Parkinson's May Start in the Gut and Spread to the Brain, New Study Suggests

What role might the gut microbiome play in Parkinson’s disease? A new study published in Nature Communications adds to the growing body of research linking gut microbiome health to neurodegeneration. The stool samples of 490 people with Parkinson’s disease and 234 “control” healthy individuals were examined to compare microbial DNA, which was then sequenced to see which microbial features were present or elevated in the Parkinson’s fecal samples vs the control samples. 

One of the results of this study showed the Parkinson’s fecal samples were lower in anti-inflammatory short-chain fatty acids and, interestingly, elevated in what is usually considered “good” probiotics such as Lactobacillus and Bifidobacterium. So what does this mean? The researchers have generated significant new data about the gut microbiome of people with Parkinson’s, which could open the door to further studies, research, and treatments for a condition that currently has no cure.

“PD-associated species form polymicrobial clusters that grow or shrink together, and some compete. PD microbiome is disease permissive, evidenced by overabundance of pathogens and immunogenic components, dysregulated neuroactive signaling, preponderance of molecules that induce alpha-synuclein pathology, and over-production of toxicants; with the reduction in anti-inflammatory and neuroprotective factors limiting the capacity to recover,” reads the study abstract, making the important point that this new data is confirming in humans what was previously known only through animal (mice) studies. What else do we know about Parkinson’s and gut health? Here is what the experts have to say. Read on—and to ensure your health and the health of others, don’t miss these Sure Signs You’ve Already Had COVID.

open the bathroom door, go to toilet

The impact of the gut microbiome on Parkinson’s disease has been extensively studied. “There is a gut-brain connection in Parkinson’s,” says Kuldip Dave, PhD, Vice President of Research at The ALS Association and former director of research programs at The Michael J. Fox Foundation for Parkinson’s Research. “One of the earliest symptoms of the disease, starting before most people are diagnosed, is constipation. Studies have found toxic forms of the protein alpha-synuclein in the colon of Parkinson’s patients. The incidence of Parkinson’s is higher in people with Crohn’s disease, inflammatory bowel disease and ulcerative colitis. And other research has shown that people with Parkinson’s have an altered microbiome, with higher levels of H. Pylori bacteria.”

The Nature Communications article recognizes and thanks the Michael J. Fox Foundation in their acknowledgements. “Fundamental questions remain unanswered about the microbiome and Parkinson’s disease,” says Dr. Kuldip. “What is secreted by the microbiome and can we measure it? What is in the gut microbiome of healthy people that’s different from people with Parkinson’s? And perhaps most importantly, what do we want to change about the microbiome to improve health, and how do we do that? Finding these answers will guide our investments as we continue to support research into the microbiome and the gut-brain connection in Parkinson’s.”

Female scientist working in the CDC laboratory.

The new research showing lower SCFA in Parkinson’s microbiome is noteworthy, and confirms what previous research has indicated. “Short chain fatty acids (SCFAs) are one of the main products of the microbiome,” says the American Parkinson Disease Association. “Research has shown that SCFAs can enter the brain and exert neuroprotective effects via increase of nerve growth factors. A number of research studies have shown that there are less SCFAs in fecal samples from people with PD as compared to healthy controls and this could contribute to a lack of neuroprotection that then fuels PD.”

According to gastroenterologist Ali Keshavarzian, MD, “PD itself can cause many GI symptoms (constipation, bloating, diarrhea, abdominal pain, nausea) and these symptoms can overlap with other GI conditions (such as colon cancer and celiac disease). Therefore, if a person with PD has a new GI symptom, he/she should not assume that it is related to PD. Rather a more thorough GI evaluation needs to be performed.”

bad sleep

Previous research has linked Parkinson’s disease to sleep disruption. “In REM sleep behavior disorder, a person acts out their dreams, says Rachel Dolhun, MD. “Because these dreams often involve being chased or attacked, people will yell, punch, kick or even leap out of bed. REM is the period of sleep during which we dream. Normally, the brain inhibits muscle movement during this time. In RBD, the brain pathways that suppress muscle activity are disrupted, and people are able to move to act out their dreams.”

REM sleep behavior disorder is a symptom of PD that can precede official diagnosis by years. “Sleep problems, including RBD, are common in people who’ve been diagnosed with Parkinson’s,” says Dr. Dolhun. “But studies suggest that REM sleep behavior disorder also can be one of the first symptoms of PD, occurring years before motor symptoms. (Other possible early signs include constipation, depression and smell loss.) These studies demonstrate a strong link between having RBD and later being diagnosed with Parkinson’s or related conditions such as dementia with Lewy bodies or multiple system atrophy, which have PD symptoms. Not everyone with RBD goes on to develop PD, though.”

weight loss

Parkinson’s-related constipation can lead to weight loss, experts say. “Weight loss in Parkinson’s is common, but it’s usually mild or, at most, moderate,” says Dr. Dolhun. “Changes can occur at any time with Parkinson’s disease (PD), but may be more likely in later phases. It’s important to recognize and address weight loss because it could lead to malnutrition or exacerbate motor and non-motor symptoms. Smell loss or depression can lead to loss of appetite and decreased food intake; constipation and slowed stomach emptying may cause nausea, abdominal bloating or a full feeling after consuming small amounts; and swallowing problems might require a change in diet or make mealtimes difficult.”

Unexplained weight loss should always be addressed by a healthcare professional. “Significant weight loss in PD is associated with a lower quality of life,” says Dr. Dolhun. “This is because it can make it harder to control motor and non-motor symptoms, and increase risk of infection and bone loss (osteoporosis). If you notice a shift in your weight, make sure you talk with your doctor. He or she can monitor your weight and together you can work to figure out the reason(s). Your physician may start by asking about changes in mood or eating habits, as well as difficulty with swallowing or constipation.”

mature woman sleeping peacefully

The role of inflammation in Parkinson’s disease continues to be studied. “So the immune system is our body’s response to something bad we are exposed to,” says Dr. Dave. “Bacteria, viruses, and there’s this concept of good and bad inflammation. So you know when you get a cut or you get a burn and you get redness and swelling, that’s good inflammation. We want that to happen. But when that persists over a long period of time, when that starts to affect our normal function, our cells, our tissues, at that point it becomes bad for our body and that’s what we call bad inflammation.

“If we can understand that interplay between good and bad inflammation in Parkinson’s disease, we can then leverage the immune system to make better drugs for PD. We don’t fully appreciate and understand where and when it happens. Does it happen before Parkinson’s disease sets in, or does it happen after Parkinson’s disease sets in and kind of helps the progression of the disease, or maybe a little of both? If we can understand that better, we would have a better sense of using immune system to have better therapeutics for Parkinson’s.”

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