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

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

doi:10.1016/j.ebiom.2019.08.048

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

Huanzi Zhong, Huahui Ren, Yan Lu, Chao Fang, Guixue Hou, Ziyi Yang, Bing Chen, Fangming Yang, Yue Zhao, Zhun Shi, Baojin Zhou, Jiegen Wu, Hua Zou, Jin Zi, Jiayu Chen, Xiao Bao, Yihe Hu, Yan Gao, Jun Zhang, Xun XuYong Hou, Huanming Yang, Jian Wang, Siqi Liu, Huijue Jia, Lise Madsen, Susanne Brix, Karsten Kristiansen^*, Fang Liu, Junhua Li

^*Corresponding author for this work

Genome Research and Molecular Bio Medicine

15 Citations (Scopus)

145 Downloads (Pure)

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.

Original language	English
Journal	EBioMedicine
Volume	47
Pages (from-to)	373-383
Number of pages	11
ISSN	2352-3964
DOIs	https://doi.org/10.1016/j.ebiom.2019.08.048
Publication status	Published - Sept 2019

Keywords

Metagenomics
Metaproteomics
Prediabetes
Treatment-naïve type 2 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ebiom.2019.08.048Licence: CC BY-NC-ND

Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-naïve type 2 diabeticsFinal published version, 2.41 MBLicence: CC BY-NC-ND

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Zhong, H., Ren, H., Lu, Y., Fang, C., Hou, G., Yang, Z., Chen, B., Yang, F., Zhao, Y., Shi, Z., Zhou, B., Wu, J., Zou, H., Zi, J., Chen, J., Bao, X., Hu, Y., Gao, Y., Zhang, J., ... Li, J. (2019). Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-naïve type 2 diabetics. EBioMedicine, 47, 373-383. https://doi.org/10.1016/j.ebiom.2019.08.048

Zhong, H, Ren, H, Lu, Y, Fang, C, Hou, G, Yang, Z, Chen, B, Yang, F, Zhao, Y, Shi, Z, Zhou, B, Wu, J, Zou, H, Zi, J, Chen, J, Bao, X, Hu, Y, Gao, Y, Zhang, J, Xu, X, Hou, Y, Yang, H, Wang, J, Liu, S, Jia, H, Madsen, L, Brix, S, Kristiansen, K, Liu, F & Li, J 2019, 'Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-naïve type 2 diabetics', EBioMedicine, vol. 47, pp. 373-383. https://doi.org/10.1016/j.ebiom.2019.08.048

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title = "Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-na{\"i}ve 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-na{\"i}ve 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-na{\"i}ve 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.",

keywords = "Metagenomics, Metaproteomics, Prediabetes, Treatment-na{\"i}ve type 2 diabetes",

author = "Huanzi Zhong and Huahui Ren and Yan Lu and Chao Fang and Guixue Hou and Ziyi Yang and Bing Chen and Fangming Yang and Yue Zhao and Zhun Shi and Baojin Zhou and Jiegen Wu and Hua Zou and Jin Zi and Jiayu Chen and Xiao Bao and Yihe Hu and Yan Gao and Jun Zhang and Xun Xu and Yong Hou and Huanming Yang and Jian Wang and Siqi Liu and Huijue Jia and Lise Madsen and Susanne Brix and Karsten Kristiansen and Fang Liu and Junhua Li",

year = "2019",

month = sep,

doi = "10.1016/j.ebiom.2019.08.048",

language = "English",

volume = "47",

pages = "373--383",

journal = "EBioMedicine",

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TY - JOUR

T1 - Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-naïve type 2 diabetics

AU - Zhong, Huanzi

AU - Ren, Huahui

AU - Lu, Yan

AU - Fang, Chao

AU - Hou, Guixue

AU - Yang, Ziyi

AU - Chen, Bing

AU - Yang, Fangming

AU - Zhao, Yue

AU - Shi, Zhun

AU - Zhou, Baojin

AU - Wu, Jiegen

AU - Zou, Hua

AU - Zi, Jin

AU - Chen, Jiayu

AU - Bao, Xiao

AU - Hu, Yihe

AU - Gao, Yan

AU - Zhang, Jun

AU - Xu, Xun

AU - Hou, Yong

AU - Yang, Huanming

AU - Wang, Jian

AU - Liu, Siqi

AU - Jia, Huijue

AU - Madsen, Lise

AU - Brix, Susanne

AU - Kristiansen, Karsten

AU - Liu, Fang

AU - Li, Junhua

PY - 2019/9

Y1 - 2019/9

N2 - 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.

AB - 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.

KW - Metagenomics

KW - Metaproteomics

KW - Prediabetes

KW - Treatment-naïve type 2 diabetes

U2 - 10.1016/j.ebiom.2019.08.048

DO - 10.1016/j.ebiom.2019.08.048

M3 - Journal article

C2 - 31492563

AN - SCOPUS:85071606525

SN - 2352-3964

VL - 47

SP - 373

EP - 383

JO - EBioMedicine

JF - EBioMedicine

ER -

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

Abstract

Keywords

UN SDGs

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