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Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-naive type 2 diabetics.

ABSTRACT: BACKGROUND:The gut microbiota plays important roles in modulating host metabolism. Previous studies have demonstrated differences in the gut microbiome of T2D and prediabetic individuals compared to healthy individuals, with distinct disease-related microbial profiles being reported in groups of different age and ethnicity. However, confounding factors such as anti-diabetic medication hamper identification of the gut microbial changes in disease development. METHOD:We used a combination of in-depth metagenomics and metaproteomics analyses of faecal samples from treatment-naïve type 2 diabetic (TN-T2D, n?=?77), pre-diabetic (Pre-DM, n?=?80), and normal glucose tolerant (NGT, n?=?97) individuals to investigate compositional and functional changes of the gut microbiota and the faecal content of microbial and host proteins in Pre-DM and treatment-naïve T2D individuals to elucidate possible host-microbial interplays characterizing different disease stages. FINDINGS:We observed distinct differences characterizing the gut microbiota of these three groups and validated several key features in an independent TN-T2D cohort. We also demonstrated that the content of several human antimicrobial peptides and pancreatic enzymes differed in faecal samples between three groups. INTERPRETATION:Our findings suggest a complex, disease stage-dependent interplay between the gut microbiota and the host and point to the value of metaproteomics to gain further insight into interplays between the gut microbiota and the host. FUND: The study was supported by the National Natural Science Foundation of China (No. 31601073), the National Key Research and Development Program of China (No. 2017YFC0909703) and the Shenzhen Municipal Government of China (No. JCYJ20170817145809215). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

SUBMITTER: Zhong H

PROVIDER: S-EPMC6796533 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-naïve type 2 diabetics.

Zhong Huanzi H Ren Huahui H Lu Yan Y Fang Chao C Hou Guixue G Yang Ziyi Z Chen Bing B Yang Fangming F Zhao Yue Y Shi Zhun Z Zhou Baojin B Wu Jiegen J Zou Hua H Zi Jin J Chen Jiayu J Bao Xiao X Hu Yihe Y Gao Yan Y Zhang Jun J Xu Xun X Hou Yong Y Yang Huanming H Wang Jian J Liu Siqi S Jia Huijue H Madsen Lise L Brix Susanne S Kristiansen Karsten K Liu Fang F Li Junhua J

EBioMedicine 20190903

<h4>Background</h4>The gut microbiota plays important roles in modulating host metabolism. Previous studies have demonstrated differences in the gut microbiome of T2D and prediabetic individuals compared to healthy individuals, with distinct disease-related microbial profiles being reported in groups of different age and ethnicity. However, confounding factors such as anti-diabetic medication hamper identification of the gut microbial changes in disease development.<h4>Method</h4>We used a combi ...[more]

PMID: 31492563

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Project description:Diabetes in India has distinct genetic, nutritional, developmental and socio-economic aspects; owing to the fact that changes in gut microbiota are associated with diabetes, we employed semiconductor-based sequencing to characterize gut microbiota of diabetic subjects from this region. We suggest consolidated dysbiosis of eubacterial, archaeal and eukaryotic components in the gut microbiota of newly diagnosed (New-DMs) and long-standing diabetic subjects (Known-DMs) compared to healthy subjects (NGTs). Increased abundance of phylum Firmicutes (p = 0.010) and Operational Taxonomic Units (OTUs) of Lactobacillus (p < 0.01) were observed in Known-DMs subjects along with the concomitant graded decrease in butyrate-producing bacterial families like Ruminococcaceae and Lachnospiraceae. Eukaryotes and fungi were the least affected components in these subjects but archaea, except Methanobrevibacter were significantly decreased in them. The two dominant archaea viz. Methanobrevibacater and Methanosphaera followed opposite trends in abundance from NGTs to Known-DMs subjects. There was a substantial reduction in eubacteria, with a noticeable decrease in Bacteroidetes phylum (p = 0.098) and an increased abundance of fungi in New-DMs subjects. Likewise, opportunistic fungal pathogens such as Aspergillus, Candida were found to be enriched in New-DMs subjects. Analysis of eubacterial interaction network revealed disease-state specific patterns of ecological interactions, suggesting the distinct behavior of individual components of eubacteria in response to the disease. PERMANOVA test indicated that the eubacterial component was associated with diabetes-related risk factors like high triglyceride (p = 0.05), low HDL (p = 0.03), and waist-to-hip ratio (p = 0.02). Metagenomic imputation of eubacteria depict deficiencies of various essential functions such as carbohydrate metabolism, amino acid metabolism etc. in New-DMs subjects. Results presented here shows that in diabetes, microbial dysbiosis may not be just limited to eubacteria. Due to the inter-linked metabolic interactions among the eubacteria, archaea and eukarya in the gut, it may extend into other two domains leading to trans-domain dysbiosis in microbiota. Our results thus contribute to and expand the identification of biomarkers in diabetes.

Dataset Information

Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-naive type 2 diabetics.

Publications

Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-naïve type 2 diabetics.

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