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Changes of gut microbiota in diabetic nephropathy and its effect on the progression of kidney injury

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Abstract

Purpose

We aimed to illustrate gut microbiota and short chain fatty acid (SCFA) levels in diabetic nephropathy (DN) patients, and investigate the mechanism of sodium butyrate in diabetic mellitus (DM) rats.

Methods

Gut microbiota and serum SCFA levels were measured by 16S rDNA and GC-MS. After being built by streptozotocin (DM rats), the DM rats were administered 300 mg/kg sodium butyrate for 12 weeks (DM + BU rats). Gut microbiota, serum and fecal butyrate level were measured. RT-PCR, WB and transmission electron microscopy were performed to explore LC3mRNA or LC3B protein expression, and autophagosomes in kidney tissues. AMPK/mTOR protein expression in renal tissue were also measured.

Results

The gut microbial dysbiosis was found in DM and DN groups, and some SCFAs-producing bacteria were decreased in DN group. The serum butyrate concentrations were lower in SCFA-DN group compared with SCFA-HC group and SCFA-DM group in the other cohort. Serum butyrate level was positively correlated with eGFR. Sodium butyrate increased serum and fecal butyrate levels, and improved the enlargement of glomerular area and fibronectin and collagen IV expressions in renal tissues in DM + BU rats. The LC3 mRNA, LC3BII/I ratio and number of autophagosomes were increased in renal tissue of DM + BU rats. Higher p-AMPK/AMPK ratio and lower p-mTOR/ mTOR ratio were shown in renal tissue of DM + BU rats compared with DM rats.

Conclusions

We found the decrease in SCFAs-producing bacteria and low SCFAs concentrations in DN patients. Oral butyrate supplementation may improve kidney injury in DM rats, possibly by increasing autophagy via activating AMPK/mTOR pathway.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request

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Acknowledgements

We acknowledge Qili Shi, studying in Fudan University for his expert technical assistance

Author contribution

Research idea and study design: F.H., K.D.C. and Y.H.M.; sample collection: K.C. Y.H.M., C.Y.Z. and P.P.R.; data acquisition and analysis: F.H., K.D.C., Y.H.M.; Experiments performed: F.H., K.D.C., Y.H.M., F.H.C. X.H.H. and L.X.; supervision or mentorship: F.H., Q.L., J.H.C. F.H. and K.D.C. wrote the first draft of the manuscript. F.H. reviewed and edited the manuscript. K.D.C. and Y.H.M. contributed equally in the study. All the authors approved of the final version of the manuscript.

Funding

This study was supported by the funds from National Key R&D Program of China (2018YFC1314003), Zhejiang Provincial Natural Science Foundation of China (LY20H05005, Q19H050030), Medical Scientific Research Foundation of Zhejiang Province, China (2019KY174) and Ningbo Public Service Technology Foundation, China (2019C50084).

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Author notes

  1. These authors contributed equally: Kedan Cai, Yanhong Ma

Authors and Affiliations

  1. HwaMei Hospital, University of Chinese Academy of Sciences; Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China

    Kedan Cai, Chenyu Zhong & Qun Luo

  2. Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University; Institute of Nephrology, Zhejiang University; Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang Province, China

    Kedan Cai, Yanhong Ma, Fanghao Cai, Xiaohan Huang, Liang Xiao, Pingping Ren, Jianghua Chen & Fei Han

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  1. Kedan Cai
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Correspondence to Fei Han.

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The research protocols were conformed to the provisions of the Declaration of Helsinki and were approved by the Ethic Committee of the First Affiliated Hospital of Zhejiang University School of Medicine and HwaMei Hospital, University of Chinese Academy of Sciences.

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Cai, K., Ma, Y., Cai, F. et al. Changes of gut microbiota in diabetic nephropathy and its effect on the progression of kidney injury. Endocrine 76, 294–303 (2022). https://doi.org/10.1007/s12020-022-03002-1

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