Toxic microbiome and chronic kidney disease: insights from the CKD-REIN cohort study
Résumé
Introduction Chronic kidney disease (CKD) is often associated with alterations in gut microbiome composition and functions, particularly with food-derived proteins fermentation in the colon, leading to the production of uremic toxins. Nevertheless, the identification of the relations between the aberrant and “toxic” microbiome, the CKD severity and the potential impact of diet have not been exhaustively explored in humans. We investigated the associations between gut microbiome composition, blood uremic toxins, clinical metadata and food intake over a subsample of 240 patients (mean age, 68 [SD 11.6] years; 71% male) with non-dialysis CKD and an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 from the CKD-REIN study. Moreover, an observational comparison with a healthy cohort (Milieu Interieur[4], n=938) was also performed to find out microbial biomarkers characterizing the gut microbiome-related toxicity in CKD.
Results Using species level profiling, we observed that CKD patients showed a significant reduced gut microbiome health index compared to controls. Several CKD-related potential biomarkers were retrieved, like toxins producer species Negativibacillus massiliensis and Victivallis vadensis among others after adjusting for age, BMI, gender and diabetes condition as confounders. In addition, taxa belonging to Enterocloster and Hungatella clades (Lachnospiraceae family) were found negatively correlated to eGFR and positively associated with C-reactive protein (CRP) levels. A supervised modelling for data integration was carried out to explore associations between multiomics’ biomarkers differentiating moderate (n=130,
eGFR≥ 30 mL/min) and severe (n=110, eGFR< 30 mL/min) CKD phenotypes. In particular, severe-related taxa carrying genes involved in the production of metabolites causing uremic toxicity were linked to serum uremic toxins as indoxyl sulphate, trimethylamine-N-oxide, phenylacetylglutamine and kynurenic acid, along with CRP levels, alcohol consumption and low vegetables intake.
Conclusions Our study highlights the important associations of gut microbiome composition and uremic toxins accumulations with CKD severity. Moreover, the findings might open to promising therapeutic strategy to diminish microbiome-related toxicity and to potentially attenuate CKD severity, by regulating the gut microbial configuration possibly through the modulating effect of dietary intakes.
Domaines
Santé publique et épidémiologieOrigine | Fichiers produits par l'(les) auteur(s) |
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Licence |
Domaine public
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