Mount Sinai Researchers Identify Key Gut Sensor That Regulates Digestion and Immunity
New study in Cell explains how Piezo1 helps food move and keeps the immune system balanced
Researchers at the Icahn School of Medicine at Mount Sinai have made an exciting discovery about how the gut senses the movement of food, which could lead to better treatments for digestive problems.
Published today in the journal Cell, this research demonstrates that Piezo1, a special pressure sensor in the gut, plays an essential role in maintaining gut motility (the ability of the muscles in the gastrointestinal tract to contract and propel food and waste through the digestive system) and immune balance. It does this by helping nerve cells in the enteric nervous system (ENS), a part of the nervous system known as the “second brain” because it controls digestion without the help from the brain, to sense pressure and movement in the gut.
Led by Hongzhen Hu, PhD, MS, Professor of Neuroscience, and Dermatology, and Scientific Director of the Mark Lebwohl Center for Neuroinflammation and Sensation at the Icahn School of Medicine, the study found that Piezo1 is important for gut nerve cells to control digestion, absorb nutrients, and reduce inflammation. These findings highlight the ENS as a key player in gut function, with implications for treating digestive diseases such as inflammatory bowel disease and problems with gut movement.
“Mechanosensation is fundamental for normal gut function, influencing peristalsis and immune responses. However, how the gut senses and responds to mechanical forces has remained poorly understood until now,” said Zili Xie, PhD, Assistant Professor of Dermatology, the Hu Lab at the Icahn School of Medicine, and the first author of the study. “Our study establishes Piezo1 as a crucial pressure sensor in enteric neurons, linking its function to gut motility, exercise-induced motility changes, and inflammation regulation.”
The research also explains how mechanical forces—such as those brought on by exercise—affect gut movement, offering new insights into how lifestyle interventions can improve digestive health.
“The ENS is an incredibly complex and autonomous network that influences not just digestion but also immune function, brain health, and systemic disease,” said Dr. Hu. “By identifying this molecular mechanism behind how the gut senses movement, this work advances the fundamental understanding of gut physiology and sets the stage for future therapeutic innovations,” said Brian Kim, MD, Director of the Lebwohl Center.
Next, the research team plans to explore whether Piezo1 in gut nerve cells regulates other gut functions and contributes to additional gastrointestinal diseases. Future studies will aim to translate these findings into potential clinical applications for treating gut motility disorders and inflammatory conditions.
This research was conducted in collaboration with Ruaidhri Jackson, PhD, and colleagues at Harvard Medical School, and collaborators at Washington University School of Medicine in St. Louis, Johns Hopkins University, the Shanghai Institute of Materia Medica, Flinders University in Australia, and Maynooth University in Ireland. This work was supported by grants from the National Institutes of Health, the Paul G Allen Frontiers Group and Family Foundation, the Paul Allen Distinguished Investigator Program, the Kenneth Rainin Innovator Award, the Crohn’s & Colitis Foundation, and other funding agencies.
About the Icahn School of Medicine at Mount Sinai
The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the eight- member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to New York City’s large and diverse patient population.
The Icahn School of Medicine at Mount Sinai offers highly competitive MD, PhD, MD-PhD, and master’s degree programs, with enrollment of more than 1,200 students. It has the largest graduate medical education program in the country, with more than 2,600 clinical residents and fellows training throughout the Health System. Its Graduate School of Biomedical Sciences offers 13 degree-granting programs, conducts innovative basic and translational research, and trains more than 500 postdoctoral research fellows.
Ranked 11th nationwide in National Institutes of Health (NIH) funding, the Icahn School of Medicine at Mount Sinai is among the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges. More than 4,500 scientists, educators, and clinicians work within and across dozens of academic departments and multidisciplinary institutes with an emphasis on translational research and therapeutics. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai.
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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Beth Israel; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across seven hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2024-2025.
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