Intestinal in vitro and ex vivo models to study host-microbiome interactions and acute stressors

Frontiers in Physiology

Volumn 9, Issue NOV, 2018, Pages

  Pearce, Sarah C ^a   Coia, Heidi G ^b,c   Karl, J P ^d   Pantoja Feliciano, Ida G ^a   Zachos, Nicholas C ^e   Racicot, Kenneth ^a  

^a DEVELOPMENT AND ENGINEERING CENTER   (United States)

^b NATIONAL RESEARCH COUNCIL   (United States)

^c AIR FORCE RESEARCH LABORATORY   (United States)

^d U S ARMY RESEARCH INSTITUTE OF ENVIRONMENTAL MEDICINE   (United States)

^e JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

DoD; Ex vivo; In vitro; Intestine; Physiology; Stress

Indexed keywords

DRUG METABOLITE;

ACUTE STRESS; ALTITUDE; ARMY; BACTERIAL METABOLISM; BIOINFORMATICS; CACO-2 CELL LINE; COCULTURE; COLD STRESS; ENTEROID; EX VIVO STUDY; FOOD DEPRIVATION; HEAT STRESS; HOST PATHOGEN INTERACTION; HT-29 CELL LINE; HUMAN; HYPOXIA; IEC-18 CELL LINE; IEC-6 CELL LINE; IN VITRO STUDY; INTESTINE FLORA; INTESTINE FUNCTION; IPEC-1 CELL LINE; IPEC-J2 CELL LINE; METABOLITE; MICROFLUIDICS; NONHUMAN; OMICS; ORGAN ON A CHIP; ORGANOID; REVIEW; T84 CELL LINE; TISSUE ENGINEERING;

EID: 85057013614     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2018.01584     Document Type: Review

References (190)

1. Aleksandrova, K., Romero-Mosquera, B., and Hernandez, V. (2017). Diet, gut microbiome and epigenetics: emerging links with inflammatory bowel diseases and prospects for management and prevention. Nutrients 9:E962. doi: 10.3390/nu9090962
2. Alexander, D. A., and Klein, S. (2009). First responders after disasters: a review of stress reactions, at-risk, vulnerability, and resilience factors. Prehosp. Disaster Med. 24, 87-94. doi: 10.1017/S1049023X00006610
3. Allen, J. M., Mailing, L. J., Cohrs, J., Salmonson, C., Fryer, J. D., Nehra, V., et al. (2017). Exercise training-induced modification of the gut microbiota persists after microbiota colonization and attenuates the response to chemically-induced colitis in gnotobiotic mice. Gut Microbes 9, 115-130. doi: 10.1080/19490976.2017.1372077
4. Altamimi, M., Abdelhay, O., and Rastall, R. A. (2016). Effect of oligosaccharides on the adhesion of gut bacteria to human HT-29 cells. Anaerobe 39, 136-142. doi: 10.1016/j.anaerobe.2016.03.010
5. Anand, A. C., Sashindran, V. K., and Mohan, L. (2006). Gastrointestinal problems at high altitude. Trop. Gastroenterol. 27, 147-153.
6. Aoki-Yoshida, A., Saito, S., Fukiya, S., Aoki, R., Takayama, Y., Suzuki, C., et al. (2016). Lactobacillus rhamnosus GG increases toll-like receptor 3 gene expression in murine small intestine ex vivo and in vivo. Benef. Microbes 7, 421-429. doi: 10.3920/BM2015.0169
7. Arboleya, S., Bahrami, B., Macfarlane, S., Gueimonde, M., Macfarlane, G. T., and de los Reyes-Gavilan, C. G. (2015). Production of immune response mediators by HT-29 intestinal cell-lines in the presence of bifidobacterium-treated infant microbiota. Benef. Microbes 6, 543-552. doi: 10.3920/BM2014.0111
8. Arce, C., Ramirez-Boo, M., Lucena, C., and Garrido, J. J. (2010). Innate immune activation of swine intestinal epithelial cell lines (IPEC-J2 and IPI-2I) in response to LPS from Salmonella typhimurium. Comp. Immunol. Microbiol. Infect. Dis. 33, 161-174. doi: 10.1016/j.cimid.2008.08.003
9. Beltinger, J., del Buono, J., Skelly, M. M., Thornley, J., Spiller, R. C., Stack, W. A., et al. (2008). Disruption of colonic barrier function and induction of mediator release by strains of Campylobacter jejuni that invade epithelial cells. World J. Gastroenterol. 14, 7345-7352. doi: 10.3748/wjg.14.7345
10. Bermudez-Brito, M., Munoz-Quezada, S., Gomez-Llorente, C., Matencio, E., Romero, F., and Gil, A. (2015). Lactobacillus paracasei CNCM I-4034 and its culture supernatant modulate Salmonella-induced inflammation in a novel transwell co-culture of human intestinal-like dendritic and Caco-2 cells. BMC Microbiol. 15:79. doi: 10.1186/s12866-015-0408-6
11. Bitar, K. N., Raghavan, S., and Zakhem, E. (2014). Tissue engineering in the gut: developments in neuromusculature. Gastroenterology 146, 1614-1624. doi: 10.1053/j.gastro.2014.03.044
12. Blutt, S. E., Crawford, S. E., Ramani, S., Zou, W. Y., and Estes, M. K. (2018). Engineered human gastrointestinal cultures to study the microbiome and infectious diseases. Cell. Mol. Gastroenterol. Hepatol. 5, 241-251. doi: 10.1016/j.jcmgh.2017.12.001
13. Bonde, J. P., Utzon-Frank, N., Bertelsen, M., Borritz, M., Eller, N. H., Nordentoft, M., et al. (2016). Risk of depressive disorder following disasters and military deployment: systematic review with meta-analysis. Br. J. Psychiatry 208, 330-336. doi: 10.1192/bjp.bp.114.157859
14. Botic, T., Klingberg, T. D., Weingartl, H., and Cencic, A. (2007). A novel eukaryotic cell culture model to study antiviral activity of potential probiotic bacteria. Int. J. Food Microbiol. 115, 227-34. doi: 10.1016/j.ijfoodmicro.2006.10.044
15. Boyen, F., Pasmans, F., Van Immerseel, F., Donne, E., Morgan, E., Ducatelle, R., et al. (2009). Porcine in vitro and in vivo models to assess the virulence of Salmonella enterica serovar Typhimurium for pigs. Lab. Anim. 43, 46-52. doi: 10.1258/la.2007.007084
16. Breiman, L. (2001). Random forests. Mach. Learn. 45, 5-32. doi: 10.1023/A:1010933404324
17. Brosnahan, A. J., and Brown, D. R. (2012). Porcine IPEC-J2 intestinal epithelial cells in microbiological investigations. Vet. Microbiol. 156, 229-237. doi: 10.1016/j.vetmic.2011.10.017
18. Browning, T. H., and Trier, J. S. (1969). Organ culture of mucosal biopsies of human small intestine. J. Clin. Invest. 48, 1423-1432. doi: 10.1172/JCI106108
19. Cani, P. D., Geurts, L., Matamoros, S., Plovier, H., and Duparc, T. (2014). Glucose metabolism: focus on gut microbiota, the endocannabinoid system and beyond. Diabetes Metab. 40, 246-257. doi: 10.1016/j.diabet.2014.02.004
20. Carabotti, M., Scirocco, A., Maselli, M. A., and Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann. Gastroenterol. 28, 203-209.
21. Carra, G. E., Ibanez, J. E., and Saravi, F. D. (2013). The effect of acute hypoxia on short-circuit current and epithelial resistivity in biopsies from human colon. Digest. Dis. Sci. 58, 2499-2506. doi: 10.1007/s10620-013-2711-0
22. Caspi, R., Foerster, H., Fulcher, C. A., Kaipa, P., Krummenacker, M., Latendresse, M., et al. (2008). The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases. Nucleic Acids Res. 36, D.623-D.631. doi: 10.1093/nar/gkr1014
23. Chen, H. Q., Yang, J., Zhang, M., Zhou, Y. K., Shen, T. Y., Chu, Z. X., et al. (2010). Lactobacillus plantarum ameliorates colonic epithelial barrier dysfunction by modulating the apical junctional complex and PepT1 in IL-10 knockout mice. Am. J. Physiol. Gastrointest. Liver Physiol. 299, G1287-G1297. doi: 10.1152/ajpgi.00196.2010
24. Chevalier, C., Stojanovic, O., Colin, D. J., Suarez-Zamorano, N., Tarallo, V., Veyrat-Durebex, C., et al. (2015). Gut microbiota orchestrates energy homeostasis during cold. Cell 163, 1360-1374. doi: 10.1016/j.cell.2015.11.004
25. Cinova, J., De Palma, G., Stepankova, R., Kofronova, O., Kverka, M., Sanz, Y., et al. (2011). Role of intestinal bacteria in gliadin-induced changes in intestinal mucosa: study in germ-free rats. PLoS ONE 6:e16169. doi: 10.1371/journal.pone.0016169
26. Clark, A., and Mach, N. (2016). Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes. J. Int. Soc. Sports Nutr. 13:43. doi: 10.1186/s12970-016-0155-6
27. Clarke, G., Stilling, R. M., Kennedy, P. J., Stanton, C., Cryan, J. F., and Dinan, T. G. (2014). Minireview: gut microbiota: the neglected endocrine organ. Mol. Endocrinol. 28, 1221-1238. doi: 10.1210/me.2014-1108
28. Coskun, T., Yegen, B. C., Alican, I., Peker, O., and Kurtel, H. (1996). Cold restraint stress-induced gastric mucosal dysfunction. Role of nitric oxide. Digest. Dis. Sci. 41, 956-963. doi: 10.1007/BF02091537
29. Creamer, M., Wade, D., Fletcher, S., and Forbes, D. (2011). PTSD among military personnel. Int. Rev. Psychiatry 23, 160-165. doi: 10.3109/09540261.2011.559456
30. Dahiya, R., Lesuffleur, T., Kwak, K. S., Byrd, J. C., Barbat, A., Zweibaum, A., et al. (1992). Expression and characterization of mucins associated with the resistance to methotrexate of human colonic adenocarcinoma cell line HT29. Cancer Res. 52, 4655-4662.
31. David, L. A., Weil, A., Ryan, E. T., Calderwood, S. B., Harris, J. B., Chowdhury, F., et al. (2015). Gut microbial succession follows acute secretory diarrhea in humans. MBio 6:e00381-15. doi: 10.1128/mBio.00381-15
32. De Simone, V., Franze, E., Ronchetti, G., Colantoni, A., Fantini, M. C., Di Fusco, D., et al. (2015). Th17-type cytokines, IL-6 and TNF-alpha synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth. Oncogene 34, 3493-3503. doi: 10.1038/onc.2014.286
33. Deiana, M., Corona, G., Incani, A., Loru, D., Rosa, A., Atzeri, A., et al. (2010). Protective effect of simple phenols from extravirgin olive oil against lipid peroxidation in intestinal Caco-2 cells. Food Chem. Toxicol. 48, 3008-3016. doi: 10.1016/j.fct.2010.07.041
34. Deitch, E. A., Haskel, Y., Cruz, N., Xu, D., and Kvietys, P. R. (1995). Caco-2 and IEC-18 intestinal epithelial cells exert bactericidal activity through an oxidant-dependent pathway. Shock 4, 345-350. doi: 10.1097/00024382-199511000-00006
35. Ding, J., Magnotti, L. J., Huang, Q., Xu, D. Z., Condon, M. R., and Deitch, E. A. (2001). Hypoxia combined with Escherichia coli produces irreversible gut mucosal injury characterized by increased intestinal cytokine production and DNA degradation. Shock 16, 189-195. doi: 10.1097/00024382-200116030-00004
36. Doe, W. F. (1989). The intestinal immune system. Gut 30, 1679-1685. doi: 10.1136/gut.30.12.1679
37. Dokladny, K., Moseley, P. L., and Ma, T. Y. (2006). Physiologically relevant increase in temperature causes an increase in intestinal epithelial tight junction permeability. Am. J. Physiol. Gastrointest. Liver Physiol. 290, G204-G212. doi: 10.1152/ajpgi.00401.2005
38. Dokladny, K., Zuhl, M. N., and Moseley, P. L. (2016). Intestinal epithelial barrier function and tight junction proteins with heat and exercise. J. Appl. Physiol. (1985) 120, 692-701. doi: 10.1152/japplphysiol.00536.2015
39. Donowitz, M., Keusch, G. T., and Binder, H. J. (1975). Effect of Shigella enterotoxin on electrolyte transport in rabbit ileum. Gastroenterology 69, 1230-1237.
40. Eckburg, P. B., Bik, E. M., Bernstein, C. N., Purdom, E., Dethlefsen, L., Sargent, M., et al. (2005). Diversity of the human intestinal microbial flora. Science 308, 1635-1638. doi: 10.1126/science.1110591
41. Elson, C. O., and Alexander, K. L. (2015). Host-microbiota interactions in the intestine. Dig. Dis. 33, 131-136. doi: 10.1159/000369534
42. Engevik, M. A., Aihara, E., Montrose, M. H., Shull, G. E., Hassett, D. J., and Worrell, R. T. (2013). Loss of NHE3 alters gut microbiota composition and influences Bacteroides thetaiotaomicron growth. Am. J. Physiol. Gastrointest. Liver Physiol. 305, G697-G711. doi: 10.1152/ajpgi.00184.2013
43. Engevik, M. A., Engevik, K. A., Yacyshyn, M. B., Wang, J., Hassett, D. J., Darien, B., et al. (2015). Human clostridium difficile infection: inhibition of NHE3 and microbiota profile. Am. J. Physiol. Gastrointest. Liver Physiol. 308, G497-G509. doi: 10.1152/ajpgi.00090.2014
44. Everson, C. A., and Toth, L. A. (2000). Systemic bacterial invasion induced by sleep deprivation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 278, R905-R916. doi: 10.1152/ajpregu.2000.278.4.R905
45. Farzi, A., Frohlich, E. E., and Holzer, P. (2018). Gut microbiota and the neuroendocrine system. Neurotherapeutics 15, 5-22. doi: 10.1007/s13311-017-0600-5
46. Forbester, J. L., Goulding, D., Vallier, L., Hannan, N., Hale, C., Pickard, D., et al. (2015). Interaction of Salmonella enterica serovar typhimurium with intestinal organoids derived from human induced pluripotent stem cells. Infect. Immun. 83, 2926-2934. doi: 10.1128/IAI.00161-15
47. Frasca, L., and Lande, R. (2012). Role of defensins and cathelicidin LL37 in auto-immune and auto-inflammatory diseases. Curr. Pharm. Biotechnol. 13, 1882-1897. doi: 10.2174/138920112802273155
48. Friedl, K. E., Moore, R. J., Martinez-Lopez, L. E., Vogel, J. A., Askew, E. W., Marchitelli, L. J., et al. (1994). Lower limit of body fat in healthy active men. J. Appl. Physiol. (1985) 77, 933-940. doi: 10.1152/jappl.1994.77.2.933
49. Furrie, E., Macfarlane, S., Thomson, G., and Macfarlane, G. T. (2005). Toll-like receptors-2,−3 and−4 expression patterns on human colon and their regulation by mucosal-associated bacteria. Immunology 115, 565-574. doi: 10.1111/j.1365-2567.2005.02200.x
50. Galley, J. D., and Bailey, M. T. (2014). Impact of stressor exposure on the interplay between commensal microbiota and host inflammation. Gut Microbes 5, 390-396. doi: 10.4161/gmic.28683
51. Gonzalez-Sarrias, A., Tome-Carneiro, J., Bellesia, A., Tomas-Barberan, F. A., and Espin, J. C. (2015). The ellagic acid-derived gut microbiota metabolite, urolithin A, potentiates the anticancer effects of 5-fluorouracil chemotherapy on human colon cancer cells. Food Funct. 6, 1460-1469. doi: 10.1039/C5FO00120J
52. Gruning, B. A., Fallmann, J., Yusuf, D., Will, S., Erxleben, A., Eggenhofer, F., et al. (2017). The RNA workbench: best practices for RNA and high-throughput sequencing bioinformatics in galaxy. Nucleic Acids Res. 45, W560-W566. doi: 10.1093/nar/gkx409
53. Guarino, A., Cohen, M., Thompson, M., Dharmsathaphorn, K., and Giannella, R. (1987). T84 cell receptor binding and guanyl cyclase activation by Escherichia coli heat-stable toxin. Am. J. Physiol. 253, G775-G780. doi: 10.1152/ajpgi.1987.253.6.G775
54. Hampton, T. (2017). Organoids reveal clues to gut-brain communication. JAMA 318, 787-788. doi: 10.1001/jama.2017.11545
55. Hecht, G., Marrero, J. A., Danilkovich, A., Matkowskyj, K. A., Savkovic, S. D., Koutsouris, A., et al. (1999). Pathogenic Escherichia coli increase Cl-secretion from intestinal epithelia by upregulating galanin-1 receptor expression. J. Clin. Invest. 104, 253-262. doi: 10.1172/JCI6373
56. Henning, P. C., Park, B. S., and Kim, J. S. (2011). Physiological decrements during sustained military operational stress. Mil. Med. 176, 991-997. doi: 10.7205/MILMED-D-11-00053
57. Henry, O. Y. F., Villenave, R., Cronce, M. J., Leineweber, W. D., Benz, M. A., and Ingber, D. E. (2017). Organs-on-chips with integrated electrodes for trans-epithelial electrical resistance (TEER) measurements of human epithelial barrier function. Lab. Chip 17, 2264-2271. doi: 10.1039/C7LC00155J
58. Hering, N. A., Luettig, J., Krug, S. M., Wiegand, S., Gross, G., van Tol, E. A., et al. (2017). Lactoferrin protects against intestinal inflammation and bacteria-induced barrier dysfunction in vitro. Ann. N. Y. Acad. Sci. 1405, 177-188. doi: 10.1111/nyas.13405
59. Hershko, D. D., Robb, B. W., Luo, G. J., Paxton, J. H., and Hasselgren, P. O. (2003). Interleukin-6 induces thermotolerance in cultured Caco-2 cells independent of the heat shock response. Cytokine 21, 1-9. doi: 10.1016/S1043-4666(02)00488-X
60. Hill, D. R., Huang, S., Nagy, M. S., Yadagiri, V. K., Fields, C., Mukherjee, D., et al. (2017). Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium. Elife 6:e29132. doi: 10.7554/eLife.29132
61. Holmes, E., Li, J. V., Marchesi, J. R., and Nicholson, J. K. (2012). Gut microbiota composition and activity in relation to host metabolic phenotype and disease risk. Cell Metab. 16, 559-64. doi: 10.1016/j.cmet.2012.10.007
62. Hooper, L. V., Littman, D. R., and Macpherson, A. J. (2012). Interactions between the microbiota and the immune system. Science 336, 1268-73. doi: 10.1126/science.1223490
63. Huet, G., Kim, I., de Bolos, C., Lo-Guidice, J. M., Moreau, O., Hemon, B., et al. (1995). Characterization of mucins and proteoglycans synthesized by a mucin-secreting HT-29 cell subpopulation. J. Cell Sci. 108 (Pt 3), 1275-85.
64. Hwang, J. H., Kim, J. Y., Cha, M. R., Ryoo, I. J., Choo, S. J., Cho, S. M., et al. (2008). Etoposide-resistant HT-29 human colon carcinoma cells during glucose deprivation are sensitive to piericidin A, a GRP78 down-regulator. J. Cell. Physiol. 215, 243-250. doi: 10.1002/jcp.21308
65. In, J., Foulke-Abel, J., Zachos, N. C., Hansen, A. M., Kaper, J. B., Bernstein, H. D., et al. (2016). Enterohemorrhagic Escherichia coli reduce mucus and intermicrovillar bridges in human stem cell-derived colonoids. Cell. Mol. Gastroenterol. Hepatol. 2, 48-62.e3. doi: 10.1016/j.jcmgh.2015.10.001
66. Isenmann, R., Schwarz, M., Rozdzinski, E., Marre, R., and Beger, H. G. (2000). Aggregation substance promotes colonic mucosal invasion of Enterococcus faecalis in an ex vivo model. J. Surg. Res. 89, 132-138. doi: 10.1006/jsre.1999.5813
67. Jafari, N. V., Kuehne, S. A., Minton, N. P., Allan, E., and Bajaj-Elliott, M. (2016). Clostridium difficile-mediated effects on human intestinal epithelia: modelling host-pathogen interactions in a vertical diffusion chamber. Anaerobe 37, 96-102. doi: 10.1016/j.anaerobe.2015.12.007
68. Jennis, M., Cavanaugh, C. R., Leo, G. C., Mabus, J. R., Lenhard, J., and Hornby, P. J. (2018). Microbiota-derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo. Neurogastroenterol. Motil. 30:e13178. doi: 10.1111/nmo.13178
69. Jin, Y., and Blikslager, A. T. (2016). Myosin light chain kinase mediates intestinal barrier dysfunction via occludin endocytosis during anoxia/reoxygenation injury. Am. J. Physiol. Cell Physiol. 311, C996-C1004. doi: 10.1152/ajpcell.00113.2016
70. Johansson, M. E., Phillipson, M., Petersson, J., Velcich, A., Holm, L., and Hansson, G. C. (2008). The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc. Natl. Acad. Sci. U.S.A. 105, 15064-15069. doi: 10.1073/pnas.0803124105
71. Kanehisa, M., Goto, S., Sato, Y., Kawashima, M., Furumichi, M., and Tanabe, M. (2014). Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Res. 42, D199-D205. doi: 10.1093/nar/gkt1076
72. Karl, J. P., Hatch, A. M., Arcidiacono, S. M., Pearce, S. C., Pantoja-Feliciano, I. G., Doherty, L. A., et al. (2018). Effects of psychological, environmental and physical stressors on the gut microbiota. Front. Microbiol. 9:2013. doi: 10.3389/fmicb.2018.02013
73. Karl, J. P., Margolis, L. M., Madslien, E. H., Murphy, N. E., Castellani, J. W., Gundersen, Y., et al. (2017a). 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. 312, G559-G571. doi: 10.1152/ajpgi.00066.2017
74. Karl, J. P., Margolis, L. M., Murphy, N. E., Carrigan, C. T., Castellani, J. W., Madslien, E. H., et al. (2017b). Military training elicits marked increases in plasma metabolomic signatures of energy metabolism, lipolysis, fatty acid oxidation, and ketogenesis. Physiol Rep 5:e13407. doi: 10.14814/phy2.13407
75. Karve, S. S., Pradhan, S., Ward, D. V., and Weiss, A. A. (2017). Intestinal organoids model human responses to infection by commensal and Shiga toxin producing Escherichia coli. PLoS ONE 12:e0178966. doi: 10.1371/journal.pone.0178966
76. Kasendra, M., Tovaglieri, A., Sontheimer-Phelps, A., Jalili-Firoozinezhad, S., Bein, A., Chalkiadaki, A., et al. (2018). Development of a primary human small intestine-on-a-chip using biopsy-derived organoids. Sci. Rep. 8:2871. doi: 10.1038/s41598-018-21201-7
77. Khailova, L., Mount Patrick, S. K., Arganbright, K. M., Halpern, M. D., Kinouchi, T., and Dvorak, B. (2010). Bifidobacterium bifidum reduces apoptosis in the intestinal epithelium in necrotizing enterocolitis. Am. J. Physiol. Gastrointest. Liver Physiol. 299, G1118-G1127. doi: 10.1152/ajpgi.00131.2010
78. Khan Mirzaei, M., Haileselassie, Y., Navis, M., Cooper, C., Sverremark-Ekstrom, E., and Nilsson, A. S. (2016). Morphologically distinct Escherichia coli bacteriophages differ in their efficacy and ability to stimulate cytokine release in vitro. Front. Microbiol. 7:437. doi: 10.3389/fmicb.2016.00437
79. Khanna, K., Mishra, K. P., Ganju, L., Kumar, B., and Singh, S. B. (2017). High-altitude-induced alterations in gut-immune axis: a review. Int. Rev. Immunol. 37, 119-126. doi: 10.1080/08830185.2017.1407763
80. Khodaii, Z., Ghaderian, S. M. H., and Natanzi, M. M. (2017). Probiotic bacteria and their supernatants protect enterocyte cell lines from Enteroinvasive Escherichia coli (EIEC) invasion. Int. J. Mol. Cell. Med. 6, 183-189. doi: 10.22088/acadpub.BUMS.6.3.183
81. Kim, H. J., Lee, J., Choi, J. H., Bahinski, A., and Ingber, D. E. (2016a). Co-culture of living microbiome with microengineered human intestinal villi in a gut-on-a-chip microfluidic device. J. Vis. Exp. 114:e54344. doi: 10.3791/54344
82. Kim, H. J., Li, H., Collins, J. J., and Ingber, D. E. (2016b). Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. Proc. Natl. Acad. Sci. U.S.A. 113, E7-E15. doi: 10.1073/pnas.1522193112
83. Kinross, J. M., Darzi, A. W., and Nicholson, J. K. (2011). Gut microbiome-host interactions in health and disease. Genome Med. 3, 14-14. doi: 10.1186/gm228
84. Kleessen, B., Schroedl, W., Stueck, M., Richter, A., Rieck, O., and Krueger, M. (2005). Microbial and immunological responses relative to high-altitude exposure in mountaineers. Med. Sci. Sports Exerc. 37, 1313-1318. doi: 10.1249/01.mss.0000174888.22930.e0
85. Knight, R., Vrbanac, A., Taylor, B. C., Aksenov, A., Callewaert, C., Debelius, J., et al. (2018). Best practices for analysing microbiomes. Nat. Rev. Microbiol. 16, 410-422. doi: 10.1038/s41579-018-0029-9
86. Knights, D., Costello, E. K., and Knight, R. (2011). Supervised classification of human microbiota. FEMS Microbiol. Rev. 35, 343-359. doi: 10.1111/j.1574-6976.2010.00251.x
87. Lafuse, W. P., Gearinger, R., Fisher, S., Nealer, C., Mackos, A. R., and Bailey, M. T. (2017). Exposure to a social stressor induces translocation of commensal lactobacilli to the spleen and priming of the innate immune system. J. Immunol. 198, 2383-2393. doi: 10.4049/jimmunol.1601269
88. Lambert, G. P. (2008). Intestinal barrier dysfunction, endotoxemia, and gastrointestinal symptoms: the 'canary in the coal mine' during exercise-heat stress? Med. Sport Sci. 53, 61-73. doi: 10.1159/000151550
89. Larsen, N., Nissen, P., and Willats, W. G. (2007). The effect of calcium ions on adhesion and competitive exclusion of Lactobacillus ssp. and E. coli O138. Int. J. Food Microbiol. 114, 113-119. doi: 10.1016/j.ijfoodmicro.2006.10.033
90. Le Bacquer, O., Laboisse, C., and Darmaun, D. (2003). Glutamine preserves protein synthesis and paracellular permeability in Caco-2 cells submitted to “luminal fasting.” Am. J. Physiol. Gastrointest. Liver Physiol. 285, G128-G136. doi: 10.1152/ajpgi.00459.2002
91. LeBlanc, J. G., Milani, C., de Giori, G. S., Sesma, F., van Sinderen, D., and Ventura, M. (2013). Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr. Opin. Biotechnol. 24, 160-168. doi: 10.1016/j.copbio.2012.08.005
92. Lee, S. Y., Madan, A., Furuta, G. T., Colgan, S. P., and Sibley, E. (2002). Lactase gene transcription is activated in response to hypoxia in intestinal epithelial cells. Mol. Genet. Metab. 75, 65-69. doi: 10.1006/mgme.2001.3263
93. Lei, Q., Qiang, F., Chao, D., Di, W., Guoqian, Z., Bo, Y., et al. (2014). Amelioration of hypoxia and LPS-induced intestinal epithelial barrier dysfunction by emodin through the suppression of the NF-kappaB and HIF-1alpha signaling pathways. Int. J. Mol. Med. 34, 1629-1639. doi: 10.3892/ijmm.2014.1965
94. Leslie, J. L., Huang, S., Opp, J. S., Nagy, M. S., Kobayashi, M., Young, V. B., et al. (2015). Persistence and toxin production by clostridium difficile within human intestinal organoids result in disruption of epithelial paracellular barrier function. Infect. Immun. 83, 138-145. doi: 10.1128/IAI.02561-14
95. Li, J., Ayene, R., Ward, K. M., Dayanandam, E., and Ayene, I. S. (2009). Glucose deprivation increases nuclear DNA repair protein Ku and resistance to radiation induced oxidative stress in human cancer cells. Cell Biochem. Funct. 27, 93-101. doi: 10.1002/cbf.1541
96. Li, X., Kan, E. M., Lu, J., Cao, Y., Wong, R. K., Keshavarzian, A., et al. (2013). Combat-training increases intestinal permeability, immune activation and gastrointestinal symptoms in soldiers. Aliment. Pharmacol. Therap. 37, 799-809. doi: 10.1111/apt.12269
97. Li, X., Wilder-Smith, C. H., Kan, M. E., Lu, J., Cao, Y., and Wong, R. K. (2014). Combat-training stress in soldiers increases S100B, a marker of increased blood-brain-barrier permeability, and induces immune activation. Neuro Endocrinol. Lett. 35, 58-63.
98. Li, X. L., Peng, Y. Z., Yuan, Z. Q., Huang, Y. S., and Yang, Z. C. (2003). Protection on proliferation of intestinal epithelial cells against hypoxia-reoxygenation through recombinant heat shock protein 70 adenovirus transfection. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 15, 81-83.
99. Li, Y. Y., Ishihara, S., Aziz, M. M., Oka, A., Kusunoki, R., Tada, Y., et al. (2011). Autophagy is required for toll-like receptor-mediated interleukin-8 production in intestinal epithelial cells. Int. J. Mol. Med. 27, 337-344. doi: 10.3892/ijmm.2011.596
100. Lievin-Le Moal, V., and Servin, A. L. (2013). Pathogenesis of human enterovirulent bacteria: lessons from cultured, fully differentiated human colon cancer cell lines. Microbiol. Mol. Biol. Rev. 77, 380-439. doi: 10.1128/MMBR.00064-12
101. Liu, Y., Fatheree, N. Y., Mangalat, N., and Rhoads, J. M. (2010). Human-derived probiotic Lactobacillus reuteri strains differentially reduce intestinal inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 299, G1087-G1096. doi: 10.1152/ajpgi.00124.2010
102. Lukovac, S., Belzer, C., Pellis, L., Keijser, B. J., de Vos, W. M., Montijn, R. C., et al. (2014). Differential modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids. mBio 5:e01438-14. doi: 10.1128/mBio.01438-14
103. Maccaferri, S., Klinder, A., Cacciatore, S., Chitarrari, R., Honda, H., Luchinat, C., et al. (2012). In vitro fermentation of potential prebiotic flours from natural sources: impact on the human colonic microbiota and metabolome. Mol. Nutr. Food Res. 56, 1342-1352. doi: 10.1002/mnfr.201200046
104. Macfarlane, S., and Macfarlane, G. T. (2004). Bacterial diversity in the human gut. Adv. Appl. Microbiol. 54, 261-289. doi: 10.1016/S0065-2164(04)54010-8
105. Mackos, A. R., Maltz, R., and Bailey, M. T. (2017). The role of the commensal microbiota in adaptive and maladaptive stressor-induced immunomodulation. Horm. Behav. 88, 70-78. doi: 10.1016/j.yhbeh.2016.10.006
106. Madara, J. L., and Dharmsathaphorn, K. (1985). Occluding junction structure-function relationships in a cultured epithelial monolayer. J. Cell Biol. 101, 2124-2133. doi: 10.1083/jcb.101.6.2124
107. Manna, C., Galletti, P., Cucciolla, V., Moltedo, O., Leone, A., and Zappia, V. (1997). The protective effect of the olive oil polyphenol (3,4-dihydroxyphenyl)-ethanol counteracts reactive oxygen metabolite-induced cytotoxicity in Caco-2 cells. J. Nutr. 127, 286-292. doi: 10.1093/jn/127.2.286
108. Margolis, L. M., Murphy, N. E., Martini, S., Gundersen, Y., Castellani, J. W., Karl, J. P., et al. (2016). Effects of supplemental energy on protein balance during 4-d arctic military training. Med. Sci. Sports Exerc. 48, 1604-1612. doi: 10.1249/MSS.0000000000000944
109. Margolis, L. M., Murphy, N. E., Martini, S., Spitz, M. G., Thrane, I., McGraw, S. M., et al. (2014). Effects of winter military training on energy balance, whole-body protein balance, muscle damage, soreness, and physical performance. Appl. Physiol. Nutr. Metab. 39, 1395-1401. doi: 10.1139/apnm-2014-0212
110. Mariani, V., Palermo, S., Fiorentini, S., Lanubile, A., and Giuffra, E. (2009). Gene expression study of two widely used pig intestinal epithelial cell lines: IPEC-J2 and IPI-2I. Vet. Immunol. Immunopathol. 131, 278-284. doi: 10.1016/j.vetimm.2009.04.006
111. Mayer, E. A., Tillisch, K., and Gupta, A. (2015). Gut/brain axis and the microbiota. J. Clin. Invest. 125, 926-938. doi: 10.1172/JCI76304
112. McCabe, R. E., Yu, G. S., Conteas, C., Morrill, P. R., and McMorrow, B. (1991). In vitro model of attachment of Giardia intestinalis trophozoites to IEC-6 cells, an intestinal cell line. Antimicrob. Agents Chemother. 35, 29-35. doi: 10.1128/AAC.35.1.29
113. McOrist, S., Jasni, S., Mackie, R. A., Berschneider, H. M., Rowland, A. C., and Lawson, G. H. (1995). Entry of the bacterium ileal symbiont intracellularis into cultured enterocytes and its subsequent release. Res. Vet. Sci. 59, 255-260. doi: 10.1016/0034-5288(95)90013-6
114. Miki, K., Unno, N., Nagata, T., Uchijima, M., Konno, H., Koide, Y., et al. (2004). Butyrate suppresses hypoxia-inducible factor-1 activity in intestinal epithelial cells under hypoxic conditions. Shock 22, 446-452. doi: 10.1097/01.shk.0000140664.80530.bd
115. Montain, S. J., and Young, A. J. (2003). Diet and physical performance. Appetite 40, 255-267. doi: 10.1016/S0195-6663(03)00011-4
116. Mowat, A. M. (2003). Anatomical basis of tolerance and immunity to intestinal antigens. Nat. Rev. Immunol. 3, 331-341. doi: 10.1038/nri1057
117. Mukherjee, P., and Mani, S. (2013). Methodologies to decipher the cell secretome. Biochim. Biophys. Acta 1834, 2226-2232. doi: 10.1016/j.bbapap.2013.01.022
118. Naito, T., Mulet, C., De Castro, C., Molinaro, A., Saffarian, A., Nigro, G., et al. (2017). Lipopolysaccharide from crypt-specific core microbiota modulates the colonic epithelial proliferation-to-differentiation balance. mBio 8:e01680-17. doi: 10.1128/mBio.01680-17
119. Nepelska, M., Cultrone, A., Beguet-Crespel, F., Le Roux, K., Dore, J., Arulampalam, V., et al. (2012). Butyrate produced by commensal bacteria potentiates phorbol esters induced AP-1 response in human intestinal epithelial cells. PLoS ONE 7:e52869. doi: 10.1371/journal.pone.0052869
120. Nguyen, T. L., Vieira-Silva, S., Liston, A., and Raes, J. (2015). How informative is the mouse for human gut microbiota research? Dis. Model Mech. 8, 1-16. doi: 10.1242/dmm.017400
121. Nigro, G., Rossi, R., Commere, P. H., Jay, P., and Sansonetti, P. J. (2014). The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration. Cell Host Microbe 15, 792-798. doi: 10.1016/j.chom.2014.05.003
122. Nindl, B. C., Castellani, J. W., Warr, B. J., Sharp, M. A., Henning, P. C., Spiering, B. A., et al. (2013). Physiological employment standards III: physiological challenges and consequences encountered during international military deployments. Eur. J. Appl. Physiol. 113, 2655-2672. doi: 10.1007/s00421-013-2591-1
123. Noel, G., Baetz, N. W., Staab, J. F., Donowitz, M., Kovbasnjuk, O., Pasetti, M. F., et al. (2017). A primary human macrophage-enteroid co-culture model to investigate mucosal gut physiology and host-pathogen interactions. Sci. Rep. 7:45270. doi: 10.1038/srep45270
124. Osborne, D. L., and Seidel, E. R. (1989). Microflora-derived polyamines modulate obstruction-induced colonic mucosal hypertrophy. Am. J. Physiol. 256, G1049-G1057. doi: 10.1152/ajpgi.1989.256.6.G1049
125. Pan, F., Han, L., Zhang, Y., Yu, Y., and Liu, J. (2015). Optimization of Caco-2 and HT29 co-culture in vitro cell models for permeability studies. Int. J. Food Sci. Nutr. 66, 680-685. doi: 10.3109/09637486.2015.1077792
126. Park, J. H., Kotani, T., Konno, T., Setiawan, J., Kitamura, Y., Imada, S., et al. (2016). Promotion of intestinal epithelial cell turnover by commensal bacteria: role of short-chain fatty acids. PLoS ONE 11:e0156334. doi: 10.1371/journal.pone.0156334
127. Pearce, S. C., Al-Jawadi, A., Kishida, K., Yu, S., Hu, M., Fritzky, L. F., et al. (2018). Marked differences in tight junction composition and macromolecular permeability among different intestinal cell types. BMC Biol. 16:19. doi: 10.1186/s12915-018-0481-z
128. Pearce, S. C., Mani, V., Weber, T. E., Rhoads, R. P., Patience, J. F., Baumgard, L. H., et al. (2013). Heat stress and reduced plane of nutrition decreases intestinal integrity and function in pigs. J. Anim. Sci. 91, 5183-5193. doi: 10.2527/jas.2013-6759
129. Pearce, S. C., Sanz-Fernandez, M. V., Hollis, J. H., Baumgard, L. H., and Gabler, N. K. (2014). Short-term exposure to heat stress attenuates appetite and intestinal integrity in growing pigs. J. Anim. Sci. 92, 5444-5454. doi: 10.2527/jas.2014-8407
130. Phua, L. C., Wilder-Smith, C. H., Tan, Y. M., Gopalakrishnan, T., Wong, R. K., Li, X., et al. (2015). Gastrointestinal symptoms and altered intestinal permeability induced by combat training are associated with distinct metabotypic changes. J. Proteome Res. 14, 4734-4742. doi: 10.1021/acs.jproteome.5b00603
131. Pierzchalska, M., Panek, M., Czyrnek, M., Gielicz, A., Mickowska, B., and Grabacka, M. (2017). Probiotic Lactobacillus acidophilus bacteria or synthetic TLR2 agonist boost the growth of chicken embryo intestinal organoids in cultures comprising epithelial cells and myofibroblasts. Comp. Immunol. Microbiol. Infect. Dis. 53, 7-18. doi: 10.1016/j.cimid.2017.06.002
132. Pompaiah, M., and Bartfeld, S. (2017). Gastric organoids: an emerging model system to study Helicobacter pylori pathogenesis. Curr. Top. Microbiol. Immunol. 400, 149-168. doi: 10.1007/978-3-319-50520-6_7
133. Porter, C. K., Olson, S., Hall, A., and Riddle, M. S. (2017). Travelers' diarrhea: an update on the incidence, etiology, and risk in military deployments and similar travel populations. Mil. Med. 182, 4-10. doi: 10.7205/MILMED-D-17-00064
134. Raja, S. B., Murali, M. R., Devaraj, H., and Devaraj, S. N. (2012). Differential expression of gastric MUC5AC in colonic epithelial cells: TFF3-wired IL1 beta/Akt crosstalk-induced mucosal immune response against Shigella dysenteriae infection. J. Cell Sci. 125, 703-713. doi: 10.1242/jcs.092148
135. Rajan, A., Vela, L., Zeng, X. L., Yu, X., Shroyer, N., Blutt, S. E., et al. (2018). Novel segment- and host-specific patterns of enteroaggregative Escherichia coli adherence to human intestinal enteroids. mBio 9:e02419-17. doi: 10.1128/mBio.02419-17
136. Resta-Lenert, S., and Barrett, K. E. (2003). Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC). Gut 52, 988-997. doi: 10.1136/gut.52.7.988
137. Rhoads, J. M., Chen, W., Chu, P., Berschneider, H. M., Argenzio, R. A., and Paradiso, A. M. (1994). L-glutamine and L-asparagine stimulate Na+-H+ exchange in porcine jejunal enterocytes. Am. J. Physiol. 266, G828-G838. doi: 10.1152/ajpgi.1994.266.5.G828
138. Riddle, M. S., Martin, G. J., Murray, C. K., Burgess, T. H., Connor, P., Mancuso, J. D., et al. (2017). Management of acute diarrheal illness during deployment: a deployment health guideline and expert panel report. Mil. Med. 182, 34-52. doi: 10.7205/MILMED-D-17-00077
139. Roeselers, G., Ponomarenko, M., Lukovac, S., and Wortelboer, H. M. (2013). Ex vivo systems to study host-microbiota interactions in the gastrointestinal tract. Best Pract. Res. Clin. Gastroenterol. 27, 101-113. doi: 10.1016/j.bpg.2013.03.018
140. Rothschild, D. E., Srinivasan, T., Aponte-Santiago, L. A., Shen, X., and Allen, I. C. (2016). The ex vivo culture and pattern recognition receptor stimulation of mouse intestinal organoids. J. Vis. Exp. 111:e54033. doi: 10.3791/54033
141. Round, J. L., O'Connell, R. M., and Mazmanian, S. K. (2010). Coordination of tolerogenic immune responses by the commensal microbiota. J. Autoimmun. 34, J220-J225. doi: 10.1016/j.jaut.2009.11.007
142. Roussel, G., Stevens, V., Cottin, S., and McArdle, H. J. (2017). The effect of amino acid deprivation on the transfer of iron through Caco-2 cell monolayers. J. Trace Elem. Med. Biol. 40, 82-90. doi: 10.1016/j.jtemb.2016.12.016
143. Rousset, M. (1986). The human colon carcinoma cell lines HT-29 and Caco-2: two in vitro models for the study of intestinal differentiation. Biochimie 68, 1035-1040. doi: 10.1016/S0300-9084(86)80177-8
144. Russell, W. R., Hoyles, L., Flint, H. J., and Dumas, M. E. (2013). Colonic bacterial metabolites and human health. Curr. Opin. Microbiol. 16, 246-254. doi: 10.1016/j.mib.2013.07.002
145. Saito, Y., Iwatsuki, K., Hanyu, H., Maruyama, N., Aihara, E., Tadaishi, M., et al. (2017). Effect of essential amino acids on enteroids: methionine deprivation suppresses proliferation and affects differentiation in enteroid stem cells. Biochem. Biophys. Res. Commun. 488, 171-176. doi: 10.1016/j.bbrc.2017.05.029
146. Saravi, F. D., Chirino, D. R., Saldena, T. A., Cincunegui, L. M., Carra, G. E., and Ituarte, L. M. (2002). Chronic hypobaric hypoxia effects on rat colon in vitro sensitivity to acute hypoxia and amiloride. Digest. Dis. Sci. 47, 1086-1090. doi: 10.1023/A:1015094225062
147. Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., et al. (2009). Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459, 262-265. doi: 10.1038/nature07935
148. Saunders, P. R., Kosecka, U., McKay, D. M., and Perdue, M. H. (1994). Acute stressors stimulate ion secretion and increase epithelial permeability in rat intestine. Am. J. Physiol. 267, G794-G799. doi: 10.1152/ajpgi.1994.267.5.G794
149. Schierack, P., Nordhoff, M., Pollmann, M., Weyrauch, K. D., Amasheh, S., Lodemann, U., et al. (2006). Characterization of a porcine intestinal epithelial cell line for in vitro studies of microbial pathogenesis in swine. Histochem. Cell Biol. 125, 293-305. doi: 10.1007/s00418-005-0067-z
150. Schilderink, R., Verseijden, C., Seppen, J., Muncan, V., van den Brink, G. R., Lambers, T. T., et al. (2016). The SCFA butyrate stimulates the epithelial production of retinoic acid via inhibition of epithelial HDAC. Am. J. Physiol. Gastrointest. Liver Physiol. 310, G1138-46. doi: 10.1152/ajpgi.00411.2015
151. Schmid, S. M., Hallschmid, M., and Schultes, B. (2015). The metabolic burden of sleep loss. Lancet Diabetes Endocrinol. 3, 52-62. doi: 10.1016/S2213-8587(14)70012-9
152. Segata, N., Boernigen, D., Tickle, T. L., Morgan, X. C., Garrett, W. S., and Huttenhower, C. (2013). Computational meta'omics for microbial community studies. Mol. Syst. Biol. 9:666. doi: 10.1038/msb.2013.22
153. Shah, P., Fritz, J. V., Glaab, E., Desai, M. S., Greenhalgh, K., Frachet, A., et al. (2016). A microfluidics-based in vitro model of the gastrointestinal human-microbe interface. Nat. Commun. 7:11535. doi: 10.1038/ncomms11535
154. Shi, C. Z., Chen, H. Q., Liang, Y., Xia, Y., Yang, Y. Z., Yang, J., et al. (2014). Combined probiotic bacteria promotes intestinal epithelial barrier function in interleukin-10-gene-deficient mice. World J. Gastroenterol. 20, 4636-4647. doi: 10.3748/wjg.v20.i16.4636
155. Shi, Y. H., Xiao, J. J., Feng, R. P., Liu, Y. Y., Liao, M., Wu, X. W., et al. (2017). Factors affecting the bioaccessibility and intestinal transport of difenoconazole, hexaconazole, and spirodiclofen in human Caco-2 cells following in vitro digestion. J. Agric. Food Chem. 65, 9139-9146. doi: 10.1021/acs.jafc.7b02781
156. Skjolaas, K. A., Burkey, T. E., Dritz, S. S., and Minton, J. E. (2007). Effects of Salmonella enterica serovar Typhimurium, or serovar Choleraesuis, Lactobacillus reuteri and Bacillus licheniformis on chemokine and cytokine expression in the swine jejunal epithelial cell line, IPEC-J2. Vet. Immunol. Immunopathol. 115, 299-308. doi: 10.1016/j.vetimm.2006.10.012
157. Smirnova, M. G., Guo, L., Birchall, J. P., and Pearson, J. P. (2003). LPS up-regulates mucin and cytokine mRNA expression and stimulates mucin and cytokine secretion in goblet cells. Cell Immunol. 221, 42-49. doi: 10.1016/S0008-8749(03)00059-5
158. Sommer, F., Anderson, J. M., Bharti, R., Raes, J., and Rosenstiel, P. (2017). The resilience of the intestinal microbiota influences health and disease. Nat. Rev. Microbiol. 15, 630-638. doi: 10.1038/nrmicro.2017.58
159. Swank, G. M., Lu, Q., Xu, D. Z., Michalsky, M., and Deitch, E. A. (1998). Effect of acute-phase and heat-shock stress on apoptosis in intestinal epithelial cells (Caco-2). Crit. Care Med. 26, 1213-1217. doi: 10.1097/00003246-199807000-00023
160. Thaiss, C. A., Levy, M., Korem, T., Dohnalova, L., Shapiro, H., Jaitin, D. A., et al. (2016). Microbiota diurnal rhythmicity programs host transcriptome oscillations. Cell 167, 1495-1510.e12. doi: 10.1016/j.cell.2016.11.003
161. Tharion, W. J., Lieberman, H. R., Montain, S. J., Young, A. J., Baker-Fulco, C. J., Delany, J. P., et al. (2005). Energy requirements of military personnel. Appetite 44, 47-65. doi: 10.1016/j.appet.2003.11.010
162. Toki, S., Kagaya, S., Shinohara, M., Wakiguchi, H., Matsumoto, T., Takahata, Y., et al. (2009). Lactobacillus rhamnosus GG and Lactobacillus casei suppress Escherichia coli-induced chemokine expression in intestinal epithelial cells. Int. Arch. Allergy Immunol. 148, 45-58. doi: 10.1159/000151505
163. Townsend, J. H., Davis, S. R., Mackey, A. D., and Gregory, J. F. I. I. I. (2004). Folate deprivation reduces homocysteine remethylation in a human intestinal epithelial cell culture model: role of serine in one-carbon donation. Am. J. Physiol. Gastrointest. Liver Physiol. 286, G588-G595. doi: 10.1152/ajpgi.00454.2003
164. Trapecar, M., Goropevsek, A., Gorenjak, M., Gradisnik, L., and Slak Rupnik, M. (2014). A co-culture model of the developing small intestine offers new insight in the early immunomodulation of enterocytes and macrophages by Lactobacillus spp. through STAT1 and NF-kB p65 translocation. PLoS ONE 9:e86297. doi: 10.1371/journal.pone.0086297
165. Unno, N., Menconi, M. J., Salzman, A. L., Smith, M., Hagen, S., Ge, Y., et al. (1996). Hyperpermeability and ATP depletion induced by chronic hypoxia or glycolytic inhibition in Caco-2BBe monolayers. Am. J. Physiol. 270, G1010-G1021. doi: 10.1152/ajpgi.1996.270.6.G1010
166. Van den Abbeele, P., Belzer, C., Goossens, M., Kleerebezem, M., De Vos, W. M., Thas, O., et al. (2013). Butyrate-producing clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model. ISME J. 7, 949-961. doi: 10.1038/ismej.2012.158
167. van Kooyk, Y. (2008). C-type lectins on dendritic cells: key modulators for the induction of immune responses. Biochem. Soc. Trans. 36, 1478-1481. doi: 10.1042/BST0361478
168. Voigt, R. M., Forsyth, C. B., Green, S. J., Engen, P. A., and Keshavarzian, A. (2016). Circadian rhythm and the gut microbiome. Int. Rev. Neurobiol. 131, 193-205. doi: 10.1016/bs.irn.2016.07.002
169. Wang, H., Bastian, S. E., Cheah, K. Y., Lawrence, A., and Howarth, G. S. (2014). Escherichia coli nissle 1917-derived factors reduce cell death and late apoptosis and increase transepithelial electrical resistance in a model of 5-fluorouracil-induced intestinal epithelial cell damage. Cancer Biol. Ther. 15, 560-569. doi: 10.4161/cbt.28159
170. Weeks, S. R., McAuliffe, C. L., Durussel, D., and Pasquina, P. F. (2010). Physiological and psychological fatigue in extreme conditions: the military example. PM R. 2, 438-441. doi: 10.1016/j.pmrj.2010.03.023
171. Winter, S. E., and Baumler, A. J. (2014). Why related bacterial species bloom simultaneously in the gut: principles underlying the 'Like will to like' concept. Cell Microbiol. 16, 179-184. doi: 10.1111/cmi.12245
172. Wlodarska, M., Luo, C., Kolde, R., d'Hennezel, E., Annand, J. W., Heim, C. E., et al. (2017). Indoleacrylic acid produced by commensal peptostreptococcus species suppresses inflammation. Cell Host Microbe 22, 25-37.e6. doi: 10.1016/j.chom.2017.06.007
173. Workman, M. J., Gleeson, J. P., Troisi, E. J., Estrada, H. Q., Kerns, S. J., Hinojosa, C. D., et al. (2018). Enhanced utilization of induced pluripotent stem cell-derived human intestinal organoids using microengineered chips. Cell. Mol. Gastroenterol. Hepatol. 5, 669-677.e2. doi: 10.1016/j.jcmgh.2017.12.008
174. Xiao, G., Tang, L., Yuan, F., Zhu, W., Zhang, S., Liu, Z., et al. (2013). Eicosapentaenoic acid enhances heat stress-impaired intestinal epithelial barrier function in Caco-2 cells. PLoS ONE 8:e73571. doi: 10.1371/journal.pone.0073571
175. Xu, D. Z., Lu, Q., Kubicka, R., and Deitch, E. A. (1999). The effect of hypoxia/reoxygenation on the cellular function of intestinal epithelial cells. J. Trauma 46, 280-285. doi: 10.1097/00005373-199902000-00014
176. Xu, D. Z., Lu, Q., Swank, G. M., and Deitch, E. A. (1996). Effect of heat shock and endotoxin stress on enterocyte viability apoptosis and function varies based on whether the cells are exposed to heat shock or endotoxin first. Arch. Surg. 131, 1222-1228. doi: 10.1001/archsurg.1996.01430230104018
177. Yang, X., Gao, X. C., Liu, J., and Ren, H. Y. (2017). Effect of EPEC endotoxin and bifidobacteria on intestinal barrier function through modulation of toll-like receptor 2 and toll-like receptor 4 expression in intestinal epithelial cell-18. World J. Gastroenterol. 23, 4744-4751. doi: 10.3748/wjg.v23.i26.4744
178. Yazdani, B. C. T. M., Debelius, J. W., Li, W., Knight, R., and Smarr, L. (2016). “Using machine learning to identify major shifts in human gut microbiome protein family abundance in disease,” in 2016 IEEE International Conference on Big Data (Big Data) (San Diego, CA), 1272-1280.
179. Yin, X., Farin, H. F., van Es, J. H., Clevers, H., Langer, R., and Karp, J. M. (2014). Niche-independent high-purity cultures of Lgr5+ intestinal stem cells and their progeny. Nat. Methods 11, 106-112. doi: 10.1038/nmeth.2737
180. Yoo, B. B., and Mazmanian, S. K. (2017). The enteric network: interactions between the immune and nervous systems of the gut. Immunity 46, 910-926. doi: 10.1016/j.immuni.2017.05.011
181. Yu, J., Liu, F., Yin, P., Zhao, H., Luan, W., Hou, X., et al. (2013). Involvement of oxidative stress and mitogen-activated protein kinase signaling pathways in heat stress-induced injury in the rat small intestine. Stress 16, 99-113. doi: 10.3109/10253890.2012.680526
182. Zeitouni, N. E., Dersch, P., Naim, H. Y., and von Kockritz-Blickwede, M. (2016). Hypoxia decreases invasin-mediated yersinia enterocolitica internalization into Caco-2 cells. PLoS ONE 11:e0146103. doi: 10.1371/journal.pone.0146103
183. Zenhom, M., Hyder, A., de Vrese, M., Heller, K. J., Roeder, T., and Schrezenmeir, J. (2011). Prebiotic oligosaccharides reduce proinflammatory cytokines in intestinal Caco-2 cells via activation of PPARgamma and peptidoglycan recognition protein 3. J. Nutr. 141, 971-977. doi: 10.3945/jn.110.136176
184. Zhang, Y. G., Wu, S., Xia, Y., and Sun, J. (2014). Salmonella-infected crypt-derived intestinal organoid culture system for host-bacterial interactions. Physiol. Rep. 2:e12147. doi: 10.14814/phy2.12147
185. Zhou, Q. Q., Yang, D. Z., Luo, Y. J., Li, S. Z., Liu, F. Y., and Wang, G. S. (2011). Over-starvation aggravates intestinal injury and promotes bacterial and endotoxin translocation under high-altitude hypoxic environment. World J. Gastroenterol. 17, 1584-1593. doi: 10.3748/wjg.v17.i12.1584
186. Zhu, A., Sunagawa, S., Mende, D. R., and Bork, P. (2015). Inter-individual differences in the gene content of human gut bacterial species. Genome Biol. 16:82. doi: 10.1186/s13059-015-0646-9
187. Zhu, X., Han, Y., Du, J., Liu, R., Jin, K., and Yi, W. (2017). Microbiota-gut-brain axis and the central nervous system. Oncotarget 8, 53829-53838. doi: 10.18632/oncotarget.17754
188. Zietak, M., Kovatcheva-Datchary, P., Markiewicz, L. H., Stahlman, M., Kozak, L. P., and Backhed, F. (2016). Altered microbiota contributes to reduced diet-induced obesity upon cold exposure. Cell Metab. 23, 1216-1223. doi: 10.1016/j.cmet.2016.05.001
189. Zomer-van Ommen, D. D., Pukin, A. V., Fu, O., Quarles van Ufford, L. H., Janssens, H. M., Beekman, J. M., et al. (2016). Functional characterization of cholera toxin inhibitors using human intestinal organoids. J. Med. Chem. 59, 6968-6972. doi: 10.1021/acs.jmedchem.6b00770
190. Zuhl, M., Schneider, S., Lanphere, K., Conn, C., Dokladny, K., and Moseley, P. (2014). Exercise regulation of intestinal tight junction proteins. Br. J. Sports Med. 48, 980-986. doi: 10.1136/bjsports-2012-091585