Alterations in gut microbiota among maintenance hemodialysis patients with CKD-associated pruritus: a cross-sectional comparative study of two cohorts.
Huang M, Chen S, et al. • Frontiers in cellular and infection microbiology • 2026
Active CKD-associated pruritus in maintenance hemodialysis patients was associated with selective differences in gut microbial relative abundance rather than broad alterations in microbial richness, diversity, or dominant community structure.
Key Findings
Results
Alpha-diversity indices did not differ significantly between MHD patients with active CKD-aP and those without active pruritus.
89 patients receiving maintenance hemodialysis were enrolled: 45 with active CKD-aP (HDUP) and 44 without active pruritus (HDNUP)
Fecal samples were analyzed using 16S rRNA gene sequencing
Alpha-diversity metrics showed no statistically significant differences between the two groups
This suggests microbial richness and evenness are not broadly altered in CKD-aP
Results
Bray-Curtis-based analysis of similarities showed no significant difference in overall gut community structure between groups, while unweighted UniFrac detected a statistically significant but very small difference.
Bray-Curtis ANOSIM: R = -0.00463, p = 0.5882 (non-significant)
Unweighted UniFrac ANOSIM: R = 0.03449, p = 0.0183 (statistically significant)
The UniFrac effect size (R = 0.03449) was described as 'very small'
Results indicate that phylogenetic community composition differs minimally at most
Results
Fourteen genera showed nominal differences in univariable analyses, but after multivariable adjustment and FDR correction, significant associations were identified only at the family and order levels.
Multivariable association analysis was performed using MaAsLin2 at phylum, class, order, family, genus, and species levels
Covariates adjusted for included age, sex, post-dialysis dry weight, dialysis vintage, presence of diabetes mellitus, and documented history of hyperphosphataemia
No genus- or species-level associations survived FDR correction
Significant associations after FDR correction were confined to the family and order taxonomic levels
Results
Parasutterella showed a nominal genus-level association with the absence of active pruritus but did not remain statistically significant after FDR correction.
Parasutterella was nominally associated with the HDNUP (no active pruritus) group at the genus level
This association did not survive false-discovery-rate correction
The finding is therefore considered exploratory rather than confirmatory
Parasutterella is noted as a candidate genus for future investigation
Results
LEfSe analysis identified 31 candidate differentially enriched taxonomic features between the two groups.
LEfSe (Linear discriminant analysis Effect Size) was applied to identify differentially abundant taxa
31 taxonomic features were identified as candidates for differential enrichment
These findings are described as exploratory and requiring external validation
LEfSe results were not subjected to the same multivariable adjustment as MaAsLin2 analyses
Results
PICRUSt2 functional prediction analysis suggested nominal differences in six predicted metabolic pathways between groups.
Six predicted functional pathways showed nominal differences between HDUP and HDNUP groups
Higher predicted protein digestion and absorption was observed in HDNUP (no active pruritus) patients
Higher predicted RIG-I-like receptor signaling and ether lipid metabolism were observed in HDUP (active pruritus) patients
These functional findings are based on predicted rather than measured metabolic activity and are described as exploratory
Discussion
The study design was cross-sectional and single-center, limiting causal inference and generalizability.
Single-center cross-sectional design precludes determination of temporal or causal relationships
The authors call for validation in 'longitudinal, multicenter studies incorporating absolute microbial quantification and metabolomic analyses'
Relative abundance data from 16S rRNA sequencing cannot distinguish changes in absolute bacterial counts
The study enrolled 89 total participants, which may limit statistical power for FDR-corrected analyses
What This Means
This research suggests that patients on maintenance hemodialysis who suffer from chronic kidney disease-associated pruritus (CKD-aP) — a persistent and often severe itch — have some differences in their gut bacteria compared to hemodialysis patients without this symptom, but these differences are relatively subtle. Specifically, the overall richness and diversity of gut bacteria were similar between itchy and non-itchy patients, and the broad composition of the gut microbial community was largely similar as well. The differences that were detected were confined to specific bacterial groups at higher taxonomic levels (family and order), while differences at the genus and species levels — which are more biologically specific — did not hold up after statistical correction for multiple comparisons. One bacterial genus, Parasutterella, showed a trend toward being more common in patients without pruritus, but this was not statistically robust after correction.
The study also used computational tools to predict what metabolic functions the gut bacteria might be performing. Patients without pruritus showed higher predicted activity in protein digestion and absorption pathways, while patients with pruritus showed higher predicted activity in immune signaling (RIG-I-like receptor) and ether lipid metabolism pathways. These are intriguing signals, but because they are based on predicted rather than directly measured functions, they should be treated as hypothesis-generating only.
This research suggests that the gut microbiome may play a role in CKD-associated pruritus, but the relationship appears to involve selective shifts in certain bacterial groups rather than a wholesale disruption of the gut microbial ecosystem. Because this was a single-center study conducted at one point in time, the findings cannot establish cause and effect. Larger, multi-site studies that track patients over time and directly measure bacterial metabolites will be needed to determine whether gut bacteria are truly contributing to this common and distressing condition.
Huang M, Chen S, Wang Y, Wang J, Liu J, Wu M, et al.. (2026). Alterations in gut microbiota among maintenance hemodialysis patients with CKD-associated pruritus: a cross-sectional comparative study of two cohorts.. Frontiers in cellular and infection microbiology. https://doi.org/10.3389/fcimb.2026.1917432