Intestine-brain axis: the first images of choroid plexus modifications in patients with Crohn’s disease

Depression and anxiety often affect those suffering from chronic intestinal diseases, such as Ulcerative Colitis and Crohn’s Disease. The scientific community agrees that there is a link between the intestine and the brain, about which we gained new insights in 2021, when a team of researchers from Humanitas identified a previously unknown vascular barrier in the choroid plexus in the brain. The scientists discovered that this barrier opens and closes based on the integrity of the intestinal barrier and therefore on the presence of chronic inflammation in the intestine.

The data, then published in Science, showed that the closure of the choroid plexus, aimed at protecting the brain from intestinal inflammation, was associated with states of anxiety and depression, at least in laboratory models. If confirmed in clinical settings, it would mean that such psychological disorders – often found in patients with Crohn’s Disease and Ulcerative Colitis – are part of the disease and not just secondary, extra-intestinal manifestations.

In a new study recently published in Neurobiology of Disease, researchers and doctors from Humanitas investigated the phenomenon clinically: using non-invasive diagnostic systems, they measured the modifications of the choroid plexus in Crohn’s disease patients.

The study was authored by a multidisciplinary team of doctors and scientists coordinated by Dr. Cristiana Bonifacio, Responsible for the Radiodiagnostic of the Gastrointestinal Tract Section at the IRCCS Humanitas Research Hospital, and by Prof. Letterio Salvatore Politi, Head of High-Field Neuroradiology and Functional Diagnostics Unit, as well as Full Professor and Co-Director of the Radiodiagnostic Residency Program at Humanitas University. Among the collaborators, also Prof. Maria Rescigno, Head of the Mucosal Immunology Laboratory at Humanitas and Vice Rector for Research at Humanitas University, who led the study published in Science.

“Through Magnetic Resonance Imaging examination,” explains Dr. Bonifacio, “we tried to observe the modifications at the level of the choroid plexus in 17 Crohn’s disease patients. We were able to observe that the markers of intestinal and systemic inflammation in these individuals are indeed correlated with morphological and functional modifications of the choroid plexus. In particular, the exams highlighted modifications in the volume and permeability of the membrane.”

Each participant in the study underwent magnetic resonance imaging of the abdomen to assess the course of Crohn’s disease and of the head to assess the effects of the disease’s activity on the choroid plexus. In addition, all participants underwent endoscopic evaluation and blood tests to detect inflammation biomarkers.

“This is the first clinical study that has investigated these phenomena in patients,” continues Prof. Politi. “The next steps will involve interpreting the modifications detected in the choroid plexus to seek direct correlations with inflammatory states. The data collected support the existence of a vascular axis between the intestine and the brain and constitute the basis for future research to investigate communication between the two organs.”

The discovery of the “brain gate”: the choroid plexus and the intestine-brain axis

The choroid plexus is a brain structure where the fluid that surrounds the brain and spinal cord is produced, protecting the delicate structures of the central nervous system. Furthermore, the choroid plexus serves as a conduit for the entry of nutrients and the elimination of waste substances, and plays a role in immune defense. According to recent discoveries conducted in Humanitas laboratories, within the choroid plexus, in addition to the well-known epithelial barrier, exists a vascular barrier similar to the one previously discovered in the intestine. Under healthy conditions, this “gate” allows molecules derived from the blood to enter. However, during intestinal inflammation, the barrier closes to prevent the entry of harmful substances and pathogens.

The research group has also demonstrated how this mechanism, which effectively isolates the brain from the rest of the body, could be responsible for behavioral alterations falling within the spectrum of anxiety and depression. Preclinical data in Science have shown that intestine-brain communication is fundamental for proper brain activity, opening up important new lines of research, including for other pathologies such as neurodegenerative diseases, which are also characterized by a strong inflammatory state.