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

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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 control subjects (1:4 ratio). We further analyzed the association between microbial taxa and indices of glycemic control derived from continuous glucose monitoring measure-ments and blood tests and constructed a prediction model that solely takes micro-biome features as input to evaluate the discriminative power of microbial composition for distinguishing individuals with T1D from control subjects. RESULTS Adults with T1D had a distinct microbial signature that separated them from control subjects when using prediction algorithms on held-out subjects (area under the receiver operating characteristic curve 5 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 control subjects, including Firmicutes bacterium and Faecalibacterium prausnitzii (P < 0.05, false discovery rate 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.

Original languageEnglish
Pages (from-to)555-563
Number of pages9
JournalDiabetes Care
Volume45
Issue number3
DOIs
StatePublished - Mar 2022

Funding

FundersFunder number
Federal Ger-man Ministry for Education and Research
Federal German Ministry for Education and Research
Joyce E. Eisenberg Foundation
White Rose International Foundation
Masonic Charitable Foundation
European Research Council
Minerva Foundation
Else Kröner-Fresenius-Stiftung
Israel Science Foundation3-14762
Crown Human Genome Center

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