n=124) were collected during the first (n=18), second (n=47) and/or third trimester of pregnancy (n=59), defined as gestational age (weeks) of 1-14, 15-26 and 27-42, respectively. Maternal T1D and virus positivity examined using generalised estimating equations. Differential abundance analysed using edgeR in R (version 3.3.0).

RESULTS: 63% of samples (78/124) tested positive for >1 virus. Picobirnavirus, Parechovirus and Enteroviruses were among the most frequent genera of vertebrate-infecting viruses and there was a trend to higher virus positivity in mothers with T1D. After adjusting for maternal age, two viruses remained more prevalent in women with T1D: Picobirnavirus (OR 4.2, 95% CI 1.0?17.1; p=0.046) and Tobamovirus (OR 3.2, 1.1-9.3; p=0.037). Furthermore, 77 viruses were differentially abundant between the two maternal groups (?2-fold difference; p<0.02), including 8 enterovirus B genotypes present at a higher abundance in women with T1D. These findings provide novel insight into the composition of the gut virome during pregnancy and demonstrate a distinct virus profile in women with T1D.