화학공학소재연구정보센터
Journal of Industrial and Engineering Chemistry, Vol.101, 126-134, September, 2021
A Gut-Brain Axis-on-a-Chip for studying transport across epithelial and endothelial barriers
E-mail:
Recent research on Gut-Brain Axis (GBA) has suggested that the gut luminal environment, including the dietary components and commensal microbiota, could affect behavior, emotion, and cognitive abilities in the brain. Various signaling pathways exist between the gut and the brain, and several studies have implied exosomes could mediate the communication. Current research on GBA has relied heavily on animal models, making the research challenging. Recent advances in organ-on-a-chip technology could be a solution for GBA research. In present work, we have developed a modular microfluidic chip, where gut epithelial and brain endothelial cells were co-cultured to form the gut epithelial barrier and the Blood-Brain Barrier (BBB) interconnected via microfluidic channels. These modules can be easily assembled and disassembled, and cell barriers were well formed when co-cultured under appropriate fluidic flow. Responses to microbial byproducts were consistent with previously known observations of interaction between gut epithelium and BBB. We observed the transport of fluorescently labeled exosomes across the gut barrier towards the BBB. Our results suggest this model can be used as a novel in vitro model of GBA for studying the interaction between the gut and the brain.
  1. Dinan TH, Cryan JF, Nat. Rev. Gastroenterol. Hepatol., 14, 69 (2017)
  2. Iannone LF, Preda A, Blottiere HM, Clarke G, Albani D, Belcastro V, Carotenuto M, Cattaneo A, Citraro R, Ferraris C, Expert Rev. Neurother., 19, 1037 (2019)
  3. Gorecki AM, et al., Anderton in The gut-brain axis and gut inflammation in Parkinson’s disease, 2020 Taylor & Francis.
  4. Sandhu KV, Sherwin E, Schellekens H, Stanton C, Dinan TG, Cryan JF, Trans. Res., 179, 223 (2017)
  5. Galmiche M, Achamrah N, Dechelotte P, Ribet D, J. Breton, Nutr. Rev. (2021).
  6. Mao XY, Yin XX, Guan QW, Xia QX, Yang N, Zhou HH, Liu ZQ, Jin WL, Pharmacol. Ther. (2021).
  7. Martin CR, Osadchiy V, Kalani A, Mayer EA, Cell. Mol. Gastroenterol. Hepatol., 6, 133 (2018)
  8. Raimondi I, Izzo L, Tunesi M, Comar M, Albani D, Giordano C, Front. Bioeng. Biotechnol., 7, 435 (2020)
  9. Shimizu F, Nishihara H, Kanda T, Immunol. Med., 41, 120 (2018)
  10. Sharma G, Sharma AR, Lee SS, Bhattacharya M, Nam JS, Chakraborty C, Int. J. Pharm., 559, 360 (2019)
  11. Jiang L, Li S, Zheng J, Li Y, Huang H, Micromachines, 10, 375 (2019)
  12. Evrensel A, Ceylan ME, Clin. Psychopharmacol. Neurosci., 13, 239 (2015)
  13. Haas-Neill S, Forsythe P, Int. J. Mol. Sci., 21, 8899 (2020)
  14. Lauritzen KH, Morland C, Puchades M, Holm-Hansen S, Hagelin EM, et al., Cereb. Cortex, 24, 2784 (2014)
  15. McAllister MS, Krizanac-Bengez L, Macchia F, Naftalin RJ, Pedley KC, et al., Brain Res., 904, 20 (2001)
  16. Parker A, Fonseca S, Carding SR, Gut Microbes, 11, 135 (2020)
  17. Maheshwari R, et al., Guiding Principles for Human and Animal Research During Pharmaceutical Product Development, pp. 621-664, Elsevier, (2018).
  18. Voelkl B, et al., Nat. Rev. Neurosci., 1 (2020).
  19. Zhang B, Korolj A, Lai BFL, Radisic M, Nat. Rev. Mater., 3, 257 (2018)
  20. Ma C, Peng Y, Li H, Chen W, Trends Pharmacol. Sci. (2020).
  21. Wang X, Hou Y, Ai X, Sun J, Xu B, Meng X, Zhang Y, Zhang S, Biomed. Pharmacother.., 132 (2020)
  22. Sung Y.I. Wang N. Narasimhan Sriram M. Jackson C. Long J.J. Hickman M.L. Shuler, Anal. Chem. 91 2018 330 351.
  23. Lee SH, Sung JH, Adv. Healthcare Mater., 7, 170041 (2018)
  24. Lee SY, Sung JH, Biotechnol. Bioeng., 115(11), 2817 (2018)
  25. Lee DW, Ha SK, Choi I, Sung JH, Biomed. Microdev., 19, 1 (2017)
  26. Lee HR, Sung JH, J. Ind. Eng. Chem., 87, 60 (2020)
  27. Jeon JW, Lee SH, Kim D, Sung JH, Biotechnol. Prog., e3121.
  28. Lee SH, Jung BH, J. Ind. Eng. Chem., 71, 65 (2019)
  29. Kim JH, Ahn SI, Kim YT, J. Ind. Eng. Chem., 73, 8 (2019)
  30. Park SJ, Lee DY, J. Ind. Eng. Chem., 50, 29 (2017)
  31. Edington CD, Chen WLK, Geishecker E, Kassis T, Soenksen LR, Bhushan BM, Freake D, Kirschner J, Maass C, Tsamandouras N, Sci. Rep., 8, 1 (2018)
  32. Shemesh J, Jalilian I, Shi A, Yeoh GH, Tate MLK, Warkiani ME, Lab Chip, 15, 4114 (2015)
  33. Elbrecht DH, Long CJ, Hickman JJ, tc, 1, 1 (2016).
  34. avan der Meer AD, JungaKim H, avan der Helm MW, den Berg A, Lab Chip, 15, 745 (2015)
  35. Booth R, Kim H, Lab Chip, 12, 17884 (2012)
  36. Chi M, Yi B, Oh S, Park DJ, Sung JH, Park S, Biomed. Microdev., 17, 58 (2015)
  37. Puscas I, Bernard-Patrzynski F, Jutras M, Lecuyer MA, Bourbonniere L, Prat A, Leclair G, Roullin VG, Pharmaceutics, 11, 587 (2019)
  38. Choe A, Ha SK, Choi I, Choi N, Sung JH, Biomed. Microdevices, 19, 4 (2017)
  39. Kim HJ, Huh D, Hamilton G, Ingber DE, Lab Chip, 12, 2165 (2012)
  40. Ashammakhi A, Nasiri R, De Barros NR, Tebon P, Thakor J, Goudie M, Shamloo A, Martin MG, Khademhosseni A, Biomaterials (2020).
  41. Colgan OC, et al., Am. J. Physiol. Heart Circul. Physiol., 292, H3190 (2007).
  42. Oddo A, Peng B, Tong Z, Wei Y, Tong WY, Thissen H, Voelcker NH, Trends Biotechnol., 37, 1295 (2019)
  43. Schumann R, Res. Immunol., 143, 11 (1992)
  44. Hirotani Y, Ikeda K, Kato R, Myotoku M, Umeda T, Ijiri Y, Tanaka K, Yakugaku Zasshi, 128, 1363 (2008)
  45. Ghosh SS, Wang J, Yannie PJ, Ghosh S, J. Endocr. Soc., 4, bvz039 (2020)
  46. Banks WA, Erickson MA, Neurobiol. Disease, 37, 26 (2010)
  47. Zhu X, Han Y, Du J, Liu R, Jin K, Yi W, Oncotarget, 8, 53829 (2017)
  48. Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong jS, Knapp DJ, Crews FT, Glia, 55, 453 (2007)
  49. Srinivasan B, Kolli AR, Esch MB, Abaci HE, Shuler ML, Hickman JJ, J. Lab. Autom., 20, 107 (2015)
  50. Zucco F, Batto AF, Bises G, Chambaz J, Chiusolo A, Consalvo R, Cross H, Dal Negro G, de Angelis I, Fabre G, Altern. Lab. Anim., 33, 603 (2005)
  51. Ehrlich LC, Hu S, Sheng WS, Sutton RL, Rockswold GL, Peterson PK, Chao CC, J. Immunol., 160, 1944 (1998)
  52. Chen P, Shibata M, Zidovetzki R, Fisher M, Zlokovic B, Hofman F, J. Neuroimmunol., 116, 62 (2001)
  53. Verma S, Nakaoke R, Dohgu S, Banks WA, Brain Behav. Immun., 20, 449 (2006)
  54. Asfaha S, Dubeykovskiy AN, Tomita H, Yang X, Stokes S, Shibata W, et al., Gastroenterology, 144, 155 (2013)
  55. Peng L, He Z, Chen W, Holzman IR, Lin J, Pediatr. Res., 61, 37 (2007)
  56. Bedford A, Gong J, Animal Nutr., 4, 151 (2018)
  57. Braniste V, et al., Sci. Transl. Med., 6, 263ra158 (2014).
  58. Li H, Sun J, Wang F, Ding G, Chen W, Fang R, Yao Y, Pang M, Lu ZQ, Liu J, Brain Res., 1642, 70 (2016)
  59. Carobolante G, Mantaj J, Ferrari E, Vllasaliu D, Pharmaceutics, 12, 226 (2020)
  60. Saeedi S, Israel S, Nagy C, Turecki G, Transl. Psychiatry, 9, 1 (2019)
  61. Manca S, Upadhyaya B, Mutai E, Desaulniers AT, Cederberg RA, White BR, Zempleni J, Sci. Rep., 8, 1 (2018)
  62. Zempleni J, Sukreet S, Zhou F, Wu D, Mutai E, Annu. Rev. Anim. Biosci., 7, 245 (2019)
  63. Mutai E, Zhou F, Zempleni J, Faseb J., 31, 150 (2017)
  64. Peng H, Ji W, Zhao R, Yang J, Lu Z, Li Y, Zhang X, J. Mater. Chem. B, 8, 7591 (2020)
  65. Papademetriou I, Vedula E, Charest J, Porter T, PLoS ONE, 13 (2018)
  66. Zheng M, Huang M, Ma X, Chen H, Gao X, Bioconjug. Chem., 30, 994 (2019)
  67. Jin GZ, Chakraborty A, Lee JH, Knowles JC, Kim HW, J. Tissue Eng., 11 2041731419897460 (2020).
  68. Sung JH, Expert Opinion on Drug Metabolism & Toxicology 2021.
  69. Li XH, Zhang J, Li DF, Wu W, Xie ZW, Liu Q, Zool. Res., 41, 365 (2020)