Stress Hijacks Bidirectional Brain-to-Gut Connections

Emotional hubs in the cerebral cortex connect to the stomach via vagal pathways.

Posted May 19, 2020

 Image credited to David Levinthal, M.D., Ph.D., and Peter Strick, Ph.D.
Two opposing circuits connecting the brain to the stomach convey either "fight or flight" or "rest and digest" commands to the gut.
Source: Image credited to David Levinthal, M.D., Ph.D., and Peter Strick, Ph.D.

New research from the University of Pittsburgh Brain Institute identifies how multiple regions of the cerebral cortex influence the stomach via the vagus nerve and its numerous pathways. This study by David Levinthal and Peter Strick traces brain-to-gut connections that may lead to stomach ulcers when someone suffers from chronic stress.

These findings (Levinthal & Strick, 2020) were published this week in the Proceedings of the National Academy of Sciences (PNAS). This research was funded by grants from the National Institutes of Health (NIH), the U.S. Army Research Office (ARO), and the DSF Charitable Foundation.

"The bidirectional connections between brain and gut are important conduits for communication within the mind-body axis," Frederick Gregory, ARO program manager, said in a May 18 news release about the study.

The study's first author, David Levinthal, is a gastroenterologist and director of UPMC's Neurogastroenterology and Motility Center. His team's most recent paper is a follow-up to another study (Dum, Levinthal & Strick, 2019) that identified mind-body connections associated with circuits linking the cerebral cortex to the innermost part of adrenal glands published last year in PNAS.

"Pavlov demonstrated many years ago that the central nervous system uses environmental signals and past experience to generate anticipatory responses that promote efficient digestion," co-author Peter Strick, director and chair of neurobiology at Pitt Med, said in a news release.

"The stomach sends sensory information to the cortex, which sends instructions back to the gut," he added. "That means our 'gut feelings' are constructed not only from signals derived from the stomach, but also from all the other influences on the rostral insula, such as past experiences and contextual knowledge."

"We have long known that every increase in unemployment and its associated stress is accompanied by an increase in death rates from stomach ulcers," Strick noted. As of this writing, over 36 million jobless claims have been filed in the United States during the past two months of the coronavirus crisis.

Multiple Cerebral Cortex Areas Communicate With the Stomach

Wikipedia/Public Domain
An anatomical illustration of the insula's short gyri and long gyrus from the 1908 edition of Sobotta's Anatomy Atlas.
Source: Wikipedia/Public Domain

Through a series of elaborate experiments in mice, Levinthal and Strick recently found (2020) that vagal pathways associated with the parasympathetic nervous system—which facilitates "rest and digest" responses—can be traced directly from the stomach to a brain region called the insula, which plays a role in emotion regulation.

Anyone who dreads public speaking or experiences stage fright knows how the nerve-racking anticipation of having to get up in front of a crowd for a presentation can cause gut-churning indigestion. In the age of COVID-19, the same brain-to-gut stress response can happen just before sharing your screen during a Zoom call or making a company-wide PowerPoint presentation in a virtual meeting. 

Because vagal pathways along the gut-brain axis are bidirectional, when someone is really stressed out, these brain-gut connections create a superhighway of back-and-forth communication that can snowball out of control. The insula picks up signs of stress from the gut, which causes the brain to sound more stress-related alarm bells in the stomach.  

Source: metamorworks/Shutterstock 

The latest research from Levinthal and Strick (2020) suggests that the brain instantaneously sends stress signals from the insula to the gut. Over time, chronic stress hijacks these brain-to-gut connections in a way that may cause stomach ulcers.

Interestingly, Strick and Levinthal speculate that the sympathetic nervous system—which facilitates "fight or flight" responses—sends brain-to-gut messages along vagal pathways more closely tied to motor regions of the cerebral cortex. 

According to the authors: "These insights also could change clinical gastroenterology practice." Having a better understanding of how brain-to-gut connections exert control over the stomach could lead to new and better ways for gastroenterologists to treat bowel problems and GI disorders.

For example, gut-brain communication influences the potential growth of specific bacteria such as Helicobacter pylori, that can provoke peptic ulcers. Hacking brain-gut connections from the top-down could adjust gastric secretions in a way that makes the stomach less hospitable to bacterial invaders.

"Several common gut disorders, such as dyspepsia or irritable bowel syndrome, might not get better with current treatments," Levinthal concluded. "Our results provide cortical targets that will be critical for developing new brain-based therapies that might be helpful for our patients."


David J. Levinthal and Peter L. Strick "Multiple Areas of the Cerebral Cortex Influence the Stomach." PNAS (First published: May 20, 2020) DOI: 10.1073/pnas.2002737117

Richard P. Dum, David J. Levinthal, and Peter L. Strick. "The Mind-Body Problem: Circuits That Link the Cerebral Cortex to the Adrenal Medulla." PNAS (First published: December 23, 2019) DOI: 10.1073/pnas.1902297116