• Fasting benefits
• Microbial metabolites

What is already known on this topic
Studies have shown that intermittent fasting could improve insulin resistance and reduce age-related brain inflammation in animal models through the modulation of the gut microbiota. But the protective effects of intermittent fasting on the cognitive deficits associated with diabetes remain unclear.

What this research adds
By studying diabetic mice subjected to alternate-day fasting for 28 days, researchers found that intermittent fasting can lower blood sugar levels and alleviate the cognitive deficits associated with diabetes. The beneficial effects of intermittent fasting are likely a result of altering the gut microbiota.

The findings suggest that intermittent fasting could be used as a new approach for treating metabolic and neurodegenerative diseases.

Eating patterns that cycle between periods of fasting and eating, known as intermittent fasting regimens, have been linked to improved insulin resistance and reduced diabetes-related symptoms in animal models. Now, a study in mice suggests that short-term, intermittent fasting alters the gut microbiota, alleviating the cognitive deficits associated with diabetes.

The findings, published in Nature Communications, could lead to the development of intermittent fasting approaches for treating metabolic diseases.

“The prevalence of type 2 diabetes is on the rise worldwide, and cognitive decline is a severe complication of type 2 diabetes,” the researchers say. Previous studies have suggested that intermittent fasting could reduce age-related and Alzheimer’s disease-associated brain inflammation and cognitive decline in animal models through the modulation of the gut microbiota and microbial metabolites.

But the protective effects of intermittent fasting on the cognitive deficits associated with diabetes remain unclear, so Zhigang Liu at Northwest A&F University in Yangling and his colleagues set out to study the impact of intermittent fasting on diabetes-related cognitive impairment in a mouse model of diabetes.

Fasting benefits

Three-month-old diabetic mice were either allowed to eat as much as they wanted or subjected to alternate-day fasting for 28 days. Fasting mice performed better in behavioral and spatial memory tests and had nearly 55% lower sugar levels than mice on the unrestricted diet.

However, the fasting-induced benefits on cognitive function were suppressed after removing the gut microbiota of diabetic mice through antibiotic treatment. This suggests that gut microbes play a key role in mediating the beneficial effects of intermittent fasting.

Microbial metabolites

Next, the researchers looked at how fasting changed the gut microbiota of diabetic mice. After 28 days of intermittent fasting, the levels of Lactobacillus and Odoribacter increased, while those of bacteria such as Candidatus Arthromitus and unknown Enterococcaceae, which have been linked to blood sugar and bodyweight, decreased.

Intermittent fasting also increased blood levels of metabolites including serotonin, tauroursodeoxycholic acid, and 3-indolepropionic acid, and it improved the concentration of short-chain fatty acids such as acetate, propionate, and butyrate—which have been shown to regulate insulin sensitivity—in the feces of diabetic mice.

Administering serotonin, tauroursodeoxycholic acid, 3-indolepropionic acid, and short-chain fatty acids individually improved cognitive function and insulin sensitivity in diabetic mice. Treatment with tauroursodeoxycholic also suppressed weight gain.

“Our findings indicated that an [intermittent fasting] regimen improved brain energy metabolism and cognitive function via restructuring gut microbiota and metabolites,” the researchers say. But the team cautions that the effects of intermittent fasting should be further evaluated in clinical trials. “Once validated, [intermittent fasting] can be translated into a novel ecological approach for managing metabolic and neurodegenerative diseases,” the researchers say.