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Comprehensive relationships between gut microbiome and faecal metabolome in individuals with type 2 diabetes and its complications

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Abstract

Purpose

As the treatment regimens such as metformin could confound the correlation between type 2 diabetes (T2D) and gut microbiome, we should revisit the relationship between gut microbiota and T2D patients who are not currently treated with metformin.

Methods

The study recruited 65 T2D patients: 49 with and 16 without diabetic complications, and 35 healthy controls. We sequenced the 16S rRNA V3-V4 region of gut microbiota and detected metabolites based on liquid chromatography mass spectrometry (LC/MS) and gas chromatography mass spectrometry (GC/MS) in faecal samples.

Results

The composition of both the gut microbiota and faecal metabolites changed significantly with T2D patients. The abundance of Proteobacteria and the ratio of Firmicutes/Bacteroidetes were higher in T2D patients than healthy subjects, and the short chain fatty acids (SCFAs), bile acids and lipids of T2D patients were significantly disordered. Moreover, the abundances of certain SCFA-producing bacteria (Lachnospiraceae and Ruminococcaceae etc.) were significantly increased in T2D patients, while the faecal SCFAs concentrations were significantly decreased. It’s suggested that the role of SCFA-producing bacteria was not simply to produce SCFAs. Then we identified 44 microbial modules to explore the correlations between the gut microbiota and metabolic traits. Specially, most modules including certain SCFA-producing bacteria were comprehensively correlated to body mass index, the levels of blood glucose, blood pressure, blood cholesterol and faecal bile acids and lipids.

Conclusions

Our study identified the relationships between the gut microbiota and faecal metabolites, and provided a resource for future studies to understand host–gut microbiota interactions in T2D.

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Acknowledgements

The authors are indebted to all subjects for agreeing to participate in this study. We thank Huiling Song, Fudun Sun, Xianghua Zhuang and Aili Sun for professional assistance of T2D and diabetic complications register. We also thank Instrumental Analysis Center of SJTU for help with LC/MS and GC/MS analysis and NovelBio Bio-Pharm Technology Co., Ltd for help with 16S rRNA sequencing.

Funding

This study was funded by the National Natural Science Foundation of China (No. 81673588).

Author contributions

X.L., H.L. and L.Z. conceived and designed the study. Material preparation and data collection were performed by L.Z., H.L. and S.C., L.Z., Y.P. and Y.Z. analysed and interpreted the data. The first draft of the manuscript was written by L.Z. and authors read and approved the final manuscript.

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Authors and Affiliations

  1. School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240, Shanghai, China

    Lijuan Zhao, Ying Peng, Yulong Zhang & Xiaobo Li

  2. Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, 250012, Jinan, China

    Hongxiang Lou

  3. Department of Endocrinology, The Second Hospital of Shandong University, 247 Beiyuan Road, 250033, Jinan, China

    Shihong Chen

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  1. Lijuan Zhao
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Correspondence to Xiaobo Li.

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All procedures performed in the study involving human participants were in accordance with the ethical standards of the Committee on the Ethics of the Second Hospital of Shandong University (reference number: KYLL-2015(KJ)P-0103) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Zhao, L., Lou, H., Peng, Y. et al. Comprehensive relationships between gut microbiome and faecal metabolome in individuals with type 2 diabetes and its complications. Endocrine 66, 526–537 (2019). https://doi.org/10.1007/s12020-019-02103-8

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