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

View ORCID ProfileHuanzi 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, Fang Liu, Karsten Kristiansen, View ORCID ProfileJunhua Li
doi: https://doi.org/10.1101/666263
Huanzi Zhong
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
3Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark
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  • ORCID record for Huanzi Zhong
Huahui Ren
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
3Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark
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Yan Lu
4Suzhou Centre for Disease Control and Prevention, Suzhou 215007, China
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Chao Fang
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
3Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark
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Guixue Hou
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
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Ziyi Yang
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
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Bing Chen
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
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Fangming Yang
1BGI-Shenzhen, Shenzhen 518083, China
5BGI Education Centre, University of Chinese Academy of Sciences
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Yue Zhao
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
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Zhun Shi
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
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Baojin Zhou
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
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Jiegen Wu
1BGI-Shenzhen, Shenzhen 518083, China
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Hua Zou
1BGI-Shenzhen, Shenzhen 518083, China
5BGI Education Centre, University of Chinese Academy of Sciences
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Jin Zi
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
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Jiayu Chen
2China National GeneBank, Shenzhen 518120, China
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Xiao Bao
2China National GeneBank, Shenzhen 518120, China
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Yihe Hu
4Suzhou Centre for Disease Control and Prevention, Suzhou 215007, China
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Yan Gao
4Suzhou Centre for Disease Control and Prevention, Suzhou 215007, China
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Jun Zhang
4Suzhou Centre for Disease Control and Prevention, Suzhou 215007, China
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Xun Xu
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
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Yong Hou
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
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Huanming Yang
1BGI-Shenzhen, Shenzhen 518083, China
6James D. Watson Institute of Genome Sciences, Hangzhou 310058, China
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Jian Wang
1BGI-Shenzhen, Shenzhen 518083, China
6James D. Watson Institute of Genome Sciences, Hangzhou 310058, China
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Siqi Liu
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
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Huijue Jia
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
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Lise Madsen
1BGI-Shenzhen, Shenzhen 518083, China
3Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark
8Institute of Marine Research, P.O. Box 7800, 5020 Bergen, Norway
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Susanne Brix
9Department of Biotechnology and Biomedicine, Technical University of Denmark, Soltofts Plads, 2800 Kgs. Lyngby, Denmark
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Fang Liu
4Suzhou Centre for Disease Control and Prevention, Suzhou 215007, China
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  • For correspondence: lijunhua@genomics.cn kk@bio.ku.dk 13306135766@163.com
Karsten Kristiansen
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
3Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark
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  • For correspondence: lijunhua@genomics.cn kk@bio.ku.dk 13306135766@163.com
Junhua Li
1BGI-Shenzhen, Shenzhen 518083, China
2China National GeneBank, Shenzhen 518120, China
7School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China
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  • ORCID record for Junhua Li
  • For correspondence: lijunhua@genomics.cn kk@bio.ku.dk 13306135766@163.com
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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 characterising 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, such as reduced faecal level of antimicrobial peptides and pancreatic enzymes in TN-T2D.

Interpretation Our findings suggest a complex, disease stage-dependent interplay between the gut microbiota and the host and emphasize the value of metaproteomics to gain further insight into interplays between the gut microbiota and the host.

Funding National Key Research and Development Program of China, No. 2017YFC0909703, Shenzhen Municipal Government of China, No. JCYJ20170817145809215, and National Natural Science Foundation of China, No. 31601073.

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Posted June 12, 2019.
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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, Fang Liu, Karsten Kristiansen, Junhua Li
bioRxiv 666263; doi: https://doi.org/10.1101/666263
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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, Fang Liu, Karsten Kristiansen, Junhua Li
bioRxiv 666263; doi: https://doi.org/10.1101/666263

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