August 03, 2023

04/08/2023

How sensory neurons impact the gut Scripps Research scientists show that the receptor PIEZO2 in sensory neurons controls gut motility and transit time, which are important for digestion and nutrient absorption.

August 03, 2023

LA JOLLA, CA Gastrointestinal and digestive issues impact roughly 3 million people across the United States alone, and that number is growing. A new study from Scripps Research scientists shows how sensory neurons control our gastrointestinal tracts critical information that could shape our understanding of related diseases and disorders.

The study, published in the journal Cell on Aug. 3rd, 2023, used a combination of human clinical data and animal models to reveal that the receptor PIEZO2 controls gastrointestinal transit through the stomach, small intestine, and colon by sensing the presence of food and slowing the rate of gut motility accordingly. These findings could lead to therapeutic applications for a range of gastrointestinal conditions, such as Inflammatory Bowel Disease and Irritable Bowel Syndrome.

PIEZO2 plays a crucial role in gastrointestinal physiology and is necessary for normal gut function, says senior author Ardem Patapoutian, PhD, professor in the Dorris Neuroscience Center at Scripps Research and a Howard Hughes Medical Institute investigator. Patapoutian received the 2021 Nobel Prize in Physiology for discovering that PIEZO2 and a related receptor, PIEZO1, are necessary for the cells to respond to mechanical stimuli. Food and other ingested contents activate PIEZO2, which in turn dramatically slows gut transit.

Gut transit time the rate at which food moves through our gastrointestinal tracts is essential for digestion, nutrient absorption and waste removal. Optimal digestion requires an optimal transit time: too slow, and you end up with constipation; too fast, and you risk diarrhea. Up until now, there's been a limited understanding of how sensory pathways guide this process.

Patapoutian's team decided to investigate whether sensory input from the receptor PIEZO2 plays a role in gut motility. PIEZO2 proteins are activated by mechanical forces or pressure and are found throughout the body, though their role in gastrointestinal motility has not been previously explored. PIEZO2 receptors are also involved in sensing the degree of lung inflation or bladder filling, so it made sense that these receptors might also be able to detect distension of the gastrointestinal tract.

We wanted to understand the consequences of lacking this mechano-sensation and whether people without PIEZO2 have gastrointestinal problems, says M. Rocio Servin-Vences, PhD, the study's first author and a postdoctoral fellow in the Patapoutian lab at Scripps Research and the Howard Hughes Medical Institute.

Humans are sometimes though rarely born without functional PIEZO2 genes, and studying these individuals provides a window into the protein's function. In collaboration with Alexander Chesler's team at the National Institutes of Health (NIH), the researchers assessed the gastrointestinal health and medical history of a cohort of 12 humans, ranging in age from 9 to 42, who carried non-functional variants of the PIEZO2 gene.

Compared to members of the general population, the PIEZO2-deficient individuals reported a range of gastrointestinal dysfunctions including lumpy and watery stools. Notably, six of the individuals reported that they could not sense bowel movements, and five reported using medications to relieve gastrointestinal distress.

The gastrointestinal dysfunction that these PIEZO2-deficient individuals described was striking, says Servin-Vences. It suggests that PIEZO2-deficient individuals have impaired sensation in bowel function that affects their quality of life, and also that the mechanosensitive channel PIEZO2 plays a crucial role in human gastrointestinal physiology and pathophysiology.

To explore the mechanism behind how PIEZO2 governs gut physiology, the researchers next turned to animal models. They found that when PIEZO2 was removed from sensory neurons, the mice had much faster gut transit times, more frequent defecation and their stools had a higher water content.

We were able to show that PIEZO2 is important for slowing down gastrointestinal transit, says Servin-Vences. When mice do not have PIEZO2 in these neurons, their gastrointestinal transit goes super fast, which has important consequences because it suggests that there is not enough time for proper nutrient absorption.

Since PIEZO2 is expressed by multiple groups of neurons that innervate the gut, the researchers also wanted to pinpoint which neural pathway is responsible for controlling gut transit time. By using genetic and viral tools to selectively shut down PIEZO2 in two neural pathways the nodose ganglia and dorsal root ganglia the researchers were able to show that neurons in the dorsal root ganglia are exclusively responsible for controlling gut motility.

It was very surprising that neurons from the dorsal root ganglia but not from the nodose ganglia have a homeostatic function in gut motility, says Servin-Vences. The nodose ganglia is known to regulate many functions in the gut, lungs and heart, whereas neurons from the dorsal root ganglia are more known for innervating the skin and detecting temperature and pain.

The team also used fluorescent imaging to show that PIEZO2 control of gut motility occurs along the entire gastrointestinal tract from stomach to small intestine to colon.

Though this is just an initial glimpse into how sensory neurons control gut motility, the researchers say it opens a slew of new research questions, and the possibility for future therapeutics. Servin-Vences says next steps are to assess how diet, lifestyle, stress and even microbiota affect this complicated system.

In the long term, if we are able to

LINK:	https://www.scripps.edu/news-and-events/press-room/2023/20230803-patap...
	See more stories from scripps

Most recent headlines

05/01/2027

Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be demoed at CES 2026

Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...

01/06/2026

Dolby Sets the New Standard for Premium Entertainment at CES 2026

January 6 2026, 05:30 (PST) Dolby Sets the New Standard for Premium Entertainment at CES 2026 Throughout the week, Dolby brings to life the latest innovatio...

02/05/2026

Dalet Flex LTS Delivers Smarter Search, Faster Editing, and an AI-Ready Foundation for Modern Media

Dalet, a leading technology and service provider for media-rich organizations, t...

01/05/2026

NBCUniversal's Peacock to Be First Streamer to Integrate Dolby's Full Suite of Premium Picture and Sound Innovations

January 5 2026, 18:30 (PST) NBCUniversal's Peacock to Be First Streamer to ...

01/04/2026

DOLBY AND DOUYIN EMPOWER THE NEXT GENERATON OF CREATORS WITH DOLBY VISION

January 4 2026, 18:00 (PST) DOLBY AND DOUYIN EMPOWER THE NEXT GENERATON OF CREATORS WITH DOLBY VISION Douyin Users Can Now Create And Share Videos With Stun...

18/03/2026

Net Insight Names Larissa GrnerMeeus CPO

Newly named chief product officer (CPO), Larissa G rner Meeus will return to Net Insight on May 4. Larissa G rner Meeus will become CPO of Net Insight on May 4...

18/03/2026

SVG Europe's The Football Summit 2026: Select Sessions Now Available to Watch on SVG PLAY

SVG Europe's The Football Summit 2026 explored how the sports broadcasting i...

18/03/2026

SVG's SportsTech@NABShow Blog Goes Live as Countdown to Vegas Heats Up

The 2026 NAB Show kicks off one month from today and SVG is once again set to cover the show from every angle. SVG's SportsTech@NAB Show Blog is now live - ...

18/03/2026

The Premiere of Dead Lover Showcases Grave Robbing and Sex With a Giant Finger

(L-R) The cast and crew of Dead Lover at The Ray Theater for its premiere at the 2025 Sundance Film Festival. (Photo by Robin Marshall/Shutterstock for Sundan...

18/03/2026

Music Row Piano from Wiltone Productions

Yamaha C7 captured in Nashville Wiltone Productions have announced the release of Music Row Piano, a deeply sampled Yamaha C7 piano library that's been ...

18/03/2026

Techivation introduce T-Warmer Mk2

Bass-enhancement plug-in upgraded Along with a steady stream of new releases, Techivation have recently been revisiting some of the older plug-ins in their ...

18/03/2026

Tonal Balance Control 3 from iZotope

Mix-reference plug-in overhauled iZotope's powerful mix-referencing plug-in has just reached its third major version, and now boasts a new capture proce...

18/03/2026

Toontrack Transistor Organ EKX

Latest EZKeys 2 expansion arrives Toontrack's staggering collection of EZKeys 2 expansions has grown once again, and the latest instalment delivers a on...

18/03/2026

Jess Ho explores the politics of food in new SBS Audio podcast For The Culture

Jess Ho explores the politics of food in new SBS Audio podcast For The Culture 18 March, 2026 Media releases New SBS Audio podcast For The Culture, hosted ...

18/03/2026

Future-ready broadcasts with ATSC 3.0 and enhanced services from Rohde & Schwarz at NAB 2026

Future-ready broadcasts with ATSC 3.0 and enhanced services from Rohde & Schwarz...

18/03/2026

LCTWS 2026

London Calling - When The Industry Convened to Help Streaming Find its MoJo In this blog, Laura Rognoni reflects on key discussions from the Connected TV World...

18/03/2026

SMPTE Unveils 2026 NAB Show Educational Presentations

SMPTE Unveils 2026 NAB Show Educational Presentations Brie Clayton March 18, 2026 0 Comments SMPTE , the home of media professionals, technologists, a...

18/03/2026

Auditel Ad Campaign Shot on Blackmagic PYXIS 12K

Auditel Ad Campaign Shot on Blackmagic PYXIS 12K Brie Clayton March 18, 2026 0 Comments LED wall virtual production blends 12K open gate acquisition w...

18/03/2026