In the news: Emerging Evidence For a Gut-Retina Axis

High Glycemic Index Diets Linked to AMD

Analyses of large-scale studies such as the Nurses Study, Blue Mountains Eye Study and AREDS, suggest that high glycemic index diets are a risk factor for AMD onset or progression in nondiabetics (1-3). High glycemic index (GI) diets are characterized by consumption of carbohydrates that cause a rapid rise in blood glucose, such as white bread and rice, sugars, and processed foods with no to low fiber.

Scientists Allen Taylor and Sheldon Rowan of Tufts Human Nutrition Research Center, Nutrition and Vision Research Lab, have embarked on a project to explore the underlying mechanisms connecting the consumption of refined carbohydrates and AMD.

Low GI Diets Protective Against AMD Features

In a recently published experiment (4), Taylor, Sheldon and colleagues uncovered an interaction between carbohydrate quality and the gut microbiota in mice.

The Tufts team fed wild-type mice either low or high GI isocaloric diets beginning at 12 months of age (middle-age) through 24 months of age (old age). After 6 months, half of the mice receiving the high GI diet were switched to the low GI diet. Despite lacking a macula, this wild-type aged mouse model has been previously shown to be useful in exhibiting retinal damage characteristic of dry AMD.

Mice fed the high GI diet displayed many features of AMD, including retinal pigment epithelial hyper-pigmentation and atrophy, lipofuscin accumulation, and photoreceptor cell loss, while those in low-GI diet group did not. The low GI diet also limited advanced glycation end products (AGEs) and peroxidized lipids, as well as increased C3-carnitine in retina, plasma or urine. (We refer to AGEs in later text).

Critically, the damage seen while on the high GI diets washalted or reversedwhen mature mice were switched from the high to the low GI diet.

Gut Microbiota and Bacterial Metabolites

The team also looked at the animals’ gut microbiota and found a difference in response to the diets. They identified microbiota in Clostridales order as being associated with the high GI diet.

With the low GI diet, protection from the features of AMD, was associated with Bacteroidales order.

Untargeted metabolic analysis revealed that microbial co-metabolites, particularly higher blood levels of serotonin, were protective against AMD features. Serotonin is synthesized in the intestine in response to signals produced by gut microbes.

In addition to serotonin, increased blood levels of C-3 carnitine (propionylcarnitine) were associated with less AMD features. C3-carnitine plays a role in cellular fatty acid metabolism, and is found in many low GI foods including whole wheat and legumes (beans and peas).

Currently there is a lack of early biomarkers for AMD, and this work identifies potential markers for future testing: AGEs, peroxidized fats, C-3 carnitine, and serotonin.

Identifying metabolites associated with changes in gut microbiota and protection against AMD features, has led the researchers to propose the existence of a gut-retina axis. In a more recent paper (5), the Tufts team explored additional gut microbiota-AMD interactions that point toward possible pathogenic roles for some microbiota families (e.g. Ruminococcaceae, Lachnospiraceae, and some members of Clostridiaceae and others). 

Nutrition research has traditionally focused on direct interactions between nutrients and physiological organ systems to learn how diet influences health and disease. Now, it’s increasingly important to consider nutrient effects on the microbiome as well for a more complete picture. Diet impacts the risk for and pro-gression of AMD. Could a gut-retina axis be part of that picture?

References

1. Kaushik S, et al. Dietary glycemic index and the risk of age-related macular degeneration. Am J Clin Nutr. 88: 1104–10, 2008.
2. Chiu CJ, et al. Dietary carbohydrate and the progression of age-related macular degeneration: a prospective study from the age-related eye disease study. Am J Clin Nutr. 86: 1210–18, 2007.
3. Chiu CJ, et al. Dietary glycemic index and carbohydrate in relation to early age-related macular degeneration. Am J Clin Nutr. 83:880–6, 2006.
4. Rowan S, et al. Involvement of a gut-retina axis in protection against dietary glycemia-induced age-related macular degeneration. PNAS,
5. Rowan S, et al. Gut microbiota modify risk for dietary glycemia-induced age-related macular degeneration. Gut Microbes. 21:1-6, 2018.