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Integrated Gut Microbiota and Urine Metabolite Analyses of T2DM with NAFLD Rat Model

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Abstract

Globally 80% type 2 diabetes mellitus (T2DM) patients suffer nonalcoholic fatty liver disease (NAFLD). The interplay of gut microbiota and endogenous metabolic networks has not yet been reported in the setting of T2DM with NAFLD. As such, this study utilized 16S rRNA gene sequencing to assess the changes in intestinal flora and nuclear magnetic resonance spectroscopy (1H NMR) to identify potential metabolites in a T2DM with NAFLD rat model. Spearman correlation analysis was performed to explore the relationship between gut microbiota and metabolites. Results revealed that among T2DM with NAFLD rats, diversity indexes of intestinal microbiota were distinctly decreased while levels of 18 bacterial genera within the intestinal tract were significantly altered. In addition, levels of eight metabolites mainly involved in the synthesis and degradation of ketone bodies, the TCA cycle, and butanoate metabolism were altered. Correlation analysis revealed that gut bacteria such as Blautia, Ruminococcus torques group, Allobaculum, and Lachnoclostridium strongly associate with 3-hydroxybutyrate, acetone, acetoacetate, 2-oxoglutarate, citrate, creatinine, hippurate, and allantoin. Our findings can provide a basis for future development of targeted treatments.

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All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Funding

This work was supported by grants from the Natural Science Foundation of China (nos. 81660697 and 81603533), Program for Teacher’s Promotion of Guangxi Higher Education Institutions (no. KY2016LX04), the Youth Science Foundation of Guangxi Medical University (nos. GXMUYSF13 and GXMUYSF18), Guangxi First-class Discipline Project for Pharmaceutical Sciences (no. GXFCDP-PS-2018), and Open Project of Guangxi Key Laboratory of Regenerative Medicine (202002).

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Author notes

  1. Jinghua Qin and Xue Ling contributed equally to this work.

Authors and Affiliations

  1. Pharmaceutical College, Guangxi Medical University, Nanning, 530021, China

    Jinghua Qin, Xue Ling, Qianyi Wang, Zheng Huang, Bingjian Guo, Chi Zhang, Mingwei Meng, Shisui Feng, Yue Guo, Yonghong Liang & Zhiheng Su

  2. Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning, 530022, People’s Republic of China

    Yue Guo

  3. Life Sciences Institute, Guangxi Medical University, Nanning, 530021, China

    Hua Zheng

  4. Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Nanning, 530021, China

    Zhiheng Su

  5. Guangxi Engineering Research Center for Beibu Gulf Marine Biomedicine Precision Development and High-Value Utilization, Nanning, 530021, China

    Zhiheng Su

  6. Guangxi Health Commission Key Laboratory of Basic Research On Antigeriatric Drugs, Nanning, 530021, China

    Zhiheng Su

Authors
  1. Jinghua Qin
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Contributions

All authors contributed to the study conception and design. Methodology, writing—original draft [Jinghua Qin], formal analysis [Xue Ling], visualization [Qianyi Wang], resources [Zheng Huang], investigation [ Bingjian Guo], software [Chi Zhang], software and data curation [Mingwei Meng], validation [Shisui Feng]. Conceptualization [Yue Guo]. Writing—review and editing [Hua Zheng]. Supervision, writing—review and editing [Zhiheng Su]. Conceptualization, project administration [Yonghong Liang]. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Hua Zheng, Yonghong Liang or Zhiheng Su.

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This study was performed in line with the guideline accepted by the institutional ethics committee of Guangxi Medical University.

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Qin, J., Ling, X., Wang, Q. et al. Integrated Gut Microbiota and Urine Metabolite Analyses of T2DM with NAFLD Rat Model. Appl Biochem Biotechnol 195, 6478–6494 (2023). https://doi.org/10.1007/s12010-023-04419-8

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