What do the brain and the intestines have in common? Gastroenterologist Rodger Liddle and his laboratory are focused on this question as they study the role of enteroendocrine cells (EECs) in the intestines. EECs not only sense what is inside the intestines and respond to nutrient and bacterial stimulation but also connect to nerves that communicate with the brain. These EECs, then, are a key connection between the food and bacteria in our digestive system and our nervous system. Dr. Liddle says, “It leads to new ways of thinking about how the gut ‘talks’ to the brain,” and his work with the VA, facilitated by Merit Review grant funding and the Institute for Medical Research, aims to explore how those responses specifically affect neurological health.
After Dr. Liddle’s laboratory discovered that EECs connect to nerves, he considered how a gut-to-brain transmission of disease may explain the origin of some neurological conditions. His current research is focused on Parkinson’s disease, in which misfolded proteins infect neighboring nerve cells, causing their proteins to misfold, and eventually these abnormally folded nerve cells accumulate in clumps, called Lewy bodies, in the brain. Over time, these changes in the brain can cause problems with body movement, thinking, moods, and other behavior. Parkinson’s patients have also been found to have these abnormal proteins in the gut, which brings this disease to the attention of gastroenterologists as well as neurologists.
Researchers do not yet know what initiates the chain reaction of degenerating nerve cells in Parkinson’s disease, but one hypothesis is that environmental toxins are ingested and cause a reaction in the EECs, which then infect the nervous system. For example, Vietnam War veterans have a higher-than-average incidence of Parkinson’s; some researchers suggest that the toxicity of Agent Orange has caused the neurologic damage.
When asked what motivates Dr. Liddle’s research, he remarked that he finds the science fascinating but he’s ultimately driven to work toward improving patient care. He notes that, as a researcher, there is a significant delay to his gratification because the timeline for laboratory discoveries being translated into improvements in the life of a patient with Parkinson’s is a very long one. But Dr. Liddle is hopeful that continued research in this area will help doctors to recognize the causes and risk factors for Parkinson’s and maybe even prevent its occurrence, even if a cure or effective treatment are still awaiting discovery.