Plant-based fasting-mimicking diet reduces IBD pathology

The fasting-mimicking diet (FMD) changes gut microbiota and reduces inflammatory bowel disease (IBD) pathology in mice, according to a recent study published in the journal Cell Reports.

Researchers induced IBD symptoms and pathology by feeding mice dextran sodium sulfate (DSS), a molecule that causes gut inflammation in mice. Markers of IBD pathology include leaky gut, infiltration of the immune cells in the gut, reduced length of the gut, and blood in the stools, according to researchers. 

The mice then received multiple FMD cycles involving several days of human-grade plant-based foods. The mice received the same FMD diet as human study subjects in other trials. Another group of DSS-treated mice underwent water-only fasting.

Researchers found that mice receiving the FMD showed reduced intestinal inflammation, increased stem cell number, stimulated protective gut microbiota and reversed intestinal pathology caused by DSS. In contrast, the water-only fasting increased regenerative and reduced inflammatory markers but did not reverse IBD pathology.

The study was led by Valter Longo, PhD, lead author of the study and professor at the University of Southern California Leonard Davis School of Gerontology, who briefly mentioned the new study during his keynote session at the 2019 Integrative Healthcare Symposium in February.  

"In both groups of mice, we saw markers of regeneration in the gut," said Longo. "But looking at the length of the colon of the small intestine and inflammation, only the FMD brings them back to better health while the water-only fasting does not."

The FMD is low calorie, low sugar, low protein, and high in unsaturated fats. The idea is to “trick” the body in to entering a period of fasting. According to Longo, an FMD is as effective as water-only fasting in altering genetic markers such as IGF-1, IGF-BP1, glucose, and ketone bodies. The purpose is to regulate IGF-1 and ketone bodies in the same way starvation would, he said.

Many of the ingredients in the diet, which is classified as vegan or plant-based, are known to foster growth of certain bacterial populations as pre-biotics. In this study, the researchers found that transplants of Lactobacillus or fecal microbiota reversed DSS-induced colon shortening, reduced inflammation, and increased colonic stem cells. Longo said with the FMD, Lactobacillus reseeding may be responsible for many of these effects.

Longo concluded that the contents of the FMD, along with the fasting protocol, allowed the mice gut microbiota to repopulate bacterial populations like Lactobacillus that are responsible for achieving part of the improved IBD pathology effects.

Also included in this study, researchers re-examined patient samples from an earlier FMD human clinical trial unrelated to IBD. They studied white blood cells and inflammatory markers such as C-reactive protein.

“We found that, in the people who had higher inflammatory markers, the white blood cells were elevated as you would expect in a system that is in a pre-inflammatory disease condition," said Longo. "Then we showed that the inflammatory markers and white blood cells came down in response to multiple cycles of the FMD."

In mice, the FMD has previously been shown to play a role in reducing the symptoms of several chronic illnesses, like multiple sclerosis and diabetes.

Looking ahead, Longo said the researchers are finalizing the protocol for a randomized clinical trial of a modified FMD in humans to see if the microbiota changes and produces any effects on IBD pathology.