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Article

Swiss Cheese Gene Is Important for Intestinal Barrier, Microbiome, and Lipid Metabolism Regulation in Drosophila Gut

by
Ekaterina A. Ivanova
,
Elena V. Ryabova
,
Artem E. Komissarov
,
Elizaveta E. Slepneva
,
Anton A. Stulov
,
Sergey A. Bulat
and
Svetlana V. Sarantseva
*
Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre «Kurchatov Institute», 188300 Gatchina, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(22), 11085; https://doi.org/10.3390/ijms262211085
Submission received: 30 September 2025 / Revised: 9 November 2025 / Accepted: 12 November 2025 / Published: 16 November 2025
(This article belongs to the Special Issue Drosophila: A Versatile Model in Biology and Medicine—2nd Edition)

Abstract

Mutations in the human patatin-like lysophospholipase domain containing the 6 gene PNPLA6 encode an evolutionarily conserved (lyso)phospholipase, leading to the development of a complex hereditary spastic paraplegia 39 (SPG 39) and a number of rare severe syndromes in humans. Diseases disrupt the functioning of the nervous and reproductive systems and the gastrointestinal tract. The study aims to investigate the role of the Drosophila melanogaster swiss cheese gene, an ortholog of the human PNPLA6 gene, in gut function. We showed that the swiss cheese gene knockout leads to changes in the morphology of the midgut, disruption of the septate junction structure and the intestinal barrier permeability, and a decrease in the lipid droplet number in enterocytes. As a result of such disturbances, intestinal stem cells (ISCs) proliferation is activated, and the gut microbiome is altered. Ectopic expression of human PNPLA6 leads to the recovery of the intestinal barrier in the fly gut. The example of Drosophila demonstrates the important role of evolutionarily conserved (lyso)phospholipase in intestinal homeostasis.
Keywords: swiss cheese; PNPLA6; Drosophila melanogaster; septate junctions; intestinal barrier; lipid metabolism; microbiome swiss cheese; PNPLA6; Drosophila melanogaster; septate junctions; intestinal barrier; lipid metabolism; microbiome

Share and Cite

MDPI and ACS Style

Ivanova, E.A.; Ryabova, E.V.; Komissarov, A.E.; Slepneva, E.E.; Stulov, A.A.; Bulat, S.A.; Sarantseva, S.V. Swiss Cheese Gene Is Important for Intestinal Barrier, Microbiome, and Lipid Metabolism Regulation in Drosophila Gut. Int. J. Mol. Sci. 2025, 26, 11085. https://doi.org/10.3390/ijms262211085

AMA Style

Ivanova EA, Ryabova EV, Komissarov AE, Slepneva EE, Stulov AA, Bulat SA, Sarantseva SV. Swiss Cheese Gene Is Important for Intestinal Barrier, Microbiome, and Lipid Metabolism Regulation in Drosophila Gut. International Journal of Molecular Sciences. 2025; 26(22):11085. https://doi.org/10.3390/ijms262211085

Chicago/Turabian Style

Ivanova, Ekaterina A., Elena V. Ryabova, Artem E. Komissarov, Elizaveta E. Slepneva, Anton A. Stulov, Sergey A. Bulat, and Svetlana V. Sarantseva. 2025. "Swiss Cheese Gene Is Important for Intestinal Barrier, Microbiome, and Lipid Metabolism Regulation in Drosophila Gut" International Journal of Molecular Sciences 26, no. 22: 11085. https://doi.org/10.3390/ijms262211085

APA Style

Ivanova, E. A., Ryabova, E. V., Komissarov, A. E., Slepneva, E. E., Stulov, A. A., Bulat, S. A., & Sarantseva, S. V. (2025). Swiss Cheese Gene Is Important for Intestinal Barrier, Microbiome, and Lipid Metabolism Regulation in Drosophila Gut. International Journal of Molecular Sciences, 26(22), 11085. https://doi.org/10.3390/ijms262211085

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