IBD may disrupt gut-brain axis, raising risk of anxiety, depression

IBD may disrupt gut-brain axis, raising risk of anxiety, depression

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New research in mice suggests that a broken link between the gut and the brain may explain the effect of IBD on mental health. RapidEye/Getty Images
  • Around 30% of patients with inflammatory bowel disease (IBD) experience depression, anxiety, or both.
  • A new study in mice suggests that impaired communication between the gut and the brain may be partly responsible.
  • The study found that a gateway between the bloodstream and cerebrospinal fluid may close to protect the brain from inflammation during flare-ups.
  • This may disrupt the gut-brain axis, a communication channel between the gut and brain with possible links to mental health.

IBD involves chronic inflammation of the gut.

There are two main types: Crohn’s disease, which can affect any part of the gastrointestinal tract, and ulcerative colitis, which only affects the large intestine and rectum.

In 2015, an estimated 3.1 million adults in the United States, or 1.3% of the adult population, had received an IBD diagnosis.

Symptoms of IBD include persistent diarrhea, abdominal pain, weight loss, and fatigue.

According to one study, around 30% of individuals with IBD also experience depression, anxiety, or both.

The pain and discomfort that some people experience with certain chronic illnesses increase their risk of developing mental health illnesses. However, that does not appear to be the whole story in IBD.

“While the overall impact of the disease on overall quality of life no doubt plays an important role in triggering anxiety and depression in IBD, there is also increasing evidence of direct biological connections between IBD-associated inflammation and neuropsychiatric diseases,” said Dr. Gerard Honig, director of research innovation at the Crohn’s & Colitis Foundation in New York, NY.

“Anxiety and depression are, in fact, experienced by a large proportion of patients affected by [IBD],” he told Medical News Today.

“These comorbid conditions are also associated with worsened IBD outcomes,” said Dr. Honig.

According to Crohn’s & Colitis UK, feelings of stress, anxiety, or depression can trigger new symptoms in the gut.

A newly published study now suggests that IBD directly affects the brain by disrupting the gut-brain axis.

The gut-brain axis is a two-way channel of communication between the gut and the central nervous system. Microorganisms living in the gut play a prominent role in the relationship, although, as in this new study, findings to date are mainly in rodent models.

The new study found that inflammation in the gut may close a key gateway in this communication system that controls the exchange of signals between the blood and cerebrospinal fluid (CSF).

Unlike the blood-brain barrier, which prevents large molecules in the bloodstream from entering the brain, the gateway between the CSF and blood usually permits the passage of smaller molecules.

But the study found that it responds to inflammatory signals from the gut by slamming shut, presumably to prevent inflammation from spreading to the brain.

The research showed that in a mouse model of IBD, closure of the gateway disrupted memory and caused anxiety.

The research contradicts the widely accepted idea that brain inflammation in IBD leads to cognitive and psychiatric symptoms.

The study appears in the journal Science.

The authors conclude:

“Our data support the possibility that at least part of the behavioral and cognitive alterations that have been described in patients with IBD may result not from the enhanced inflammation, as generally hypothesized, but rather from the defense strategy activated by the organism to protect the brain from damage and guarantee its function.”

The barrier between the bloodstream and CSF comprises a membrane in a specialized region at the base of the brain known as the choroid plexus.

“Under healthy conditions, the choroid plexus connects the brain with the rest of the organism for both nutrient and metabolite exchange,” said co-senior author Dr. Maria Rescigno of Humanitas University and Humanitas Hospital in Milan, Italy.

“During intestinal inflammation, in order to avoid inflammation further propagating to the brain, the choroid plexus closes down, and this interaction with the rest of the organism is interrupted,” Dr. Resigno told MNT.

Previous research by the same scientists revealed a “gut vascular barrier” that usually prevents bacteria from passing from the gut to the liver via the circulatory system.

They found that inflammation in the intestines disrupts this barrier, which allows bacteria to spread to the liver and promotes inflammation elsewhere in the body.

The new study found evidence that people with ulcerative colitis have an impaired gut vascular barrier.

They confirmed that this is the case in a mouse model of ulcerative colitis.

A subsequent set of experiments with mice showed that gut inflammation goes on to trigger the closure of the blood-CSF barrier in the choroid plexus.

Closure of the barrier had associations with changes in the behavior of the mice, reducing movement and exploratory activity.

However, there remained a possibility that the pain of ulcerative colitis rather than the shutdown caused these behavioral changes.

To rule out this possibility, the scientists studied genetically engineered mice in which the barrier stays shut even in the absence of inflammation.

Compared with normal animals, these mice also showed signs of anxiety-like behavior. They also performed worse on standard lab tests of episodic memory.

Overall, the research suggests that closure of this brain barrier due to gut inflammation may cause the anxiety and depression that some people with IBD experience.

“We observe that closure of the choroid plexus isolates the brain and leads to anxiety-like behaviors and defects in episodic memory,” Prof. Rescigno told MNT.

“We do not know whether other defects may be occurring,” she added.

The authors conclude that it may be possible to develop treatments that restore healthy communication between the gut and the brain in conditions that involve gut inflammation.

However, a major limitation of the study was that it relied on a mouse model of ulcerative colitis. The relationship between the gut and brain in humans may be more complex and it will be necessary to conduct human studies to elucidate any relationship between IBD and mental health.


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