Gut Microbiota Profile in Indian Children with Chronic Kidney Disease

Dear Editor,

An alteration in the composition and function of intestinal microbiota in chronic kidney disease (CKD) leads to gut dysbiosis, characterized by a decline in beneficial bacteria and a concurrent growth of pathogenic bacteria. This facilitates conversion of urea to ammonia, increases the gut pH, promoting the production of uremic toxins, and compromises the integrity of the epithelial barrier, thereby triggering low-grade systemic inflammation leading to progression of disease. The human colon is mainly composed of five bacterial phyla- Firmicutes, Bacteroidetes, Actinobacteria, Verrucomicrobia, and Proteobacteria. In the uremic milieu, studies in adults have revealed overgrowth or abundance of proteolytic and urease-producing bacteria (e.g., Enterobacteriaceae genera, Clostridium species), reduced short-chain fatty acid (SCFA)-producing bacteria (e.g., Faecalibacterium, Roseburia), shift in microbial phyla (e.g., decrease in Firmicutes and Actinobacteria), and a lower microbial diversity.^1,2

Circulating gut microbiota-derived uremic toxins are elevated in children with CKD and correlate with declining kidney function.³ However, data describing gut microbiota profiles in children with CKD remain limited,⁴ with no published studies from India to date. Children with CKD in India often present with more advanced disease and are reported to have faster progression than those in high-income countries.⁵ In this context, the present study was undertaken to assess the profile of gut microbiota in Indian children with CKD in comparison to their respective siblings.

This prospective study conducted at the Department of Pediatric Nephrology, St. John’s Medical College Hospital, Bengaluru, between January-September 2024 compared the gut microbiota profile of 10 adolescents with CKD with 10 respective healthy siblings. A stool collection kit from Leucine Rich Bio (LRB) Pvt Ltd included an instruction sheet, a stool-collecting paper band with gloves, a stool collection tube with a 6 mL DNA stabilizer, a return box, and a courier envelope addressed to LRB. Patients were advised to collect 2-3 spoonfuls of samples, seal them in a return box, and return them to the department within 24 h. Stool samples were analyzed after collection. DNA was extracted, purified, and quantified. All samples were subsequently subjected to long-read whole metagenome sequencing.⁶ Details of the methodology are provided in the supplementary file.

The stool samples of 10 adolescents with CKD [6 males; median age 14.5 years (12.0-16.75); median weight 28.1 kg (IQR 20.0-43.0); 6 on haemodialysis, 2 on peritoneal dialysis (PD), and 1 kidney transplant recipient at 6 months post-transplant with stable kidney function] and 10 respective healthy siblings [2 males; median age 13.5 years (10.0, 14.75)] were analyzed. Gut dysbiosis and microbial diversity measures in patients and their siblings have been summarized in Table 1.

We found evidence of gut dysbiosis in children with CKD, characterized by a shift toward potentially pathogenic taxa such as Bacteroides fragilis, Clostridium scindens, Staphylococcus pseudintermedius, and Bacteroides caccae, whereas beneficial commensals like Intestinibacter were relatively enriched in healthy siblings. Despite these taxon-level differences, alpha and beta diversity were comparable between groups, suggesting preservation of overall microbial richness and community structure with selective compositional alterations. These findings align partly with prior paediatric data. The Midwest Paediatric Nephrology Consortium study⁷ demonstrated dialysis modality-specific differences in gut microbiota in 26 children, with increased Proteobacteria and Enterobacteriaceae in children on PD, reduced Bifidobacterium in PD and transplant recipients, and lower alpha diversity in those on PD and transplant recipients compared to 13 healthy controls; Kidney transplantation did not consistently restore microbial diversity. Data on paediatric gut microbiota from India remain sparse, with existing studies largely limited to healthy or nutrition-based cohorts rather than chronic disease populations, and adult Indian CKD literature is limited to probiotic or intervention studies without comprehensive microbiome profiling. We compared children with CKD to their healthy siblings to minimize dietary and environmental confounding. Similar preservation of alpha and beta diversity has been reported in 20 adults on PD compared to 20 age-matched household contacts, suggesting that shared environmental and dietary exposure may modulate disease-related microbial changes.⁸

This preliminary study in Indian adolescents with CKD suggests that gut dysbiosis may be characterized by selective taxonomic shifts rather than global loss of microbial diversity. While the overall within-sample diversity and between-group community structure were similar, children with CKD showed enrichment of potentially pathogenic taxa with relative depletion of beneficial commensals, indicating compositional imbalance despite preserved diversity indices. The use of healthy sibling controls is a key strength, as it helps account for shared dietary, environmental, and socio-cultural factors that may influence gut microbiota composition. The small sample size and cross-sectional design, however, limit causal interference and generalizability of these findings. Future multicenter longitudinal studies in diverse Indian children are needed to validate these observations and clarify the specific determinants and clinical relevance of gut dysbiosis.