Recognizing Gastrointestinal Symptoms as Early Indicators of Parkinson Disease

Laren Becker, MD, PhD

Gastrointestinal (GI) symptoms are among the most common and burdensome nonmotor complications in Parkinson’s disease (PD), affecting up to 81% of patients. Constipation, dysphagia, and nausea or vomiting are particularly frequent and can significantly impair daily functioning. In advanced cases, the impact of GI issues on quality of life may surpass that of motor symptoms.

GI issues have been shown to significantly impact the effectiveness of levodopa treatment in PD due to impaired absorption. Specifically, researchers have found that these symptoms may affect levodopa absorption through delaying gastric emptying, constipation, foot interactions, and other conditions like small intestinal bacterial overgrowth. At the 4th Annual Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress, held by the PMD Alliance from June 27-30, 2025, Laren Becker, MD, PhD, presented a talk on overcoming GI barriers in the care paradigm for PD, focusing specific on acute OFF episode management from carbidopa/levodopa therapy.

Becker, a physician-scientist in the Division of Gastroenterology at Stanford University, sat down with NeurologyLive^® during the meeting to discuss the presentation, giving clinicians insights on the reasons behind the talk. In the interview, he explained how enzymes involved in dopamine biosynthesis are active both in the brain and the gut, and how GI abnormalities—ranging from dysphagia and delayed gastric emptying to SIBO and constipation—can significantly impact levodopa bioavailability. In addition, Becker emphasized the need for clinicians to account for gut-related factors when evaluating levodopa responsiveness and motor symptom control.

NeurologyLive: Provide an overview of your presentation, why was this a topic of interest for you?

Laren Becker, MD, PhD: I'd like to start off by saying it's kind of an emerging field—understanding that these neurodegenerative diseases affect the periphery, particularly the gut. It's increasingly recognized, especially in Parkinson’s disease, that the gut is involved. So we can start with the implications this has for treatment and management.

If we start with the dopamine biosynthetic pathway, the key enzymes—tyrosine hydroxylase and amino acid decarboxylase—are certainly present in the brain, but that’s not exclusive. They’re also present in the gut. The gut has its own dopaminergic neurons. So, when there’s a deficiency in the brain, the easiest route would be to give dopamine. However, dopamine does not cross the blood-brain barrier. It has to be supplied in the form of levodopa—or potentially earlier—but tyrosine isn’t a great starting point because tyrosine hydroxylase is the rate-limiting step. So, we tend to think about using levodopa.

The problem is that because these enzymes are present in both locations, there are challenges in getting appropriate levels to the brain, particularly crossing the blood-brain barrier. These challenges are, to some extent, driven by what’s happening in the GI tract. This reinforces the point that Parkinson’s appears to evolve beyond just the brain. This has been noted in the fact that many Parkinson’s patients have non-motor symptoms, particularly GI disturbances, and these often occur decades before patients develop motor symptoms.

This led to the Braak hypothesis. Braak proposed that the disease actually starts in the gut and ascends into the brain through the vagus nerve. There’s increasing evidence for peripheral involvement—it’s not just that α-synuclein has been detected in the gut. It has also been detected in peripheral nerves via skin biopsies. The gut itself shows α-synuclein aggregates similar to those in the brain. This occurs throughout the entire GI tract.

So, the GI symptoms and alterations in gut physiology aren’t specific to any one region. Constipation is the most commonly recognized symptom, but it starts from the top down. Individuals with Parkinson’s have difficulty swallowing. When Parkinson’s patients have been assessed by esophageal manometry—which tests motor function of the esophagus—abnormalities have been detected in up to 30% of patients.

Farther down, the stomach is involved. Gastric emptying scans done on Parkinson’s patients have found delays in between 70–100% of them. Many of these individuals are asymptomatic—they’re not necessarily vomiting all the time. Lower down in the small intestine, dysmotility contributes to higher rates of small intestinal bacterial overgrowth (SIBO), which has been detected in up to 50% of patients.

Finally, constipation—the symptom most people recognize—occurs in the vast majority of patients. When testing has been done, two-thirds of these patients have both slow transit (meaning motility of the colon is affected) and dyssynergic defecation (meaning the mechanism of having a bowel movement at the outlet is also impaired). The fact that both conditions are present makes constipation even more difficult to treat in Parkinson’s patients.

This has important implications for therapies. For PD, it's about the bioavailability of levodopa. We want high enough concentrations reaching the brain via the bloodstream. If that doesn’t happen, there’s a delay in symptom relief. The GI factors that can influence this include:

• Difficulty swallowing, which can affect adherence to taking medications.
• Delayed gastric emptying, which reduces bioavailability because levodopa is absorbed later.
• SIBO or H. pylori, which may metabolize levodopa and lower blood levels.
• Dietary factors, such as high protein content, which can compete with levodopa for conversion by amino acid decarboxylase.

The main point is that GI involvement can have serious implications for PD therapy. It must be considered, especially when individuals aren’t responding appropriately to treatment.

Transcript was edited for clarity.