OJGas  Vol.5 No.10 , October 2015
Inflammatory Bowel Diseases: What Do We Still Need to Investigate?
ABSTRACT
Inflammatory bowel disease (IBD) including Crohn (CD) and ulcerative colitis (UC), is intestinal disorders with an unknown specific etiology. Many factors are involved in the pathogenesis: genetic, environment, nutrition, immunity and intestinal dysbiosis. In the present work, we review the most important trigger mechanisms involved in IBD, with a particular regard to the role of microbiota and fecal mass transplantation as a new therapeutic approach, that even if it can be considered safe and effective, data are necessary regarding all procedures not yet standardized and timing of treatment.

Cite this paper
Taus, M. , Busni, D. , Fumelli, D. , Paci, A. , Nicolai, G. and Nicolai, A. (2015) Inflammatory Bowel Diseases: What Do We Still Need to Investigate?. Open Journal of Gastroenterology, 5, 146-154. doi: 10.4236/ojgas.2015.510024.
References
[1]   Levine, A. and Wine, E. (2013) Effects of Enteral Nutrition on Crohn’s Disease: Clues to the Impact of Diet on Disease Pathogenesis. Inflammatory Bowel Diseases, 19, 1322-1329.
http://dx.doi.org/10.1097/MIB.0b013e3182802acc

[2]   Riordan, A.M., Hunter, J.O., Cowan, R.E., Crampton, J.R., Davidson, A.R., Dickinson, R.J., Dronfield, M.W., Fellows, I.W., Hishon, S., Kerrigan, G.N., et al. (1993) Treatment of Ac-tive Crohn’s Disease by Exclusion Diet: East Anglian Multicentre Controlled Trial. The Lancet, 342, 1131-1134.
http://dx.doi.org/10.1016/0140-6736(93)92121-9

[3]   Gibson, P.R. and Shepherd, S.J. (2005) Personal View: Food for Thought—Western Lifestyle and Susceptibility to Crohn’s Disease. The FODMAP Hypothesis. Alimentary Pharmacology & Therapeutics, 21, 1399-1409.
http://dx.doi.org/10.1111/j.1365-2036.2005.02506.x

[4]   Gearry, R.B., Irving, P.M., Barrett, J.S., Nathan, D.M., Shepherd, S.J. and Gibson, P.R. (2009) Reduction of Dietary Poorly Absorbed Short-Chain Carbohydrates (FODMAPs) Improves Abdominal Symptoms in Patients with Inflammatory Bowel Disease—A Pilot Study. Journal of Crohn’s and Colitis, 3, 8-14.
http://dx.doi.org/10.1016/j.crohns.2008.09.004

[5]   Danese, S. and Fiocchi, C. (2006) Etiopathogenesis of Inflammatory Bowel Diseases. World Journal of Gastroenterology, 12, 4807-4812.

[6]   David, L.A., Maurice, C.F., Carmody, R.N., Gootenberg, D.B., Button, J.E., Wolfe, B.E., Ling, A.V., Devlin, A.S., Varma, Y., Fischbach, M.A., Biddinger, S.B., Dutton, R.J. and Turnbaugh, P.J. (2014) Diet Rapidly and Reproducibly Alters the Human Gut Microbiome. Nature, 505, 559-563.
http://dx.doi.org/10.1038/nature12820

[7]   Cadwell, K., Patel, K.K., Maloney, N.S., Liu, T.C., Ng, A.C., Storer, C.E., Head, R.D., Xavier, R., Stappenbeck, T.S. and Virgin, H.W. (2010) Virus-Plus-Susceptibility Gene Interaction Determines Crohn’s Disease Gene Atg16L1 Phenotypes in Intestine. Cell, 141, 1135-1145.
http://dx.doi.org/10.1016/j.cell.2010.05.009

[8]   Caprilli, R., Lapaquette, P. and Darfeuille-Michaud, A. (2010) Eating the Enemy in Crohn’s Disease: An Old Theory Revisited. Journal of Crohn’s and Colitis, 4, 377-383.
http://dx.doi.org/10.1016/j.crohns.2010.05.007

[9]   Cho, J.H. (2008) The Genetics and Immunopathogenesis of Inflammatory Bowel Disease. Nature Reviews Immunology, 8, 458-466.
http://dx.doi.org/10.1038/nri2340

[10]   Lee, G. and Buchman, A.L. (2009) DNA-Driven Nutritional Therapy of Inflammatory Bowel Disease. Nutrition, 25, 885-891.
http://dx.doi.org/10.1016/j.nut.2009.06.011

[11]   Zhou, S.F., Lim, L.Y. and Chowbay, B. (2004) Herbal Modulation of P-Glycoprotein. Drug Metabolism Reviews, 36, 57-104.
http://dx.doi.org/10.1081/DMR-120028427

[12]   Guagnozzi, D., González-Castillo, S., Olveira, A. and Lucendo, A.J. (2012) Nutritional Treatment in Inflammatory Bowel Disease. An Update. Revista Espanola de Enfermedades Digestivas, 104, 479-488.
http://dx.doi.org/10.4321/S1130-01082012000900006

[13]   Ventham, N.T., Kennedy, N.A., Nimmo, E.R. and Satsangi, J. (2013) Beyond Gene Discovery in Inflammatory Bowel Disease: The Emerging Role of Epigenetics. Gastroenterology, 145, 293-308.
http://dx.doi.org/10.1053/j.gastro.2013.05.050

[14]   Clayburgh, D.R., Shen, L. and Turner, J.R. (2004) A Porous Defense: The Leaky Epithelial Barrier in Intestinal Disease. Laboratory Investigation, 84, 282-291.
http://dx.doi.org/10.1038/labinvest.3700050

[15]   Collett, A., Higgs, N.B., Gironella, M., Zeef, L.A., Hayes, A., Salmo, E., Haboubi, N., Iovanna, J.L., Carlson, G.L. and Warhurst, G. (2008) Early Molecular and Functional Changes in Colonic Epithelium That Precede Increased Gut Permeability during Colitis Development in Mdr1a(-/-) Mice. Inflammatory Bowel Diseases, 14, 620-631.
http://dx.doi.org/10.1002/ibd.20375

[16]   Clemente, J.C., Ursell, L.K., Parfrey, L.W. and Knight, R. (2012) The Impact of the Gut Microbiota on Human Health: An Integrative View. Cell, 148, 1258-1270.
http://dx.doi.org/10.1016/j.cell.2012.01.035

[17]   Vetrano, S., Rescigno, M., Cera, M.R., Correale, C., Rumio, C., Doni, A., Fantini, M., Sturm, A., Borroni, E., Repici, A., Locati, M., Malesci, A., Dejana, E. and Danese, S. (2008) Unique Role of Junctional Adhesion Molecule-A in Maintaining Mucosal Homeostasis in Inflammatory Bowel Disease. Gastroenterology, 135, 173-184.
http://dx.doi.org/10.1053/j.gastro.2008.04.002

[18]   Sartor, R.B. (2008) Microbial Influences in Inflammatory Bowel Diseases. Gastroenterology, 134, 577-594.
http://dx.doi.org/10.1053/j.gastro.2007.11.059

[19]   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. The American Journal of Pathology, 166, 409-419.
http://dx.doi.org/10.1016/S0002-9440(10)62264-X

[20]   Lomer, M.C., Harvey, R.S., Evans, S.M., Thompson, R.P. and Powell, J.J. (2001) Efficacy and Tolerability of a Low Microparticle Diet in a Double Blind, Randomized, Pilot Study in Crohn’s Disease. European Journal of Gastroenterology & Hepatology, 13, 101-106.
http://dx.doi.org/10.1097/00042737-200102000-00003

[21]   Barrett, J.C., Hansoul, S., Nicolae, D.L., Cho, J.H., Duerr, R.H., Rioux, J.D., Brant, S.R., Silverberg, M.S., et al. (2008) Genome-Wide Association Defines More than 30 Distinct Susceptibility Loci for Crohn’s Disease. Nature Genetics, 40, 955-962.
http://dx.doi.org/10.1038/ng.175

[22]   Peeters, H., Bogaert, S., Laukens, D., Rottiers, P., De Keyser, F., Darfeuille-Michaud, A., Glasser, A.L., Elewaut, D. and De Vos, M. (2007) CARD15 Variants Determine a Disturbed Early Response of Monocytes to Adherent-Invasive Escherichia coli Strain LF82 in Crohn’s Disease. International Journal of Immunogenetics, 34, 181-191.
http://dx.doi.org/10.1111/j.1744-313X.2007.00670.x

[23]   Cho, J.H. and Weaver, C.T. (2007) The Genetics of Inflammatory Bowel Disease. Gastroenterology, 133, 1327-1339.
http://dx.doi.org/10.1053/j.gastro.2007.08.032

[24]   Kao, D., Hotte, N., Gillevet, P. and Madsen, K. (2014) Fecal Microbiota Transplantation Inducing Remission in Crohn’s Colitis and the Associated Changes in Fecal Microbial Profile. Journal of Clinical Gastroenterology, 48, 625-628.
http://dx.doi.org/10.1097/MCG.0000000000000131

[25]   Wine, E., Ossa, J.C., Gray-Owen, S.D. and Sherman, P.M. (2009) Adherent-Invasive Escherichia coli, Strain LF82 Disrupts Apical Junctional Complexes in Polarized Epithelia. BMC Microbiology, 9, 180.
http://dx.doi.org/10.1186/1471-2180-9-180

[26]   Wang, Z.K., Yang, Y.S., Chen, Y., Yuan, J., Sun, G. and Peng, L.H. (2014) Intestinal Microbiota Pathogenesis and Fecal Microbiota Transplantation for Inflammatory Boweldisease. World Journal of Gastroenterology, 20, 14805-14820.
http://dx.doi.org/10.3748/wjg.v20.i40.14805

[27]   Sokol, H., Pigneur, B., Watterlot, L., Lakhdari, O., Bermúdez-Humarán, L.G., Gratadoux, J.J., Blugeon, S., Bridonneau, C., Furet, J.P., Corthier, G., Grangette, C., Vasquez, N., Pochart, P., Trugnan, G., Thomas, G., Blottière, H.M., Doré, J., Marteau, P., Seksik, P. and Langella, P. (2008) Faecalibacterium prausnitzii Is an Anti-Inflammatory Commensal Bacterium Identified by Gut Microbiota Analysis of Crohn Disease Patients. Proceedings of the National Academy of Sciences of the United States of America, 105, 16731-16736.
http://dx.doi.org/10.1073/pnas.0804812105

[28]   Ramirez-Farias, C., Slezak, K., Fuller, Z., Duncan, A., Holtrop, G. and Louis, P. (2009) Effect of Inulin on the Human Gut Microbiota: Stimulation of Bifidobacterium adolescentis and Faecalibacterium prausnitzii. British Journal of Nutrition, 101, 541-550.
http://dx.doi.org/10.1017/S0007114508019880

[29]   Schaubeck, M., Clavel, T., Calasan, J., Lagkouvardos, I., Haange, S.B., Jehmlich, N., Basic, M., Dupont, A., Hornef, M., Bergen, M.V., Bleich, A. and Haller, D. (2015) Dysbiotic Gut Micro-biota Causes Transmissible Crohn’s Disease-Like Ileitis Independent of Failure in Antimicrobial Defence. Gut, 0, 1-13.
http://dx.doi.org/10.1136/gutjnl-2015-309333

[30]   Simrén, M., Barbara, G., Flint, H.J., Spiegel, B.M., Spiller, R.C., Vanner, S., Verdu, E.F., Whorwell, P.J. and Zoetendal, E.G., Rome Foundation Committee (2013) Intestinal Microbiota in Functional Bowel Disorders: A Rome Foundation Report. Gut, 62, 159-176.
http://dx.doi.org/10.1136/gutjnl-2012-302167

[31]   Marafini, I., Zorzi, F., Codazza, S., Pallone, F. and Monteleone, G. (2013) TGF-Beta Signaling Manipulation as Potential Therapy for IBD. Current Drug Targets, 14, 1400-1404.
http://dx.doi.org/10.2174/13894501113149990157

[32]   Triantafillidis, J.K. and Papalois, A.E. (2014) The Role of Total Parenteral Nutrition in Inflammatory Bowel Disease: Current Aspects. Scandinavian Journal of Gastroenterology, 49, 3-14.
http://dx.doi.org/10.3109/00365521.2013.860557

[33]   Annaházi, A. and Molnár, T. (2015) Optimal Endpoint of Therapy in IBD: An Update on Factors Determining a Successful Drug Withdrawal. Gastroenterology Research and Practice, 2015, Article ID: 832395.
http://dx.doi.org/10.1155/2015/832395

[34]   Johnson, S.L., Bartels, C.M., Palta, M., Thorpe, C.T., Weiss, J.M. and Smith, M.A. (2015) Biological and Steroid Use in Relationship to Quality Measures in Older Patients with Inflammatory Bowel Disease: A US Medicare Cohort Study. BMJ Open, 5, e008597.
http://dx.doi.org/10.1136/bmjopen-2015-008597

[35]   Delzenne, N.M., Neyrinck, A.M. and Cani, P.D. (2011) Modulation of the Gut Microbiota by Nutrients with Prebiotic Properties: Consequences for Host Health in the Context of Obesity and Metabolic Syndrome. Microbial Cell Factories, 10, S10.
http://dx.doi.org/10.1186/1475-2859-10-s1-s10

[36]   Sinagra, E., Tomasello, G., Cappello, F., Leone, A., Cottone, M., Bellavia, M., Rossi, F., Facella, T., Damiani, P., Zeenny, M.N., Damiani, F., Abruzzo, A., Damiano, G., Palumbo, V.D., Cocchi, M., Jurjus, A., Spinelli, G., Lo Monte, A.I. and Raimondo, D. (2013) Probiotics, Prebiotics and Symbiotics in Inflammatory Bowel Diseases: State-of-the-Art and New Insights. Journal of Biological Regulators & Homeostatic Agents, 27, 919-933.

[37]   Veerappan, G.R., Betteridge, J. and Young, P.E. (2012) Probiotics for the Treatment of Inflammatory Bowel Disease. Current Gastroenterology Reports, 14, 324-333.
http://dx.doi.org/10.1007/s11894-012-0265-5

[38]   Alhagamhmad, M.H., Day, A.S., Lemberg, D.A. and Leach, S.T. (2012) An Update of the Role of Nutritional Therapy in the Management of Crohn’s Disease. Journal of Gastroenterology, 47, 872-882.
http://dx.doi.org/10.1007/s00535-012-0617-9

[39]   Zachos, M., Tondeur, M. and Griffiths, A.M. (2007) Enteral Nutritional Therapy for Induction of Remission in Crohn’s Disease. Cochrane Database of Systematic Reviews, No. 1, Article No.: CD000542.
http://dx.doi.org/10.1002/14651858.cd000542.pub2

[40]   Yamamoto, T., Shiraki, M., Nakahigashi, M., Umegae, S. and Matsumoto, K. (2013) Enteral Nutrition to Suppress Postoperative Crohn’s Disease Recurrence: A Five-Year Prospective Cohort Study. International Journal of Colorectal Disease, 28, 335-340.
http://dx.doi.org/10.1007/s00384-012-1587-3

[41]   D’Argenio, V., Precone, V., Casaburi, G., Miele, E., Martinelli, M., Staiano, A., Salvatore, F. and Sacchetti, L. (2013) An Altered Gut Microbiome Profile in a Child Affected by Crohn’s Disease Normalized after Nutritional Therapy. The American Journal of Gastroenterology, 108, 851-852.
http://dx.doi.org/10.1038/ajg.2013.46

[42]   Hartman, C., Berkowitz, D., Weiss, B., Shaoul, R., Levine, A., Adiv, O.E., Shapira, R., Fradkin, A., Wilschanski, M., Tamir, A. and Shamir, R. (2008) Nutritional Supplementation with Polymeric Diet Enriched with Transforming Growth Factor-Beta 2 for Children with Crohn’s Disease. The Israel Medical Association Journal, 10, 503-507.

[43]   Benjamin, J., Makharia, G., Ahuja, V., Anand Rajan, K.D., Kalaivani, M., Gupta, S.D. and Joshi, Y.K. (2012) Glutamine and Whey Protein Improve Intestinal Permeability and Morphology in Patients with Crohn’s Disease: A Randomized Controlled Trial. Digestive Diseases and Sciences, 57, 1000-1012.
http://dx.doi.org/10.1007/s10620-011-1947-9

[44]   Ockenga, J., Borchert, K., Stüber, E., Lochs, H., Manns, M.P. and Bischoff, S.C. (2005) Glutamine-Enriched Total Parenteral Nutrition in Patients with Inflammatory Bowel Disease. European Journal of Clinical Nutrition, 59, 1302-1309.
http://dx.doi.org/10.1007/s10620-011-1947-9

[45]   Bennet, J.D. and Brinkman, M. (1989) Treatment of Ulcerative Colitis by Implantation of Normal Colonic Flora. Lancet, 333, 164.
http://dx.doi.org/10.1016/S0140-6736(89)91183-5

[46]   Borody, T.J., George, L., Andrews, P., Brandl, S., Noonan, S., Cole, P., Hyland, L., Morgan, A., Maysey, J. and Moore-Jones, D. (1989) Bowel-Flora Alteration: A Potential Cure for Inflammatory Bowel Disease and Irritable Bowel Syndrome? Medical Journal of Australia, 150, 604.

[47]   Borody, T.J., Fin-layson, S. and Paramsothy, S. (2014) Is Crohn’s Disease Ready for Fecal Microbiota Transplantation? Journal of Clinical Gastroenterology, 48, 582-583.
http://dx.doi.org/10.1097/MCG.0000000000000155

[48]   Borody, T.J., Warren, E.F., Leis, S.M., Surace, R., Ashman, O. and Siarakas, S. (2004) Bacteriotherapy Using Fecal Flora: Toying with Human Motions. Journal of Clinical Gastroenterology, 38, 475-483.
http://dx.doi.org/10.1097/01.mcg.0000128988.13808.dc

[49]   Borody, T.J., Warren, E.F., Leis, S., Surace, R. and Ashman, O. (2003) Treatment of Ulcerative Colitis Using Fecal Bacteriotherapy. Journal of Clinical Gastroenterology, 37, 42-47.
http://dx.doi.org/10.1097/00004836-200307000-00012

[50]   Anderson, J.L., Edney, R.J. and Whelan, K. (2012) Systematic Review: Faecal Microbiota Transplantation in the Management of Inflammatory Bowel Disease. Alimentary Pharmacology & Therapeutics, 36, 503-516.
http://dx.doi.org/10.1111/j.1365-2036.2012.05220.x

[51]   Allegretti, J.R. and Hamilton, M.J. (2014) Restoring the Gut Microbiome for the Treatment of Inflammatory Bowel Diseases. World Journal of Gastroenterology, 20, 3468-3474.
http://dx.doi.org/10.3748/wjg.v20.i13.3468

[52]   Borody, T.J. and Campbell, J. (2012) Fecal Microbiota Transplantation: Techniques, Applications, and Issues. Gastroenterology Clinics of North America, 41, 781-803.
http://dx.doi.org/10.1016/j.gtc.2012.08.008

[53]   Petrof, E.O., Gloor, G.B., Vanner, S.J., Weese, S.J., Carter, D., Daigneault, M.C., Brown, E.M., Schroeter, K. and Allen-Vercoe, E. (2013) Stool Substitute Transplant Therapy for the Eradication of Clostridium difficile Infection: “RePOOPulating” the Gut. Microbiome, 1, 3.
http://dx.doi.org/10.1186/2049-2618-1-3

[54]   Allen-Vercoe, E., Reid, G., Viner, N., Gloor, G.B., Hota, S., Kim, P., Lee, C., O’Doherty, K., Vanner, S.J., Weese, J.S. and Petrof, E.O. (2012) A Canadian Working Group Report on Fecal Microbial Therapy: Microbial Ecosystems Therapeutics. The Canadian Journal of Gastroenterology, 26, 457-462.

[55]   Angelberger, S., Reinisch, W., Makristathis, A., Lichtenberger, C., Dejaco, C., Papay, P., Novacek, G., Trauner, M., Loy, A. and Berry, D. (2013) Temporal Bacterial Community Dynamics Vary among Ulcerative Colitis Patients after Fecal Microbiota Transplantation. The American Journal of Gastroenterology, 108, 1620-1630.
http://dx.doi.org/10.1038/ajg.2013.257

[56]   De Leon, L.M., Watson, J.B. and Kelly, C.R. (2013) Transient Flare of Ulcerative Colitis after Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection. Clinical Gastroenterology and Hepatology, 11, 1036- 1038.
http://dx.doi.org/10.1016/j.cgh.2013.04.045

[57]   Schwartz, M., Gluck, M. and Koon, S. (2013) Norovirus Gastroenteritis after Fecal Microbiota Transplantation for Treatment of Clostridium difficile Infection Despite Asymptomatic Donors and Lack of Sick Contacts. The American Journal of Gastroenterology, 108, 1367.
http://dx.doi.org/10.1038/ajg.2013.164

[58]   Ianiro, G., Bibbiò, S., Scaldaferri, F., Gasbarrini, A. and Cammarota, G. (2014) Fecal Microbiota Transplantation in Inflammatory Bowel Disease: Beyond the Excitement. Medicine, 93, e97.
http://dx.doi.org/10.1097/MD.0000000000000097

[59]   Moayyedi, P., Surette, M.G., Kim, P.T., Libertucci, J., Wolfe, M., Onischi, C., Armstrong, D., Marshall, J.K., Kassam, Z., Reinisch, W. and Lee, C.H. (2015) Fecal Microbiota Transplantation Induces Remission in Patients with Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology, 149, 102.e6-109.e6.
http://dx.doi.org/10.1053/j.gastro.2015.04.001

[60]   Cammarota, G., Ianiro, G., Cianci, R., Bibbiò, S., Gasbarrini, A. and Currò, D. (2015) The Involvment of Gut Micro-biota in Inflammatory Bowel Disease Pathogenesis: Potential for Therapy. Pharmacology & Therapeutics, 149, 191-212.
http://dx.doi.org/10.1016/j.pharmthera.2014.12.006

[61]   Vandenplas, Y., Pierard, D. and De Greef, E. (2015) Fecal Microbiota Transplantation: Just a Fancy Trend? Journal of Pediatric Gastroenterology and Nutrition, 61, 4-7.
http://dx.doi.org/10.1097/mpg.0000000000000816

 
 
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