Repeated cycles of a low-calorie, plant-based diet have shown promise as a treatment for inflammatory bowel disease.
Scientists at the University of Southern California in Los Angeles recently tested what they describe as the "fasting-mimicking" diet on a mouse model of inflammatory bowel disease (IBD).
In a study paper that now features in the journal Cell Reports, they describe how, compared with water-only fasting, periodic 4-day cycles of the fasting-mimicking diet "partially reversed" hallmarks of IBD in the mice.
In addition, the team observed that these effects appeared, in part, to be due to an increase in beneficial gut bacteria.
Results from humans also showed that the diet reduced markers of inflammation and associated immune cells.
Taking these results together, the researchers conclude that a low-calorie, plant-based, fasting-mimicking diet has potential as an effective treatment for IBD.
Corresponding study author Valter Longo, a professor of biological sciences, says that their investigation is the first IBD study to bring together "two worlds of research."
"The first [world]," he explains, "is about what you should eat every day, and many studies point to a diet rich in vegetables, nuts, and olive oil. The second is fasting and its effects on inflammation, regeneration, and aging."
He and his colleagues suggest that the reason that water-based fasting does not seem to be as effective as the fasting-mimicking diet could be because while fasting produces many of the desired effects, the body still needs essential nutrients to do the rest.
IBD and gut inflammation
The term IBD mainly covers two conditions, Crohn's disease and ulcerative colitis, whose principal feature is long-term inflammation of the intestines. The protracted inflammation eventually damages the tissue of the gut.
The main difference between these conditions is that Crohn's disease can occur anywhere in the gut between the mouth and the anus, while ulcerative colitis affects the colon and rectum.
According to 2015 survey data in a Centers for Disease Control and Prevention (CDC) study, about 3 million adults in the United States have reported ever having had a diagnosis of IBD.
This figure suggests that at least 1.3 percent of the U.S. adult population has IBD, which often occurs with other illnesses and results in poor quality of life and "complications requiring hospitalizations and surgical procedures."
The main symptoms of IBD are abdominal pain and diarrhea. People with ulcerative colitis can also experience bleeding through the anus.
The risk factors for IBD include "genetic predisposition and factors that alter gut microbiota, such as antibiotics," note the study authors.
For a while, experts thought that IBD was a "classic autoimmune" disease, wherein the immune system attacks the tissue of the gut as if it were a threat similar to that of disease-causing viruses and bacteria.
More recently, however, other explanations about the origins of IBD have emerged, and there is a growing view that Crohn's disease and ulcerative colitis are "complex barrier disorders."
Fasting-mimicking diet and IBD
Prof. Longo and colleagues write that while scientists do not yet fully understand the effect of diet on IBD, diets that alter gut bacteria in ways that promote inflammation "have consistently been associated" with the development of IBD.
For their investigation, they put one group of mice on a low-calorie, low-protein, fasting-mimicking diet and another on a water-only fast.
Both groups of mice had long-term intestinal features of IBD as a result of treatment with chronic dextran sodium sulfate.
The mice on the fasting-mimicking diet consumed 50 percent of their normal intake of calories for 1 day, and then only 10 percent of their normal calories for a further 3 days. The mice on the water-only fast consumed no food at all; they only had water for 48 hours.
The results revealed reductions, and even reversals, in some IBD features in the fasting-mimicking diet mice that had two cycles of the 4-day diet and then resumed their normal food intake.
In comparison, the mice on the water-only fasting diet showed fewer improvements.
This would suggest that the fasting-mimicking diet contains certain nutrients that increase the effect of fasting on gut bacteria to reduce inflammation.
'It's about cells and microbes'
As Prof. Longo remarks, "[I]t's not just about the cells of the human body but it's also about the microbes that are affected by both the fasting and the diet."
He and his colleagues also saw tissue regeneration and an increase in stem cell activity in the colon and small intestine of the mice on the fasting-mimicking diet. Also, the animals' small intestines grew longer after several cycles on the diet.
The team suggests that this confirms that while fasting readies the tissue for improvement, replenishing cells and repairing tissue only occurs when "refeeding" takes place.
"It is really remarkable," Prof. Longo observes, "that in the past 100 years of research into calorie restriction, no one recognized the importance of the refeeding."
He likens the process to that of demolishing and rebuilding houses. Calorie restriction is about demolition and rubble clearing, while refeeding is about rebuilding.
In this study, and also in previous work, the team had tested the effect of "fasting-mimicking diet cycles" on humans. This showed that people with high levels of C-reactive protein (CRP) experienced a drop in the inflammation marker.
The fasting-mimicking diet also reversed the increase in white blood cells that accompanies a rise in CRP.
The investigators are already planning a randomized clinical trial to evaluate the safety and effectiveness of fasting-mimicking diet cycles in humans with IBD.
"The ingredients in the diet pushed the microbes to help the fasting maximize the benefits against IBD."
Prof. Valter Longo