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.
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