Metabiotics: One step ahead of probiotics; an insight into mechanisms involved in anticancerous effect in colorectal cancer

Frontiers in Microbiology

Volumn 7, Issue DEC, 2016, Pages

  Sharma, Mridul ^a   Shukla, Geeta ^a  

^a PANJAB UNIVERSITY   (India)

Author keywords

Colorectal cancer; Metabiotics; Metabolites; Probiotics; Short chain fatty acids

Indexed keywords

ANTIMUTAGENIC AGENT; ANTINEOPLASTIC AGENT; BUTYRIC ACID; GELATINASE B; INTERLEUKIN 10; INTERLEUKIN 2; INTERLEUKIN 6; INTERLEUKIN 8; METABIOTICS; MONOCARBOXYLATE TRANSPORTER 1; POLYPHOSPHATE; PROBIOTIC AGENT; SHORT CHAIN FATTY ACID; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG;

ANTIBIOTIC RESISTANCE; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; COLORECTAL CANCER; DIET; EPIGENETICS; GENOTOXICITY; HUMAN; IMMUNOCOMPROMISED PATIENT; IMMUNOMODULATION; LIFESTYLE; METABOLITE; METASTASIS INHIBITION; MUTAGENESIS; NONHUMAN; PHYSIOLOGY; PROTEIN EXPRESSION; REVIEW;

EID: 85009200614     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2016.01940     Document Type: Review

References (187)

1. Adom, D., and Nie, D. (2013). "Regulation of autophagy by short chain fatty acids in colon cancer cells, " in Autophagy-A Double-Edged Sword-Cell Survival or Death?, ed. Y. Bailly (Rijeka: INTECH). doi: 10.5772/54999
2. Ahn, J., Sinha, R., Pei, Z., Dominianni, C., Wu, J., Shi, J., et al. (2013). Human gut microbiome and risk for colorectal cancer. J. Natl. Cancer Inst. 105, 1907-1911. doi: 10.1093/jnci/djt300
3. Aktipis, C. A., and Nesse, R. M. (2013). Evolutionary foundations for cancer biology. Evol. Appl. 6, 144-159. doi: 10.1111/eva.12034
4. Andoh, A., Tsujikawa, T., and Fujiyama, Y. (2003). Role of dietary fiber and short-chain fatty acids in the colon. Curr. Pharm. Des. 9, 347-358. doi: 10.2174/1381612033391973
5. Archer, S., Meng, S., Shei, A., and Hodin, R. A. (1998). p21(WAF1) is required for butyrate mediated growth inhibition of human colon cancer cells. Proc. Natl. Acad. Sci. U.S.A. 95, 6791-6796. doi: 10.1073/pnas.95.12.6791
6. Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., et al. (2013). Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451-455. doi: 10.1038/nature12726
7. Ashktorab, H., Belgrave, K., Hosseinkhah, F., Brim, H., Nouraie, M., Takkikto, M., et al. (2009). Global histone H4 acetylation and HDAC2 expression in colon adenoma and carcinoma. Dig. Dis. Sci. 54, 2109-2117. doi: 10.1007/s10620-008-0601-7
8. Baker, E. A., and Leaper, D. J. (2002). Measuring gelatinase activity in colorectal cancer. Eur. J. Surg. Oncol. 28, 24-29. doi: 10.1053/ejso.2001.1179
9. Bassaganya-Riera, J., Viladomiu, M., and Pedragosa, M. (2012a). Probiotic bacteria produce conjugated linoleic acid locally in the gut that targets macrophage PPAR γ to suppress colitis. PLoS ONE 7:e31238. doi: 10.1371/journal.pone.0031238
10. Bassaganya-Riera, J., Viladomiu, M., Pedragosa, M., Simone, C. D., and Hontecilla, R. (2012b). Immunoregulatory mechanisms underlying prevention of colitis-associated colorectal cancer by probiotic bacteria. PLoS ONE 7:e34676. doi: 10.1371/journal.pone.0034676
11. Belousova, E. F., Nikitina, Y. V., Mishurovskaya, N. C., and Zlatkina, A. R. (2005). Possibilities of microbial metabolite preparations for intestinal microbiota restoration. Consilium Medicum. 7, 9-13.
12. Berer, K., Mues, M., Koutrolos, M., Rasbi, Z. A., Boziki, M., Johner, C., et al. (2011). Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 479, 538-541. doi: 10.1038/nature10554
13. Bertkova, I., Hijova, E., Chmelarova, A., Mojzisova, G., Petrasova, D., Strojny, L., et al. (2010). The effect of probiotic microorganisms and bioactive compounds on chemically induced carcinogenesis in rats. Neoplasma 57, 422-428. doi: 10.4149/neo_2010_05_422
14. Besten, G. D., Eunen, K. V., Groen, A. K., Venema, K., Reijngoud, D. J., and Bakker, B. M. (2013). The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J. Lipid Res. 54, 2325-2340. doi: 10.1194/jlr.R036012
15. Bindels, L. B., Dewulf, E. M., and Delzenne, N. M. (2013). GPR43/FFA2: physiopathological relevance and therapeutic prospects. Trends Pharmacol. Sci. 34, 226-232. doi: 10.1016/j.tips.2013.02.002
16. Bindels, L. B., Porporato, P., Dewulf, E. M., Verrax, J., Neyrinck, A. M., Martin, J. C., et al. (2012). Gut microbiota-derived propionate reduces cancer cell proliferation in the liver. Br. J. Cancer 107, 1337-1344. doi: 10.1038/bjc.2012.409
17. Birt, D. F., and Phillips, G. J. (2014). Diet, genes, and microbes: complexities of colon cancer prevention. Toxicol. Pathol. 42, 182-188. doi: 10.1177/0192623313506791
18. Blad, C. C., Tang, C., and Offermanns, S. (2012). G protein-coupled receptors for energy metabolites as new therapeutic targets. Nat. Rev. Drug Discov. 11, 603-619. doi: 10.1038/nrd3777
19. Bolden, J. E., Peart, M. J., and Johnstone, R. W. (2006). Anticancer activities of histone deacetylase inhibitors. Nat. Rev. Drug Discov. 5, 769-784. doi: 10.1038/nrd2133
20. Boleij, A., and Tjalsma, H. (2013). The itinerary of Streptococcus gallolyticus infection in patients with colonic malignant disease. Lancet Infect. Dis. 13, 719-724. doi: 10.1016/S1473-3099(13)70107-5
21. Bordin, M., D'Atri, F., Guillemot, L., and Citi, S. (2004). Histone deacetylase inhibitors upregulate the expression of tight junction proteins. Mol. Cancer Res. 2, 692-701.
22. Bourdichon, F., Berger, B., Casaregola, S., Frisvad, J. C., Gerds, M. L., Hammes, W. P., et al. (2012). Safety demonstration of microbial food cultures in fermented food products. Bull. Int. Dairy Fed. 455, 7-8.
23. Breuer, R. I., Buto, S. K., Christ, M. L., Bean, J., Vernia, P., Paoluzi, P., et al. (1991). Rectal irrigation with short-chain fatty acids for distal ulcerative colitis. Preliminary report. Dig. Dis. Sci. 36, 185-187. doi: 10.1007/BF01300754
24. Brown, A. J., Goldsworthy, S. M., Barnes, A. A., Eilert, M. M., Tcheang, L., Daniels, D., et al. (2003). The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem. 278, 11312-11319. doi: 10.1074/jbc.M211609200
25. Bultman, S. J. (2014). Emerging roles of the microbiome in cancer. Carcinogenesis 35, 249-255. doi: 10.1093/carcin/bgt392
26. Burns, A. J., and Rowland, I. R. (2004). Antigenotoxicity of probiotics and prebiotics on faecal water-induced DNA damage in human colon adenocarcinoma cells. Mutat. Res. 13, 233-243. doi: 10.1016/j.mrfmmm.2004.03.010
27. Cabana, M. D., Shane, A. L., Chao, C., and Oliva-Hemker, M. (2006). Probiotics in primary care pediatrics. Clin. Pediatr. (Phila). 45, 405-410. doi: 10.1177/0009922806289614
28. Cancer Facts and Figures (2016). Cancer Facts and Figures 2016. Atlanta, GA: American Cancer Society.
29. Choi, S. S., Kim, Y., Han, K. S., You, S., Oh, S., and Kim, S. H. (2006). Effects of Lactobacillus strains on cancer cell proliferation and oxidative stress in vitro. Lett. Appl. Microbiol. 42, 452-458. doi: 10.1111/j.1472-765X.2006.01913.x
30. Christophersen, C. T., Petersen, A., Licht, T. R., and Conlon, M. A. (2013). Xylo-oligosaccharides and inulin affect genotoxicity and bacterial populations differently in a human colonic simulator challenged with soy protein. Nutrients 5, 3740-3756.
31. Clarke, J. M., Young, G. P., Topping, D. L., Bird, A. R., Cobiac, L., Scherer, B. L., et al. (2012). Butyrate delivered by butyrylated starch increases distal colonic epithelial apoptosis in carcinogen-treated rats. Carcinogenesis 33, 197-202. doi: 10.1093/carcin/bgr254
32. Colin, H., Francisco, G., Gregor, R., Gibson, G. R., Merenstein, D. J., Pot, B., et al. (2014). Expert consensus document: the International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 11, 506-514. doi: 10.1038/nrgastro.2014.66
33. Coppedè, F. (2014). Epigenetic biomarkers of colorectal cancer: focus on DNA methylation. Cancer Lett. 342, 238-247. doi: 10.1016/j.canlet.2011.12.030
34. Cousin, F. J., Jouan-Lanhouet, S., Dimanche-Boitrel, M. T., Corcos, L., and Jan, G. (2012). Milk fermented by Propionibacterium freudenreichii induces apoptosis of HGT-1human gastric cancer cells. PLoS ONE 7:e31892. doi: 10.1371/journal.pone.0031892
35. Coussens, L. M., Zitvogel, L., and Palucka, A. K. (2013). Neutralizing tumor-promoting chronic inflammation: a magic bullet? Science 339, 286-291. doi: 10.1126/science.1232227
36. Cresci, G. A., Thangaraju, M., Mellinger, J. D., Liu, K., and Ganapathy, V. (2010). Colonic gene expression in conventional and germ-free mice with a focus on the butyrate receptor GPR109A and the butyrate transporter SLC5A8. J. Gastrointest. Surg. 14, 449-461. doi: 10.1007/s11605-009-1045-x
37. Crim, K. C., Sanders, L. M., Hong, M. Y., Taddeo, S. S., Turner, N. D., Chapkinet, R. S., et al. (2008). Upregulation of p21Waf1/Cip1 expression in vivo by butyrate administration can be chemoprotective or chemopromotive depending on the lipid component of the diet. Carcinogenes 29, 1415-1420. doi: 10.1093/carcin/bgn144
38. Cuevas-Ramos, G., Petit, C. R., Marcq, I., Boury, M., Oswald, E., and Nougayrede, J. P. (2010). Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proc. Natl. Acad. Sci. U.S.A. 107, 11537-11542. doi: 10.1073/pnas.1001261107
39. Davis, C. D., and Milner, J. A. (2009). Gastrointestinal microflora, food components and colon cancer prevention. J. Nutr. Biochem. 20, 743-752. doi: 10.1016/j.jnutbio.2009.06.001
40. Di Caro, S., Tao, H., Grillo, A., Elia, C., Gasbarrini, G., Sepulveda, A. R., et al. (2005). Effects of Lactobacillus GG on gene expression pattern in small bowel mucosa. Dig. Liver Dis. 37, 320-329. doi: 10.1016/j.dld.2004.12.008
41. Dirienzo, D. B. (2013). Effect of probiotics on biomarkers of cardiovascular disease: implications for heart-healthy diets. Nutr. Rev. 72, 18-29. doi: 10.1111/nure.12084
42. Dokmanovic, M., and Marks, P. A. (2005). Prospects: histone deacetylase inhibitors. J. Cell. Biochem. 96, 293-304. doi: 10.1002/jcb.20532
43. Escamilla, J., Lane, M. A., and Maitin, V. (2012). Cell-free supernatants from probiotic Lactobacillus casei and Lactobacillus rhamnosus GG decrease colon cancer cell invasion in vitro. Nutr. Cancer 64, 871-878. doi: 10.1080/01635581.2012.700758
44. Ewaschuk, J. B., Diaz, H., Meddings, L., Diederichs, B., Dmytrash, A., Backer, J., et al. (2008). Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am. J. Physiol. Gastrointest. Liver Physiol. 295, G1025-G1034. doi: 10.1152/ajpgi.90227.2008
45. Ewaschuk, J. B., Walker, J. W., Diaz, H., and Madsen, K. L. (2006). Bioproduction of conjugated linoleic acid by probiotic bacteria occurs in vitro and in vivo in mice. J. Nutr. 136, 1483-1487.
46. Fijan, S. (2014). Microorganisms with claimed probiotic properties: an overview of recent literature. Int. J. Environ. Res. Public Health 11, 4745-4767. doi: 10.3390/ijerph110504745
47. Fotiadis, C. I., Stoidis, C. N., Spyropoulos, B. G., and Zografos, E. D. (2008). Role of probiotics, prebiotics and synbiotics in chemoprevention for colorectal cancer. World J. Gastroenterol. 14, 6453-6457. doi: 10.3748/wjg.14.6453
48. Francescone, R., Hou, V., and Grivennikov, S. I. (2014). Microbiome, inflammation, and cancer. Cancer J. 20, 181-189. doi: 10.1097/PPO.0000000000000048
49. Fujiya, M., Musch, M. W., Nakagawa, Y., Hu, S., Alverdy, J., Kohgo, Y., et al. (2007). The Bacillus subtilis quorum-sensing molecule CSF contributes to intestinal homeostasis via OCTN2, a host cell membrane transporter. Cell Host Microbe 1, 299-308. doi: 10.1016/j.chom.2007.05.004
50. Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., et al. (2013). Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446-450. doi: 10.1038/nature12721
51. Ganapathy, V., Thangaraju, M., Prasad, P. D., Martin, P. M., and Singh, N. (2013). Transporters and receptors for short-chain fatty acids as the molecular link between colonic bacteria and the host. Curr. Opin. Pharmacol. 13, 869-874. doi: 10.1016/j.coph.2013.08.006
52. Gill, R. K., Saksena, S., Alrefai, W. A., Sarwar, Z., Goldstein, J. L., Carroll, R. E., et al. (2005). Expression and membrane localization of MCT isoforms along the length of the human intestine. Am. J. Physiol Cell Physiol. 289, C846-C852. doi: 10.1152/ajpcell.00112.2005
53. Gonçalves, P., Araújo, J. R., and Martel, F. (2011). Characterization of butyrate uptake by non transformed intestinal epithelial cell lines. J. Membr. Biol. 240, 35-46. doi: 10.1007/s00232-011-9340-3
54. Gopal, E., Fei, Y. J., Sugawara, M., Miyauchi, S., Zhuang, L., Martin, P., et al. (2004). Expression of slc5a8 in kidney and its role in Na+-coupled transport of lactate. J. Biol. Chem. 279, 44522-44532. doi: 10.1074/jbc.M405365200
55. Gratz, S. W., Mykkanen, H., and El-Nezami, H. S. (2010). Probiotics and gut health: a special focus on liver diseases. World J. Gastroenterol. 16, 403-410. doi: 10.3748/wjg.v16.i4.403
56. Grivennikov, S. I., Greten, F. R., and Karin, M. (2010). Immunity, inflammation, and cancer. Cell 140, 883-899. doi: 10.1016/j.cell.2010.01.025
57. Grivennikov, S. I., Wang, K., Mucida, D., Stewart, C. A., Schnabl, B., Jauch, D., et al. (2012). Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 491, 254-258.
58. Hijova, E., and Chmelarova, A. (2007). Short chain fatty acids and colonic health. Bratisl. Med. J. 108, 354-358.
59. Hinnebusch, B. F., Meng, S., Wu, J. T., Archer, S. Y., and Hodin, R. A. (2002). The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation. J. Nutr. 132, 1012-1017.
60. Hong, Y. H., Nishimura, Y., Hishikawa, D., Tsuzuki, H., Miyahara, H., Gotoh, C., et al. (2005). Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology 146, 5092-5099. doi: 10.1210/en.2005-0545
61. Hosseini, E., Grootaert, C., Verstraete, W., and Van de Wiele, T. (2011). Propionate as a health-promoting microbial metabolite in the human gut. Nutr. Rev. 69, 245-258. doi: 10.1111/j.1753-4887.2011.00388.x
62. Hsieh, M. L., and Chou, C. C. (2006). Mutagenicity and antimutagenic effect of soymilk fermented with lactic acid bacteria and bifidobacteria. Int. J. Food Microbiol. 111, 43-47. doi: 10.1016/j.ijfoodmicro.2006.04.034
63. Hu, S., Dong, T. S., Dalal, S. R., Wu, F., Bissonnette, M., Kwon, J. H., et al. (2011). The microbe-derived short chain fatty acid butyrate targets mirna-dependent p21 gene expression in human colon cancer. PLoS ONE 6:e16221. doi: 10.1371/journal.pone.0016221
64. Islam, R., Anzai, N., Ahmed, N., Ellapan, B., Jin, C. J., Srivastava, S., et al. (2008). Mouse organic anion transporter 2 (mOat2) mediates the transport of short chain fatty acid propionate. J. Pharmacol. Sci. 106, 525-528. doi: 10.1254/jphs.SC0070291
65. Iyer, C., Kosters, A., Sethi, G., Kunnumakkara, A. B., Aggarwal, B. B., and Versalovic, J. (2008). Probiotic Lactobacillus reuteri promotes TNF-induced apoptosis in human myeloid leukemia-derived cells by modulation of NFkB and MAPK signalling. Cell. Microbiol. 10, 1442-1452.
66. Jacobi, C. A., Grundler, S., Hsieh, C.-J., Frick, J. S., Adam, P., Lamprecht, G., et al. (2012). Quorum sensing in the probiotic bacterium Escherichia coli Nissle 1917 (Mutaflor)-evidence that furanosyl borate diester (AI-2) is influencing the cytokine expression in the DSS colitis mouse model. Gut Pathog. 4:8. doi: 10.1186/1757-4749-4-8
67. Jan, G., Belzacq, A. S., Haouzi, D., Rouault, A., Métivier, D., Kroemer, G., et al. (2002). Propionibacteria induce apoptosis of colorectal carcinoma cells via short-chain fatty acids acting on mitochondria. Cell Death. Differ. 9, 179-188. doi: 10.1038/sj.cdd.4400935
68. Jemal, A., Siegel, R., Xu, J., and Ward, E. (2010). Cancer statistics. CA Cancer J. Clin. 60, 277-300. doi: 10.3322/caac.20073
69. Johnson, C. H., Patterson, A. D., Idle, J. R., and Gonzalez, F. J. (2012). Xenobiotic metabolomics: major impact on the metabolome. Annu. Rev. Pharmacol. Toxicol. 52, 37-56. doi: 10.1146/annurev-pharmtox-010611-134748
70. Kaihara, T., Kawamata, H., Imura, J., Fujii, S., Kitajima, K., Omotehara, F., et al. (2003). Redifferentiation and ZO-1 reexpression in liver-metastasized colorectal cancer: possible association with epidermal growth factor receptor-induced tyrosine phosphorylation of ZO-1. Cancer Sci. 94, 166-172. doi: 10.1111/j.1349-7006.2003.tb01414.x
71. Kazemi Sefat, N. A., Mohammadi, M. M., Hadjati, J., Talebi, S., Ajami, M., and Daneshvar, H. (2015). The cytotoxicity of a short chain fatty acid histone deacetylase inhibitor on HCT116 human colorectal carcinoma cell line. MO J. Immunol. 2:00034.
72. Kechagia, M., Basoulis, D., Konstantopoulou, S., Dimitriadi, D., Gyftopoulou, K., Skarmoutsou, N., et al. (2013). Health benefits of probiotics: a review. ISRN Nutr. 2013:481651. doi: 10.5402/2013/481651
73. Kim, C. H., Park, J., and Kim, M. (2014). Gut microbiota-derived short-chain fatty acids, T cells, and inflammation. Immune Netw. 14, 277-288. doi: 10.4110/in.2014.14.6.277
74. Kim, J. U., Kim, Y., Han, K. S., Oh, S. J., Wang, K. Y., Kim, J. N., et al. (2006). Function of cell bound and released exopolysaccharides produced by Lactobacillus rhamnosus ATCC 9595. J. Microbiol. Biotechnol. 16, 939-945.
75. Kim, Y., Lee, D., Kim, D., Cho, J., Yang, J., Chung, M., et al. (2008). Inhibition of proliferation in colon cancer cell lines and harm ful enzyme activity of colon bacteria by Bifidobacterium adolescentis SPM0212. Arch. Pharm. Res. 1, 468-473. doi: 10.1007/s12272-001-1180-y
76. Kimura, I., Inoue, D., Maeda, T., Hara, T., Ichimura, A., Miyauchi, S., et al. (2011). Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc. Natl. Acad. Sci. U.S.A. 108, 8030-8035. doi: 10.1073/pnas.1016088108
77. Kostic, A. D., Chun, E., Robertson, L., Glickman, J. N., Gallini, C. A., Michaud, M., et al. (2013). Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14, 207-215. doi: 10.1016/j.chom.2013.07.007
78. Kumar, K. S., Sastry, N., Polaki, H., and Mishra, V. (2015). Colon cancer prevention through probiotics: an overview. J. Cancer Sci. Ther. 7, 081-092.
79. Kumar, M., Nagpal, R., Verma, V., Kumar, A., Kaur, N., Hemalatha, R., et al. (2013). Probiotic metabolites as epigenetic targets in the prevention of colon cancer. Nutr. Rev. 7, 23-34. doi: 10.1111/j.1753-4887.2012.00542.x
80. Kundu, J. K., and Surh, Y. L. (2012). Emerging avenues linking inflammation and cancer. Free Radic. Biol. Med. 52, 2013-2037. doi: 10.1016/j.freeradbiomed.2012.02.035
81. Lahtinen, S. J. (2012). Probiotic viability does it matter? Microb. Ecol. Health Dis. 23:18567.
82. Lambert, D. W., Wood, I. S., Ellis, A., and Shirazi-Beechey, S. P. (2002). Molecular changes in the expression of human colonic nutrient transporters during the transition from normality to malignancy. Br. J. Cancer 86, 1262-1269. doi: 10.1038/sj.bjc.6600264
83. Lan, A., Lagadic-Gossmann, D., Lemaire, C., Brenner, C., and Jan, G. (2007). Acidic extracellular pH shifts colorectal cancer cell death from apoptosis to necrosis upon exposure to propionate and acetate, major end-products of the human probiotic propionibacteria. Apoptosis 12, 573-591. doi: 10.1007/s10495-006-0010-3
84. Lankaputhra, W. E. V., and Shah, N. P. (1998). Antimutagenic properties of probiotic bacteria and of organic acids. Mutat. Res. 397, 169-182. doi: 10.1016/S0027-5107(97)00208-X
85. Le Marechal, C., Peton, V., Ple, C., Vroland, C., Jardin, J., Briard-Bion, V., et al. (2014). Surface proteins of Propionibacterium freudenreichii are involved in its anti-inflammatory properties. J. Proteomics 113, 447-461. doi: 10.1016/j.jprot.2014.07.018
86. Le Poul, E., Loison, C., Struyf, S., Springael, J. Y., Lannoy, V., Decobecq, M. E., et al. (2003). Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J. Biol. Chem. 278, 25481-25489. doi: 10.1074/jbc.M301403200
87. Lee, D. K., Jang, S., Kim, M. J., Kim, J. H., Chung, M. J., Kim, K. J., et al. (2008). Anti-proliferative effects of Bifidobacterium adolescentis SPM0212 extract on human colon cancer cell lines. BMC Cancer 8:310. doi: 10.1186/1471-2407-8-310
88. Leeman, M. F., Curran, S., and Murray, G. I. (2003). Newinsights into the roles of matrix metalloproteinases in colorectal cancer development and progression. J. Pathol. 201, 528-534. doi: 10.1002/path.1466
89. Li, H., Myeroff, L., Smiraglia, D., Romero, M. F., Pretlow, T. P., Kasturi, L., et al. (2003). SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proc. Natl. Acad. Sci. U.S.A. 100, 8412-8417. doi: 10.1073/pnas.1430846100
90. Liboredo, J. C., Anastacio, L. R., Mattos, L. V., Nicoli, J. R., and Correia, M. I. (2010). Impact of probiotic supplementation on mortality of induced 1, 2-dimethylhydrazine carcinogenesis in a mouse model. Nutrition 26, 779-783. doi: 10.1016/j.nut.2010.01.008
91. Licciardi, P. V., Wong, S. S., Tang, M. L. K., and Karagiannis, T. C. (2010). Epigenome targeting by probiotic metabolites. Gut Pathog. 2:24. doi: 10.1186/1757-4749-2-24
92. Liong, M. T. (2008). Roles of probiotics and prebiotics in colon cancer prevention: postulated mechanisms and in-vivo evidence. Int. J. Mol. Sci. 9, 854-863. doi: 10.3390/ijms9050854
93. Louis, P., and Flint, H. J. (2009). Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol. Lett. 294, 1-8. doi: 10.1111/j.1574-6968.2009.01514.x
94. Lupton, J. R. (2000). Is fiber protective against colon cancer? Where the research is leading us. Nutrition 16, 558-561. doi: 10.1016/S0899-9007(00)00350-6
95. Ma, E. L., Choi, Y. J., Choi, J., Pothoulakis, C., Rhee, S. H., and Im, E. (2010). The anticancer effect of probiotic Bacillus polyfermenticus on human colon cancer cells is mediated through ErbB2 and ErbB3 inhibition. Int. J. Cancer 127, 780-790.
96. Maier, S., Daroqui, M. C., Scherer, S., Roepcke, S., Velcich, A., Shenoy, S. M., et al. (2009). Butyrate and vitamin D3 induce transcriptional attenuation at the cyclin D1 locus in colonic carcinoma cells. J. Cell. Physiol. 218, 638-642. doi: 10.1002/jcp.21642
97. Matsuguchi, T., Takagi, A., Matsuzaki, T., Nagaoka, M., Ishikawa, K., Yokokura, T., et al. (2003). Lipoteichoic acids from Lactobacillus strains elicit strong tumor necrosis factor a-inducing activities in macrophages through Toll-like receptor 2. Clin. Diagn. Lab. Immunol. 10, 259-266.
98. Matsumoto, S., Hara, T., Nagaoka, M., Mike, A., Mitsuyama, K., Sako, T., et al. (2008). A component of polysaccharide peptidoglycan complex on Lactobacillus induced an improvement of murine model of inflammatory bowel disease and colitis-associated cancer. Immunology 128(1 Suppl.), e170-e180. doi: 10.1111/j.1365-2567.2008.02942.x
99. Medina, V., Young, G. P., Edmonds, B., James, R., Appleton, S., and Zalewski, P. D. (1997). Induction of caspase-3 protease activity and apoptosis by butyrate and trichostatin a (inhibitors of histone deacetylase): dependence on protein synthesis and synergy with a mitochondrial/cytochrome C-dependent pathway. Cancer Res. 57, 3697-3707.
100. Menard, S., Candalh, C., Bambou, J. C., Terpend, K., Cerf-Bensussan, N., and Heyman, M. (2004). Lactic acid bacteria secrete metabolites retaining anti-inflammatory properties after intestinal transport. Gut 53, 821-828. doi: 10.1136/gut.2003.026252
101. Mitsuma, T., Odajima, H., Momiyama, Z., Watanabe, K., Masuguchi, M., Sekine, T., et al. (2008). Enhancement of gene expression by a peptide (CHWPR) produced by Bifidobacterium lactis BB-12. Microbiol. Immunol. 52, 144-155. doi: 10.1111/j.1348-0421.2008.00022.x
102. Miyauchi, S., Gopal, E., Fei, Y. J., and Ganapathy, V. (2004). Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na+-coupled transporter for short-chain fatty acids. J. Biol. Chem. 279, 13293-13296. doi: 10.1074/jbc.C400059200
103. Mook, O. R., Frederiks, W. M., and Van Noorden, C. J. (2004). The role of gelatinases in colorectal cancer progression and metastasis. Biochim. Biophys. Acta 1705, 69-89.
104. Nadathur, S. R., Gould, S. J., and Bakalinsky, A. T. (1995). Antimutagenicity of an acetone extract of yogurt. Mutat. Res. 334, 213-224. doi: 10.1016/0165-1161(95)90014-4
105. Nami, Y., Haghshenas, B., Haghshenas, M., Abdullah, N., and Yari, K. A. (2015). The prophylactic effect of probiotic Enterococcus lactis IW5 against different human cancer cells. Front. Microbiol. 6:1317. doi: 10.3389/fmicb.2015.01317
106. Narayanan, A., Baskaran, S. A., Amalaradjou, M. A., and Venkitanarayanan, K. (2015). Anticarcinogenic properties of medium chain fatty acids on human colorectal, skin and breast cancer cells in vitro. Int. J. Mol. Sci. 16, 5014-5027. doi: 10.3390/ijms16035014
107. Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., et al. (2012). Host-gut microbiota metabolic interactions. Science 336, 1262-1267. doi: 10.1126/science.1223813
108. Nilsson, N. E., Kotarsky, K., Owman, C., and Olde, B. (2003). Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem. Biophys. Res. Commun. 303, 1047-1052. doi: 10.1016/S0006-291X(03)00488-1
109. Ohishi, A., Takahashi, S., Ito, Y., Tsukamoto, K., Nanba, Y., Ito, N., et al. (2010). Bifidobacterium septicemia associated with postoperative probiotic therapy in a neonate with omphalocele. J. Pediatrics 156, 679-681. doi: 10.1016/j.jpeds.2009.11.041
110. Ohtani, S., Terashima, M., Satoh, J., Soeta, N., Saze, Z., Kashimura, S., et al. (2009). Expression of tight-junction-associated proteins in human gastric cancer: downregulation of claudin-4 correlates with tumor aggressiveness and survival. Gastric Cancer 12, 43-51. doi: 10.1007/s10120-008-0497-0
111. Orlando, A., Messa, C., Linsalata, M., Cavallini, A., and Russo, F. (2009). Effects of Lactobacillus rhamnosus GG on proliferation and polyamine metabolism in HGC-27 human gastric and DLD-1 colonic cancer cell lines. Immunopharmacol. Immunotoxicol. 31, 108-116. doi: 10.1080/08923970802443631
112. Pan, X., Yang, Y., and Zhang, J. R. (2014). Molecular basis of host specificity in human pathogenic bacteria. Emerg. Microbes Infect. 3:e23. doi: 10.1038/emi.2014.23
113. Papadimitriou, K., Zoumpopoulou, G., Foligné, B., Alexandraki, V., Kazou, M., Pot, B., et al. (2015). Discovering probiotic microorganisms: in vitro, in vivo, genetic and omics approaches. Front. Microbiol. 6:58. doi: 10.3389/fmicb.2015.00058
114. Park, J., Kim, M., Kang, S. G., Jannasch, A. H., Cooper, B., Patterson, J., et al. (2015). Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol. 8, 80-93. doi: 10.1038/mi.2014.44
115. Patel, R. M., Myers, L. S., Kurundkar, A. R., Maheshwari, A., Nusrat, A., and Lin, P. W. (2012). Probiotic bacteria induce maturation of intestinal claudin 3 expression and barrier function. Am. J. Pathol. 180, 626-635. doi: 10.1016/j.ajpath.2011.10.025
116. Peng, L., Li, Z. R., Green, R. S., Holzman, I. R., and Lin, J. (2009). Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J. Nutr. 139, 1619-1625. doi: 10.3945/jn.109.104638
117. Pool-Zobel, B. L. (2005). Inulin-type fructans and reduction in colon cancer risk: review of experimental and human data. Br. J. Nutr. 93, S73-S90. doi: 10.1079/BJN20041349
118. Pool-Zobel, B. L., and Sauer, J. (2007). Overview of experimental data on reduction of colorectal cancer risk by inulin-type fructans. J. Nutr. 137, 2580S-2584S.
119. Putaala, H., Salusjärvi, T., Nordström, M., Saarinen, M., Ouwehand, A. C., Bech Hansen, E., et al. (2008). Effect of four probiotic strains and Escherichia coli O157:H7 on tight junction integrity and cyclo-oxygenase expression. Res. Microbiol. 159, 692-698. doi: 10.1016/j.resmic.2008.08.002
120. Raman, M., Ambalam, P., Kondepudi, K. K., Pithva, S., Kothari, C., Patel, A. T., et al. (2013). Potential of probiotics, prebiotics and synbiotics for management of colorectal cancer. Gut Microbes 4, 181-192. doi: 10.4161/gmic.23919
121. Rao, R. K., and Samak, G. (2013). Protection and restitution of gut barrier by probiotics: nutritional and clinical implications. Curr. Nutr. Food Sci. 9, 99-107. doi: 10.2174/1573401311309020004
122. Rhee, C. H., and Park, H. D. (2001). Three glycoproteins with antimutagenic activity identified in Lactobacillus plantarum KLAB21. Appl. Environ. Microbiol. 67, 3445-3449. doi: 10.1128/AEM.67.8.3445-3449.2001
123. Roda, A., Simoni, P., Magliulo, M., Nanni, P., Baraldini, M., Roda, G., et al. (2007). A new oral formulation for the release of sodium butyrate in the ileocecal region and colon. World J. Gastroenterol. 13, 1079-1084. doi: 10.3748/wjg.v13.i7.1079
124. Round, J. L., and Mazmanian, S. K. (2010). Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc. Natl. Acad. Sci. U.S.A. 107, 12204-12209. doi: 10.1073/pnas.0909122107
125. Ruemmele, F. M., Schwartz, S., Seidman, E. G., Dionne, S., Levy, E., and Lentze, M. J. (2003). Butyrate induced Caco-2 cell apoptosis is mediated via the mitochondrial pathway. Gut 52, 94-100. doi: 10.1136/gut.52.1.94
126. Sadeghi-Aliabadi, H., Mohammadi, F., Fazeli, H., and Mirlohi, M. (2014). Effects of Lactobacillus plantarum A7 with probiotic potential on colon cancer and normal cells proliferation in comparison with a commercial strain. Iran J. Basic Med. Sci. 17, 815-819.
127. Saldanha, S. N., Kalaa, R., and Tollefsbol, T. O. (2014). Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate. Exp. Cell Res. 324, 40-53. doi: 10.1016/j.yexcr.2014.01.024
128. Sankpal, U. T., Pius, H., Khan, M., Shukoor, M. I., Maliakal, P., Lee, C. M., et al. (2012). Environmental factors in causing human cancers: emphasis on tumorigenesis. Tumour Biol. 33, 1265-1274. doi: 10.1007/s13277-012-0413-4
129. Scharlau, D., Borowicki, A., and Habermann, N. (2009). Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. Mutat. Res. 682, 39-53. doi: 10.1016/j.mrrev.2009.04.001
130. Sears, C. L. (2009). Enterotoxigenic Bacteroides fragilis: a rogue among symbiotes. Clin. Microbiol. Rev. 22, 349-369. doi: 10.1128/CMR.00053-08
131. Segawa, S., Fujiya, M., Konishi, H., Ueno, N., Kobayashi, N., Shigyo, T., et al. (2011). Probiotic-derived polyphosphate enhances the epithelial barrier function and maintains intestinal homeostasis through integrin-p38 MAPK pathway. PLoS ONE 6:e23278. doi: 10.1371/journal.pone.0023278
132. Sellin, J. H. (1999). SCFAs: the enigma of weak electrolyte transport in the colon. News Physiol. Sci. 14, 58-64.
133. Seth, A., Yan, F., Polk, D. B., and Rao, R. K. (2008). Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC-and MAP kinase-dependent mechanism. Am. J. Physiol. Gastrointest. Liver Physiol. 294, G1060-G1069. doi: 10.1152/ajpgi.00202.2007
134. Sevda, E. R., Koparal, A. T., and Kivan, M. (2015). Cytotoxic effects of various lactic acid bacteria on Caco-2 cells. Turk. J. Biol. 39, 23-30. doi: 10.3906/biy-1402-62
135. Shenderov, B. A. (2011). Probiotic (symbiotic) bacterial languages. Anaerobe 17, 490-495. doi: 10.1016/j.anaerobe.2011.05.009
136. Shenderov, B. A. (2013). Metabiotics: novel idea or natural development of probiotic conception. Microb. Ecol. Health Dis. 24:20399.
137. Shin, H. J., Anzai, N., Enomoto, A., He, X., Kim, D. K., Endou, H., et al. (2007). Novel liver-specific organic anion transporter OAT7 that operates the exchange of sulfate conjugates for short chain fatty acid butyrate. Hepatology 45, 1046-1055. doi: 10.1002/hep.21596
138. Shyu, P. T., Oyong, G. G., and Cabrera, E. C. (2014). Cytotoxicity of probiotics from philippine commercial dairy products on cancer cells and the effect on expression of cfos and cjun early apoptotic-promoting genes and interleukin-1β and tumor necrosis factor-a proinflammatory cytokine genes. BioMed Res. Int. 9:491740.
139. Sina, C. O., Gavrilova, M., Forster, M., Till, A., Derer, S., Hildebrand, F., et al. (2009). G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation. J. Immunol. 183, 7514-7522. doi: 10.4049/jimmunol.0900063
140. Singh, N., Gurav, A., Sivaprakasam, S., Brady, E., Padia, R., Shi, H., et al. (2014). Activation of the receptor (Gpr109a) for niacin and the commensal metabolite butyrate suppresses colonic inflammation and carcinogenesis. Immunity 40, 128-139. doi: 10.1016/j.immuni.2013.12.007
141. Singh, N., Thangaraju, M., Prasad, P. D., Martin, P. M., Lambert, N. A., Boettger, T., et al. (2010). Blockade of dendritic cell development by bacterial fermentation products butyrate and propionate through a transporter (Slc5a8)-dependent inhibition of histone deacetylases. J. Biol. Chem. 285, 27601-27608. doi: 10.1074/jbc.M110.102947
142. Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly, Y. M., et al. (2013). The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569-573. doi: 10.1126/science.1241165
143. Snydman, D. R. (2008). The safety of probiotics. Clin. Infect. Dis. 46, S104-S111. doi: 10.1086/523331
144. Sokol, H., Pigneur, B., Watterlot, L., Lakhdari, O., Bermúdez-Humarán, L. G., Gratadoux, J. J., et al. (2008). Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn's disease patients. Proc. Natl. Acad. Sci. U.S.A. 105, 16731-16736. doi: 10.1073/pnas.0804812105
145. Song, C. H., Liu, Z. Q., Huang, S., Zheng, P. Y., and Yang, P. C. (2012). Probiotics promote endocytic allergen degradation in gut epithelial cells. Biochem. Biophys. Res. Commun. 426, 135-140. doi: 10.1016/j.bbrc.2012.08.051
146. Sougioultzis, S., Simeonidis, S., Bhaskar, K. R., Chen, X., Anton, P. M., Keates, S., et al. (2006). Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NFkB-mediated IL-8 gene expression. Biochem. Biophys. Res. Commun. 343, 69-76.
147. Sparmann, A., and Bar-Sagi, D. (2004). Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell 6, 447-458. doi: 10.1016/j.ccr.2004.09.028
148. Stein, J., Schroder, O., Bonk, M., Oremek, G., Lorenz, M., and Caspary, W. F. (1996). Induction of glutathione-S-transferase-pi by short-chain fatty acids in the intestinal cell line Caco-2. Eur. J. Clin. Invest. 26, 84-87. doi: 10.1046/j.1365-2362.1996.113252.x
149. Switzer, C. H., Glynn, S. A., Ridnour, L. A., Cheng, R. Y., Vitek, M. P., Ambs, S., et al. (2011). Nitric oxide and protein phosphatase 2A provide novel therapeutic opportunities in ER-negative breast cancer. Trends Pharmacol. Sci. 32, 644-651. doi: 10.1016/j.tips.2011.07.001
150. Tang, Y., Chen, Y., Jiang, H., and Nie, D. (2011a). The role of short-chain fatty acids in orchestrating two types of programmed cell death in colon cancer. Autophagy 7, 235-237. doi: 10.4161/auto.7.2.14277
151. Tang, Y., Chen, Y., Jiang, H., Robbins, G. T., and Nie, D. (2011b). G-protein-coupled receptor for short-chain fatty acids suppresses colon cancer. Int. J. Cancer 128, 847-856. doi: 10.1002/ijc.25638
152. Thangaraju, M., Cresci, G., Itagaki, S., Mellinger, J., Browning, D. D., Berger, F. G., et al. (2008). Sodium-coupled transport of the short chain fatty acid butyrate by SLC5A8 and its relevance to colon cancer. J. Gastrointest. Surg. 12, 1773-1781. doi: 10.1007/s11605-008-0573-0
153. Thomas, C. M., and Versalovic, J. (2010). Probiotics-host communication; Modulation of signaling pathways in the intestine. Gut Microbes. 1, 148-163. doi: 10.4161/gmic.1.3.11712
154. Tobioka, H., Isomura, H., Kokai, Y., Tokunaga, Y., Yamaguchi, J., Sawada, N., et al. (2004). Occludin expression decreases with the progression of human endometrial carcinoma. Hum. Pathol. 35, 159-164. doi: 10.1016/j.humpath.2003.09.013
155. Topping, D. L., and Clifton, P. M. (2001). Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol. Rev. 81, 1031-1064.
156. Treptow-van, L. S., Rechkemmer, G., Rowland, I., Dolara, P., and Pool-Zobel, B. L. (1999). The carbohydrate crystalean and colonic microflora modulate expression of glutathione S-transferase subunits in colon of rats. Eur. J. Nutr. 38, 76-83. doi: 10.1007/s003940050047
157. Tsuda, H., Hara, K., and Miyamoto, T. (2008). Binding of mutagens to exopolysaccharide produced by Lactobacillus plantarum mutant strain 301102S. J. Dairy Sci. 91, 2960-2966. doi: 10.3168/jds.2007-0538
158. Uccello, M., Malaguarnera, G., Basile, F., D'agata, V., Malaguarnera, M., Bertino, G., et al. (2012). Potential role of probiotics on colorectal cancer prevention. BMC Surg. 12(Suppl. 1):S35. doi: 10.1186/1471-2482-12-S1-S35
159. Urbanska, A. M., Bhathena, J., Martoni, C., and Prakash, S. (2009). Estimation of the potential antitumor activity of microencapsulated Lactobacillus acidophilus yogurt formulation in the attenuation of tumorigenesis in Apc(Min/+) mice. Dig. Dis. Sci. 54, 264-273. doi: 10.1007/s10620-008-0363-2
160. Van Reenen, C. A., and Dicks, L. M. T. (2011). Horizontal gene transfer amongst probiotic lactic acid bacteria and other intestinal microbiota: what are the possibilities? A review. Arch. Microbiol. 193, 157-168. doi: 10.1007/s00203-010-0668-3
161. Verma, A., and Shukla, G. (2013). Administration of prebiotic inulin suppresses 1, 2 dimethylhydrazine dihydrochloride induced procarcinogenic biomarkers fecal enzymes and preneoplastic lesions in early colon carcinogenesis in Sprague Dawley rats. J. Funct. Foods 5, 991-996. doi: 10.1016/j.jff.2013.02.006
162. Verma, A., and Shukla, G. (2014). Synbiotic (Lactobacillus rhamnosus+Lactobacillus acidophilus+inulin) attenuates oxidative stress and colonic damage in 1, 2 dimethylhydrazine dihydrochloride-induced colon carcinogenesis in Sprague-Dawley rats: a long-term study. Eur. J. Cancer Prev. 23, 550-559. doi: 10.1097/CEJ.0000000000000054
163. Verma, A., and Shukla, G. (2015). Modulation of apoptosis and immune response by synbiotic in experimental colorectal cancer. Int. J. Pharm. Biol. Sci. 6, 529-543.
164. Verna, E. C., and Lucak, S. (2010). Use of probiotics in gastrointestinal disorders: what to recommend? Therap. Adv. Gastroenterol. 3, 307-319. doi: 10.1177/1756283X10373814
165. Vernia, P., Cittadini, M., Caprilli, R., and Torsoli, A. (1995). Topical treatment of refractory distal ulcerative colitis with 5-ASA and sodium butyrate. Dig. Dis. Sci. 40, 305-307. doi: 10.1007/BF02065414
166. Vieira, E. L., Leonel, A. J., Sad, A. P., Beltrão, N. R., Costa, T. F., Ferreira, T. M., et al. (2012). Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis. J. Nutr. Biochem. 23, 430-436. doi: 10.1016/j.jnutbio.2011.01.007
167. Vinolo, M. A., Rodrigues, H. G., Hatanaka, E., Sato, F. T., Sampaio, S. C., and Curi, R. (2011). Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. J. Nutr. Biochem. 22, 849-855. doi: 10.1016/j.jnutbio.2010.07.009
168. Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., and Kinzler, K. W. (2013). Cancer genome landscapes. Science 339, 1546-1558. doi: 10.1126/science.1235122
169. Waldecker, M., Kautenburger, T., Daumann, H., Busch, C., and Schrenk, D. (2008). Inhibition of histone-deacetylase activity by short chain fatty acids and some polyphenol metabolites formed in the colon. J. Nutr. Biochem. 19, 587-593. doi: 10.1016/j.jnutbio.2007.08.002
170. Wan, Y., Xin, Y., Zhang, C., Wu, D., Ding, D., Tang, L., et al. (2014). Fermentation supernatants of Lactobacillus delbrueckii inhibit growth of human colon cancer cells and induce apoptosis through a caspase 3-dependent pathway. Oncol. Lett. 7, 1738-1742.
171. Wang, F., Graham, W. V., Wang, Y., Witkowski, E. D., Schwarz, B. T., and Turner, J. R. (2005). Interferon-gamma and tumor necrosis factor-alpha synergize to induce intestinal epithelial barrier dysfunction by up-regulating myosin light chain kinase expression. Am. J. Pathol. 166, 409-419. doi: 10.1016/S0002-9440(10)62264-X
172. Wang, L., Cao, H., Liu, L., Wang, B., Walker, W. A., Acra, S. A., et al. (2014). Activation of epidermal growth factor receptor mediates mucin production stimulated by p40, a Lactobacillus rhamnosus GG-derived protein. J. Biol. Chem. 289, 20234-20244. doi: 10.1074/jbc.M114.553800
173. Wang, Y., Kirpich, I., Liu, Y., Ma, Z., Barve, S., Mc Clain, C. J., et al. (2011). Lactobacillus rhamnosus GG treatment potentiates intestinal hypoxia-inducible factor, promotes intestinal integrity and ameliorates alcohol-induced liver injury. Am. J. Pathol. 79, 2866-2875. doi: 10.1016/j.ajpath.2011.08.039
174. Wang, Y., Liu, Y., Sidhu, A., Ma, Z., Mc Clain, C., and Feng, W. (2012). Lactobacillus rhamnosus GG culture supernatant ameliorates acute alcohol-induced intestinal permeability and liver injury. Am. J. Physiol. Gastrointest. Liver Physiol. 303, G32-G41. doi: 10.1152/ajpgi.00024.2012
175. Wollowski, I. (1998). Studies on the Protective Effects of Bacterial Metabolites on Molecular Processes of Colon Carcinogenesis. Giessen: Fachverlag Kohler.
176. Wollowski, I., Rechkemmer, G., and Pool-Zobel, B. L. (2001). Protective role of probiotics and prebiotics in colon cancer. Am. J. Clin. Nutr. 73, 451S-455S.
177. Wu, G. D., Huang, N., Wen, X., Keilbaugh, S. A., and Yang, H. (1999). High-level expression of IkB-bin the surface epithelium of the colon: in vitro evidence for an immunomodulatory role. J. Leukoc. Biol. 66, 1049-1056.
178. Wu, S., Rhee, K. J., Albesiano, E., Rabizadeh, S., Wu, X., Yen, H. R., et al. (2009). A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat. Med. 15, 1016-1022. doi: 10.1038/nm.2015
179. Xiong, Y., Miyamoto, N., Shibata, K., Valasek, M. A., Motoike, T., Kedzierski, R. M., et al. (2004). Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proc. Natl. Acad. Sci. U.S.A. 101, 1045-1050. doi: 10.1073/pnas.2637002100
180. Yan, F., Cao, H., Cover, T. L., Washington, M. K., Shi, Y., Liu, L., et al. (2011). Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism. J. Clin. Investig. 121, 2242-2253. doi: 10.1172/JCI44031
181. Yan, F., Cao, H., Cover, T. L., Whitehead, R., Washington, M. K., and Polk, D. B. (2007). Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology 132, 562-575. doi: 10.1053/j.gastro.2006.11.022
182. Yazdankhah, S. P., Midtvedt, T., Narvhus, J. A., Berstad, A., Lassen, J., and Halvorsen, R. (2009). The use of probiotics for critically ill patients in hospitals. Microb. Ecol. Health Dis. 21, 114-121. doi: 10.3109/08910600903495046
183. Yu, D. C., Waby, J. S., Chirakkal, H., Staton, C. A., and Corfe, B. M. (2010). Butyrate suppresses expression of neuropilin I in colorectal cell lines through inhibition of Sp1 transactivation. Mol. Cancer. 9:276. doi: 10.1186/1476-4598-9-276
184. Yu Danny, C., Bury, J. P., Tiernan, J., Waby, J. S., Staton, C. A., and Corfe, B. M. (2011). Short-chain fatty acid level and field cancerization show opposing associations with enteroendocrine cell number and neuropilin expression in patients with colorectal adenoma. Mol. Cancer. 10:27. doi: 10.1186/1476-4598-10-27
185. Zakostelska, Z., Kverka, M., Klimesova, K., Rossmann, P., Mrazek, J., Kopecny, J., et al. (2011). Lysate of probiotic Lactobacillus casei DN-114 001 ameliorates colitis by strengthening the gut barrier function and changing the gut microenvironment. PLoS ONE 6:e27961. doi: 10.1371/journal.pone.0027961
186. Zeng, H., Lazarova, D. L., and Bordonaro, M. (2014). Mechanisms linking dietary fiber, gut microbiota and colon cancer prevention. World J. Gastrointest. Oncol. 6, 41-51. doi: 10.4251/wjgo.v6.i2.41
187. Zhong, L., Zhang, X., and Covasa, M. (2014). Emerging roles of lactic acid bacteria in protection against colorectal cancer. World J. Gastroenterol. 20, 7878-7886. doi: 10.3748/wjg.v20.i24.7878