Abstract

ObjectiveMounting evidence has suggested a link between gut microbiome characteristics and type 2 diabetes (T2D). To determine whether these alterations occur before the impairment of glucose regulation, we characterize gut microbiota in normoglycemic individuals who go on to develop T2D.MethodsWe designed a nested case-control study, and enrolled individuals with a similar living environment. A total of 341 normoglycemic individuals were followed for 4 years, including 30 who developed T2D, 33 who developed prediabetes, and their matched controls. Fecal samples (developed T2D, developed prediabetes and controls: n=30, 33, and 63, respectively) collected at baseline underwent metagenomics sequencing.ResultsCompared with matched controls, individuals who went on to develop T2D had lower abundances of Bifidobacterium longum, Coprobacillus unclassified, and Veillonella dispar and higher abundances of Roseburia hominis, Porphyromonas bennonis, and Paraprevotella unclassified. The abundance of Bifidobacterium longum was negatively correlated with follow-up blood glucose levels. Moreover, the microbial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of carbohydrate metabolism, methane metabolism, amino acid metabolism, fatty acid metabolism, and membrane transport were changed between the two groups.ConclusionsWe found that fecal microbiota of healthy individuals who go on to develop T2D had already changed when they still were normoglycemic. These alterations of fecal microbiota might provide insights into the development of T2D and a new perspective for identifying individuals at risk of developing T2D.

Highlights

  • According to the latest report of the International Diabetes Federation Diabetes Atlas in 2019 (International Diabetes Federation, 2019), there are 463 million diabetes patients worldwide

  • It is likely that the changes in gut microbiota diverge between different populations, patients with Type 2 diabetes (T2D) were characterized by the similar alterations, a reduction in the abundance of certain common butyrateproducing bacteria and an augmentation in some opportunistic pathogens, which can lead to enhanced inflammatory stress in T2D (Qin et al, 2012; Karlsson et al, 2013)

  • We analyzed the fecal microbiota from participants of a 4-year follow-up survey, and we studied whether the alterations in their gut microbiota occurred earlier than impaired glucose regulation

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Summary

Introduction

According to the latest report of the International Diabetes Federation Diabetes Atlas in 2019 (International Diabetes Federation, 2019), there are 463 million diabetes patients worldwide. It is likely that the changes in gut microbiota diverge between different populations, patients with T2D were characterized by the similar alterations, a reduction in the abundance of certain common butyrateproducing bacteria and an augmentation in some opportunistic pathogens, which can lead to enhanced inflammatory stress in T2D (Qin et al, 2012; Karlsson et al, 2013). Metformin increases short-chain fatty acid (SCFA)-producing bacteria, and SCFAs are known to improve glucose regulation. This increases the abundance of Escherichia species (Forslund et al, 2015; Wu et al, 2017), which are known to produce intestinal side effects similar to those seen with metformin. Dietary fiber improved T2D-associated metabolic disorder by regulating gut microbiome (Dewulf et al, 2013; Zhao et al, 2018)

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