The Eye-Gut Connection: Tinkering With the Gut Microbiome Might Be a Way to Address Diabetic Retinopathy

The gut microbiota of people with diabetes and those with diabetic retinopathy differs from those without diabetes. This offers an area of research for potentially addressing diabetic retinopathy, a complication of diabetes, according to a recent study in the online journal Investigative Ophthalmology & Visual Science.

The microbiome is the community of microorganisms (such as fungi, bacteria and viruses) that exists on and within the human body. The imbalance of the microorganisms in the intestines can trigger inflammation and the production of some toxins that can lead to some types of cancer, some studies have found. This has led increased research about the implication of such dysbiosis and whether therapeutics can be developed to prevent or treat diseases with microbiome-targeted therapies.

Over the last few years, research begun to show a connection between the gut microbiome and diabetes and possibly diabetic retinopathy, which is an eye condition caused by damage to the blood vessels in the back of the eye. The human gut microbiota consists of at least 1,500 different microbial species, and changes in this system have been associated with diabetes. Previous studies have indicated that the onset of type 1 diabetes follows an increase in inflammation associated micro-organisms.

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In the paper in Investigative Ophthalmology & Visual Science, investigators conducted a literature review over the last five years to assess the connection between the gut microbiota’s impact on the eye, called the gut-retinal axis. Investigators, led by Pratima Singh Thakur, LV Prasad Eye Institute, Hyderabad, India, wanted to determine if changes in the gut microbiome were more common in patients with diabetic retinopathy.

Investigators reviewed the literature using predetermined keywords, and they summarized the evidence generated that so far supports the role of gut dysbiosis in diabetic retinopathy. This review found that at least four mechanisms have been suggested to explain the relationship between diabetes and the gut. Several bacteria are known to downregulate — and others can upregulate — inflammatory cytokines in the gut. Various species of Bacteroides and Lactobacillus can increase glucose uptake, and Lactobacillus and Akkermansia can decrease carbohydrate metabolism. Many probiotic bacteria can induce fatty acid metabolism, reducing obesity.

Investigators have found that gut dysbiosis has been studied less in patients with diabetic retinopathy. A study in mice found that an increase in one bacteria, Firmicutes, led to an increase in tauroursodeoxycholate (TUDCA), which is known to stimulate retinal ganglion cells and act as a neuroprotective agent. In a study in rats, the microbiome in the control rats was different from that of the diabetic rats, and there were overlaps between the microbiomes of the diabetic rats with or without retinopathy.

In clinical studies in people with diabetes and diabetic retinopathy, investigators found the gut microbiome of the diabetic retinopathy cohort in one study differed from that of the controls and in type 2 diabetes. “We linked increased inflammation in DR [diabetic retinopathy] to a reduced abundance of anti-inflammatory bacteria. An increase in abundance of only a single proinflammatory bacterium (Shigella) was demonstrated in our study in DR [diabetic retinopathy],” investigators wrote.

The study also demonstrated a decrease of two probiotic bacteria (Bifidobacterium and Lactobacillus), and they concluded that diabetes and diabetic retinopathy changes could be attributed to an altered balance between proinflammatory, anti-inflammatory, and pathogenic gut bacteria. In another study the investigators reviewed, gut dysbiosis was found to vary among people with diabetes. The changes — including an increase of Bifidobacterium and Lactobacillus and an decrease in Faecalibacterium, Escherichia, Shigella, Eubacterium, and Clostridium — indicated a complex diversity in people with diabetes.

Investigators also found that two studies showed that the gut bacteria could be a marker for diabetic retinopathy. One identified 25 families of bacteria that can be potentially employed for differentiating people with and without diabetic retinopathy.

Investigators pointed out that one of the challenges of assessing the impact of gut bacteria on diabetic retinopathy is that other variables, including genomics and lifestyle factors such as diet, smoking, and physical activity, and other comorbidities can contribute to disease progression.