The Gut-Brain Axis
The gut-brain axis is the complex, bidirectional communication network that links the central nervous system (CNS), which includes the brain and spinal cord, with the enteric nervous system (ENS) of the gastrointestinal tract. This key communication is facilitated in one of the following ways:
- Nervous System:
The vagus nerve is a major pathway through which the brain and gut communicate. It transmits signals in both directions, influencing digestion, mood, and immune response. - Microbiota:
The gut is home to trillions of microorganisms, collectively called the gut microbiome. These microbes produce neurotransmitters like serotonin, dopamine, and GABA, which affect mood, anxiety, and cognition. Imbalances in the gut microbiome also known as dysbiosis has been linked to different types of psychological distress. - Immune System:
About 70% of the body’s immune cells are located in the gut. The immune system mediates the interaction between gut bacteria and the brain, responding to inflammation and infection. - Hormonal Signaling:
Gut hormones that get released from enteroendocrine cells in the gut influence brain function, appetite and mood.
In our lab, we have been studying the interplay between gut related diseases, such as Inflammatory Bowel Disease (IBD) and brain diseases, including Parkinson’s Disease (PD) and REM Sleep Behavior Disorder (RBD). IBD manifests itself as either Crohn’s disease or ulcerative colitis. Approximately 1.4 million people in the US have been affected by IBD; the prevalence among Ashkenazi Jews is about two to four times higher than among non-Jewish whites.
PD, a chronic, degenerative neurological disorder of the central nervous system, is the 2nd most common and fastest growing neurological disorder with approximately 60,000 Americans diagnosed annually. PD symptoms are not limited to motor dysfunction but also non-motor symptoms including GI (Gastrointestinal) related problems, In fact, GI symptoms are one of the most common non motor feature of PD. About 50-80% of PD patients experience constipation years before motor manifestation of PD. The presence and severity of PD associated constipation are associated with cognitive decline and affects levodopa uptake. Additionally, mutations in the LRRK2 gene, the greatest genetic contributor to Parkinson’s disease, were recently found in patients with IBD, placing individuals at greater risk of developing either (or both) diseases.
RBD is a sleep disorder where individuals act out their dreams during REM sleep and is also associated with higher risk of developing PD.
The goal of our studies is to determine whether diverse biomarkers of intestinal inflammation found in stool, blood, and urine, genetic inflammatory scores and microbiota composition may help in identifying PD subtypes. This will further allow us to stratify patients, and enable us to develop targeted therapies.
Therapeutic Implications
Although many studies have highlighted the link between gut diseases and PD, the role of intestinal biomarkers in disease risk is largely unknown. Our study focuses on identifying non-invasive biomarkers to help us predict and prevent the onset of future PD.