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

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posted on 25.01.2022, 17:30 authored by Smadar Shilo, Anastasia Godneva, Marianna Rachmiel, Tal Korem, Yuval Bussi, Dmitry Kolobkov, Tal Karady, Noam Bar, Bat Chen Wolf, Yitav Glantz-Gashai, Michal Cohen, Nehama Zuckerman Levin, Naim Shehadeh, Noah Gruber, Neriya Levran, Shlomit Koren, Adina Weinberger, Orit Pinhas-Hamiel, Eran Segal
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.

Funding

This work is supported by the Israel Science Foundation (ISF) (grant no. 3-14762). E.S. is supported by the Crown Human Genome Center; Larson Charitable Foundation New Scientist Fund; Else Kroener Fresenius Foundation; White Rose International Foundation; Ben B. and Joyce E. Eisenberg Foundation; Nissenbaum Family; Marcos Pinheiro de Andrade and Vanessa Buchheim; Lady Michelle Michels; Aliza Moussaieff; and grants funded by the Minerva foundation with funding from the Federal German Ministry for Education and Research and by the European Research Council and the Israel Science Foundation. These funding sources had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results.

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