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The gut microbiota has gained immense interest in chronic kidney disease. Dysbiosis describes both quantitative and qualitative changes in microbiota composition and function in disease. CKD dysbiosis has been associated with reduced species richness, a decrease in beneficial bacteria such as Lactobacillus and Bifidobacterium, and an increase in pathogens such as Enterobacteriaceae. Additionally, the gut microbiota has a role in the progression of CKD through the production of microbiome-derived uraemic toxins.
Short-chain fatty acids (SCFAs) are microbial metabolites produced from the breakdown of fermentable fibres such as lactulose or inulin, by gut microbiota. SCFA have acquired considerable attention due to their potential health benefits including anti-inflammatory effects, cholesterol-lowering, and improving insulin resistance.
Peritoneal dialysis (PD) is a form of dialysis which uses a PD catheter to drain sterile PD fluid infused into the peritoneum. Constipation is common in PD patients and can lead to catheter dysfunction with poor PD fluid drainage. Therefore, PD patients are requested to take regular laxatives. Lactulose a commonly prescribed laxative also functions as a prebiotic with the potential to have a positive effect on gut microbiota.
Therefore, we plan to examine changes in gut microbiota over 16 weeks when a stable cohort of prevalent PD patients start lactulose for constipation or other clinical reasons. This will be the first study looking at the effects of lactulose on modulation of the gut microbiota looking at clinical parameters such as insulin resistance and cholesterol levels in a multi-ethnic prevalent dialysis cohort.
Patients on PD have been donating biological samples to the Diabetic Kidney Centre Biobank (DKC-B). In this pilot and feasibility study, we plan to perform analysis of human tissue samples already donated to the biobank. Samples include stools and rectal swabs enabling changes in gut microbiota composition to be assessed using 16sS RNA amplicon sequencing. Incident PD patients and all patients prescribed antibiotics, immunosuppression, calcium acetate and sodium bicarbonate within 3 months of donating either stool or rectal swabs to DKC will be excluded. The DKC-B is also linked to a renal patient database Registry which includes clinical details and pathology results. Data extraction will also include anthropometrics, dietary and medication changes, and pathology results. We shall determine if any change in gut microbiota is independent of any dietary changes (which is also known to affect gut microbiota).
The study population is 20 patients.
No interim analyses are planned.
Points less well described in the literature that we will be able to analyse from the results of this study include the following:
• Effect of lactulose on insulin resistance and cholesterol levels in a prevalent dialysis cohort
• Effect of lactulose on SCFA levels in serum and stool and correlation with SCFA-producing bacteria in the gut microbiome
• Prevalence of IBS/ GI symptoms in our PD cohort
• Tolerability of Lactulose as an alternative laxative
• Renal patient views on donating human tissue samples to a Biobank
• Feasibility and validation of methods in clinical microbiota research
• Comparing 2 valid tissue sampling methods: rectal swabs vs faecal samples
This will be the first study looking at the effect of lactulose on the gut microbiome in dialysis patients with ESRD. We hope to demonstrate that modulation of the gut microbiota will improve clinical parameters such as insulin resistance and cholesterol levels. By utilising the DKC-B, we believe this will be a cost-effective study. A positive signal generated by this pilot study demonstrating patient tolerability, improved GI symptoms, and increased SCFA-producing bacteria with increased SCFA levels in stool and blood, would provide future opportunities for further studies. We look forward to sharing our results soon.