GAin-PD

The gut, particularly the large intestine, is home to trillions of microorganisms, collectively known as the gut microbiota, which interact with the digestive system to help maintain our health. These microbes carry out a number of vital functions, including breaking down food, making essential nutrients the body cannot produce on its own, and regulating immune responses. While the precise ways in which the gut microbiota interact with and influence other parts of the body are still being studied, we do know that maintaining a balanced gut microbiome is essential for our wellbeing.

An imbalance in the gut microbiome has been linked to several medical conditions, such as Inflammatory Bowel Diseases (IBDs) and Type 2 diabetes. Recent research also suggests a role for the gut microbiome in neurological conditions like Parkinson’s, which may partly be explained by the connection between the gut and the brain. The gut and brain communicate with one another via the gut-brain axis, and is increasingly recognised as an important route through which changes in the gut may influence brain health.

The idea that Parkinson’s pathology originates in the gut is called “gut-first Parkinson’s”. Given how gastro-intestinal symptoms (ex. constipation) are some of the most common and earliest symptoms of Parkinson’s, it makes sense that researchers are interested in how the gut influences Parkinson’s onset and progression. To learn more about some of the pathways researchers propose for this, please watch our previous webinar.

One proposed pathway for gut-first Parkinson’s is via inflammation. Inflammation on its own is a normal, short-term immune response, which typically subsides once a threat (ex. virus, foreign bacteria, etc) is dealt with. When inflammation is prolonged or chronic, however, this can cause issues in the body as immune cells begin to attack healthy body cells. Chronic inflammation is considered a driver of several conditions, including Crohn’s disease and Parkinson’s.

When our gut microbiome becomes out-of-balance, the microbes here may release more pro-inflammatory molecules. Chronic inflammation here can have many implications, including damaging the gut lining. This can make the gut more “leaky”, allowing these pro-inflammatory molecules to leave the gut and circulate throughout the rest of the body.

What happens next is still being investigated, and multiple mechanisms may be involved. There is some evidence to suggest that body-wide inflammation can make the blood-brain barrier (BBB) more permeable (leaky). The BBB is a highly selective, semipermeable layer of cells that prevents unwanted substances in the blood from crossing into the central nervous system. With the BBB more leaky, this could allow inflammatory molecules to enter the brain and trigger neuroinflammation, therefore damaging neurons. Another possible route is via the gut-brain axis, where inflammation may spread from the gut’s nervous system to the brain.