Decoding Two-Way Brain-Gut Communication Unveils New Insights into Neurological Diseases

Cells move from the brain to the gut and back. – A new paper by Rhonda McFleder et al. reveals a groundbreaking discovery in the intricate world of brain-gut communication. Published in “Nature Communications,” the study challenges the conventional wisdom that communication between the brain and the gut is a one-way street.

“In our latest study, we demonstrate that brain-to-gut communication is a dynamic two-way process. Cells can migrate from the brain to the gut, influencing the spread of diseases,” explains neurobiologist Professor Rhonda McFleder, who lead the study alongside Professor Chi Wang Ip.

The research focuses on the role of immune cells, particularly macrophages, in the progression of Parkinson’s disease. The team discovered that proteins linked to Parkinson’s, specifically α-Synuclein (αSyn), migrate from the brain to the gut, causing disruptions. Notably, these protein accumulations were found in macrophages, not the neurons controlling the gut’s autonomous nervous system.

“To definitively test the migration of macrophages from the brain to the gut, we developed a method to label brain cells and track their migration,” says Rhonda McFleder, who teamed up with the Beilhack lab to uncover a unique communication between the brain and gut, suggesting its involvement in Parkinson’s disease spread.

Professor Chi Wang Ip adds a crucial finding: “We observed that macrophages not only migrate in Parkinson’s but also under control conditions, broadening the relevance to other neurological diseases. Just as these cells drive pathology in Parkinson’s, they may also promote disease spread in other neurological conditions.”

Next steps involve fully characterizing these migrating cells and identifying homing molecules guiding them to the gut. “Once identified, we can develop therapeutics targeting these molecules, potentially halting the progression of Parkinson’s and other neurological diseases,” says Rhonda McFleder.

The study involved collaboration from various research groups and received support from the Alexander von Humboldt Foundation, the Bavarian Ministry of Economic Affairs, the German Research Foundation (DFG), the Interdisciplinary Center for Clinical Research (IZKF) at the University of Würzburg, the VERUM Foundation, and the former EU Horizon 2020 research and innovation program.

McFleder RL, Makhotkina A, Groh J, Keber U, Imdahl F, Peña Mosca J, Peteranderl A, Wu J, Tabuchi S, Hoffmann J, Karl AK, Pagenstecher A, Vogel J, Beilhack A, Koprich JB, Brotchie JM, Saliba AE, Volkmann J, Ip CW. (2023). Brain-to-gut trafficking of alpha-Synuclein by CD11c+ cells in a mouse model of Parkinson’s disease. Nature Communications, 14(1):7529.

This research article was also highlighted in Nature Reviews Neurology.

Link to press release from Würzburg University Hospital, Germany (in German).