口腔微生物移位定植——中医药干预结肠炎癌转化新窗口
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摘要
结肠炎癌转化并非一个孤立事件,微生物移位定植诱发细胞基因表达、黏附及增殖等行为是其演进基础并贯穿全程。研究表明,慢性牙周炎患者罹患结肠癌风险较高,与口腔特定菌移位定植于肠道引发的级联反应密切相关。中医药调控口腔微生态效果显著、干预结肠炎癌转化临床证据丰富,但鲜少将二者结合阐发。本文以此为切入点,通过探讨中医药视角下口腔—结肠病变纠缠的微生态学内涵、口腔特定菌移位定植于肠道动态过程与中医病机的表征关联等,认为中医药调控口腔微生态干预结肠炎癌转化切实可行,且口腔微生态可反映结肠炎癌动态演进、评估疗效,为结肠炎癌早期检测、治疗及疗效评价提供新的观察窗口。
Inflammatory bowel disease-associated colorectal cancer(IBD-CRC) is not an isolated disease. It is tied up to the biomechanical behaviors such as cell gene expression, adhesion and proliferation induced by microbial transplantation/colonization, and the biomechanical behaviors go through the whole IBD-CRC process. Recent studies have revealed that patients with chronic periodontitis have a higher risk of CRC. Frontier studies have also found that Fusobacterium nucleatum translocated and colonized in colonic epithelial cells promotes downstream cascade and drives the progression of CRC. The controlling effect of traditional Chinese medicine(TCM) on oral microorganism is remarkable and abundant clinical evidence shows that TCM can intervene in IBD-CRC. But almost no one considers oral microecology as a key point to study TCM intervention in IBD-CRC. In this article, we discussed the relationship between oral microecology and colorectal diseases from the perspective of TCM as well as the correlation between the dynamic process of specific oral bacteria colonized in the intestine and the pathogenesis. We found that TCM regulation of oral microecology is feasible in the intervention of IBD-CRC, and oral microecology has the role of reflecting the variable process of IBD-CRC and the treatment efficacy. Therefore, oral microecology research can provide a new observation window for the early detection, treatment and outcome evaluation of CRC.
Inflammatory bowel disease-associated colorectal cancer(IBD-CRC) is not an isolated disease. It is tied up to the biomechanical behaviors such as cell gene expression, adhesion and proliferation induced by microbial transplantation/colonization, and the biomechanical behaviors go through the whole IBD-CRC process. Recent studies have revealed that patients with chronic periodontitis have a higher risk of CRC. Frontier studies have also found that Fusobacterium nucleatum translocated and colonized in colonic epithelial cells promotes downstream cascade and drives the progression of CRC. The controlling effect of traditional Chinese medicine(TCM) on oral microorganism is remarkable and abundant clinical evidence shows that TCM can intervene in IBD-CRC. But almost no one considers oral microecology as a key point to study TCM intervention in IBD-CRC. In this article, we discussed the relationship between oral microecology and colorectal diseases from the perspective of TCM as well as the correlation between the dynamic process of specific oral bacteria colonized in the intestine and the pathogenesis. We found that TCM regulation of oral microecology is feasible in the intervention of IBD-CRC, and oral microecology has the role of reflecting the variable process of IBD-CRC and the treatment efficacy. Therefore, oral microecology research can provide a new observation window for the early detection, treatment and outcome evaluation of CRC.
引文
[1]刘钊.炎症性肠病患者肠外临床症状及并发症治疗措施探讨[J].临床医学研究与实践, 2017, 2(10):142-143.
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[3]尹小五,黄晓宇,鲁斌.炎症性肠病的肠外表现和并发症[J].临床消化病杂志, 2015, 27(2):126-128.
[4]邹鹏,蓝程,周旭春.炎性肠病的肠外表现研究进展[J].检验医学与临床, 2015, 12(16):2468-2470.
[5]喻春梅,王承党.溃疡性结肠炎相关性结肠癌化学预防的研究进展[J].国际消化病杂志, 2011, 31(2):71-74.
[6]郑礼胜,邰文,兰新新,等.基于肠道菌群新靶点的中药防治糖尿病研究进展[J].药物评价研究, 2017,40(8):1173-1181.
[7]李强,郭蕾,陈少丽,等.补中益气汤治疗胃肠病的实验研究进展[J].中成药, 2016, 38(6):1360-1363.
[8]王占云.补中益气汤治疗慢性结肠炎120例疗效观察[J].当代医学, 2010, 16(12):153.
[9]程兴群,徐欣,周学东.口腔微生物与肠道微生物的关系[J].华西口腔医学杂志, 2017, 35(3):322-327.
[10]何金枝,徐欣,周学东.口腔微生物与全身健康研究进展[J].微生物与感染, 2017, 12(3):139-145.
[11]喻丽,葛颂,冯馨仪,等.牙龈卟啉单胞菌的研究进展[J].口腔疾病防治, 2016, 24(5):314-317.
[12]林欣.具核梭杆菌通过调控miR-181b在结肠癌细胞中形成炎性微环境的机制[D].广州:广州医科大学, 2017.
[13]韩伶娜,潘春玲,张树伟,等.牙龈卟啉单胞菌、嵴链球菌、口腔链球菌属在口腔内不同解剖部位的分布[J].中国微生态学杂志, 2017, 29(4):423-426, 444.
[14]耿奉雪,潘亚萍.生物膜中不同定植阶段细菌间的相互作用及模型[J].国际口腔医学杂志, 2014, 41(4):431-435.
[15]万晓.肠内营养对小鼠肠道粘膜屏障及肠道微生态的保护作用及机制研究[D].南京:南京大学, 2015.
[16]洪南,湛先保.肠道微生态系统与肠黏膜免疫关系研究进展[J].医学研究生学报, 2014, 27(4):444-446.
[17]李楠.小鼠巨噬细胞S100A9/NF-κB/SAA3/miR-204环路在炎症相关性结肠癌发展中的作用[D].长沙:中南大学, 2013.
[18]Ren D, Lin B, Zhang X, et al. Maintenance of cancer stemness by miR-196b-5p contributes to chemoresistance of colorectal cancer cells via activating STAT3 signaling pathway[J]. Oncotarget, 2017, 8(30):49807-49823.
[19]温珍珍. Nrip2通过非经典Wnt通路调控大肠癌干细胞的自我更新[D].杭州:浙江大学, 2015.
[20]齐丽莎. Wnt/β-catenin通路在结肠癌血管生成拟态形成中的作用[D].天津:天津医科大学, 2012.
[21]徐浩,王玥.肿瘤微环境与肿瘤的发生、发展、转移[C]//中国商品学会第五届全国中药商品学术大会论文集, 2017:8.
[22]Viennois E, Chen F, Merlin D. NF-κB pathway in colitisassociated cancers[J]. Transl Gastrointest Cancer, 2013,2(1):21-29.
[23]Chi Y, Zhou D. MicroRNAs in colorectal carcinoma-from pathogenesis to therapy[J]. J Exp Clin Cancer Res, 2016, 35:43.
[24]Nosho K, Sukawa Y, Adachi Y, et al. Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer[J]. World J Gastroenterol,2016, 22(2):557-566.
[25]Yang Y, Weng W, Peng J, et al. Fusobacterium nucleatum increases proliferation of colorectal cancer cells and tumor development in mice by activating Toll-like receptor 4signaling to nuclear factor-κB, and up-regulating expression of microRNA-21[J]. Gastroenterology, 2017, 152(4):851-866.
[26]Yao J, Zhao L, Zhao Q, et al. NF-κB and Nrf2 signaling pathways contribute to wogonin-mediated inhibition of inflammation-associated colorectal carcinogenesis[J]. Cell Death Dis, 2014, 5(6):e1283.
[27]龙惠珍,殷洁,夏永良.补中益气汤对脾虚型复发性口腔溃疡小鼠IL-2 IFN-γ表达的影响[J].中华中医药学刊,2010, 28(3):523-525.
[28]罗书.补中益气汤预防给药对UC小鼠NLRP3炎性体调控研究[D].广东:广州中医药大学, 2016.
[29]张芳,路东升,蔡哲,等.扶脾温肾汤对8例牙周炎患者成骨的评价[J].中华中医药杂志, 2013, 28(1):268-271.
[30]邵铁娟,李海昌,谢志军,等.基于脾主运化理论探讨脾虚湿困与肠道菌群紊乱的关系[J].中华中医药杂志,2014, 29(12):3762-3765.
[31]金赟,武建毅,冯煜.四君子汤对化疗的结直肠癌术后肝转移患者口腔黏膜细胞凋亡率及肠道屏障功能的影响[J].上海中医药大学学报, 2013, 27(4):35-38.
[32]车宇薇,王燕一.宏基因组学在口腔微生物研究中的应用进展[J].中华老年口腔医学杂志, 2015, 13(4):249-252.
[33]He J, Li Y, Cao Y, et al. The oral microbiome diversity and its relation to human diseases[J]. Folia Microbiol(Praha),2015, 60(1):69-80.
[2]Barton MK. Evidence accumulates indicating periodontal disease as a risk factor for colorectal cancer or lymphoma[J].CA Cancer J Clin, 2017, 67(3):173-174.
[3]尹小五,黄晓宇,鲁斌.炎症性肠病的肠外表现和并发症[J].临床消化病杂志, 2015, 27(2):126-128.
[4]邹鹏,蓝程,周旭春.炎性肠病的肠外表现研究进展[J].检验医学与临床, 2015, 12(16):2468-2470.
[5]喻春梅,王承党.溃疡性结肠炎相关性结肠癌化学预防的研究进展[J].国际消化病杂志, 2011, 31(2):71-74.
[6]郑礼胜,邰文,兰新新,等.基于肠道菌群新靶点的中药防治糖尿病研究进展[J].药物评价研究, 2017,40(8):1173-1181.
[7]李强,郭蕾,陈少丽,等.补中益气汤治疗胃肠病的实验研究进展[J].中成药, 2016, 38(6):1360-1363.
[8]王占云.补中益气汤治疗慢性结肠炎120例疗效观察[J].当代医学, 2010, 16(12):153.
[9]程兴群,徐欣,周学东.口腔微生物与肠道微生物的关系[J].华西口腔医学杂志, 2017, 35(3):322-327.
[10]何金枝,徐欣,周学东.口腔微生物与全身健康研究进展[J].微生物与感染, 2017, 12(3):139-145.
[11]喻丽,葛颂,冯馨仪,等.牙龈卟啉单胞菌的研究进展[J].口腔疾病防治, 2016, 24(5):314-317.
[12]林欣.具核梭杆菌通过调控miR-181b在结肠癌细胞中形成炎性微环境的机制[D].广州:广州医科大学, 2017.
[13]韩伶娜,潘春玲,张树伟,等.牙龈卟啉单胞菌、嵴链球菌、口腔链球菌属在口腔内不同解剖部位的分布[J].中国微生态学杂志, 2017, 29(4):423-426, 444.
[14]耿奉雪,潘亚萍.生物膜中不同定植阶段细菌间的相互作用及模型[J].国际口腔医学杂志, 2014, 41(4):431-435.
[15]万晓.肠内营养对小鼠肠道粘膜屏障及肠道微生态的保护作用及机制研究[D].南京:南京大学, 2015.
[16]洪南,湛先保.肠道微生态系统与肠黏膜免疫关系研究进展[J].医学研究生学报, 2014, 27(4):444-446.
[17]李楠.小鼠巨噬细胞S100A9/NF-κB/SAA3/miR-204环路在炎症相关性结肠癌发展中的作用[D].长沙:中南大学, 2013.
[18]Ren D, Lin B, Zhang X, et al. Maintenance of cancer stemness by miR-196b-5p contributes to chemoresistance of colorectal cancer cells via activating STAT3 signaling pathway[J]. Oncotarget, 2017, 8(30):49807-49823.
[19]温珍珍. Nrip2通过非经典Wnt通路调控大肠癌干细胞的自我更新[D].杭州:浙江大学, 2015.
[20]齐丽莎. Wnt/β-catenin通路在结肠癌血管生成拟态形成中的作用[D].天津:天津医科大学, 2012.
[21]徐浩,王玥.肿瘤微环境与肿瘤的发生、发展、转移[C]//中国商品学会第五届全国中药商品学术大会论文集, 2017:8.
[22]Viennois E, Chen F, Merlin D. NF-κB pathway in colitisassociated cancers[J]. Transl Gastrointest Cancer, 2013,2(1):21-29.
[23]Chi Y, Zhou D. MicroRNAs in colorectal carcinoma-from pathogenesis to therapy[J]. J Exp Clin Cancer Res, 2016, 35:43.
[24]Nosho K, Sukawa Y, Adachi Y, et al. Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer[J]. World J Gastroenterol,2016, 22(2):557-566.
[25]Yang Y, Weng W, Peng J, et al. Fusobacterium nucleatum increases proliferation of colorectal cancer cells and tumor development in mice by activating Toll-like receptor 4signaling to nuclear factor-κB, and up-regulating expression of microRNA-21[J]. Gastroenterology, 2017, 152(4):851-866.
[26]Yao J, Zhao L, Zhao Q, et al. NF-κB and Nrf2 signaling pathways contribute to wogonin-mediated inhibition of inflammation-associated colorectal carcinogenesis[J]. Cell Death Dis, 2014, 5(6):e1283.
[27]龙惠珍,殷洁,夏永良.补中益气汤对脾虚型复发性口腔溃疡小鼠IL-2 IFN-γ表达的影响[J].中华中医药学刊,2010, 28(3):523-525.
[28]罗书.补中益气汤预防给药对UC小鼠NLRP3炎性体调控研究[D].广东:广州中医药大学, 2016.
[29]张芳,路东升,蔡哲,等.扶脾温肾汤对8例牙周炎患者成骨的评价[J].中华中医药杂志, 2013, 28(1):268-271.
[30]邵铁娟,李海昌,谢志军,等.基于脾主运化理论探讨脾虚湿困与肠道菌群紊乱的关系[J].中华中医药杂志,2014, 29(12):3762-3765.
[31]金赟,武建毅,冯煜.四君子汤对化疗的结直肠癌术后肝转移患者口腔黏膜细胞凋亡率及肠道屏障功能的影响[J].上海中医药大学学报, 2013, 27(4):35-38.
[32]车宇薇,王燕一.宏基因组学在口腔微生物研究中的应用进展[J].中华老年口腔医学杂志, 2015, 13(4):249-252.
[33]He J, Li Y, Cao Y, et al. The oral microbiome diversity and its relation to human diseases[J]. Folia Microbiol(Praha),2015, 60(1):69-80.