Study Shows Fasting Could Reduce Gastrointestinal Inflammation

A new study suggests that fasting triggers molecular activity in the brain that can reduce bowel inflammation.

The study, conducted by researchers at the Salk Institute for Biological Studies in California, shows that the brain communicates with the gastrointestinal tract through a molecular channel. This line of communication strengthens the gut’s barrier against microbes in the GI tract, which prevents the immune system from activating during fasting. The discovery of this communication channel could lead to improved treatments for inflammatory bowel diseases.

The study was led by Mark Montminy of the Clayton Foundation Laboratories for Peptide Biology and John Thomas of the Salk Institute. Montminy says that fasting can affect the GI tract, the metabolic system, and brain function. Further understanding of how the GI tract maintains its barrier against microbes will allow the creation of more effective medicines that can reinforce that barrier and treat inflammatory bowel diseases.

This study was one in a series of experiments by the Montminy and Thomas research teams to examine a genetic switch called Crtc that occurs in the brain to control the balance of energy. 

Communication networks between the brain, the GI tract, and other tissues in the body helps to regulate the expenditure and storage of energy.

To investigate the Crtc mechanism, the research teams used fruit flies, because fruit flies and humans share many metabolic genes. Prior experiments by the researchers showed that flies whose Crtc gene had been deleted were more sensitive to fasting and lived half as long when deprived of food compared to flies whose Crtc gene was intact. The researchers hypothesized that the non-Crtc flies died more quickly because their bodies stored fewer fats and sugars.

When the researchers examined the flies more closely, they found that the non-Crtc fruit flies’ immune systems had kicked into overdrive. Without the Crtc gene, the flies’ immune systems were activated, which used up a lot of their energy. In the absence of Crtc, many gut bacteria leaked into the flies’ circulation, which is what triggered the immune system.

In normal fruit flies, the Crtc gene is used to strengthen the GI tract’s defenses to prevent bacteria from leaking into the bloodstream and activating the immune system. When the Crtc gene is removed, the cells in the gut lining were disrupted and caused the bacteria leak.

While performing these experiments, the researchers also discovered a molecular protein in the fruit flies’ brains called short neuropeptide F, or sNPF. Its counterpart in human brains is called neuropeptide Y. This protein causes flies and mammals to respond to hunger signals by seeking out food. Fruit flies without sNPF exhibited GI tract inflammation just like the flies without Crtc. Additionally, the non-sNPF flies showed breaks in the lining of the GI tract, which allowed bacteria to escape.

Flies with above average levels of Crtc or sNPF survived longer without food and displayed less disruption in their GI tract’s barriers.

So far, the results are very promising, and the researchers hope to continue experimenting on flies to better understand how the neuropeptides communicate with receptors in the gut.