Researchers at the University of Alabama at Birmingham have discovered an unexpected correlation between maintaining the angiotensin-converting enzyme-2 (ACE2) level in the gut and preventing—or even reversing—damage caused by diabetic retinopathy (DR). (via)
Give me the study background.
Researchers compared the blood from both human and mice subjects with Type 1 diabetes to evaluate the mechanisms that regulate diabetic retinopathy progression.
Tell me about the mice subjects.
At the onset of diabetes, mice were orally given a modified gut bacterial strain of Lactobacillus paracasei, which was developed to produce human ACE2.
This probiotic treatment prevented the loss of gut epithelial ACE2 and prevented intestinal epithelial and endothelial barrier damage. On top of these effects, the probiotic also reduced high blood sugar levels in mice.
A portion of the mice received delayed treatment, where the probiotic was withheld until six months after diabetes was established.
Even with this delay, the treatment reversed both the gut barrier dysfunction and progression of diabetic retinopathy, including a reduction in the number of damaged capillaries in the retina. (via)
How about the human subjects?
A control group was compared to patients with type 1 diabetes; the Type 1 diabetes patients were further separated into three groups: no DR, non-proliferative DR, and proliferative DR. Investigators measured immune cells and biomarkers in the blood of the patients with type 1 diabetes.
What did they find?
The investigators discovered that the Type 1 diabetes patients had a dysregulated renin-angiotensin system (RAS), and that gut permeability defects activated both adaptive and innate immune responses.
Additionally, increased DR severity correlated with elevated levels of gut permeability biomarkers and a gut microbial antigen.
Anything else?
Researchers found evidence of several mechanisms that contribute to the ACE2-reduced gut barrier damage and ACE2-lowering of blood sugar.
Significance?
Lead study author Maria Grant, MD, emphasized that this is the first study to show a gut barrier disruption is involved in the pathogenesis of DR, and that there is a direct link between gut leakage and retinopathy severity in patients with Type 1 diabetes.