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BOSTON -- Patients with chronic kidney disease (CKD) and type 2 diabetes had a significantly different make-up of gut bugs compared with healthy controls, researchers reported here.
In a small, ongoing study of 40 participants, those with CKD-diabetes were found to have significantly higher levels of serum zonulin, and cytokines that affect inflammation. In addition, on the order level -- above genus and species -- the healthy controls had more Clostridiales, while the CKD-diabetes group had higher abundance of Bacteroidales and Acidimicrobiales, according to , and , of Texas Tech University School of Health Sciences in Amarillo.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Clostridiales has been linked to metabolic syndrome, while Bacteroidales has been tied to .
On the lower level, the healthy controls had a higher abundance of genera Bacteroides, Butyrivibrio, Blautia, and Coprococcus, while the CKD-diabetes group had more Oscillospira, Bacillus, and Syntrophomonas, they reported in a poster presentation at the National Kidney Foundation meeting.
"There are studies that support the concept that the microbes associated with this family could lead to inflammatory processes, and the onset of inflammatory diseases such as ulcerative colitis," according to Vasylyeva.
Some of the microbes that were found in higher levels in the patients with CKD-diabetes -- Dethiosulfovibrionaceae and Syntrophomonas bacteria, specifically -- are associated with inflammation, the authors noted, pointing out that "it is well established that patients with type 2 diabetes mellitus often experience persistent low-grade inflammation leading to microvascular deterioration and progression of vascular complications along with impaired gut motility, which impacts their microbiota."
"This study led to a lot of great surprises," Vasylyeva told ľֱ. A pediatric endocrinologist in Texas, Vasyleyeva said that she became interested in the , and then expanded her research to other patient populations.
For the current study, they stool and blood samples from the participants. CKD-diabetes patients had stage 4-5 CKD. Uremic toxins, levels of endotoxins, vitamin D levels, and other measures were also assessed, and Vasylyeva said they are still analyzing the results for future publication.
Using an ELISA assay, the authors found some serum measures varied significantly between the group with CKD-diabetes and the control group. They found that many measures correlated with zonulin, a marker of leaky gut syndrome:
- IL-6: r=0.11 (P=0.05)
- FGF 23: r=0.48 (P=0.05)
- LPS: r=0.48 (P=0.007)
- CRP: r=0.10 (P=0.07)
- ET-1: (r=0.13 (P=NS)
"Gut microbiota is a modifiable factor and zonulin could be a potential future target to control chronic inflammatory responses," they noted.
They also compared inflammation parameters between the two groups and reported the following for CKD-diabetes patients versus controls:
- ET-1: 3.57 versus 2.35 (P=0.01)
- FGF-23: 33.1 versus 25.8 (P=0.01)
- CRP: 1,706 versus 1,219 (P=0.05)
- IL-6: 2.42 versus 1.85 (P=NS)
On the species level, Faecalibacterium prausnitzii, Bacteroides ovatus, Parabacteroides distasonis, and Bacteroides uniformis were significantly higher in controls, while Ruminococcus gnavus was higher in the diabetes group.
Vasylyeva acknowledged that the clinical application of these findings is uncertain.
"We are not ready yet to provide specific recommendations for the patients, but we strongly recommend complying with prescribed phosphate binders and nutritional regimens because ... it might significantly decrease level of systemic inflammation and improve cardiovascular health," she stated.
As for possible interventions, she pointed out that "there are no good case-controlled studies for all of these probiotics," she said, adding that companies will claim that their probiotic "diminishes uremic toxins. But where are the studies?" she said.
She added that many products that claim to impact the microbiome do not require FDA approval, much like nutritional supplements.
"We are just at the beginning of great discovery." she wrote. "Interorganismal cross-talk interruption leads to profound and diverse cellular and metabolic changes observed in gut dysbiosis."
Disclosures
The study was funded by Sanofi.
Singh disclosed support from Sanofi.
Vasylyeva disclosed no relevant relationships with industry.
Primary Source
National Kidney Foundation
Singh R and Vasylyeva T "Does Gut Microbiota affect Endothelial Functions in Chronic Kidney Disease Patients with Type 2 Diabetes Mellitus?" NKF 2016; Poster 191.