Chronic gut inflammation may initiate processes in the body that give rise to Parkinson disease, according to a study published in Free Neuropathology. The results of the study are consistent with several large-scale epidemiological studies that show an association between Parkinson and inflammatory bowel diseases, such as ulcerative colitis and Crohn disease.
“There is increasing evidence that changes in the gut can affect a variety of neurological and psychiatric brain disorders,” said Patrik Brundin, MD, PhD, in a press release. “[Parkinson disease] is a complex disease with a wide range of factors that work in concert to spark its onset and progression. We need to understand the gut's likely influence on [Parkinson disease] development better. This study provides novel insights, and this new knowledge can facilitate the development of improved treatment approaches.”
Using an experimental mouse model, the investigators found that chronic gut inflammation triggers a protein, alpha-synuclein, to clump together in walls of the colon, as well as in local immune cells called macrophages. Studies by other groups suggest that this process increases the risk of developing Parkinson disease, and a similar process may occur in the colons of individuals with inflammatory bowel diseases.
Alpha-synuclein aggregates also develop in the brains of patients with Parkinson, which can result in the disruption of molecular processes that keep neurons alive. The resulting loss of some critical brain cells, as well as a subsequent decrease in dopamine, results in the movement-related symptoms associated with Parkinson, such as freezing and loss of voluntary movement. The wide-spread development of alpha-synuclein aggregates throughout the brain also may be associated with the disease's non-motor symptoms and may fuel its progression.
The study also suggests that chronic inflammation in the gut early in life can exacerbate alpha-synuclein clumping throughout the brain in older mice. The exact mechanism of this process is currently unknown, but the researchers theorize that inflammatory chemicals may travel from the gut to the brain via the bloodstream, triggering a runaway inflammatory immune response that leads to protein aggregation. They also said it was possible that alpha-synuclein aggregates travel to the brain via the vagus nerve.
“We now know that systems throughout the body contribute to [Parkinson disease],” said Emmanuel Quansah, PhD, in the press release. “It was striking to see protein aggregation pathology in the brain that mirrored pathology in the colon brought on by inflammation. A particularly intriguing observation was the loss dopamine-producing nerve cells—which play a major role in onset [of Parkinson disease]—in our models that had gut inflammation a year-and-a-half earlier.”
The investigators also found that modulating immune activation in the colitis mouse model by genetic or therapeutic means tuned the level of alpha-synuclein clumps in the colon up or down.
“Our results in mice, together with the genetic and epidemiological data by others in humans, make a strong case for further exploring systemic immune pathways for future therapies and biomarkers for [Parkinson disease],” said Markus Britschgi, PhD, in the press release.
Understanding gut inflammation may hold clues to mitigating Parkinson's onset [news release]. EurekAlert; June 9, 2021. Accessed June 10, 2021. https://www.eurekalert.org/pub_releases/2021-06/vari-ugi060921.php