The Gut Microbiome of Adults With Type 1 Diabetes and Its Association With the Host Glycemic Control
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posted on 2022-01-25, 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<b><i>OBJECTIVE </i></b>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.
<p><b><i>RESEARCH DESIGN AND METHODS</i></b><i> </i>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. </p>
<p><b><i>RESULTS </i></b>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 <i>Prevotella copri </i>and<i> Eubacterium
siraeum, </i>and<i> </i>species with
higher scores in controls, including<i> Firmicutes bacterium </i>and<i> Faecalibacterium prausnitzii </i>(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. </p>
<p><b><i>CONCLUSIONS </i></b>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. </p>
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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