If you’ve been using our LIFE Fasting Tracker app and reading our blog, you know that intermittent fasting can restructure the microbes in your gut in ways that lead to metabolic health benefits and even resistance to jet lag. But did you know that intermittent fasting may also protect you against neurological symptoms associated with neurodegenerative diseases and diabetes… through your gut microbes?!

In a paper published just last month in Diabetes, an American Diabetes Association publication, researchers including ophthalmology professor Dr. Maria Grant from the University of Alabama, Birmingham, describe how intermittent fasting protects mice from diabetic eye disease and nerve damage. Grant and colleagues found that intermittent fasting restructures the microbiome or the collection of all gut microbes in these mice. Intermittent fasting seems to increase levels of a type of “good” gut bacteria in mice known as Firmicutes. These bacteria produce a secondary bile acid called TUDCA (tauroursodeoxycholate) that protects nerves from injury and blood glucose damage.

“What we’ve learned from animal models is that intermittent fasting can prevent the development of diabetic eye disease,” Grant said. “We are also now looking at the impact of intermittent fasting on kidney, nerve and bone marrow health and function in mice, with some promising initial results for improvements in kidney health. We believe that intermittent fasting can prevent many of the microvascular complications of diabetes, including peripheral neuropathy.”

What Biological Clocks and Gut Microbes Have to Do with Diabetic Nerve Damage

Grant’s lab studies circadian dysfunction, or disorders and diseases that involve biological clocks and the systems they regulate. We know from recent research that our biological clocks, including the master clock in our brain and local clocks in our various organs (liver, muscles, fat, etc.), are intimately linked with our metabolism and nutrient signaling. As it turns out, our gut microbes may act as yet another biological clock, helping to regulate the metabolic changes our body goes through from day to night.

“We know that diabetic patients have circadian dysfunction, and that as a society, humans today typically have what we call social jet lag,” Grant says. “People get up based on their alarm clocks, not their biological clocks, and people stay up and eat late. Sleeping and eating out of tune with the master biological clock in the brain can create symptoms of metabolic syndrome and metabolic dysfunction. [Think, worse blood sugar control when you eat late at night]. My lab has been interested in how fasting can beneficially impact circadian dysfunction.”

Both the disruption of circadian rhythms and an unhealthy gut microbe profile have been associated with diabetes and its symptoms, including poor blood sugar control and nerve damage. For example, night shift work and certain bacteria have been shown to induce symptoms of diabetes, while other bacteria can alleviate diabetes. Circadian rhythms and gut microbes can even work together to impact metabolic health. For example, time-restricted feeding (not easting for at least 12 to 16 hours per day) can help establish a healthy gut microbe profile that counteracts the negative impacts of shift work or insomnia.

Fasting kills off “bad” bacteria with short reproduction cycles and restores a healthy microbe diversity in the gut.

“Type 2 diabetes mellitus (T2DM) is complex metabolic disease that arises as a consequence of interactions between genetic predisposition and environmental triggers. One recently described environmental trigger associated with development of T2DM is disturbance of circadian rhythms due to shift work, sleep loss, or nocturnal lifestyle.” — J. Biol. Rhythms, 2011

Image credit: Maria Grant.

Grant and her colleagues set out to answer the question of whether fasting can improve circadian dysfunction. What they found was that intermittent fasting didn’t necessarily improve glucose control in diabetic mice, as they thought it might, but fasting was able to correct lipid abnormalities in these animals and protect their nerves from damage.

Grant quickly suspected that these changes were being driven by changes in the mice’s gut microbes.

“Some of the lipids that we saw changing were secondary bile acids,” Grant said. “Primary bile acids are made by the liver to help with fat absorption and digestion, but secondary bile acids are actually created through modification by gut microbes. That’s when we started to look more closely at the gut microbiome and how it may be impacted by fasting. It was clear that in our mice, there were changes in the microbiome unique to intermittent fasting. It seems that fasting was able to take a dysfunctional microbiome in these mice and make it into a beneficial one.”

While a healthy microbiome can have a range of metabolic benefits, one of its impacts appears to be production of beneficial bile acids. Through microbiome analysis, Grant and colleagues found that mice on an intermittent fasting regimen had increased levels of Firmicutes, a type of bacteria known to produce beneficial bile acids, and decreased levels of less beneficial Bacteroidetes and Verrucomicrobia.

The researchers also found that the secondary bile acids created by Firmicute bacteria in response to intermittent fasting, particular TUDCA, activate neuroprotective receptors in the retina, a structure in the eye. (Neuroprotective = protective of neuron structure and/or function). When activated, these receptors, known as TGR-5 receptors, protect nerves in the eye from injury by high glucose levels. Grant and colleagues confirmed this by artificially activating the same TGR-5 receptors in a second diabetic mouse model, with a drug called INT-767. These mice were also protected from diabetic eye disease and neuropathy.