胆汁酸代谢与结直肠息肉发生的相关性探讨
The Relationship between Bile Acid Metabolism and Colorectal Polyps
DOI: 10.12677/ACM.2021.116369, PDF,   
作者: 董书辰*：山东第一医科大学(山东省医学科学院)，山东 济南；青岛市市立医院，山东 青岛；邓晓颖：济南市槐荫人民医院，山东 济南；姜相君#：青岛市市立医院，山东 青岛
关键词: 结直肠息肉；结直肠癌；胆汁酸；脱氧胆酸；TGR5；FXR；Colorectal Polyps； Colorectal Cancer； Bile Acid； Deoxycholic Acid； TGR5； FXR
摘要: 目前结直肠息肉(Colorectal polyp, CRP)发病率高且发病机制复杂，高脂饮食、遗传因素、肠道炎症反应及胆汁酸的代谢等多种因素与CRP的发病均有一定的相关性。胆汁酸(Bile acid, BA)作为人体消化液中胆汁的重要组成部分，其在体内的合成代谢及循环与CRP的发生有着密切的关系，本文主要阐述胆汁酸代谢与结直肠息肉的发生与研究进展，为结直肠息肉的精准防治提供新的思路和方法。
Abstract: At present, colorectal polyp (Colorectal polyp, CRP) has a high incidence and complicated pathogenesis. Many factors such as high-fat diet, genetic factors, intestinal inflammation and bile acid metabolism are all related to the pathogenesis of CRP. Bile acid (BA) is an important part of bile in human digestive juice. Its anabolism and circulation in the body are closely related to the occurrence of CRP. This article mainly discusses the occurrence and research of bile acid metabolism and colorectal polyps. Progress provides new ideas and methods for the precise prevention and treatment of colorectal polyps.
文章引用：董书辰, 邓晓颖, 姜相君. 胆汁酸代谢与结直肠息肉发生的相关性探讨[J]. 临床医学进展, 2021, 11(6): 2564-2571. https://doi.org/10.12677/ACM.2021.116369

参考文献

[1] 董一凡, 郭涛, 杨红, 钱家鸣, 李景南. 幽门螺杆菌感染与结直肠息肉及结直肠癌的相关性分析[J]. 中华内科杂志, 2019, 58(2): 139-142.
[2] Cappell, M.S. (2008) Reducing the Incidence and Mortality of Colon Cancer: Mass Screening and Colonoscopic Polypectomy. Gastroenterology Clinics of North America, 37, 129-160. [Google Scholar] [CrossRef] [PubMed]
[3] Oines, M., Helsingen, L.M., Bretthauer, M. and Emilsson, L. (2017) Epidemiology and Risk Factors of Colorectal Polyps. Best Practice & Research Clinical Gastroenterology, 31, 419-424. [Google Scholar] [CrossRef] [PubMed]
[4] Cai, B., Liu, Z., Xu, Y., Wei, W. and Zhang, S. (2015) Adenoma Detection Rate in 41,010 Patients from Southwest China. Oncology Letters, 9, 2073-2077. [Google Scholar] [CrossRef] [PubMed]
[5] Lam, K.Y., Chan, S.Y. and Leung, M. (2014) Synchronous Colorectal Cancer: Clinical, Pathological and Molecular Implications. World Journal of Gastroenterology, 20, 6815-6820. [Google Scholar] [CrossRef] [PubMed]
[6] Iravani, S., Kashfi, S.M.H., Azimzadeh, P. and Lashkari, M.H. (2014) Prevalence and Characteristics of Colorectal Polyps in Symptomatic and Asymptomatic Iranian Patients Undergoing Colonoscopy from 2009-2013. Asian Pacific Journal of Cancer Prevention, 15, 9933-9937. [Google Scholar] [CrossRef] 
[7] Martin, O.C., Lin, C., Naud, N., Tache, S., Raymond-Letron, I., Corpet, D.E., et al. (2015) Antibiotic Suppression of Intestinal Microbiota Reduces Heme-Induced Lipoperoxidation Associated with Colon Carcinogenesis in Rats. Nutrition and Cancer, 67, 119-125. [Google Scholar] [CrossRef] [PubMed]
[8] Kurdi, P., Veen, H.W.V., Tanaka, H., Mierau, I., Konings, W.N., Tannock, G.W., et al. (2000) Cholic Acid Is Accumulated Spontaneously, Driven by Membrane Delta pH, in Many Lactobacilli. Journal of Bacteriology, 182, 6525-6528. [Google Scholar] [CrossRef] 
[9] Weingarden, A.R., Dosa, P.I., DeWinter, E., Steer, C.J., Shaughnessy, M.K., Johnson, J.R., et al. (2016) Changes in Colonic Bile Acid Composition Following Fecal Microbiota Transplantation Are Sufficient to Control Clostridium difficile Germination and Growth. PLoS ONE, 11, e0147210. [Google Scholar] [CrossRef] [PubMed]
[10] Hess, L.M., Krutzsch, M.F., Guillen, J., Chow, H.H., Einspahr, J., Batta, A.K., et al. (2004) Results of a Phase I Multiple-Dose Clinical Study of Ursodeoxycholic Acid. Cancer Epidemiology, Biomarkers & Prevention, 13, 861-867.
[11] Huang, C., Guo, Y. and Yuan, J. (2014) Dietary Taurine Impairs Intestinal growth and Mucosal Structure of Broiler Chickens by Increasing Toxic Bile Acid Concentrations in the Intestine. Poultry Science, 93, 1475-1483. [Google Scholar] [CrossRef] [PubMed]
[12] Nijmeijer, R.M., Gadaleta, R.M., Van Mil, S.W.C., van Bodegraven, A.A., Crusius, J.B.A., Dijkstra, G., et al. (2011) Farnesoid X Receptor (FXR) Activation and FXR Genetic Variation in Inflammatory Bowel Disease. PLoS ONE, 6, e23745. [Google Scholar] [CrossRef] [PubMed]
[13] Martínez, C., González-Castro, A. and Vicario, M. (2012) Cellular and Molecular Basis of Intestinal Barrier Dysfunction in the Irritable Bowel Syndrome. Gut & Liver, 6, 305-315. [Google Scholar] [CrossRef] [PubMed]
[14] Aymeric, L., Donnadieu, F., Mulet, C., du Merle, L., Nigro, G., Saffarian, A., et al. (2017) Colorectal Cancer Specific Conditions Promote Streptococcus gallolyticus Gut Colonization. Proceedings of the National Academy of Sciences of the United States of America, 115, E283-E291. [Google Scholar] [CrossRef] [PubMed]
[15] Theriot, C.M., Koenigsknecht, M.J., Carlson Jr., P.E., Hatton, G.E., Nelson, A.M., Li, B., et al. (2014) Antibiotic-Induced Shifts in the Mouse Gut Microbiome and Metabolome Increase Susceptibility to Clostridium difficile Infection. Nature Communications, 5, Article No. 3114. [Google Scholar] [CrossRef] [PubMed]
[16] Reddy, B.S., Simi, B., Patel, N., Aliaga, C. and Rao, C.V. (1996) Effect of Amount and Types of Dietary Fat on Intestinal Bacterial 7α-Dehydroxylase and Phosphatidylinositol-Specific Phospholipase C and Colonic Mucosal Diayclglycerol Kinase and PKC Activities during Different Stages of Colon Tumor Promotion. Cancer Research, 56, 2314-2330.
[17] Hee, K.N., Yul, S.J., Ho, P.J., Park, D.I., Cho, Y.K., Sohn, C.I., et al. (2017) Parameters of Glucose and Lipid Metabolism Affect the Occurrence of Colorectal Adenomas Detected by Surveillance Colonoscopies. Yonsei Medical Journal, 58, 347-354. [Google Scholar] [CrossRef] [PubMed]
[18] Larriba, M.J., Martín-Villar, E., García, J.M., Pereira, F., Peña, C., de Herreros, A.G., et al. (2009) Snail2 Cooperates with Snail1 in the Repression of Vitamin D Receptor in Colon Cancer. Carcinogenesis, 30, 1459-1468. [Google Scholar] [CrossRef] [PubMed]
[19] Payne, C.M., Weber, C., Crowley-Skillicorn, C., Dvorak, K., Bernstein, H., Bernstein, C., Holubec, H., Dvorakova, B. and Garewal, H. (2007) Deoxycholate Induces Mitochondrial Oxidative stress and Activates NF-κB through Multiple Mechanisms in HCT-116 Colon Epithelial Cells. Carcinogenesis, 2, 215-222. [Google Scholar] [CrossRef] [PubMed]
[20] Liu, Y.L., Wu, J. S., Yang, Y.C., Lu, F.-H., Lee, C.-T., Lin, W.-J., et al. (2018) Gallbladder Stones and Gallbladder Polyps Associated with Increased Risk of Colorectal Adenoma in Men. Journal of Gastroenterology & Hepatology, 33, 800-806. [Google Scholar] [CrossRef] [PubMed]
[21] Berloco, M., Berloco, P., Ladisa, R., Ierardi, E., Caruso, M.L., Valentini, A.M., et al. (2002) Demonstration of a Direct Stimulatory Effect of Bile Salts on Rat Colonic Epithelial Cell Proliferation. Scandinavian Journal of Gastroenterology, 37, 88-94. [Google Scholar] [CrossRef] [PubMed]
[22] Romagnolo, D.F., Chirnomas, R.B., Ku, J., Jeffy, B.D., Payne, C.M., Holubec, H., et al. (2003) Deoxycholate, an Endogenous Tumor Promoter and DNA Damaging Agent, Modulates BRCA-1 Expression in Apoptosis-Sensitive Epithelial Cells: Loss of BRCA-1 Expression in Colonic Adenocarcinomas. Nutrition & Cancer, 46, 82-92. [Google Scholar] [CrossRef] 
[23] Zhu, Y., Zhu, M. and Lance, P. (2012) Stromal COX-2 Signaling Activated by Deoxycholic Acid Mediates Proliferation and Invasiveness of Colorectal Epithelial Cancer Cells. Biochemical & Biophysical Research Communications, 425, 607-612. [Google Scholar] [CrossRef] [PubMed]
[24] Qiao, D., Gaitonde, S.V., Qi, W. and Martinez, J.D. (2001) Deoxycholic Acid Suppresses p53 by Stimulating Proteasome-Mediated p53 Protein Degradation. Carcinogenesis, 22, 957-964. [Google Scholar] [CrossRef] [PubMed]
[25] Maruyama, T., Miyamoto, Y., Nakamura, T., Tamai, Y., Okada, H., Sugiyama, E., et al. (2002) Identification of Membrane-Type Receptor for Bile Acids (M-BAR). Biochemical and Biophysical Research Communications, 298, 714-719. [Google Scholar] [CrossRef] 
[26] Kawamata, Y., Fujii, R., Hosoya, M., Harada, M., Yoshida, H., Miwa, M., et al. (2003) A G Protein-Coupled Receptor Responsive to Bile Acids. Journal of Biological Chemistry, 278, 9435-9440. [Google Scholar] [CrossRef] 
[27] Schaap, F.G., Trauner, M. and Jansen, P.L.M. (2014) Bile Acid Receptors as Targets for Drug Development. Nature Reviews Gastroenterology & Hepatology, 11, 55-67. [Google Scholar] [CrossRef] [PubMed]
[28] Ji, C.G., Xie, X.L., Yin, J., Qi, W., Chen, L., Bai, Y., et al. (2017) Bile Acid Receptor TGR5 Overexpression Is Associated with Decreased Intestinal Mucosal Injury and Epithelial Cell Proliferation in Obstructive Jaundice. Translational Research, 182, 88-102. [Google Scholar] [CrossRef] [PubMed]
[29] Xia, X., Francis, H., Glaser, S., Alpini, G. and LeSag, G. (2006) Bile acid Interactions with Cholangiocytes. World Journal of Gastroenterology, 12, 3553-3563. [Google Scholar] [CrossRef] [PubMed]
[30] Sabrina, C., Andrea, M., Giovanna, C.M., Distrutti, E., Renga, B., Bifulco, G., et al. (2011) The Bile Acid Receptor GPBAR-1 (TGR5) Modulates Integrity of Intestinal Barrier and Immune Response to Experimental Colitis. PLoS ONE, 6, e25637. [Google Scholar] [CrossRef] [PubMed]
[31] Keitel, V., Donner, M., Winandy, S., Kubitz, R. and Häussinger, D. (2008) Expression and Function of the Bile Acid Receptor TGR5 in Kupffer Cells. Biochemical & Biophysical Research Communications, 372, 78-84. [Google Scholar] [CrossRef] [PubMed]
[32] Modica, S., Gadaleta, R.M. and Moschetta, A. (2010) Deciphering the Nuclear Bile Acid Receptor FXR Paradigm. Nuclear Receptor Signaling, 8, e005. [Google Scholar] [CrossRef] 
[33] Higashiyama, H., Kinoshita, M. and Asano, S. (2008) Immunolocalization of Farnesoid X Receptor (FXR) in Mouse Tissues Using Tissue Microarray. Acta Histochemica, 110, 86-93. [Google Scholar] [CrossRef] [PubMed]
[34] Sinal, C.J., Tohkin, M., Miyata, M., Ward, J.M., Lambert, G. and Gonzalez, F. (2000) Targeted Disruption of the Nuclear Receptor FXR/BAR Impairs Bile Acid and Lipid Homeostasis. Cell, 102, 731-744. [Google Scholar] [CrossRef] 
[35] Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C.L., McDonald, J.G., et al. (2005) Fibroblast Growth Factor 15 Functions as an Enterohepatic Signal to Regulate Bile Acid Homeostasis. Cell Metabolism, 2, 217-225. [Google Scholar] [CrossRef] [PubMed]
[36] Inagaki, T., Moschetta, A., Lee, Y., Peng, L., Zhao, G., Downes, M., et al. (2006) Regulation of Antibacterial Defense in the Small Intestine by the Nuclear Bile Acid Receptor. Proceedings of the National Academy of Sciences of the United States of America, 103, 3920-3925. [Google Scholar] [CrossRef] [PubMed]
[37] Gadaleta, R.M., Van Erpecum, K.J., Oldenburg, B., Willemsen, E.C.L., Renooij, W., Murzilli, S., et al. (2011) Farnesoid X Receptor Activation Inhibits Inflammation and Preserves the Intestinal Barrier in Inflammatory Bowel Disease. Gut, 60, 463-472. [Google Scholar] [CrossRef] [PubMed]
[38] 杨博丽, 曹海龙, 王邦茂. 次级胆汁酸与结直肠癌发生的机制研究进展[J]. 中华消化杂志, 2013, 33(8): 568-570.
[39] De Gottardi, A., Touri, F., Maurer Christoph, A., Perez, A., Maurhofer, O., Ventre, G., Bentzen Craig, L., Niesor, E.J. and Dufour, J.-F. (2004). The Bile Acid Nuclear Receptor FXR and the Bile Acid Binding Protein IBABP Are Differently Expressed in Colon Cancer. Digestive Diseases and Sciences, 49, 982-989.[CrossRef] 
[40] Peng, Z., Raufman, J.-P. and Xie, G. (2012) Src-Mediated Cross-Talk between Farnesoid X and Epidermal Growth Factor Receptors Inhibits Human Intestinal Cell Proliferation and Tumorigenesis. PLoS ONE, 7, e48461. [Google Scholar] [CrossRef] [PubMed]
[41] Brenner, H., Kloor, M. and Pox, C.P. (2014) Colorectal Cancer. Lancet, 383, 1490-1502. [Google Scholar] [CrossRef] 
[42] De Aguiar Vallim, T.Q., Tarling, E.J. and Edwards, P.A. (2013) Pleiotropic Roles of Bile Acids in Metabolism. Cell Metabolism, 17, 657-669. [Google Scholar] [CrossRef] [PubMed]
[43] Ridlon, J.M., Kang, D.J., Hylemon, P.B. and Bajaj, J.S. (2014) Bile Acids and the Gut Microbiome. Current Opinion in Gastroenterology, 30, 332-338. [Google Scholar] [CrossRef] 

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