SAN DIEGO – Among patients with advanced chronic kidney disease (CKD) and type 2 diabetes, a shift in gut microbiota in combination with plasma zonulin may be linked with chronic inflammation and endothelial dysfunction, according to results from an observational study.
“Diabetes patients have compromised gut microbiome due to metabolic disorder,” lead study author Ruchi Singh, Ph.D., said in an interview in advance of Kidney Week 2015. “Due to their hyperglycemic condition they have chronic inflammation and endothelial dysfunction as a baseline. They do have increased gut permeability. Therefore, a change in gut microbiome may have a high impact on this patient population.”
Dr. Ruchi Singh
For the study, Dr. Singh, a postdoctoral research associate at Texas Tech University Health Sciences Center, Amarillo, and her associates used 16S ribosomal RNA sequencing and quantitative analysis to evaluate the composition of gut microbiota in 40 patients with CKD and diabetic neuropathy, including 20 age- and gender-matched controls. Markers of interest included serum zonulin, tumor necrosis factor–alpha (TNF-alpha), interleuikin-6 (IL-6), fibroblast growth factor 23 (FGF-23; which is considered to be strongly correlated with cardiovascular health), endothelin 1 (ET-1), and levels of lipopolysaccharide (LPS). The mean age of patients was 59 years, and 38% were male.
Compared with controls matched for age, gender, and diet, CKD patients with diabetes had significantly higher circulating levels of all studied markers except IL-6. “The biggest surprise was that zonulin was positively correlated with FGF-23,” Dr. Singh said. “We do not have a good explanation for this at the moment and further investigation needed is to answer this.”
Zonulin was also positively correlated with TNF-alpha, IL-6, and LPS. “We hope to use zonulin as a therapeutic target which might prevent further progression of chronic kidney disease and improve cardiac health,” she said.
The researchers also observed “a huge difference in microbiome profile of healthy and CKD patients. We are going to look further in microbiome profile and see which bacterial group could have most impact on gut permeability and inflammation.”
Dr. Singh acknowledged certain limitations of the study, including its observational design and the fact that only patients with advanced CKD and multiple comorbidities were included, “which could impact our findings. In future we would like to design a prospective, targeted interventional study.”
The study was funded in part by a postdoctoral training grant from Sanofi/Genzyme. Study author and a mentor of the project, Dr. Tetyana L. Vasylyeva, disclosed that she is a scientific advisor for Alexion. Dr. Singh reported having no financial disclosures. Kidney Week 2015 is sponsored by the American Society of Nephrology.