Chronic psychological stress has been associated with inflammation in the body, particularly in the setting of inflammatory bowel disease (IBD) where stress is associated with the severity of disease flares. In a recent article published in Cell, Schneider et al. demonstrated that the enteric nervous system mediates the aggravating effect of chronic stress on intestinal inflammation.
Stress alone is not enough
The researchers aimed to understand how brain-derived stress signals from psychological stress drive inflammatory responses in the intestine. Using a mouse model of prolonged stress, the team first demonstrated that stress alone was not sufficient to induce colitis. However, intestinal inflammation was exacerbated if mice were exposed to chronic stress before colitis induction. The finding suggests stress induces latent molecular changes that can exacerbate the disease phenotype under certain circumstances or with specific triggers.
The team then conducted RNA sequencing of colonic tissue of the mice. In those exposed to stress prior to colitis induction, they found decreased expression of genes linked to immunity and antimicrobial peptides and increased expression of genes associated with IBD and proinflammatory cytokines, alterations not observed in mice only exposed to stress.
Stress hormones act on gut nervous system
Delving further into the underlying molecular mechanisms, the researchers found that stress induces chronically elevated levels of glucocorticoids—steroid hormones that typically reduce inflammation—which drive a subset of cells in the nervous system of the digestive tract, called the enteric nervous system, to promote inflammation and dysmotility of the colon.
Confirmation in patients with IBD
Lastly, the investigators verified the connection between psychological state and intestinal inflammation by conducting a prospective study of 63 patients with IBD who underwent colonoscopy and completed a mental health assessment. They found perceived stress levels strongly correlated with disease severity. Additionally, in tissue from colon biopsies of these patients, expression of immune cell-related and proinflammatory genes was positively correlated with stress and disease severity.
Together, the findings provide a mechanistic explanation for the role of the brain in peripheral inflammation and identify the enteric nervous system as the mediator between psychological stress and gut inflammation, suggesting stress management could enhance treatment success in patients with IBD.
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Lauren Dembeck, Ph.D., Geneticist & Science Writer, Bridge Informatics
Lauren Dembeck, Ph.D., is an experienced science and medical writer. During her doctoral research at North Carolina State University, she conducted genome-wide association studies to identify genetic variants contributing to natural variation in complex traits and used a combination of classical and molecular genetics approaches in validation studies. Lauren was a postdoctoral fellow at the Okinawa Institute of Science and Technology in Japan. During her postdoc, she used fluorescence-activated cell sorting paired with high-throughput sequencing approaches to study the formation and regulation of neuronal circuits.
She is part of our team of expert content writers at Bridge Informatics, bringing our readers and customers everything they need to know at the cutting edge of bioinformatics research. If you’re interested in reaching out, please email [email protected] or [email protected].