Gut Microbial and Metabolic Signatures are Altered in Adolescents with Type 1 Diabetes

Abstract

BackgroundEvidence suggests that the pathogenesis and development of Type 1 Diabetes (T1D) are driven by both genetic predisposition and immune dysfunction which may be influenced by gut microbiota. The present study aimed to investigate the composition and functional pathways of the gut microbiome in adolescents with T1D, determine the association between gut microbes and clinical and dietary factors in T1D, and identify features predictive of T1D.MethodsHealthy adolescents (n=35) and adolescents with T1D (n=30) were recruited and microbial profiling in participants’ stool samples was performed using deep shotgun metagenomic sequencing. The bioBakery3 pipeline (Kneaddata, Metaphlan3 and HUMAnN) was used to analyze the reads to assign taxonomy and functional annotations. The differences in taxonomic abundances were identified using Linear Discriminant Analysis (LDA) Effect Size (LEfSe) and ecological measures (diversity) were assessed using standard methods. The association between the abundance of specific bacterial species and the metadata (HbA1C, skin carotenoids, diet and physical activity) was assessed by performing Spearman’s correlation. Random forest modeling (using the MUVR package) was used to identify features predictive of T1D.ResultsAdolescents with T1D exhibited a significant increase in Simpson α‐diversity index as compared to healthy adolescents. β‐diversity was similar between the two groups. LEfSe indicated a significant difference in the microbial community at different taxonomic levels between the two groups. Seven taxa were enriched in adolescents with T1D at the species level that includes Alistipes Shahii, Asaccharobacter celatus, Blautia obeum, Coprococcus eutactus, Coprobacillus cateniformis, Clostridium symbiosum, and Eggerthella lenta. Three species Alistripes Putredins, Dialister invisus, and Eubacterium ventriosum were enriched in healthy adolescents. Further, 33 out of 400 microbial metabolic pathways were significantly different between the two groups. Importantly, biosynthesis of amino acids, vitamins, enzyme cofactors, and electron carrier were downregulated whereas fermentation pathways were upregulated in adolescents with T1D as compared to healthy adolescents. Association analysis indicated that specific bacterial species are correlated with HbA1C, skin carotenoids, dietary factors and physical activity. Most of the bacterial species associated with these measures were different between the two groups. MUVR identified bacterial taxa predictive of T1D status (0.82 sensitivity and 0.63 specificity). The top features in using genus level abundance included Coprococcus, Faecalibaterium and Streptococcus.ConclusionThe present study indicates an extensive alteration in the composition and functional capacity of gut microbiota in adolescents with T1D providing new insight into microbial and metabolic signatures in adolescents with T1D.