‘A significant leap forward’
Commenting on the findings, David T. Rubin, MD, professor of medicine at the University of Chicago, noted that the study’s results represent “a significant leap forward” and that it highlights “another important cost to uncontrolled gut inflammation that is the potential for worsened mental health disorders.”
Dr. Rubin, whose research involves measuring metabolites of the dietary amino acid tryptophan, including melatonin and serotonin, in patients with IBD, added that the findings offer a possible explanation for the association of both Crohn’s disease and ulcerative colitis with anxiety and depressive disorders.
“There was a belief that the association was in the opposite direction, that the mental health disorder was causing or worsening the gut inflammation, but this has been disavowed,” Dr. Rubin said.
“Most recently, the recognition that the major sources of serotonin and other metabolites of tryptophan that come from the gut microbiome has led to the hypothesis that the inflamed bowel and dysbiotic gut biome may in fact be driving the mental health disorders due to the effect of neurotransmitter imbalance,” he added. Dr. Rubin also suggested that the shutdown of the choroid plexus vascular barrier may contribute to this imbalance but that this needs additional study.
“This further supports my ongoing contention that the gut really is the center of the universe,” said Dr. Rubin.
Also commenting on the findings, Miguel Rigueiro, MD, professor in the department of medicine in the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, said, “There’s an implication that anxiety and depression and other behavioral health disorders may be explained by this mechanism. If that is the case, there may be a way to target medications against the choroid plexus and potentially treat depression or anxiety.”
This prospect was echoed by Dr. Rubin, who said, “The clinical implication is that treatment of gut inflammation may restore a balance to the neurotransmitters and resolve anxiety or depressive disorders.”
To identify new therapeutic targets, investigators will study the regions and circuits of the brain that are more susceptible to this closure of the choroid plexus, said Dr. Lodato.
“If these regions are associated with depression or other psychosocial disorders, then this new understanding around the choroid plexus vascular barrier might eventually have implications for helping treat such disorders,” she noted.
Reflecting a general shift from a brain-centric view of some psychosocial disorders to an intestinal-centric one, Dr. Lodato added, “The brain cannot be considered in isolation. It is part of a much larger body, and we need to think this way.”
Dr. Rescigno, Dr. Lodato, and Dr. Rubin report no relevant financial relationships. Dr. Rigueiro has served on advisory boards and as consultant for AbbVie, Janssen, UCB, Takeda, Pfizer, Miraca Labs, Amgen, Celgene, Seres, Allergan, Genentech, Gilead, Salix, Prometheus, Lilly, TARGET Pharma Solutions, ALFASIGMA, SpA, and Bristol-Meyer Squibb.
A version of this article first appeared on Medscape.com.