研究问题
Neuropeptide regulation in intestinal homeostasis
A diverse and stable community of microorganisms in our intestines, 肠道菌群, is vital in keeping us healthy. An imbalance in 肠道菌群 can lead to various health problems, such as inflammatory bowel diseases, 自身免疫性疾病, 结肠直肠癌, and cardiovascular diseases. Our research has shown that a protein called vasoactive intestinal peptide (VIP), 在肠道中发现, helps regulate the balance of 肠道菌群. 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. 肠道菌群, 肠细胞, and immune cells communicate with each other by releasing and receiving chemical signals. 然而, 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 肠细胞 influences the activity of specific genes, which in turn affect the function of 肠道菌群 and the balance of immune cells in the gut. We study mice deficient in VIP and lacking VPAC1 in their 肠细胞. We will examine changes in 肠道菌群 and analyze how the absence of VPAC1 affects gene activity in 肠细胞.
另外, we will investigate the timing and developmental stages when VPAC1 is crucial for gut microbiota function, gene activity in 肠细胞, 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 肠道菌群.
Neuropeptide signaling bridges trans-kingdom communication between 肠道菌群 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. 研究 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. 这些脂肪酸中的一种, 丙酸, has been found to improve metabolic health by regulating glucose levels, 胰岛素敏感性, 能量消耗, 还有减肥. Our research group has discovered that a neuropeptide called vasoactive intestinal peptide (VIP) regulates diverse gut microbiota. 当VIP不见了, there is a disruption in 肠道菌群 and a reduction in SCFA levels, leading to reduced bacterial diversity. In recent studies on rats, it was found that a diet rich in 丙酸 failed to activate a key enzyme called G6Pase in the presence of a neurotoxin. This suggested that another neurotransmitter in the gut might need 丙酸 to have its effects. 基于这些发现, we are interested in asking whether VIP acts as a mediator between 丙酸, a metabolite produced by 肠道菌群, 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, 丙酸, is beneficial. We and other researchers have discovered that VIP connects 丙酸, 肠道微生物, 以及我们的整体健康. They conducted experiments on mice and found that mice lacking VIP did not respond to 丙酸 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.
