Medical Biology - Research Publications
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ItemGut microbiome dysbiosis and increased intestinal permeability in children with islet autoimmunity and type 1 diabetes: A prospective cohort study(WILEY, 2019-08)AIMS/HYPOTHESIS: To investigate the longitudinal relationship between the gut microbiome, circulating short chain fatty acids (SCFAs) and intestinal permeability in children with islet autoimmunity or type 1 diabetes and controls. METHODS: We analyzed the gut bacterial microbiome, plasma SCFAs, small intestinal permeability and dietary intake in 47 children with islet autoimmunity or recent-onset type 1 diabetes and in 41 unrelated or sibling controls over a median (range) of 13 (2-34) months follow-up. RESULTS: Children with multiple islet autoantibodies (≥2 IA) or type 1 diabetes had gut microbiome dysbiosis. Anti-inflammatory Prevotella and Butyricimonas genera were less abundant and these changes were not explained by differences in diet. Small intestinal permeability measured by blood lactulose:rhamnose ratio was higher in type 1 diabetes. Children with ≥2 IA who progressed to type 1 diabetes (progressors), compared to those who did not progress, had higher intestinal permeability (mean [SE] difference +5.14 [2.0], 95% confidence interval [CI] 1.21, 9.07, P = .006), lower within-sample (alpha) microbial diversity (31.3 [11.2], 95% CI 9.3, 53.3, P = .005), and lower abundance of SCFA-producing bacteria. Alpha diversity (observed richness) correlated with plasma acetate levels in all groups combined (regression coefficient [SE] 0.57 [0.21], 95% CI 0.15, 0.99 P = .008). CONCLUSIONS/INTERPRETATION: Children with ≥2 IA who progress to diabetes, like those with recent-onset diabetes, have gut microbiome dysbiosis associated with increased intestinal permeability. Interventions that expand gut microbial diversity, in particular SCFA-producing bacteria, may have a role to decrease progression to diabetes in children at-risk.
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ItemInfluence of fecal collection conditions and 16S rRNA gene sequencing at two centers on human gut microbiota analysis(NATURE PORTFOLIO, 2018-03-12)To optimise fecal sampling for reproducible analysis of the gut microbiome, we compared different methods of sample collection and sequencing of 16S rRNA genes at two centers. Samples collected from six individuals on three consecutive days were placed in commercial collection tubes (OMNIgeneGut OMR-200) or in sterile screw-top tubes in a home fridge or home freezer for 6-24 h, before transfer and storage at -80 °C. Replicate samples were shipped to centers in Australia and the USA for DNA extraction and sequencing by their respective PCR protocols, and analysed with the same bioinformatic pipeline. Variation in gut microbiome was dominated by differences between individuals. Minor differences in the abundance of taxa were found between collection-processing methods and day of collection, and between the two centers. We conclude that collection with storage and transport at 4 °C within 24 h is adequate for 16S rRNA analysis of the gut microbiome. Other factors including differences in PCR and sequencing methods account for relatively minor variation compared to differences between individuals.
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ItemDistinct Gut Virome Profile of Pregnant Women With Type 1 Diabetes in the ENDIA Study(OXFORD UNIV PRESS INC, 2019-02)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.