Gut microbiota in the association between obesity and kidney function decline: a metagenomics-based study in a rat model

Abstract

Objectives

Obesity can induce dysbiosis in the gut microbiota and is considered a separate risk factor for kidney function decline. Nonetheless, the precise function of intestinal microorganisms in facilitating the connection between obesity and kidney function decline remains uncertain. Hence, the objective of this study was to investigate the alterations in the gut microbiota composition that take place during obesity and their correlations with renal function utilizing a rat model.

Methods

For 20 weeks, 25 Sprague–Dawley rats were fed either a high-fat diet (HFD) or a normal-fat normal diet (ND). Physiological indices, peripheral plasma, kidney tissue, and colon contents were collected for comparison between groups. Metagenomic analysis of intestinal flora was performed.

Results

The HFD group demonstrated significantly increased levels of creatinine and urea nitrogen in the peripheral blood. Additionally, the HFD rats exhibited a significantly larger glomerular diameter compared to the ND group, accompanied by the presence of glomerulosclerosis, tubular vacuolar transformation, and other pathological changes in certain glomeruli. Metagenomics analysis revealed a notable rise in the prevalence of the Firmicutes phylum within the HFD group, primarily comprising the Rumenococcus genus. Functional analysis indicated that the gut microbiota in the HFD group primarily correlated with infectious diseases, signal transduction, and signaling molecules and interactions.

Conclusions

This study provides evidence that the consumption of a HFD induces modifications in the composition and functionality of the gut microbiome in rats, which may serve as a potential mechanism underlying the relationship between obesity and the progression of kidney function decline.

Keywords:

• Obesity-associated kidney injury
• intestinal flora
• metagenomics
• infectious disease
• cytokines

Acknowledgement

We are grateful to the services provided by OE Biotech Co., Ltd. (Shanghai, China) for the metagenome sequencing and analysis, and we extend our thanks to Editage for their assistance with English-language editing.

Author contributions

The study was conceived and designed by ZYL and AA, who also provided support for resources. GLJ performed the experiments with the animal model. AA performed the bioinformatics analysis, carried out the statistical analyses, and wrote the initial draft of the manuscript. ZYL participated in the development of the research and revised the document. The final manuscript was read and approved by all authors.

Ethics approval

The Xi’an Jiao Tong University Committee for the Ethics of Animal Experiments (permission number 2021-674) oversaw and approved all animal feeding and experimental procedures conducted.

Disclosure statement

The authors declare not conflicts of interests that are pertinent to the subject matter of this publication.

Data, material, or code availability

The metagenomic sequencing data has been submitted to BioProject (BioProject ID: PRJNA876316).