In response to gut inflammation, such as that caused by inflammatory bowel disease (IBD), the vascular barrier in the brain choroid plexus closes, locking down access to the brain, according to a new study.

While this gut-brain vascular axis deregulation likely protects the brain from inflammation, the findings suggest it may also result in the various cognitive and psychiatric symptoms that are occasionally associated with IBD.

While often linked to intestinal inflammation, IBD can also cause a wide variety of symptoms in other organs outside the gut – as much as 40% of patients with IBD also present with psychiatric symptoms like anxiety or depression. While the gut-brain axis is thought to be involved in driving these symptoms, related mechanisms are unknown.

Using a mouse model of intestinal inflammation, the researchers identified a potential pathogenic link between IBD and its associated mental comorbidities. According to the findings, the gut vascular barrier becomes more permeable due to the inflammatory process, which allows inflammation to spread beyond the intestines.

In response to this spread, the vascular barrier in the choroid plexus of the brain shuts down, which helps to protect the brain from inflammation. However, in doing so, the process also potentially impairs communications between organs and may hinder brain function.

In a mouse model of genetically driven closure of choroid plexus endothelial cells, the researchers observed a deficit in short-term memory and anxiety-like behavior.

Thus, the mental deficits observed alongside IBD may be a consequence of the deregulation of the gut-brain vascular axis, the authors say, a finding which could be leveraged to develop therapeutic targets in treating some behavioral disorders.

https://www.science.org/doi/10.1126/science.abc6108