In this solo commentary, Dr. David Perlmutter revisits the gut‑brain connection, referencing his book Brain Maker and a recent Science Translational Medicine study titled “The Vermiform Appendix Impacts the Risk of Developing Parkinson’s Disease.” The study examined 1.6 million individuals (≈91 million person‑years) and found that people who had undergone an appendectomy experienced about a 25 % lower risk of developing Parkinson’s disease after roughly 35 years. Perlmutter explains that the appendix harbors pathogenic forms of the misfolded protein alpha‑synuclein, which is central to Parkinson’s pathology and is also produced in the gut. He proposes that these proteins may travel to the brain via the vagus nerve—a route supported by observations that vagotomy reduces Parkinson’s risk. While the findings are intriguing, Perlmutter cautions against recommending routine appendectomy, emphasizing that the takeaway is the broader insight into how gut biology can influence brain disease.
Chapters
Hello everyone, Dr. David Perlmutter here. You know, we've been talking quite a bit over the past few years about the so-called gut-brain connection, the relationship of things going on within the gut in terms of how they play out in the brain, either for good or for bad. The book I wrote, Brain Maker, in fact really deals with the relationship of things going on with our gut bacteria In terms of how that might influence both brain health as well as brain functionality and even resistance or susceptibility to disease. In that line of discussion, a new and really interesting article recently came out in the journal Science of Translational Medicine. The study is called The Vermiform Appendix Impacts the Risk of Developing Parkinson's Disease. Now, the vermiform means worm-shaped appendix. That's the appendix that we all know about. And what this study looked at was really quite interesting. We know that in Parkinson's disease, there is an accumulation of misfolded, or what we call aggregated protein called alpha-synuclein that accumulates within the brain. And we now recognize that this is actually produced to a significant degree in the gut. And what these scientists wanted to determine was looking at data in terms of who developed Parkinson's and also of those individuals who may or may not have had an appendectomy, was there any information to be gleaned? And in fact, they were able to look at 1.6 million individuals, the medical records of these 1.6 million individuals. Over a period of time that spanned what is called 91 million person-years. In other words, the number of people multiplied by the time they were able to follow these individuals came out to a number of 91 million person-years, and what they found was that those people who had had their appendix removed had a substantially reduced risk of developing Parkinson's disease. The risk reduction was around 25% after around 35 years. Further, they went ahead with their research and looked at what is contained within the vermiform appendix, or the appendix that we're all familiar with, and found that there are products within the appendix that relate to the formation and the misfolding of this Parkinson's-related protein called alpha-synuclein. So they proposed that the normal human appendix contains these pathogenic forms of alpha-synuclein and that having the appendix removed was associated with a fairly dramatic risk reduction for developing Parkinson's disease. Now, does that mean what we're recommending is that everybody have an appendectomy? I'd say certainly that's not the recommendation, but it is an interesting bit of science, isn't it? That the appendix, even in normal non-Parkinson's patients or individuals, does contain these proteins. What causes them in some patients to migrate into the brain? We believe that happens through the vagus nerve in that people who have had their vagus nerve cut seem to have also a reduction in risk for Parkinson's. That used to be a very common procedure in people with stomach ulcers, that this alpha-synuclein protein might migrate through the vagus nerve, make its way into the brain, and may have a role in actually causing Parkinson's disease. Again, I think the take-home message is not that we should all run out and have our appendices removed, But rather that this is another bit of really fascinating information that relates the gut to the brain. I hope you found that interesting. I sure did. Thanks for listening. I'm Dr. David Perlmutter. Bye for now.
