Effects of Akkermansia muciniphila and Faecalibacterium prausnitzii on serotonin transporter expression in intestinal epithelial cells

Abstract

Purpose

The highest level of peripheral serotonin in the body can be found in the gastrointestinal (GI) tract as its reservoir. There is complete interaction between human gastrointestinal microbiota and serotonin system. Serotonin in the GI is transferred by serotonin transporters (SERTs), which play a crucial role in the bioavailability of serotonin in the GI. SERT impairment is associated with the pathology of GI disorders. It is known that intestinal microbiota can regulate the SERT function. Therefore, it may be useful to regulate of SERT expression by modulation of microbiota and improvement of intestinal motility and GI sensation. In this study, we aimed to evaluate the effects of two next-generation probiotics, including Akkermansia muciniphila and Faecalibacterium prausnitzii, and their supernatants on SERT gene expression in human epithelial colorectal adenocarcinoma cells (Caco-2).

Methods

The Caco-2 cells were treated with multiplicity of infection (MOI) ratio of 100 of A. muciniphila and F. prausnitzii, as well as their supernatants. After 24 h, SERT gene expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR) assay.

Results

A. muciniphila up-regulated the SERT mRNA level by 3.01 folds, compared to the control group. F. prausnitzii, similar to A. muciniphila, increased the expression of SERT gene in Caco-2 cells by 3.43 folds (P < 0.001). Moreover, the supernatants of A. muciniphila and F. prausnitzii significantly up-regulated the expression of SERT gene in the cell line by 2.4 and 5.7 folds, respectively, compared to the control group (P < 0.001).

Conclusions

The present results showed that A. muciniphila and F. prausnitzii, as well as their supernatants, increased the expression of SERT gene in Caco-2 cells. Therefore, they might be helpful in the microbiota-modulating treatment of inflammatory bowel diseases.

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References

  1. 1.

    Kho ZY, Lal SK. The human gut microbiome–a potential controller of wellness and disease. Front Microbiol. 2018;9:1835.

    PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    Belkaid Y, Harrison OJ. Homeostatic immunity and the microbiota. Immunity. 2017;46(4):562–76.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    Spohn SN, Mawe GM. Non-conventional features of peripheral serotonin signalling—the gut and beyond. Nat Rev Gastroenterol Hepatol. 2017;14(7):412.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Fuller RW, Wong DT. Serotonin uptake and serotonin uptake inhibition. Ann N Y Acad Sci. 1990;600(1):68–80.

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Jin D-C, Cao H-L, Xu M-Q, Wang S-N, Wang Y-M, Yan F, Wang B-M. Regulation of the serotonin transporter in the pathogenesis of irritable bowel syndrome. World J Gastroenterol. 2016;22(36):8137.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. 6.

    Tada Y, Ishihara S, Kawashima K, Fukuba N, Sonoyama H, Kusunoki R, et al. Downregulation of serotonin reuptake transporter gene expression in healing colonic mucosa in presence of remaining low-grade inflammation in ulcerative colitis. J Gastroenterol Hepatol. 2016;31(8):1443–52.

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    El Aidy S, Ramsteijn AS, Dini-Andreote F, van Eijk R, Houwing DJ, Salles JF, Olivier JD. Serotonin transporter genotype modulates the gut microbiota composition in young rats, an effect augmented by early life stress. Front Cell Neurosci. 2017;11:222.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  8. 8.

    Waclawiková B, El Aidy S. Role of microbiota and tryptophan metabolites in the remote effect of intestinal inflammation on brain and depression. Pharmaceuticals. 2018;11(3):63.

    PubMed Central  Article  CAS  Google Scholar 

  9. 9.

    Wang Y, Ge X, Wang W, Wang T, Cao H, Wang B, Wang B. Lactobacillus rhamnosus GG supernatant up-regulates serotonin transporter expression in intestinal epithelial cells and mice intestinal tissues. Neurogastroenterol Motil. 2015;27(9):1239–48.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Cao Y-N, Feng L-J, Wang B-M, Jiang K, Li S, Xu X, Wang W-Q, Zhao J-W, Wang Y-M. Lactobacillus acidophilus and Bifidobacterium longum supernatants upregulate the serotonin transporter expression in intestinal epithelial cells. Saudi J Gastroenterol. 2018;24(1):59.

    PubMed  PubMed Central  Article  Google Scholar 

  11. 11.

    Derrien M, Belzer C, de Vos WM. Akkermansia muciniphila and its role in regulating host functions. Microb Pathog. 2017;106:171–81.

    PubMed  Article  Google Scholar 

  12. 12.

    Miquel S, Martin R, Rossi O, Bermudez-Humaran L, Chatel J, Sokol H, Thomas M, Wells J, Langella P. Faecalibacterium prausnitzii and human intestinal health. Curr Opin Microbiol. 2013;16(3):255–61.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Iceta R, Aramayona J, Mesonero J, Alcalde A. Regulation of the human serotonin transporter mediated by long-term action of serotonin in Caco‐2 cells. Acta Physiol. 2008;193(1):57–65.

    CAS  Article  Google Scholar 

  14. 14.

    Ashrafian F, Behrouzi A. Comparative study of effect of Akkermansia muciniphila and its extracellular vesicles on toll-like receptors and tight junction. Gastroenterol Hepatol Bed Bench. 2019;12(2):163.

    PubMed  PubMed Central  Google Scholar 

  15. 15.

    Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Mazmanian SK, Hsiao EY. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161(2):264–76.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    El-Salhy M. Irritable bowel syndrome: diagnosis and pathogenesis. World J Gastroenterol. 2012;18(37):5151.

    PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Wendelbo I, Mazzawi T, El–Salhy M. Increased serotonin transporter immunoreactivity intensity in the ileum of patients with irritable bowel disease. Mol Med Rep. 2014;9(1):180–4.

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    Wang H, Wei C-X, Min L, Zhu L-Y. Good or bad: gut bacteria in human health and diseases. Biotechnol Biotechnol Equip. 2018;32(5):1075–80.

    CAS  Article  Google Scholar 

  19. 19.

    Marteau P. Probiotics in functional intestinal disorders and IBS: proof of action and dissecting the multiple mechanisms. Gut. 2010;59(3):285–6.

    PubMed  Article  Google Scholar 

  20. 20.

    Chandrasekharan B, Saeedi BJ, Alam A, Houser M, Srinivasan S, Tansey M, Jones R, Nusrat A, Neish AS. Interactions between commensal bacteria and enteric neurons, via FPR1 induction of ROS, increase gastrointestinal motility in mice. Gastroenterology. 2019;157(1):179-192.e2.

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    Rajilić–Stojanović M, Biagi E, Heilig HG, Kajander K, Kekkonen RA, Tims S, de Vos WM. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology. 2011;141(5):1792–801.

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Martín R, Miquel S, Chain F, Natividad JM, Jury J, Lu J, Sokol H, Theodorou V, Bercik P, Verdu EF. Faecalibacterium prausnitzii prevents physiological damages in a chronic low-grade inflammation murine model. BMC Microbiol. 2015;15(1):67.

    PubMed  PubMed Central  Article  Google Scholar 

  23. 23.

    Nzakizwanayo J, Dedi C, Standen G, Macfarlane WM, Patel BA, Jones BV. Escherichia coli Nissle 1917 enhances bioavailability of serotonin in gut tissues through modulation of synthesis and clearance. Sci Rep. 2015;5:17324.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Cao Y-N, Feng L-J, Liu Y-Y, Jiang K, Zhang M-J, Gu Y-X, Wang B-M, Gao J, Wang Z-L, Wang Y-M. Effect of Lactobacillus rhamnosus GG supernatant on serotonin transporter expression in rats with post-infectious irritable bowel syndrome. World J Gastroenterol. 2018;24(3):338.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Singhal M, Turturice BA, Manzella CR, Ranjan R, Metwally AA, Theorell J, Huang Y, Alrefai WA, Dudeja PK, Finn PW. Serotonin transporter deficiency is associated with dysbiosis and changes in metabolic function of the mouse intestinal microbiome. Sci Rep. 2019;9(1):2138.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  26. 26.

    Latorre E, Pradilla A, Chueca B, Pagán R, Layunta E, Alcalde AI, Mesonero J. Listeria monocytogenes inhibits serotonin transporter in human intestinal Caco-2 cells. Microb Ecol. 2016;72(3):730–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Esmaili A, Nazir SF, Borthakur A, Yu D, Turner JR, Saksena S, Singla A, Hecht GA, Alrefai WA, Gill RK. Enteropathogenic Escherichia coli infection inhibits intestinal serotonin transporter function and expression. Gastroenterology. 2009;137(6):2074–83.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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Acknowledgements

The authors would like to thank the laboratory staff of Microbiology Research Center (MRC) and Department of Mycobacteriology and Pulmonary Research of Pasteur Institute of Iran.

Funding

This study was funded by Pasteur Institute of Iran (Grant No.: B-9325).

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Correspondence to Shohreh Khatami.

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Yaghoubfar, R., Behrouzi, A., Fateh, A. et al. Effects of Akkermansia muciniphila and Faecalibacterium prausnitzii on serotonin transporter expression in intestinal epithelial cells. J Diabetes Metab Disord (2021). https://doi.org/10.1007/s40200-020-00539-8

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Keywords

  • Gut microbiota
  • Akkermansia muciniphila
  • Faecalibacterium prausnitzii
  • Serotonin transporter
  • Caco-2 cells