Association of the gut microbiome with kidney function and damage in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

ABSTRACT

Background

The gut microbiome is altered in chronic kidney disease (CKD), potentially contributing to CKD progression and co-morbidities, but population-based studies of the gut microbiome across a wide range of kidney function and damage are lacking.

Methods

In the Hispanic Community Health Study/Study of Latinos, gut microbiome was assessed by shotgun sequencing of stool (n = 2,438; 292 with suspected CKD). We examined cross-sectional associations of estimated glomerular filtration rate (eGFR), urinary albumin:creatinine (UAC) ratio, and CKD with gut microbiome features. Kidney trait-related microbiome features were interrogated for correlation with serum metabolites (n = 700), and associations of microbiome-related serum metabolites with kidney trait progression were examined in a prospective analysis (n = 3,635).

Results

Higher eGFR was associated with overall gut microbiome composition, greater abundance of species from Prevotella, Faecalibacterium, Roseburia, and Eubacterium, and microbial functions related to synthesis of long-chain fatty acids and carbamoyl-phosphate. Higher UAC ratio and CKD were related to lower gut microbiome diversity and altered overall microbiome composition only in participants without diabetes. Microbiome features related to better kidney health were associated with many serum metabolites (e.g., higher indolepropionate, beta-cryptoxanthin; lower imidazole propionate, deoxycholic acids, p-cresol glucuronide). Imidazole propionate, deoxycholic acid metabolites, and p-cresol glucuronide were associated with prospective reductions in eGFR and/or increases in UAC ratio over ~6 y.

Conclusions

Kidney function is a significant correlate of the gut microbiome, while the relationship of kidney damage with the gut microbiome depends on diabetes status. Gut microbiome metabolites may contribute to CKD progression.

KEYWORDS:

• Gut microbiome
• chronic kidney disease
• glomerular filtration rate
• metabolites

List of abbreviations

AHEI2010, Alternative Health Eating Index 2010; ANCOM, Analysis of Composition of Microbiomes; CKD, chronic kidney disease; CLR, centered log-ratio; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; FDR, false discovery rate; HCHS/SOL, Hispanic Community Health Study/Study of Latinos; HDL, high-density lipoprotein; JSD, Jensen-Shannon Divergence; PERMANOVA, permutational multivariate analysis of variance; SCFA, short-chain fatty acid; UAC ratio, urinary albumin-to-creatinine ratio.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

HCHS/SOL data are archived at the National Institutes of Health repositories dbGap and BIOLINCC. Sequence data from the samples described in this study is deposited in QIITA (study ID 11666). HCHS/SOL has established a process for the scientific community to apply for access to participant data and materials, including the metabolomics data used herein, with such requests reviewed by the project’s Steering Committee. These policies are described at https://sites.cscc.unc.edu/hchs/.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2186685

Additional information

Funding

The HCHS/SOL is a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (HHSN268201300001I/N01-HC-65233), University of Miami (HHSN268201300004I/N01-HC-65234), Albert Einstein College of Medicine (HHSN268201300002I/N01-HC-65235), University of Illinois at Chicago (HHSN268201300003I/N01-HC-65236 Northwestern Univ), and San Diego State University (HHSN268201300005I/N01-HC-65237). The following Institutes/Centers/Offices have contributed to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements. Additional funding for the “Gut Origins of Latino Diabetes” ancillary study to HCHS/SOL was provided by R01MD011389-01 from the National Institute on Minority Health and Health Disparities and the Life Course Methodology Core (LCMC) at Albert Einstein College of Medicine and the New York Regional Center for Diabetes Translation Research (P30 DK111022-8786 and P30 DK111022) through funds from the National Institute of Diabetes and Digestive and Kidney Diseases. The authors thank the staff and participants of HCHS/SOL for their important contributions.