Abstract
The gastrointestinal tract is in a state of constant motion. These movements are tightly regulated by the presence of food and help digestion by mechanically breaking down and propelling gut content. Mechanical sensing in the gut is thought to be essential for regulating motility; however, the identity of the neuronal populations, the molecules involved, and the functional consequences of this sensation are unknown. Here, we show that humans lacking PIEZO2 exhibit impaired bowel sensation and motility. Piezo2 in mouse dorsal root, but not nodose ganglia is required to sense gut content, and this activity slows down food transit rates in the stomach, small intestine, and colon. Indeed, Piezo2 is directly required to detect colon distension in vivo. Our study unveils the mechanosensory mechanisms that regulate the transit of luminal contents throughout the gut, which is a critical process to ensure proper digestion, nutrient absorption, and waste removal.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3386-3399.e15 |
| Journal | Cell |
| Volume | 186 |
| Issue number | 16 |
| DOIs | |
| State | Published - Aug 3 2023 |
Funding
We thank M. Szczot and Felipe Meira de Faria from Linköping University for their support to develop the in vivo colonic preparation. We thank R. Hill, R. Pak, and A. Dubin for their feedback on the manuscript. We also thank K. Spencer, the Nikon Center of Excellence Imaging Center, and the Scripps Research Department of Animal Resources for support services. This work was supported by the Howard Hughes Medical Institute , NIH grant R35 NS105067 (A.P.), and the intramural program of the NIH , the National Center for Complementary and Integrative Health , and National Institute of Neurological Disorders and Stroke (A.T.C.). We thank M. Szczot and Felipe Meira de Faria from Linköping University for their support to develop the in vivo colonic preparation. We thank R. Hill, R. Pak, and A. Dubin for their feedback on the manuscript. We also thank K. Spencer, the Nikon Center of Excellence Imaging Center, and the Scripps Research Department of Animal Resources for support services. This work was supported by the Howard Hughes Medical Institute, NIH grant R35 NS105067 (A.P.), and the intramural program of the NIH, the National Center for Complementary and Integrative Health, and National Institute of Neurological Disorders and Stroke (A.T.C.). M.R.S.-V. A.P. and A.T.C. conceived and designed the study. M.R.S.-V. R.M.L. A.K. Y.W. M.L. S.F. and H.K. performed experiments and analyzed data. R.M.L. performed and analyzed in vivo DRG recordings. H.K. performed and analyzed videorecorded GI transit experiments. Y.Z. performed analysis of scRNA-seq from Zeisel et al.40 M.R.S.-V. A.P. and A.T.C. wrote the manuscript. All authors provided input and reviewed the manuscript. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research.
Keywords
- dorsal root ganglia
- gastrointestinal tract
- gut motility
- gut transit
- interoception
- mechanosensation
- Piezo2
- PIEZO2 deficiency
- sensory neurons
- spinal innervation
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology