Abstract
Background: The gut microbiome is altered in chronic kidney disease (CKD), potentially contributing to CKD progression and co-morbidities such as cardiovascular disease, 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, adjusting for covariates, and also stratified by diabetes status. 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) ( Figure 1a ). Results: Higher eGFR was significantly 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) ( Figure 1b ). Imidazole propionate, deoxycholic acid metabolites, and p-cresol glucuronide were associated with prospective reductions in eGFR and/or increases in the UAC ratio ( Figure 1c ). 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.
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