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Sleeve gastrectomy reveals the plasticity of the human gastric epithelium

Author

Listed:
  • 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
    Israel Defence Forces)

  • Ki-Suk Kim

    (University of Tennessee Health Science Center
    University of Michigan)

  • Yhara Arad

    (The Hebrew University of Jerusalem
    Israel Defence Forces)

  • 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
    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
    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
    The Hebrew University of Jerusalem)

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.

Suggested Citation

  • 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 & I, 2025. "Sleeve gastrectomy reveals the plasticity of the human gastric epithelium," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56135-y
    DOI: 10.1038/s41467-025-56135-y
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