https://www.nature.com/articles/d41586-023-01700-y Skip to main content Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Advertisement Advertisement Nature * View all journals * Search * Log in * Explore content * About the journal * Publish with us * Subscribe * Sign up for alerts * RSS feed 1. nature 2. news 3. article * NEWS * 25 May 2023 Chronic stress can inflame the gut -- now scientists know why Signals originating in the brain make their way to gut nerve cells, leading to a release of inflammatory chemicals. * Saima Sidik 1. Saima Sidik View author publications You can also search for this author in PubMed Google Scholar * Twitter * Facebook * Email You have full access to this article via your institution. Download PDF A coloured scanning electron micrograph of a section of human intestine with ulcerative colitis. Intestinal tissue (artificially coloured) of a person with ulcerative colitis.Credit: Steve Gschmeissner/Science Photo Library Psychological stress is known to worsen the gut inflammation caused by certain bowel diseases. Now scientists have found out why. New research^1 outlines a sweeping narrative that begins with chemical cues produced in the brain and ends with immune cells in the gut -- a sequence that spells trouble for people with these conditions. The work, published today in Cell, helps to explain how chronic stress can trigger physical distress. And it implies that managing stress levels might have a profound influence over the effectiveness of treatments for inflammatory bowel disease (IBD). That idea runs contrary to conventional medical treatment, which has "completely neglected the psychological state of a patient as a major driver of [the] response to treatment", says study co-author Christoph Thaiss, a microbiologist at the University of Pennsylvania in Philadelphia. The path from brain to gut Abdominal pain, diarrhoea and fatigue are just a few of the symptoms that people with IBD experience. The two main types of IBD, ulcerative colitis and Crohn's disease, are mild in some people but, in others, can be debilitating or even life-threatening. Stressful events, such as losing one's job or breaking up with a partner, often precede IBD flare-ups. Thaiss and his colleagues have now traced that linkage. After a surge of stress, the brain sends signals to the adrenal glands, which release chemicals called glucocorticoids to the rest of the body. [d41586-023] Anxiety can be created by the body, mouse heart study suggests Initially, the researchers considered the idea that glucocorticoids act directly on immune cells, which respond by releasing molecules that cause inflammation. "But it turns out that there is a sort of layer in between," Thaiss says. Working in mice, they found that glucocorticoids act instead on neurons in the gut and on cells called glia that connect gut neurons to one another. Co-opted immune cells After being switched on by glucocorticoids, some glial cells release molecules that trigger immune cells. In turn, those immune cells release molecules that would normally be used to fight off pathogens, but in this case end up causing painful bowel inflammation. At the same time, glucocorticoids block immature gut neurons from developing fully, the researchers found. As a consequence, these neurons produce only low levels of signalling molecules that cause gut muscles to contract. This means food moves slowly through the digestive system, which adds to the discomfort of IBD. The researchers were surprised to learn that glucocorticoids cause gut inflammation, because these compounds are sometimes used to treat IBD. This apparent paradox might be explained by the short time frame on which such treatments are used. Although quick bursts of glucocorticoids seem to be anti-inflammatory, when stress becomes chronic, "the system completely shifts" and glucocorticoids take on a pro-inflammatory role, Thaiss says. It's a "plausible explanation", says gastroenterologist and immunologist John Chang at the University of California, San Diego. Stress management for symptom relief The brain's ability to drive inflammation in far-flung organs "seems to be much stronger" than was thought before, Thaiss says. This suggests that IBD drugs, in combination with stress-management techniques, could be more effective than the drugs alone. Molecules in the signalling pathway that runs from the brain to the gut could also become targets for new pharmacological treatments -- "an exciting possibility", Chang says. The implications of the work could reach beyond IBD. Stress is also thought to heighten inflammatory diseases of the skin and lungs, possibly through similar signalling pathways. Moving forwards, Thaiss is excited to explore whether brain states other than stress influence a person's overall health. "There's definitely a huge amount we still need to learn about the brain and how the brain controls seemingly unrelated aspects of physiology and disease." doi: https://doi.org/10.1038/d41586-023-01700-y References 1. Schneider, K. M. et al. Cell https://doi.org/10.1016/ j.cell.2023.05.001 (2023). Article Google Scholar Download references Related Articles * [d41586-023] Guardians of the brain: how a special immune system protects our grey matter * [d41586-023] Gut feeling yields evidence of microbial involvement in autoimmunity * [d41586-023] Your brain could be controlling how sick you get -- and how you recover * [d41586-023] Brain-cell growth keeps mood disorders at bay Subjects * Neuroscience * Immunology * Brain Latest on: Neuroscience Does brain stimulation boost memory and focus? Mega study tries to settle debate Does brain stimulation boost memory and focus? Mega study tries to settle debate News 26 MAY 23 Listening for neurological symptoms Listening for neurological symptoms Outlook 24 MAY 23 Accelerating drug development with 3D neural models Accelerating drug development with 3D neural models Outlook 24 MAY 23 Immunology US will vaccinate birds against avian flu for first time -- what researchers think US will vaccinate birds against avian flu for first time -- what researchers think News 26 MAY 23 COVID vaccines falter in people with severe obesity COVID vaccines falter in people with severe obesity Research Highlight 17 MAY 23 Inhibiting membrane rupture with NINJ1 antibodies limits tissue injury Article 17 MAY 23 Brain Does brain stimulation boost memory and focus? Mega study tries to settle debate Does brain stimulation boost memory and focus? Mega study tries to settle debate News 26 MAY 23 Accelerating drug development with 3D neural models Accelerating drug development with 3D neural models Outlook 24 MAY 23 Revealing vascular roadblocks in the brain Revealing vascular roadblocks in the brain Outlook 24 MAY 23 Nature Careers Jobs * Postdoctoral fellow - molecular and systems neuroscience The labs of Sandeep Robert Datta and Michael E. Greenberg are seeking a postdoctoral fellow as part of a joint project to probe the molecular basis... Boston, Massachusetts (US) Harvard Medical School Department of Neurobiology [] * CZS Endowed Professorship for artificial intelligence in neural systems imaging The Faculty of Social and Behavioural Sciences of Friedrich Schiller University Jena invites application for the CZS Endowed Professorship for art... Jena, Thuringen (DE) Friedrich-Schiller-Universitat Jena [] * The Eric and Wendy Schmidt AI in Science Postdoctoral Fellowship At Nanyang Technological University The Eric and Wendy Schmidt AI in Science Postdoctoral Fellowship at NTU supports research on applying AI techniques to STEM areas Singapore (SG) Nanyang Technological University (NTU) [] * Bioinformatics Postdoctoral Researcher 3 year fixed term full time postdoctoral opportunity available in the newly established Adelaide Centre for Epigenetics (ACE). Adelaide (LGA), Metropolitan Adelaide (AU) University of Adelaide * Faculty Positions in Westlake University Founded in 2018, Westlake University is a new type of non-profit research-oriented university in Hangzhou, China, supported by public a... Hangzhou Westlake University [] You have full access to this article via your institution. Download PDF Related Articles * [d41586-023] Guardians of the brain: how a special immune system protects our grey matter * [d41586-023] Gut feeling yields evidence of microbial involvement in autoimmunity * [d41586-023] Your brain could be controlling how sick you get -- and how you recover * [d41586-023] Brain-cell growth keeps mood disorders at bay Subjects * Neuroscience * Immunology * Brain Advertisement Sign up to Nature Briefing An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday. Email address [ ] [ ] Yes! Sign me up to receive the daily Nature Briefing email. I agree my information will be processed in accordance with the Nature and Springer Nature Limited Privacy Policy. Sign up * Close Nature Briefing Sign up for the Nature Briefing newsletter -- what matters in science, free to your inbox daily. Email address [ ] Sign up [ ] I agree my information will be processed in accordance with the Nature and Springer Nature Limited Privacy Policy. Close Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing Explore content * Research articles * News * Opinion * Research Analysis * Careers * Books & Culture * Podcasts * Videos * Current issue * Browse issues * Collections * Subjects * Follow us on Facebook * Follow us on Twitter * Subscribe * Sign up for alerts * RSS feed About the journal * Journal Staff * About the Editors * Journal Information * Our publishing models * Editorial Values Statement * Journal Metrics * Awards * Contact * Editorial policies * History of Nature * Send a news tip Publish with us * For Authors * For Referees * Language editing services * Submit manuscript Search Search articles by subject, keyword or author [ ] Show results from [All journals] Search Advanced search Quick links * Explore articles by subject * Find a job * Guide to authors * Editorial policies Nature (Nature) ISSN 1476-4687 (online) ISSN 0028-0836 (print) nature.com sitemap About Nature Portfolio * About us * Press releases * Press office * Contact us Discover content * Journals A-Z * Articles by subject * Nano * Protocol Exchange * Nature Index Publishing policies * Nature portfolio policies * Open access Author & Researcher services * Reprints & permissions * Research data * Language editing * Scientific editing * Nature Masterclasses * Nature Research Academies * Research Solutions Libraries & institutions * Librarian service & tools * Librarian portal * Open research * Recommend to library Advertising & partnerships * Advertising * Partnerships & Services * Media kits * Branded content Career development * Nature Careers * Nature Conferences * Nature events Regional websites * Nature Africa * Nature China * Nature India * Nature Italy * Nature Japan * Nature Korea * Nature Middle East * Privacy Policy * Use of cookies * Your privacy choices/Manage cookies * Legal notice * Accessibility statement * Terms & Conditions * Your US state privacy rights Springer Nature (c) 2023 Springer Nature Limited