Harmful Bacteria Breaking Down the Intestinal Mucus Layer and Causing Inflammation Identified in Parkinson’s Patients with REM Sleep Behavior Disorder

A Team of Professors Sun Ju Chung and Sungyang Jo at Asan Medical Center Presented New Evidence for Predicting Parkinson’s Progression and Developing Personalized Treatment

▲ (From left) Professors Sun Ju Chung and Sungyang Jo of the Department of Neurology at Asan Medical Center

One of the major warning signs of Parkinson’s disease, a degenerative brain disorder, is ‘REM sleep behavior disorder’, which is characterized by excessive sleep talking, shouting, or kicking during sleep. A recent study by a Korean research team revealed that the composition of gut microbiota in patients with Parkinson’s disease differs depending on whether or not they experience REM sleep behavior disorder.

A team led by Professors Sun Ju Chung and Sungyang Jo of the Department of Neurology at Asan Medical Center recently reported that patients who had experienced REM sleep behavior disorder prior to being diagnosed with Parkinson’s disease showed a disrupted gut environment from the early stages. In contrast, patients without a history of REM sleep behavior disorder initially maintained a balanced gut environment, but after two years following diagnosis, their gut microbiota changed to resemble that of patients with REM sleep behavior disorder.

This study is significant in that it analyzed the gut environment of patients with Parkinson’s disease and provided new evidence for predicting disease progression and developing personalized treatment strategies.

Parkinson’s disease is a degenerative brain disorder known to result from the abnormal accumulation of the protein alpha-synuclein, which plays a critical role in dopamine regulation, leading to damage of nerve cells in the brain.

However, since cases have been identified in which protein aggregation occurs first in the enteric nervous system or peripheral nerves rather than in the brain, Parkinson’s disease is now classified into two subtypes according to its pathway of onset: brain-first type (originating in the brain) and gut-first type (beginning in the gut or peripheral nervous system and transmitting signals to the brain).

In brain-first patients, REM sleep behavior disorder appears late or may not develop at all, whereas in gut-first patients, REM sleep behavior disorder often precedes the onset of Parkinson’s disease.

Although previous studies have reported that changes in gut microbiota are similar between patients with Parkinson’s disease and those with REM sleep behavior disorder, differences in the gut environment according to the disease pathway of Parkinson’s disease have not been clearly identified.

A team led by Professors Sun Ju Chung and Sungyang Jo of the Department of Neurology at Asan Medical Center recruited 104 patients with Parkinson’s disease and 85 control subjects who received treatment at Asan Medical Center between 2019 and 2024. They compared and analyzed changes in gut microbiota according to the presence of REM sleep behavior disorder and the stage of disease progression.

Of the 104 patients with Parkinson’s disease, 57 had experienced REM sleep behavior disorder prior to their diagnosis, while 47 had not. The control group consisted of 85 spouses of Parkinson’s patients, allowing for comparison under similar lifestyle conditions.

The analysis showed that patients who had experienced REM sleep behavior disorder before being diagnosed with Parkinson’s disease had a higher proportion of harmful bacteria such as Akkermansia and Escherichia, which break down the intestinal mucus layer and form bacterial biofilms, from the early stages of the disease. In these patients, the expression of genes important for protecting the intestinal barrier was significantly reduced, creating an environment in which harmful bacteria could easily adhere to the intestinal wall and trigger inflammation. This pattern remained largely unchanged as the disease progressed.

In contrast, patients with Parkinson’s disease who did not have REM sleep behavior disorder initially showed a gut microbiota composition similar to that of the healthy control group, with an abundance of fiber-related beneficial bacteria such as Prevotella and Faecalibacterium, which help protect the intestinal lining. However, by two years after diagnosis, their gut microbiota composition began to resemble that of patients with REM sleep behavior disorder.

Despite participants consuming 34 to 36 grams of dietary fiber per day, exceeding the general recommended intake of 25 grams, a clear imbalance in gut microbiota was observed. This finding suggests that restoring microbial balance in the gut is difficult to achieve through dietary adjustments alone.

Professor Sun Ju Chung of the Department of Neurology at Asan Medical Center stated, “As our society enters a super-aged era, the number of Parkinson’s disease patients in Korea is rapidly increasing. Because the early symptoms of Parkinson’s disease are similar to those of normal aging, the disease is difficult to detect. This study suggests the potential of gut microbiota as a biomarker for the early diagnosis of Parkinson’s disease.”

Professor Sungyang Jo of the Department of Neurology at Asan Medical Center added, “The composition of gut microbiota showed a striking difference depending on the presence of REM sleep behavior disorder. By focusing on the gut microbiome environment of Parkinson’s patients with REM sleep behavior disorder and developing personalized treatment strategies, we expect to make significant contributions to maintaining patients’ quality of life.”

The results of this study were recently published in ‘Microbiome’ (impact factor 12.7), an international SCI-level journal.