Tight junctions expression is affected by active, inactive, and derivatives of Akkermansia muciniphila
-
Farinaz Ghaderi
,
Zahra Hajebrahimi
,
Abolfazl Fateh
,
Fattah Sotoodehnejadnematalahi
,
Sara Ahmadi Badi
,
Somayeh Vaezijoze
,
Seyed Davar Siadat
Abstract
Background and Objectives: Tight junctions (TJs) in the gastrointestinal tract are comprised of various junctional proteins including Occludin and Zonula Occludens (ZO-1) that have a critical role in epithelial barrier function. Gut microbiota and their derived metabolites can maintain and regulate gut epithelial barrier integrity.
Materials and Methods: In the present study, the effects of active, heat-inactivated, cell-free supernatant, and outer membrane vesicles (OMVs) of Akkermansia muciniphila were evaluated on the expression of occludin and ZO-1 genes in Caco-2 cell line by quantitative real-time PCR.
Results: Data have shown that both forms of the active (metabolically active, growing, and dividing state), and heat inactivated (by exposure to 56°C for 20 minutes) forms of the bacteria and the cell-free supernatant could affect the expression of occludin and ZO-1 genes (P < 0.05). OMVs significantly increased the expression of the occludin gene but had no effects on the expression of ZO-1.
Conclusion: Akkermansia muciniphila and its derived metabolites might have the potential to be used in the pharmaceutical and medicinal fields as probiotic, paraprobiotic and postbiotic agents to prevent metabolic and inflammatory diseases; Although, further research is needed to understand their interactions within the complex gut microbiome and to evaluate potential side effects or risks associated with their use.
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6. Forsythe P, Kunze W, Bienenstock J. Moody microbes or fecal phrenology: what do we know about the microbiota-gut-brain axis? BMC Med 2016; 14: 58.
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8. Cone RA. Barrier properties of mucus. Adv Drug Deliv Rev 2009; 61: 75-85.
9. Sundin J, Aziz I, Nordlander S, Polster A, Hu YOO, Hugerth LW, et. al. Evidence of altered mucosa-associated and fecal microbiota composition in patients with Irritable Bowel Syndrome. Sci Rep 2020; 10: 593.
10. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 2009; 461: 1282-1286.
11. Dao MC, Everard A, Aron-Wisnewsky J, Sokolovska N, Prifti E, Verger EO, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut 2016; 65: 426-436.
12. Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med 2017; 23: 107-113.
13. Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev 2011; 91: 151-175.
14. Suzuki T. Regulation of intestinal epithelial permeability by tight junctions. Cell Mol Life Sci 2013; 70: 631-659.
15. Wegh CA, Geerlings SY, Knol J, Roeselers G, Belzer C. Postbiotics and their potential applications in early life nutrition and beyond. Int J Mol Sci 2019; 20: 4673.
16. Ahmadi Badi S, Moshiri A, Fateh A, Rahimi Jamnani F, Sarshar M, Vaziri F, et al. Microbiota-derived extracellular vesicles as new systemic regulators. Front Microbiol 2017; 8: 1610.
17. Moradi M, Tajik H, Mardani K, Ezati P. Efficacy of lyophilized cell-free supernatant of Lactobacillus salivarius (Ls-BU2) on Escherichia coli and shelf life of ground beef. Vet Res Forum 2019; 10: 193-198.
18. Elhenawy W, Debelyy MO, Feldman MF. Preferential packing of acidic glycosidases and proteases into Bacteroides outer membrane vesicles. mBio 2014; 5(2): e00909-14.
19. Vaezijoze S, Irani S, Siadat SD, Zali M. Modulation of satiety hormones by Bacteroides thetaiotaomicron, Bacteroides fragilis and their derivatives. AMB Express 2025; 15: 41.
20. Ghaderi F, Sotoodehnejadnematalahi F, Hajebrahimi Z, Fateh A, Siadat SD. Effects of active, inactive, and derivatives of Akkermansia muciniphila on the expression of the endocannabinoid system and PPARs genes. Sci Rep 2022; 12: 10031.
21. Ashrafian F, Shahriary A, Behrouzi A, Moradi HR, Keshavarz Azizi Raftar S, Lari A, et al. Akkermansia muciniphila-derived extracellular vesicles as a mucosal delivery vector for amelioration of obesity in mice. Front Microbiol 2019; 10: 2155.
22. Yaghoubfar R, Behrouzi A, Zare Banadkoki E, Ashrafian F, Lari A, Vaziri F, et al. Effect of Akkermansia muciniphila, Faecalibacterium prausnitzii, and their extracellular vesicles on the serotonin system in intestinal epithelial cells. Probiotics Antimicrob Proteins 2021; 13: 1546-1556.
23. Noori P, Sotoodehnejadnematalahi F, Rahimi P, Siadat SD. Akkermansia muciniphila and its extracellular vesicles affect endocannabinoid system in in vitro model. Digestion 2025; 106: 338-348.
24. Ashrafian F, Behrouzi A, Shahriary A, Ahmadi Badi S, Davari M, Khatami S, et al. Comparative study of effect of Akkermansia muciniphila and its extracellular vesicles on toll-like receptors and tight junction. Gastroenterol Hepatol Bed Bench 2019; 12: 163-168.
25. Chatterjee D, Chaudhuri K. Association of cholera toxin with Vibrio cholerae outer membrane vesicles which are internalized by human intestinal epithelial cells. FEBS Lett 2011; 585: 1357-1362.
26. Zhai R, Xue X, Zhang L, Yang X, Zhao L, Zhang C. Strain-specific anti-inflammatory properties of two Akkermansia muciniphila strains on chronic colitis in mice. Front Cell Infect Microbiol 2019; 9: 239.
27. Ebnerasuly F, Hajebrahimi Z, Tabaie SM, Darbouy M. Effect of simulated microgravity conditions on differentiation of adipose-derived stem cells towards fibroblasts using connective tissue growth factor. Iran J Biotechnol 2017; 15: 241-251.
28. Yang C, Yao C, Tian R, Zhu Z, Zhao L, Li P, et al. miR-202-3p regulates Sertoli cell proliferation, synthesis function, and apoptosis by targeting LRP6 and cyclin D1 of Wnt/β-catenin signaling. Mol Ther Nucleic Acids 2019; 14: 1-19.
29. Cen J, Feng L, Ke H, Bao L, Li LZ, Tanaka Y, et al. Exosomal thrombospondin-1 disrupts the integrity of endothelial intercellular junctions to facilitate breast cancer cell metastasis. Cancers (Basel) 2019; 11: 1946.
30. Hur KY, Lee M-S. Gut microbiota and metabolic disorders. Diabetes Metab J 2015; 39: 198-203.
31. Cani PD, de Vos WM. Next-generation beneficial microbes: the case of Akkermansia muciniphila. Front Microbiol 2017; 8: 1765.
32. Kang C-S, Ban M, Choi E-J, Moon H-G, Jeon J-S, Kim D-K, et al. Extracellular vesicles derived from gut microbiota, especially Akkermansia muciniphila, protect the progression of dextran sulfate sodium-induced colitis. PLoS One 2013; 8(10): e76520.
33. Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet–induced obesity and diabetes in mice. Diabetes 2008; 57: 1470-1481.
34. Muccioli GG, Naslain D, Bäckhed F, Reigstad CS, Lambert DM, Delzenne NM, et al. The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol 2010; 6: 392.
35. Ashrafian F, Keshavarz Azizi Raftar S, Shahryari A, Behrouzi A, Yaghoubfar R, Lari A, et al. Comparative effects of alive and pasteurized Akkermansia muciniphila on normal diet-fed mice. Sci Rep 2021; 11: 17898.
2. Musso G, Gambino R, Cassader M. Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded? Diabetes Care 2010; 33: 2277-2284.
3. Vajro P, Paolella G, Fasano A. Microbiota and gut-liver axis: a mini-review on their influences on obesity and obesity-related liver disease. J Pediatr Gastroenterol Nutr 2013; 56: 461-465.
4. Chelakkot C, Choi Y, Kim D-K, Park HT, Ghim J, Kwon Y, et al. Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions. Exp Mol Med 2018; 50(2): e450.
5. Karl JP, Margolis LM, Madslien EH, Murphy NE, Castellani JW, Gundersen Y, et al. Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress. Am J Physiol Gastrointest Liver Physiol 2017; 312: G559-G571.
6. Forsythe P, Kunze W, Bienenstock J. Moody microbes or fecal phrenology: what do we know about the microbiota-gut-brain axis? BMC Med 2016; 14: 58.
7. Teixeira TF, Collado MC, Ferreira CL, Bressan J, Peluzio Mdo C. Potential mechanisms for the emerging link between obesity and increased intestinal permeability. Nutr Res 2012; 32: 637-647.
8. Cone RA. Barrier properties of mucus. Adv Drug Deliv Rev 2009; 61: 75-85.
9. Sundin J, Aziz I, Nordlander S, Polster A, Hu YOO, Hugerth LW, et. al. Evidence of altered mucosa-associated and fecal microbiota composition in patients with Irritable Bowel Syndrome. Sci Rep 2020; 10: 593.
10. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 2009; 461: 1282-1286.
11. Dao MC, Everard A, Aron-Wisnewsky J, Sokolovska N, Prifti E, Verger EO, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut 2016; 65: 426-436.
12. Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med 2017; 23: 107-113.
13. Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev 2011; 91: 151-175.
14. Suzuki T. Regulation of intestinal epithelial permeability by tight junctions. Cell Mol Life Sci 2013; 70: 631-659.
15. Wegh CA, Geerlings SY, Knol J, Roeselers G, Belzer C. Postbiotics and their potential applications in early life nutrition and beyond. Int J Mol Sci 2019; 20: 4673.
16. Ahmadi Badi S, Moshiri A, Fateh A, Rahimi Jamnani F, Sarshar M, Vaziri F, et al. Microbiota-derived extracellular vesicles as new systemic regulators. Front Microbiol 2017; 8: 1610.
17. Moradi M, Tajik H, Mardani K, Ezati P. Efficacy of lyophilized cell-free supernatant of Lactobacillus salivarius (Ls-BU2) on Escherichia coli and shelf life of ground beef. Vet Res Forum 2019; 10: 193-198.
18. Elhenawy W, Debelyy MO, Feldman MF. Preferential packing of acidic glycosidases and proteases into Bacteroides outer membrane vesicles. mBio 2014; 5(2): e00909-14.
19. Vaezijoze S, Irani S, Siadat SD, Zali M. Modulation of satiety hormones by Bacteroides thetaiotaomicron, Bacteroides fragilis and their derivatives. AMB Express 2025; 15: 41.
20. Ghaderi F, Sotoodehnejadnematalahi F, Hajebrahimi Z, Fateh A, Siadat SD. Effects of active, inactive, and derivatives of Akkermansia muciniphila on the expression of the endocannabinoid system and PPARs genes. Sci Rep 2022; 12: 10031.
21. Ashrafian F, Shahriary A, Behrouzi A, Moradi HR, Keshavarz Azizi Raftar S, Lari A, et al. Akkermansia muciniphila-derived extracellular vesicles as a mucosal delivery vector for amelioration of obesity in mice. Front Microbiol 2019; 10: 2155.
22. Yaghoubfar R, Behrouzi A, Zare Banadkoki E, Ashrafian F, Lari A, Vaziri F, et al. Effect of Akkermansia muciniphila, Faecalibacterium prausnitzii, and their extracellular vesicles on the serotonin system in intestinal epithelial cells. Probiotics Antimicrob Proteins 2021; 13: 1546-1556.
23. Noori P, Sotoodehnejadnematalahi F, Rahimi P, Siadat SD. Akkermansia muciniphila and its extracellular vesicles affect endocannabinoid system in in vitro model. Digestion 2025; 106: 338-348.
24. Ashrafian F, Behrouzi A, Shahriary A, Ahmadi Badi S, Davari M, Khatami S, et al. Comparative study of effect of Akkermansia muciniphila and its extracellular vesicles on toll-like receptors and tight junction. Gastroenterol Hepatol Bed Bench 2019; 12: 163-168.
25. Chatterjee D, Chaudhuri K. Association of cholera toxin with Vibrio cholerae outer membrane vesicles which are internalized by human intestinal epithelial cells. FEBS Lett 2011; 585: 1357-1362.
26. Zhai R, Xue X, Zhang L, Yang X, Zhao L, Zhang C. Strain-specific anti-inflammatory properties of two Akkermansia muciniphila strains on chronic colitis in mice. Front Cell Infect Microbiol 2019; 9: 239.
27. Ebnerasuly F, Hajebrahimi Z, Tabaie SM, Darbouy M. Effect of simulated microgravity conditions on differentiation of adipose-derived stem cells towards fibroblasts using connective tissue growth factor. Iran J Biotechnol 2017; 15: 241-251.
28. Yang C, Yao C, Tian R, Zhu Z, Zhao L, Li P, et al. miR-202-3p regulates Sertoli cell proliferation, synthesis function, and apoptosis by targeting LRP6 and cyclin D1 of Wnt/β-catenin signaling. Mol Ther Nucleic Acids 2019; 14: 1-19.
29. Cen J, Feng L, Ke H, Bao L, Li LZ, Tanaka Y, et al. Exosomal thrombospondin-1 disrupts the integrity of endothelial intercellular junctions to facilitate breast cancer cell metastasis. Cancers (Basel) 2019; 11: 1946.
30. Hur KY, Lee M-S. Gut microbiota and metabolic disorders. Diabetes Metab J 2015; 39: 198-203.
31. Cani PD, de Vos WM. Next-generation beneficial microbes: the case of Akkermansia muciniphila. Front Microbiol 2017; 8: 1765.
32. Kang C-S, Ban M, Choi E-J, Moon H-G, Jeon J-S, Kim D-K, et al. Extracellular vesicles derived from gut microbiota, especially Akkermansia muciniphila, protect the progression of dextran sulfate sodium-induced colitis. PLoS One 2013; 8(10): e76520.
33. Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet–induced obesity and diabetes in mice. Diabetes 2008; 57: 1470-1481.
34. Muccioli GG, Naslain D, Bäckhed F, Reigstad CS, Lambert DM, Delzenne NM, et al. The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol 2010; 6: 392.
35. Ashrafian F, Keshavarz Azizi Raftar S, Shahryari A, Behrouzi A, Yaghoubfar R, Lari A, et al. Comparative effects of alive and pasteurized Akkermansia muciniphila on normal diet-fed mice. Sci Rep 2021; 11: 17898.
| Files | ||
| Issue | Vol 17 No 6 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v17i6.20355 | |
| Keywords | ||
| Akkermansia muciniphila Tight junctions Zonula occludens-1 Occludin | ||
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How to Cite
1.
Ghaderi F, Hajebrahimi Z, Fateh A, Sotoodehnejadnematalahi F, Ahmadi Badi S, Vaezijoze S, Siadat SD. Tight junctions expression is affected by active, inactive, and derivatives of Akkermansia muciniphila. Iran J Microbiol. 2025;17(6):885-892.
