Host factors dictate gut microbiome alterations in chronic kidney disease more strongly than kidney function

Despite recent progress, microbial associations reported in chronic kidney disease (CKD) remain inconsistent. Here we combined quantitative faecal metagenomics (n = 130) and cross-study biomarker comparisons (ntotal = 4,420) to study microbiome associations with estimated glomerular filtration rate (eGFR; kidney function) and 4-year CKD progression. Intestinal transit time (ITT) and medications significantly explained microbiome variation, surpassing eGFR-related effects. Lower eGFR was associated with increased p-cresol and indole biosynthetic potential and reduced plant-to-animal CAZyme ratios. This was consistent with community-wide saccharolytic-to-proteolytic microbiome transitions linked to dietary guidelines and slowed-down ITT. Peritoneal dialysis patients showed distinct microbiome dysbiosis accompanied by increased intestinal inflammation. Only Escherichia coli, an unnamed Alistipes species and Bifidobacterium adolescentis were covariate-independent markers for eGFR, but neither these nor previous microbial markers convincingly replicated across 11 studies. No predictors for CKD progression were found. Nevertheless, our study adds insight into plausible ITT and nutrition-related effects, highlighting their potential in CKD interventions. A covariate-aware analysis reveals that microbiome changes in the gut of patients with chronic kidney disease are better explained by intestinal transit time than by kidney function.