Relationship between gut microbiota and vascular calcification in hemodialysis patients

Abstract

Introduction

Vascular calcification (VC) is an independent risk factor for cardiovascular mortality in end-stage renal disease (ESRD) patients. The pathogenesis of VC is complicated and unclear. Uremic toxins produced by gut microbiota can promote VC. This study aims to identify the differences in gut microbiota between the different VC groups and the main bacteria associated with VC in hemodialysis (HD) patients in an attempt to open up new preventive and therapeutic approaches and define the probable mechanism for VC in HD patients in the future.

Methods

A total of 73 maintenance HD patients were enrolled in this cross-sectional study. According to the abdominal aortic calcification (AAC) scores, the participants were divided into the high AAC score group and the low AAC score group. High-throughput sequencing of the gut microbiota was performed and the results were evaluated by alpha diversity, beta diversity, species correlation, and model predictive analyses.

Results

The prevalence of VC was 54.79% (40/73) in the study. The majority of phyla in the two groups were the same, including Firmicutes, Actinobacteriota, Proteobacteria, and Bacteroidota. The microbial diversity in the high AAC score group had a decreasing trend (p = 0.050), and the species abundance was significantly lower (p = 0.044) than that in the low AAC score group. The HD patients with high AAC scores showed an increased abundance of Proteobacteria and decreased abundances of Bacteroidota and Synergistota at the phylum level; increased abundances of Escherichia-Shigella, Ruminococcus_gnavus_group, and Lactobacillus; and decreased abundances of Ruminococcus and Lachnospiraceae_NK4A136_group at the genus level (p<0.05). Escherichia-Shigella and Ruminococcus_gnavus_group were positively correlated with VC, and Ruminococcus, Adlercreutzia, Alistipes, and norank_f__Ruminococcaceae were negatively correlated with VC. Escherichia-Shigella had the greatest influence on VC in HD patients, followed by Ruminococcus and Butyricimonas.

Conclusions

Our results provide clinical evidence that there was a difference in gut microbiota between the different VC groups in HD patients. Escherichia–Shigella, a lipopolysaccharide (LPS)-producing bacterium, was positively correlated with VC and had the greatest influence on VC. Ruminococcus, a short-chain fatty acid (SCFA)-producing bacterium, was negatively correlated with VC and had the second strongest influence on VC in HD patients. The underlying mechanism is worth studying. These findings hint at a new therapeutic target.

Keywords:

• End-stage renal disease
• hemodialysis
• vascular calcification
• gut microbiota

Acknowledgment

The invaluable support of all staff of the HD Center in Peking University Third Hospital is gratefully acknowledged.

Ethical approval

The research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. All participants provided written informed consent, and the study protocol was approved by the Ethics Committee of the Peking University Third Hospital (IRB00006761-M2019003).

Author contributions

Wenhan Bao interpreted the results and wrote the article. Wenling Yang, Chunyan Su and Xinhong Lu contributed to the data collection. Lian He designed the study, collected the data, conceptualized the idea and was involved in revising the article. Aihua Zhang conceptualized the idea and was involved in revising the article. All authors have read and approved the final article.

Disclosure statement

No potential conflicts of interest were reported by the author(s).

Data availability statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

Additional information

Funding

The work was supported by the National Natural Science Foundation of China under Grant No. 81873619 and Grant No. 81570663 to Aihua Zhang; the Key Program of Peking University Third Hospital under Grant No. BYSY2018024 to Lian He; the Key Program of Peking University Third Hospital under Grant No. BYSYZD2021034 to Wenhan Bao; and the Research Initiation Fund for the Excellent Returned Overseas Scholars of Peking University Third Hospital under Grant No. BYSYLXHG2019007 to Wenling Yang.