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

Intestinal transit time (ITT) and medications explained microbiome variation more strongly than eGFR in CKD patients.

• Combined quantitative faecal metagenomics (n=130) with cross-study biomarker comparisons (ntotal=4,420).
• ITT and medications were found to surpass eGFR-related effects in explaining microbiome variation.
• This finding suggests host factors dictate gut microbiome alterations in CKD more strongly than kidney function itself.

Lower eGFR was associated with increased p-cresol and indole biosynthetic potential and reduced plant-to-animal CAZyme ratios.

• p-cresol and indole biosynthetic potential increased with lower kidney function.
• Plant-to-animal CAZyme (carbohydrate-active enzyme) ratios were reduced at lower eGFR.
• These findings were consistent with community-wide saccharolytic-to-proteolytic microbiome transitions.
• The transitions were linked to dietary guidelines and slowed-down intestinal transit time.

Peritoneal dialysis patients showed distinct microbiome dysbiosis accompanied by increased intestinal inflammation.

• Peritoneal dialysis patients were distinguished from other CKD stages by their microbiome profile.
• Increased intestinal inflammation markers accompanied the microbiome dysbiosis in peritoneal dialysis patients.
• This subgroup showed a notably different microbiome signature compared to other kidney disease stages.

Only three covariate-independent microbial markers for eGFR were identified: Escherichia coli, an unnamed Alistipes species, and Bifidobacterium adolescentis.

• These three taxa were identified as covariate-independent markers for eGFR after accounting for confounders including ITT and medications.
• None of these markers convincingly replicated across 11 cross-study comparisons (ntotal=4,420).
• Previously reported microbial markers from other studies also failed to replicate convincingly across the 11 studies examined.

No microbial predictors for 4-year CKD progression were found.

• The study specifically examined microbiome associations with 4-year CKD progression.
• No microbiome-based predictors of CKD progression were identified despite the quantitative metagenomic approach.
• This null finding was observed in the context of n=130 participants with quantitative faecal metagenomics.

Previously reported microbial markers for CKD did not replicate consistently across 11 independent studies.

• Cross-study biomarker comparisons included a total of ntotal=4,420 participants across 11 studies.
• Neither the three newly identified covariate-independent markers nor previously published microbial markers showed convincing replication.
• The inconsistency in microbial associations across studies is consistent with the problem of inconsistency noted in prior CKD microbiome literature.

Saccharolytic-to-proteolytic microbiome transitions in CKD are plausibly linked to ITT and nutritional factors rather than kidney function per se.

• Community-wide shifts from saccharolytic to proteolytic microbiome activity were observed with declining eGFR.
• These transitions were linked to dietary guidelines followed in CKD and to slowed-down intestinal transit time.
• The authors highlight ITT and nutrition as having potential in CKD interventions.
• The study design was quantitative faecal metagenomics with n=130 participants.