The Gut Microbiome of Adults With Type 1 Diabetes and Its Association With the Host Glycemic Control

Yuval Bussi,Tal Karady,Marianna Rachmiel,Bat Chen Wolf,Tal Korem,Adina Weinberger,Naim Shehadeh,Nehama Zuckerman Levin,Shlomit Koren,Michal Cohen,Neriya Levran,Noah Gruber,Eran Segal,Dmitry Kolobkov,Smadar Shilo,Noam Bar,Orit Pinhas-Hamiel,Yitav Glantz-Gashai,Anastasia Godneva

doi:10.2337/figshare.17430323.v1

Abstract

OBJECTIVE Previous studies have demonstrated an association between gut microbiota composition and Type 1 diabetes (T1D) pathogenesis. However, little is known about the composition and function of the gut microbiome in adults with longstanding T1D or its association with host glycemic control. RESEARCH DESIGN AND METHODS We performed a metagenomic analysis of the gut microbiome obtained from fecal samples of 74 adults with T1D, 14.6 ± 9.6 years following diagnosis, and compared their microbial composition and function to 296 age-matched healthy controls (1:4 ratio). We further analysed the association between microbial taxa and indices of glycemic control derived from continuous glucose monitoring measurements and blood tests and constructed a prediction model which solely takes microbiome features as input to evaluate the discriminative power of microbial composition for distinguishing individuals with T1D from controls. RESULTS Adults with T1D had a distinct microbial signature that separated them from controls when employing prediction algorithms on held-out subjects (auAUC=0.89±0.03). Linear discriminant analysis showed several bacterial species with significantly higher scores in T1D, including Prevotella copri and Eubacterium siraeum, and species with higher scores in controls, including Firmicutes bacterium and Faecalibacterium prausnitzii (p <0.05, FDR corrected for all). On the functional level, several metabolic pathways were significantly lower in adults with T1D. Several bacterial taxa and metabolic pathways were associated with the host’s glycemic control. CONCLUSIONS We identified a distinct gut microbial signature in adults with longstanding T1D and associations between microbial taxa, metabolic pathways, and glycemic control indices. Additional mechanistic studies are needed to identify the role of these bacteria for potential therapeutic strategies.

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