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Murine Fecal Isolation and Microbiota Transplantation
Published on: May 26, 2023
Intestinal microbiota in pediatric patients with end stage renal disease: a Midwest Pediatric Nephrology Consortium
Janice Crespo-Salgado1,2, V Matti Vehaskari1,2, Tyrus Stewart1,2
1Children's Hospital, New Orleans, LA, USA.
Insights
Children with end-stage renal disease (ESRD) exhibit significant alterations in their gut microbiota composition and elevated levels of harmful bacterial toxins in their blood. These findings highlight a critical link between gut health and kidney disease progression in pediatric patients.
Area of Science:
- Microbiology
- Nephrology
- Pediatric Medicine
Background:
- End-stage renal disease (ESRD) is characterized by uremia and systemic inflammation.
- Intestinal microbiota alterations may contribute to inflammation via endotoxin translocation.
- Children with ESRD are hypothesized to have dysbiotic gut microbiota and increased bacterial toxins.
Purpose of the Study:
- To investigate the gut microbiota composition in children with ESRD.
- To measure serum levels of bacterially derived uremic toxins in these patients.
- To explore the relationship between microbiota changes and uremic toxins.
Main Methods:
- Stool bacterial 16S rRNA gene pyrosequencing in four groups: peritoneal dialysis (PD), hemodialysis (HD), kidney transplant recipients, and healthy controls.
- Measurement of serum inflammatory markers (CRP, D-lactate) and uremic toxins (p-cresyl sulfate, indoxyl sulfate).
Main Results:
- PD patients showed decreased Firmicutes/Actinobacteria and increased Proteobacteria; HD patients had increased Bacteroidetes.
- Bifidobacteria were significantly decreased in PD and transplant patients.
- Alpha diversity was reduced in PD and transplant patients; beta diversity differed between PD patients and controls.
- ESRD patients exhibited elevated serum p-cresyl sulfate and indoxyl sulfate.
- No significant correlation found between microbiota diversity and CRP, D-lactate, or uremic toxins.
Conclusions:
- Children with ESRD possess an altered intestinal microbiota.
- Increased levels of bacterially derived uremic toxins are present in the serum of these children.
- Gut dysbiosis is a significant factor in the pathophysiology of pediatric ESRD.
Background:
End-stage renal disease (ESRD) is associated with uremia and increased systemic inflammation. Alteration of the intestinal microbiota may facilitate translocation of endotoxins into the systemic circulation leading to inflammation. We hypothesized that children with ESRD have an altered intestinal microbiota and increased serum levels of bacterially derived uremic toxins.
Methods:
Four groups of subjects were recruited: peritoneal dialysis (PD), hemodialysis (HD), post-kidney transplant and healthy controls. Stool bacterial composition was assessed by pyrosequencing analysis of 16S rRNA genes. Serum levels of C-reactive protein (CRP), D-lactate, p-cresyl sulfate and indoxyl sulfate were measured.
Results:
Compared to controls, the relative abundance of Firmicutes (P = 0.0228) and Actinobacteria (P = 0.0040) was decreased in PD patients. The relative abundance of Bacteroidetes was increased in HD patients (P = 0.0462). Compared to HD patients the relative abundance of Proteobacteria (P = 0.0233) was increased in PD patients. At the family level, Enterobacteriaceae was significantly increased in PD patients (P = 0.0020) compared to controls; whereas, Bifidobacteria showed a significant decrease in PD and transplant patients (P = 0.0020) compared to control. Alpha diversity was decreased in PD patients and kidney transplant using both phylogenetic and non-phylogenetic diversity measures (P = 0.0031 and 0.0003, respectively), while beta diversity showed significant separation (R statistic = 0.2656, P = 0.010) between PD patients and controls. ESRD patients had increased serum levels of p-cresyl sulfate and indoxyl sulfate (P < 0.0001 and P < 0.0001, respectively). The data suggests that no significant correlation exists between the alpha diversity of the intestinal microbiota and CRP, D-lactate, or uremic toxins. Oral iron supplementation results in expansion of the phylum Proteobacteria.
Conclusions:
Children with ESRD have altered intestinal microbiota and increased bacterially derived serum uremic toxins.
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