Neuropeptide regulation in intestinal homeostasis
A diverse and stable community of microorganisms in our intestines, the gut microbiota, is vital in keeping us healthy. An imbalance in the gut microbiota can lead to various health problems, such as inflammatory bowel diseases, autoimmune disorders, colorectal cancer, and cardiovascular diseases. Our research has shown that a protein called vasoactive intestinal peptide (VIP), found in the gut, helps regulate the balance of the gut microbiota. It does this by interacting with a specific receptor called VPAC1, which is on cells lining the intestine and specific immune cells in the gut. The gut microbiota, intestinal cells, and immune cells communicate with each other by releasing and receiving chemical signals. However, it is challenging to determine how VPAC1 affects gut health because it can directly and indirectly affect cellular communication. We propose that VIP signaling through VPAC1 in intestinal cells influences the activity of specific genes, which in turn affect the function of the gut microbiota and the balance of immune cells in the gut. We study mice deficient in VIP and lacking VPAC1 in their intestinal cells. We will examine changes in the gut microbiota and analyze how the absence of VPAC1 affects gene activity in intestinal cells.
Additionally, we will investigate the timing and developmental stages when VPAC1 is crucial for gut microbiota function, gene activity in intestinal cells, and the balance of immune cells in the gut. This research is important because it helps us better understand how neuropeptides like VIP influence gut health and their implications for human diseases. It may also reveal new roles for neuropeptides as essential mediators between the body and the gut microbiota.
Neuropeptide signaling bridges trans-kingdom communication between the gut microbiota and host metabolism
Obesity is a significant health problem affecting many adults in the US, contributing to severe conditions like Type-2 Diabetes and cardiovascular disease. It puts a significant financial burden on society as well. Research has shown that having a diverse community of microorganisms in our gut is essential for maintaining good metabolic health. These microorganisms produce certain chemicals called short-chain fatty acids (SCFA) by breaking down dietary fiber. One of these fatty acids, propionate, has been found to improve metabolic health by regulating glucose levels, insulin sensitivity, energy expenditure, and weight loss. Our research group has discovered that a neuropeptide called vasoactive intestinal peptide (VIP) regulates diverse gut microbiota. When VIP is missing, there is a disruption in the gut microbiota and a reduction in SCFA levels, leading to reduced bacterial diversity. In recent studies on rats, it was found that a diet rich in propionate failed to activate a key enzyme called G6Pase in the presence of a neurotoxin. This suggested that another neurotransmitter in the gut might need propionate to have its effects. Based on these findings, we are interested in asking whether VIP acts as a mediator between propionate, a metabolite produced by the gut microbiota, and positive metabolic health benefits.
Our research suggests that having a diverse community of microorganisms in our gut is vital for our health, especially regarding metabolic conditions like obesity and diabetes. One of the chemicals produced by these microorganisms, propionate, is beneficial. We and other researchers have discovered that VIP connects propionate, gut microorganisms, and our overall health. They conducted experiments on mice and found that mice lacking VIP did not respond to propionate in the same way as normal mice. This suggests that activating VIP pharmacologically could potentially be a therapeutic strategy for reducing obesity and related health problems in humans.