Metagenomic profiling of gut microbiome in early chronic kidney disease Original paper

What was studied?

This metagenomic profiling study examined the gut microbiome in early chronic kidney disease (CKD) to identify microbiome signatures linked to mild renal function decline. The investigation compared stool-derived microbial species and functional pathways between non-CKD and early CKD participants, using shotgun metagenomic sequencing to detect species-level and pathway-level shifts—especially those influencing short-chain fatty acid (SCFA) production.

Who was studied?

A total of 111 Japanese adults from the Iwaki health check-up cohort were included following strict exclusion criteria and extensive propensity score matching to control for diet, medications, comorbidities and lifestyle variables. Seventy-four participants had normal renal function and 37 had CKD G3a, with estimated glomerular filtration rates (eGFR) between 45 and 60 mL/min/1.73 m² for at least one year. Participants were stratified into diabetic and non-diabetic groups, as the mechanisms underlying CKD differ substantially between these populations. Mean eGFR values confirm the clear renal-function separation between groups.

Most important findings

Species-level analysis identified subtle but meaningful microbial shifts in early CKD. In non-diabetic participants, several SCFA-producing species—including Roseburia inulinivorans, Ruminococcus torques, and Ruminococcus lactaris—were more abundant in non-CKD controls, whereas Bacteroides caccae and Bacteroides coprocola were increased in CKD. These Roseburia and Ruminococcus species are notable butyrate producers, strongly linked to anti-inflammatory activity and gut barrier integrity. Their depletion signals reduced fermentation capacity even at the earliest stage of renal impairment. In diabetic participants, Roseburia hominis remained enriched in non-CKD, but CKD samples showed higher levels of Lactobacillus crispatus, along with lower relative abundance of Firmicutes overall. This pattern suggests that both disease status and metabolic context shape microbiome differences. Functional pathway analysis revealed no differences in unstratified pathways but clear species-specific pathway shifts. In non-diabetic CKD, taxa associated with SCFA production showed reduced activity in starch degradation, pyruvate fermentation, and amino acid biosynthesis pathways. Conversely, sucrose degradation was more abundant in CKD, driven largely by Bacteroides species. These findings are consistent with decreased SCFA outputs and altered carbohydrate metabolism.

Key implications

The study demonstrates that early CKD is associated with depletion of key butyrate-producing microbes and reduced SCFA-linked metabolic pathways, even when overall community diversity remains stable. These species-level changes suggest that microbiome disruption begins before advanced renal decline and may contribute to inflammatory and metabolic dysregulation central to CKD progression. Because SCFAs modulate immune activity, gut barrier function, and systemic inflammation, early microbial shifts may represent future clinical biomarkers or therapeutic targets. The findings also highlight the need for longitudinal microbiome monitoring and potential dietary or microbial interventions aimed at restoring SCFA-producing taxa.

Citation

Sato N, Kakuta M, Hasegawa T, et al. Metagenomic profiling of gut microbiome in early chronic kidney disease.Nephrol Dial Transplant. 2021;36(9):1675-1684. doi:10.1093/ndt/gfaa122