Distinct Gut Virome Profile of Pregnant Women With Type 1 Diabetes in the ENDIA Study

Abstract

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 are largely unknown; particularly lacking are studies in pregnancy. We used comprehensive virome capture sequencing to characterize the gut virome of pregnant women with and without type 1 diabetes (T1D), longitudinally followed in the Environmental Determinants of Islet Autoimmunity study.

Methods: In total, 61 pregnant women (35 with T1D and 26 without) from Australia were examined. Nucleic acid was extracted from serial fecal specimens obtained at prenatal visits, and viral genomes were sequenced by virome capture enrichment. The frequency, richness, and abundance of viruses were compared between women with and without T1D.

Results: Two viruses were more prevalent in pregnant women with T1D: picobirnaviruses (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.0-17.1; P = .046) and tobamoviruses (OR, 3.2; 95% CI, 1.1-9.3; P = .037). The abundance of 77 viruses significantly differed between the 2 maternal groups (≥2-fold difference; P < .02), including 8 Enterovirus B types present at a higher abundance in women with T1D.

Conclusions: These findings provide novel insight into the composition of the gut virome during pregnancy and demonstrate a distinct profile of viruses in women with T1D.

Keywords: enterovirus; pregnancy; type 1 diabetes; virome capture sequencing.

Figure 1.

Viruses detected using VirCapSeq-VERT. Heatmap of viral reads (log₂ scale) sequenced in 124 fecal samples collected from 35 women with type 1 diabetes (T1D) (n = 69 samples) and 26 without (n = 55 samples) during pregnancy. Only viruses with ≥100 reads matched by Basic Local Alignment Search Tool (BLAST) at the species level were included and represented at the genus level. Number of viruses detected per specimen, frequency of each virus within the case or control group, and the mean log read counts are summarized by bar charts.

Figure 2.

Longitudinal changes in the gut virome during pregnancy. Presence-absence heatmap of viruses detected over multiple trimesters of pregnancy (T1, T2, and T3) in women with type 1 diabetes (n = 28 individuals) and without (n = 21 individuals).

Figure 3.

Viruses differentially abundant between the gut of women with and without type 1 diabetes during pregnancy. Volcano plot of viruses with ≥2-fold difference (marked by vertical dotted lines) in abundance between pregnant women with and without type 1 diabetes. Only differences with false discovery rate below 5% (P < .05) as determined by edgeR are represented. Species A (EV-A) and B enteroviruses (EV-B) are marked in red and blue, respectively. All other viruses represented in gray.