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 and Danny Ben-Zvi ()
Additional contact information
Amit Elad: The Hebrew University of Jerusalem
Botros Moalem: The Hebrew University of Jerusalem
Dana Sender: The Hebrew University of Jerusalem
Aya Bardugo: The Hebrew University of Jerusalem
Ki-Suk Kim: University of Tennessee Health Science Center
Yhara Arad: The Hebrew University of Jerusalem
Haya Benhayon: The Hebrew University of Jerusalem
Ayelet Gal Etzyoni: The Hebrew University of Jerusalem
Nehemia Greenstein: University of Michigan
Aviv Halfon: The Hebrew University of Jerusalem
Sarah Knapp: The Hebrew University of Jerusalem
Michelle Malis: The Hebrew University of Jerusalem
Bailey Peck: University of Michigan
Itia Samuel: The Hebrew University of Jerusalem
Amram Kupietzky: Hebrew University of Jerusalem
Saleh Daher: Hebrew University of Jerusalem
Esther Forkosh: Hebrew University of Jerusalem
David Hakimian: Hebrew University of Jerusalem
Tiberiu Hershcovici: Hebrew University of Jerusalem
Nadav Ilani: Hebrew University of Jerusalem
Lior Katz: Hebrew University of Jerusalem
Moshe Rottenstreich: Hebrew University of Jerusalem
Elez Vainer: Hebrew University of Jerusalem
Yuval Ishay: Hebrew University of Jerusalem
Eitan Zlotnick: Hebrew University of Jerusalem
Abed Nasereddin: The Hebrew University of Jerusalem
Idid Shiff: The Hebrew University of Jerusalem
Ariel Benson: Hebrew University of Jerusalem
Ronit Grinbaum: Hebrew University of Jerusalem
Siddhartha Mishra: Seminar for Applied Mathematics, ETH
Shlomi Kotler: The Hebrew University of Jerusalem
Linda C. Samuelson: University of Michigan
Darleen A. Sandoval: University of Colorado
Rachel Ben-Haroush Schyr: The Hebrew University of Jerusalem
Danny Ben-Zvi: The Hebrew University of Jerusalem

Nature Communications, 2025, vol. 16, issue 1, 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.

Date: 2025
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DOI: 10.1038/s41467-025-56135-y

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