Changes to Gut Microbiota May Contribute to Inflammation and Vascular Complications in Diabetic Kidney Patients

Scientists have long known that microorganisms living within the gut aid in many important bodily processes such as digestion, production of various vitamins, and immune function. They are also learning more about how personal microbiomes influence other aspects of health. A new study, presented at ASN Kidney Week 2015, found that a shift in the gut’s microbiota in combination with higher plasma levels of a marker of bacterial toxins may be linked with chronic inflammation and endothelial dysfunction among patients with type 2 diabetes and advanced chronic kidney disease (CKD).

Ruchi Singh, PhD, of the Texas Tech Health Science Center, was the lead author of the study. She and her team assessed gut microbiota and measured markers for compromised metabolism, leaky gut syndrome, and diminished clearance that affected patients with diabetic nephropathy. These patients were matched against healthy controls.

The markers measured included inflammatory cytokines (transcription necrosis factor α [TNF-α], interleukin–6 [IL-6]) in conjunction with fibroblast growth factor 23 (FGF-23), the vasoconstrictor endothelin 1 (ET-1), and levels of lipopolysaccharide (LPS).

“We were also interested in plasma zonulin,” Singh said, referring to a protein often released by bacterial toxins. It can assist in opening tight junctions within the small intestine, and can be indicative of leaky gut syndrome. “Hence, we selected it as a biomarker.”

As part of the study, participants filled out a survey that helped researchers analyze and compare their dietary habits. Microbiota shifts are mainly caused by metabolic disorder, Singh said, adding that good dietary habits, regular exercise, and maintaining a healthy lifestyle may help individuals avoid shifts in microbiota.

“We observed significant gut microbiome shifts in CKD patients with diabetes compared with age-, gender-, and diet-matched control subjects,” Singh said. Patients with type 2 diabetes and advanced CKD exhibited a greater proportion of LPS-producing bacteria. Furthermore, significantly elevated levels of circulating serum zonulin pointed to a prominent increase in gut permeability.

“This is an intriguing novel therapeutic target, and it will be interesting to see if gut-directed therapies can be developed that will dramatically halt or delay disease progression,” said Wei Ling Lau, MD, of the Division of Nephrology and Hypertension at the University of California, Irvine, who was not involved with the study. However, Lau warned that the altered gut microbiome and “leaky gut syndrome” are not necessarily specific to diabetic patients with CKD. “It may also be interesting to investigate different etiologic subgroups of CKD (e.g., diabetic, hypertensive, glomerular) to compare microbiome composition and inflammatory markers.”

Dominic Raj, MD, Director of the Division of Renal Disease and Hypertension at GW Medical Faculty Associates in Washington, DC, said he thought it a good idea to examine the link between microbiome shifts, zonulin, and inflammation in patients with diabetic nephropathy.

Raj was also not involved with the study, but said he would be curious to learn more about the specific microbial groups that are abundant or decreased in these patients as well as whether or not the microbiome shift precedes the onset of CKD. Especially interesting is that in disease states such as CKD, bacterial abundance is generally increased, but diversity is generally decreased. This is contrary to what was observed.

“Overall, this is an excellent pilot study, that shows us we still have a lot of unknowns,” he said. “It is an excellent step in the right direction.”



Singh R, et al. Association between Gut Microbiome and Cardiovascular Risk in Chronic Kidney Disease Patients with Type 2 Diabetes Mellitus. J Am Soc Nephrol 26 (Suppl); 2015: 480A. Abstract FR-PO530.