Nature Communications (Jan 2025)
Sleeve gastrectomy reveals the plasticity of the human gastric epithelium
- Amit Elad,
- Botros Moalem,
- Dana Sender,
- Aya Bardugo,
- Ki-Suk Kim,
- Yhara Arad,
- Haya Benhayon,
- Ayelet Gal Etzyoni,
- Nehemia Greenstein,
- Aviv Halfon,
- Sarah Knapp,
- Michelle Malis,
- Bailey Peck,
- Itia Samuel,
- Amram Kupietzky,
- Saleh Daher,
- Esther Forkosh,
- David Hakimian,
- Tiberiu Hershcovici,
- Nadav Ilani,
- Lior Katz,
- Moshe Rottenstreich,
- Elez Vainer,
- Yuval Ishay,
- Eitan Zlotnick,
- Abed Nasereddin,
- Idid Shiff,
- Ariel Benson,
- Ronit Grinbaum,
- Siddhartha Mishra,
- Shlomi Kotler,
- Linda C. Samuelson,
- Darleen A. Sandoval,
- Rachel Ben-Haroush Schyr,
- Danny Ben-Zvi
Affiliations
- Amit Elad
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of Jerusalem
- Botros Moalem
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of Jerusalem
- Dana Sender
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of Jerusalem
- Aya Bardugo
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of Jerusalem
- Ki-Suk Kim
- Department of Physiology, University of Tennessee Health Science Center
- Yhara Arad
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of Jerusalem
- Haya Benhayon
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of Jerusalem
- Ayelet Gal Etzyoni
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of Jerusalem
- Nehemia Greenstein
- Department of Surgery, University of Michigan
- Aviv Halfon
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of Jerusalem
- Sarah Knapp
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of Jerusalem
- Michelle Malis
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of Jerusalem
- Bailey Peck
- Department of Surgery, University of Michigan
- Itia Samuel
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of Jerusalem
- Amram Kupietzky
- Department of Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, The Faculty of Medicine, Hebrew University of Jerusalem
- Saleh Daher
- Institute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem
- Esther Forkosh
- Institute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem
- David Hakimian
- Institute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem
- Tiberiu Hershcovici
- Institute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem
- Nadav Ilani
- Institute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem
- Lior Katz
- Institute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem
- Moshe Rottenstreich
- Institute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem
- Elez Vainer
- Institute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem
- Yuval Ishay
- Institute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem
- Eitan Zlotnick
- Institute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem
- Abed Nasereddin
- Genomics Applications Laboratory, Core Research Facility, Faculty of Medicine, The Hebrew University of Jerusalem
- Idid Shiff
- Genomics Applications Laboratory, Core Research Facility, Faculty of Medicine, The Hebrew University of Jerusalem
- Ariel Benson
- Institute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem
- Ronit Grinbaum
- Department of Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, The Faculty of Medicine, Hebrew University of Jerusalem
- Siddhartha Mishra
- Seminar for Applied Mathematics, ETH
- Shlomi Kotler
- The Racah Institute of Physics, The Hebrew University of Jerusalem
- Linda C. Samuelson
- Department of Molecular and Integrative Physiology, University of Michigan
- Darleen A. Sandoval
- Department of Pediatrics, University of Colorado
- Rachel Ben-Haroush Schyr
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of Jerusalem
- Danny Ben-Zvi
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of Jerusalem
- DOI
- https://doi.org/10.1038/s41467-025-56135-y
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 12
Abstract
Abstract Gastrin is secreted following a rise in gastric pH, leading to gastric acid secretion. Sleeve gastrectomy (SG), a bariatric surgery where 80% of the gastric corpus is excised, presents a challenge for gastric pH homeostasis. Using histology, and single-cell RNA sequencing of the gastric epithelium in 12 women, we observed that SG is associated with an increase in a sub-population of acid-secreting parietal cells that overexpress respiratory enzymes and an increase in histamine-secreting enterochromaffin-like cells (ECLs). ECLs of SG-operated patients overexpressed genes coding for biosynthesis of neuropeptides and serotonin. Mathematical modeling showed that pH homeostasis by gastrin is analogous to non-linear proportional and integral control, that drives adaptation of the epithelium to acid-secretion demand. Quantitative model predictions were validated in patients. The results demonstrate human gastric epithelium remodeling following SG at the molecular and cellular levels, and more generally how trophic hormones enable robust adaptation of tissue function to meet physiological demand.
