Effect of Selected Probiotic Strains and their Combinations on the SGLT1 and GLUT2 Gene Expressions in Porcine Intestinal Epithelial Cells
DOI:
https://doi.org/10.18690/agricsci.23.1.3Keywords:
probiotics, glucose transporters, gene expression, CLAB cellsAbstract
Intestinal morphology and glucose transporter expression are key determinants of glucose absorption and homeostasis. While probiotics beneficially modulate the gut microbiota, their role in regulating glucose transporter gene expression remains unclear. This study aimed to evaluate the effects of selected single- and multi-strain probiotic bacteria on the expression of sodium-driven glucose cotransporter 1 (SGLT1) and facilitative glucose transporter 2 (GLUT2) in porcine intestinal epithelial CLAB cells. Cells were treated with four selected probiotic strains (Lactobacillus acidophilus (ATCC 4356), Lacticaseibacillus rhamnosus GG (ATCC 53103), Lactiplantibacillus plantarum PCS 20, and Lactiplantibacillus plantarum PCS 26) at varying concentrations and in different combinations. Although none of the observed changes were statistically significant, SGLT1 expression was consistently upregulated across various treatments, whereas GLUT2 showed a more variable but predominantly downregulated response, suggesting the latter as a more susceptible target for this research. These findings indicate that selected probiotic strains may differentially regulate key intestinal glucose transporters, suggesting a potential role in modulating glucose absorption and homeostasis. Ultimately, this study offers new insights into probiotic–host interactions.
Downloads
References
1. Bao, J., Huang, X., Zeng, Y., Wu, T. T., Lu, X., Meng, G., Ren, Y., & Xiao, J. (2023). Dose-dependent inhibitory effect of probiotic Lactobacillus plantarum on Streptococcus
mutans-Candida albicans Cross-Kingdom Microorganisms. Pathogens, 12(6), 848. https://doi.org/10.3390/pathogens12060848
2. Barba-Vidal, E., Martín-Orúe, S. M., & Castillejos, L. (2019). Practical aspects of the use of probiotics in pig production: A review. Livestock Science, 223, 84–96. https://doi.org/10.1016/j.livsci.2019.02.017
3. Cencič, A., & Langerholc, T. (2010). Functional cell models of the gut and their applications in food microbiology—A review. International Journal of Food Microbiology, 141, S4–S14. https://doi.org/10.1016/j.ijfoodmicro.2010.03.026
4. Chan, L. K. Y., & Leung, P. S. (2015). Multifaceted interplay among mediators and regulators of intestinal glucose absorption: Potential impacts on diabetes research and treatment. American Journal of Physiology-Endocrinology and Metabolism, 309(11), E887–E899. https://doi.org/10.1152/ajpendo.00373.2015
5. Chapman, C. M. C., Gibson, G. R., & Rowland, I. (2011). Health benefits of probiotics: Are mixtures more effective than single strains? European Journal of Nutrition, 50(1), 1–17. https://doi.org/10.1007/s00394-010-0166-z
6. Chapman, C. M. C., Gibson, G. R., Todd, S., & Rowland, I. (2013). Comparative in vitro inhibition of urinary tract pathogens by single- and multi-strain probiotics. European Journal of Nutrition, 52(6), 1669–1677. https://doi.org/10.1007/s00394-013-0501-2
7. Dominguez Rieg, J. A., & Rieg, T. (2019). What does sodium-glucose co-transporter 1 inhibition add: Prospects for dual inhibition. Diabetes, Obesity and Metabolism, 21(S2), 43–52. https://doi.org/10.1111/dom.13630
8. Gorenjak, M., Gradišnik, L., Trapečar, M., Pistello, M., Kozmus, C. P., Škorjanc, D., Skok, P., Langerholc, T., & Cencič, A. (2014). Improvement of lipid profile by probiotic/protective cultures: Study in a non-carcinogenic small intestinal cell model. The New Microbiologica, 37(1), 51–64.
9. Gorenjak, M., Trapecar, M., Gradisnik, L., Skok, P., & Cencic, A. (2012). A novel polymerase chain reaction (PCR) based assay for authentication of cell lines or tissues from human, pig and chicken origin. Journal of BioScience and Biotechnology, 212 1(1), 1–7.
10. Gromova, L. V., Fetissov, S. O., & Gruzdkov, A. A. (2021). Mechanisms of glucose absorption in the small intestine in health and metabolic diseases and their role in appetite regulation. Nutrients, 13(7), 2474. https://doi.org/10.3390/nu13072474
11. Heczko, P. B., Giemza, M., Ponikiewska, W., & Strus, M. (2024). Importance of Lactobacilli for human health. Microorganisms, 12(12), 2382. https://doi.org/10.3390/microorganisms12122382
12. Hill, C., Guarner, F., Reid, G., Gibson, G. R., Merenstein, D. J., Pot, B., Morelli, L., Canani, R. B., Flint, H. J., Salminen, S., Calder, P. C., & Sanders, M. E. (2014). The international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology & Hepatology, 11(8), 506–514. https://doi.org/10.1038/nrgastro.2014.66
13. Howard, E. J., Lam, T. K. T., & Duca, F. A. (2022). The gut microbiome: Connecting diet, glucose homeostasis, and disease. Annual Review of Medicine, 73, 469–481. https://doi.org/10.1146/annurev-med-042220-012821
14. Hsieh, P.-S., Ho, H.-H., Hsieh, S.-H., Kuo, Y.-W., Tseng, H.-Y., Kao, H.-F., & Wang, J.-Y. (2020). Lactobacillus salivarius AP-32 and Lactobacillus reuteri GL-104 decrease glycemic levels and attenuate diabetes-mediated liver and kidney injury in db/db mice. BMJ Open Diabetes Research & Care, 8(1), e001028. https://doi.org/10.1136/bmjdrc-2019-001028
15. Huang, C.-W., Liu, S.-Y., Bhattarai, B. P., Lee, T.-Y., Chang, H.-T., Lin, H.-C., Weng, H.-M., Huang, H.-H., Lin, J.-S., & Lee, J.-W. (2024). Live multi-strain probiotics enhance growth performance by regulating intestinal morphology and microbiome population in weaning piglets. Microorganisms, 12(11), 2334. https://doi.org/10.3390/microorganisms12112334
16. Huang, Y., & Zheng, Y. (2010). The probiotic Lactobacillus acidophilus reduces cholesterol absorption through the down-regulation of Niemann-Pick C1-like 1 in Caco-2 cells. British Journal of Nutrition, 103(4), 473–478. https://doi.org/10.1017/S0007114509991991
17. Hyrslova, I., Drab, V., Cihlar, J., Krausova, G., Mrvikova, I., Kana, A., Stetina, J., & Musilova, S. (2023). Functional and probiotic characterization of newly isolated strains from infant feces and breast milk. Fermentation, 9(11), 960. https://doi.org/10.3390/fermentation9110960
18. Koepsell, H. (2020). Glucose transporters in the small intestine in health and disease. Pflügers Archiv - European Journal of Physiology, 472(9), 1207–1248. https://doi.org/10.1007/s00424-020-02439-5
19. Kwoji, I. D., Aiyegoro, O. A., Okpeku, M., & Adeleke, M. A. (2021). Multi-strain probiotics: Synergy among isolates enhances biological activities. Biology, 10(4), 322. https://doi.org/10.3390/biology10040322
20. Li, X., Xu, Q., Jiang, T., Fang, S., Wang, G., Zhao, J., Zhang, H., & Chen, W. (2016). A comparative study of the antidiabetic effects exerted by live and dead multi-strain probiotics in the type 2 diabetes model of mice. Food & Function, 7(12), 4851–4860. https://doi.org/10.1039/C6FO01147K
21. Liu, Y., Wang, J., & Wu, C. (2022). Modulation of gut microbiota and immune system by probiotics, pre-biotics, and post-biotics. Frontiers in Nutrition, 8, 634897. https://doi.org/10.3389/fnut.2021.634897
22. Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods, 25(4), 402–408. https://doi.org/10.1006/meth.2001.1262
23. Maslennikov, R., Gosteeva, E., Ananeva, V., Korshunova, L., Kravtsowa, A., Poluektova, E., Ulyanin, A., Sigidaev, A., Kikhasurova, P., & Ivashkin, V. (2026). Strain-specific systematic review with meta-analysis of probiotics efficacy in the treatment of irritable bowel syndrome. Journal of Clinical Medicine,15(3), 1152. https://doi.org/10.3390/jcm15031152
24. McFarland, L. V. (2021). Efficacy of single-strain probiotics versus multi-strain mixtures: Systematic review of strain and disease specificity. Digestive Diseases and Sciences, 66(3), 694–704. https://doi.org/10.1007/s10620-020-06244-z
25. Mercado-Monroy, J., Falfán-Cortés, R. N., Muñóz-Pérez, V. M., Gómez-Aldapa, C. A., & Castro-Rosas, J. (2026). Probiotics as modulators of intestinal barrier integrity and immune homeostasis: A comprehensive review. Journal of the Science of Food and Agriculture, 106(5), 2578–2590. https://doi.org/10.1002/jsfa.70168
26. Navarré, A., Nazareth, T., Luz, C., Meca, G., & Escrivá, L. (2024). Characterization of lactic acid bacteria isolated from human breast milk and their bioactive metabolites with potential application as a probiotic food supplement. Food & Function, 15(15), 8087–8103. https://doi.org/10.1039/D4FO02171A
27. Ouwehand, A. C. (2017). A review of dose-responses of probiotics in human studies. Beneficial Microbes, 8(2), 143–151. https://doi.org/10.3920/BM2016.0140
28. Ouwehand, A. C., Invernici, M. M., Furlaneto, F. A. C., & Messora, M. R. (2018). Effectiveness of multi-strain versus single-strain probiotics: Current status and recommendations for the future. Journal of Clinical Gastroenterology, 52, S35. https://doi.org/10.1097/MCG.0000000000001052
29. Pintarič, M., & Langerholc, T. (2022). Probiotic mechanisms affecting glucose homeostasis: A scoping review. Life, 12(8), 1187. https://doi.org/10.3390/life12081187
30. Primec, M., Škorjanc, D., Langerholc, T., Mičetić-Turk, D., & Gorenjak, M. (2021). Specific Lactobacillus probiotic strains decrease transepithelial glucose transport through GLUT2 downregulation in intestinal epithelial cell models. Nutrition Research, 86, 10–22. https://doi.org/10.1016/j.nutres.2020.11.008
31. Rahmannia, M., Poudineh, M., Mirzaei, R., Aalipour, M. A., Shahidi Bonjar, A. H., Goudarzi, M., Kheradmand, A., Aslani, H. R., Sadeghian, M., Nasiri, M. J., & Sechi, L. A. (2024). Strain-specific effects of probiotics on depression and anxiety: A meta-analysis. Gut Pathogens, 16(1), 46. https://doi.org/10.1186/s13099-024-00634-8
32. Röder, P. V., Geillinger, K. E., Zietek, T. S., Thorens, B., Koepsell, H., & Daniel, H. (2014). The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing. PLoS ONE, 9(2), e89977. https://doi.org/10.1371/journal.pone.0089977
33. Rooj, A. K., Kimura, Y., & Buddington, R. K. (2010). Metabolites produced by probiotic Lactobacilli rapidly increase glucose uptake by Caco-2 cells. BMC Microbiology, 10(1), 16. https://doi.org/10.1186/1471-2180-10-16
34. Rossi, R., & Mainardi, E. (2025). Prebiotics and probiotics supplementation in pigs as a model for human gut health and disease. Biomolecules, 15(5), 665. https://doi.org/10.3390/biom15050665
35. Sano, R., Shinozaki, Y., & Ohta, T. (2020). Sodium–glucose cotransporters: Functional properties and pharmaceutical potential. Journal of Diabetes Investigation, 11(4), 770–782. https://doi.org/10.1111/jdi.13255
36. Schmitt, C. C., Aranias, T., Viel, T., Chateau, D., Le Gall, M., Waligora-Dupriet, A.-J., Melchior, C., Rouxel, O., Kapel, N., Gourcerol, G., Tavitian, B., Lehuen, A., Brot-Laroche, E., Leturque, A., Serradas, P., & Grosfeld, A. (2017). Intestinal invalidation of the glucose transporter GLUT2 delays tissue distribution of glucose and reveals an unexpected role in gut homeostasis. Molecular Metabolism, 6(1), 61–72. https://doi.org/10.1016/j.molmet.2016.10.008
37. Shah, A. B., Baiseitova, A., Zahoor, M., Ahmad, I., Ikram, M., Bakhsh, A., Shah, M. A., Ali, I., Idress, M., Ullah, R., Nasr, F. A., & Al-Zharani, M. (n.d.). Probiotic significance of Lactobacillus strains: A comprehensive review on health impacts, research gaps, and future prospects. Gut Microbes, 2024(1), 2431643. https://doi.org/10.1080/19490976.2024.2431643
38. Shen, X., Ma, C., Yang, Y., Liu, X., Wang, B., Wang, Y., Zhang, G., Bian, X., & Zhang, N. (2024). The role and mechanism of probiotics supplementation in blood glucose regulation: A review. Foods, 13(17), 2719. https://doi.org/10.3390/foods13172719
39. Shen, Z., Hou, Y., Zhao, G., Tan, L., Chen, J., Dong, Z., Ni, C., & Pei, L. (2024). Physiological functions of glucose transporter-2: From cell physiology to links with diabetes mellitus. Heliyon, 10(3), e25459. https://doi.org/10.1016/j.heliyon.2024.e25459
40. Sun, B., Chen, H., Xue, J., Li, P., & Fu, X. (2023). The role of GLUT2 in glucose metabolism in multiple organs and tissues. Molecular Biology Reports, 50(8), 6963–6974. https://doi.org/10.1007/s11033-023-08535-w
41. Szajewska, H., Skórka, A., Ruszczyński, M., & Gieruszczak-Białek, D. (2013). Meta-analysis: Lactobacillus GG for treating acute gastroenteritis in children--updated analysis of randomised controlled trials. Alimentary Pharmacology & Therapeutics, 38(5), 467–476. https://doi.org/10.1111/apt.12403
42. Thorens, B. (2015). GLUT2, glucose sensing and glucose homeostasis. Diabetologia, 58(2), 221–232. https://doi.org/10.1007/s00125-014-3451-1
43. Timmerman, H. M., Koning, C. J. M., Mulder, L., Rombouts, F. M., & Beynen, A. C. (2004). Monostrain, multistrain and multispecies probiotics—A comparison of functionality and efficacy. International Journal of Food Microbiology, 96(3), 219–233. https://doi.org/10.1016/j.ijfoodmicro.2004.05.012
44. Wang, L., Shang, Q., Guo, W., Wu, X., Wu, L., Wu, L., & Chen, T. (2020). Evaluation of the hypoglycemic effect of probiotics via directly consuming glucose in intestines of STZ-induced diabetic mice and glucose water-induced diabetic mice. Journal of Functional Foods, 64, 103614. https://doi.org/10.1016/j.jff.2019.103614
45. Wang, S., Guo, C., Zhou, L., Zhong, Z., Zhu, W., Huang, Y., Zhang, Z., Gorgels, T. G. M. F., & Berendschot, T. T. J. M. (2016). Effects of dietary supplementation with epidermal growth factor-expressing Saccharomyces cerevisiae on duodenal development in weaned piglets. British Journal of Nutrition, 115(9), 1509–1520. https://doi.org/10.1017/S0007114516000738
46. Yamamoto, K., Harada, N., Yasuda, T., Hatoko, T., Wada, N., Lu, X., Seno, Y., Kurihara, T., Yamane, S., & Inagaki, N. (2024). Intestinal morphology and glucose transporter gene expression under a chronic intake of high sucrose. Nutrients, 16(2), 196. https://doi.org/10.3390/nu16020196
47. Yan, F., Li, N., Shi, J., Li, H., Yue, Y., Jiao, W., Wang, N., Song, Y., Huo, G., & Li, B. (2019). Lactobacillus acidophilus alleviates type 2 diabetes by regulating hepatic glucose, lipid metabolism and gut microbiota in mice. Food & Function, 10(9), 5804–5815. https://doi.org/10.1039/C9FO01062A
48. Yoon, H.-S., Ju, J.-H., Kim, H.-N., Park, H.-J., Ji, Y., Lee, J.-E., Shin, H.-K., Do, M.-S., & Holzapfel, W. (2013). Reduction in cholesterol absorption in Caco-2 cells through the down-regulation of Niemann-Pick C1-like 1 by the putative probiotic strains Lactobacillus rhamnosus BFE5264 and Lactobacillus plantarum NR74 from fermented foods. International Journal of Food Sciences and Nutrition, 64(1), 44–52. https://doi.org/10.3109/09637486.2012.706598
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Lucija Rakun, Tamara Hribernik, Tomaž Langerholc, Maša Kozmos
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.