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1.
肠道是集消化、吸收、内分泌、免疫、屏障等功能为一体的重要器官,肠道菌群的结构和功能与人体的健康、疾病的发生发展及机体的快速康复息息相关。结直肠癌变是个逐步发生发展的过程,从局部炎性反应、腺瘤、癌前病变到恶化的过程可达数年甚至数十年之久。结肠癌早期临床症状不明显且潜伏期较长,容易造成漏诊和误诊,贻误最佳治疗时机。近年来,国内外多项研究显示大肠埃希菌、粪肠球菌、脆弱拟杆菌、解没食子酸链球菌、具核梭杆菌等细菌与结直肠癌的发生发展关系密切,这为我们从另外一个角度来进行结直肠癌早期诊断提供了新思路和新途径。 相似文献
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结直肠癌是一种涉及遗传、环境和生活方式等多风险因素的疾病。越来越多的研究表明肠道菌群在结直肠癌的发生发展中起重要作用,菌群与消化道之间的共生作用对维持肠道内环境的稳定也十分重要。菌群在炎症、药物代谢,甚至癌症的发展中扮演着许多角色,然而由感染、饮食或生活方式等变化引起的菌群组成的改变却可影响这种共生关系。同样,菌群组成的变化使部分菌种在肠内引发炎症反应甚至致癌,从而对结肠直肠癌的发生发展产生实质性的影响,综述将总结目前肠道菌群与结直肠癌之间潜在的联系,重点关注细菌在肠道中所参与的各种反应,从而为治疗结直肠癌提供更多的研究思路。 相似文献
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微生态失衡会影响宿主肠道黏液屏障功能,从而导致炎症性疾病和结直肠癌的发生。结肠上皮细胞通过分泌黏蛋白形成双层黏液层来保护自己免受恶劣环境和各种病原菌的侵袭。肠道菌群的组成能够影响黏蛋白的表达和肠道黏液屏障的功能,而饮食模式的变化又可以影响肠道菌群的组成。通过菌群疗法(包括粪菌移植)调节肠道菌群已成为改善微生态失调相关病理学表现的重要手段。因此,合理的饮食模式可以调节肠道菌群、细菌代谢物(后生元)与宿主之间的相互作用,并维持肠道黏液的组成和黏蛋白的合成,从而增强肠道黏液屏障的功能,降低肠道炎症性疾病和结直肠癌的风险。
相似文献4.
近年来,肠道微生态学已经成为众学者的研究热点,肠道微生态平衡影响人体健康,尤其与结直肠癌(colorectal cancer,CRC)关系密切。许多CRC患者在早期并无明显症状,在进入中晚期时才被确诊,因错过早期治疗的机会而导致治疗效果欠佳,目前亟需更新更优的CRC早期诊断方法。基于肠道微生态与CRC的密切关系,肠道微生态已成为CRC新诊断方法的主要选择之一,主要研究方向是肠道中的细菌、病毒及其代谢产物的种类与数量的检测。本文就近年来关于肠道微生态对CRC诊断作用的相关热点问题进行概述,并展望肠道微生态在CRC诊断作用研究的主要方向及预期进展,旨在为通过肠道微生态诊断CRC提供理论依据。
相似文献5.
目的 分析结直肠癌患者与健康人的粪便微生物群落,以及结直肠癌组织与癌旁组织菌群差异,期望发现肠道内菌群差异与结直肠癌的相关性。方法 选取2021年9月至2022年10月包头市中心医院收治的结直肠癌患者和健康者,共收集60例样本,其中收集结直肠癌患者粪便11份,记为A组。采集结直肠癌组织20份,对应的癌旁组织20份,分别记为B组、C组。同时收集健康人粪便9份,记为D组。送测序公司进行菌群测序,分析A组与D组、B组与C组之间菌群的组成及多样性情况。结果 共获得4 335646条高质量扩增序列,按97%的序列相似度进行归并,与Greengenes数据库进行物种注释对比,生成特征性序列OTU和丰度数据表格。多样性稀释曲线趋于平缓,表明本次测序覆盖了绝大多数物种。在门水平上,优势菌在A、B、C、D组中大致一致,其中壁厚菌门(Firmicutes)、拟杆菌门(Bacteroidetes)、变形菌门(Proteobacteria)占据了肠道菌群的90%以上,A组与D组、B组与C组间未见相对丰度有差异的细菌。在属水平上,Lachnobacterium在D组相对丰度高于A组,且差异有统计学意义(Z=-2.309,P=0.027),瘤胃球菌(Ruminococcus)在A组相对丰度高于D组,且差异有统计学意义(Z=-2.309,P=0.027)。Chao1指数反映物种丰富度,Shannon指数反映物种多样性。A组的Chao1指数低于D组,且差异有统计学意义(Z=-3.001,P=0.003)。Chao1指数在B组与C组间差异无统计学意义。对于Shannon指数,A组与D组、B组与C组间差异均无统计学意义。对于菌群beta多样性,A组、D组之间菌群的beta多样性上存在着显著结构差异,且差异具有统计学意义(F=2.684,P=0.004),但B组、C组之间beta多样性差异无统计学意义。对于菌群差异物种筛选,A、D两组间相比,结直肠癌组(A组)出现6个差异物种,分别为瘤胃球菌属(g_Ruminococcus)、 f_Haliangiaceae、 f_[Tissierellaceae]、梭杆菌门(p_Fusobacteria)、梭杆菌目(o_Fusobacteriales)、梭杆菌纲(c_Fusobacteriia)。在健康对照组(D组)中,鉴定出14个差异物种,分别为厚壁菌门(p_Firmicutes)、梭菌目(o_Clostridiales)、梭状芽胞杆菌纲(c_Clostridia)、g_Lachnobacterium、疣微菌科-瘤胃球菌属(f_Ruminococcaceae_g_Ruminococcus)、毛螺菌属(g_Lachnospira)、f_Christensenellaceae、交替单胞菌目(o_Alteromonadales)、柔膜菌纲(c_Mollicutes)、软壁菌门(p_Tenericutes)、 o_RF39、嗜热油菌纲(c_Thermoleophilia)、副球菌属(g_Paracoccus)、诺卡菌科(f_Nocardiaceae)。对于组织样本,经过LEfSe分析后,未见结直肠癌组织与癌旁组织间存在差异物种。结论 在门、属水平上优势物种和相对丰度存在差异,其中梭杆菌可能是参与结直肠癌的发生菌群。结直肠癌患者菌群的丰富度显著降低,患者与健康者相比,存在菌群群落的结构分离,同时结直肠癌患者的产短链脂肪酸的细菌相对丰度显著减少,以及机会致病菌的增多,提示结直肠癌患者存在一定的菌群失衡现象。结直肠癌组织与癌旁组织的菌群相对丰度、多样性未见明显的改变,菌群的结构也无明显分离,提示菌群在癌与癌旁组织之间可能不存在差异。 相似文献
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目的研究结直肠癌患者肠道黏膜相关菌群组成差异,探索肠道菌群在结直肠癌发生发展中的作用。方法 用末端限制片段长度多态性(Terminal restriction fragment length polymorphism,T-RFLP)技术分析50例结直肠癌患者癌组织、癌旁正常黏膜与健康对照组肠道黏膜相关细菌组成差异。结果 与健康对照组相比,结直肠癌患者肠道黏膜相关细菌丰度显著增加(P<0.05),多样性显著降低(P<0.05)。结直肠癌患者癌组织与癌旁正常黏膜的黏膜相关细菌组成相近,但与健康对照组存在显著差异。MspI酶切的160 bp、560 bp的T-RF片段在结直肠癌癌组织及癌旁正常黏膜中为优势片段,而在健康对照组中缺失。相反,MspI酶切的66 bp、74 bp、141 bp的T-RF片段在健康对照组为优势片段,但在结直肠癌患者癌组织及癌旁正常黏膜中缺失。结论 肠道菌群失调与结直肠癌的发生发展密切相关。MspI酶切的66 bp、74 bp、141 bp、160 bp、560 bp的T-RF片段所代表的细菌可能在结直肠癌的发生发展中起重要作用。 相似文献
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目的 探讨结直肠癌患者肠道菌群变化与炎症因子水平的相关性。 方法 选取2017年3月-2019年12月我院收治的结直肠癌患者60例为研究对象,另选我院同期健康体检者60例作为对照组,比较两组肠道菌群和炎性因子血清白细胞介素6(IL 6)、白细胞介素17(IL 17)、白细胞介素22(IL 22)和肿瘤坏死因子 α(TNF α)水平变化情况。采用Pearson检验分析肠道菌群和炎性因子水平的相关性。 结果 观察组双歧杆菌、乳酸杆菌和拟杆菌的菌落数相比对照组的菌落数明显降低,差异有统计学意义(P结论 结直肠癌患者肠道菌群失衡,并与炎性因子水平密切相关,肠道菌群失衡可能是促进病情发生发展的原因之一,可为治疗结直肠癌提供新的理论依据。 相似文献
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邱真;郭志华;张春淼;牛晨光 《生命的化学》2024,(5):877-883
随着现代高通量生物组学技术的发展及菌群研究的不断深入,口腔菌群在结直肠癌发生发展中的作用逐渐凸显。口腔菌群可通过血液循环和消化道传播并定植于肠道。肠道中来自口腔的菌群及其代谢物可引起肠上皮表观遗传改变和基因突变,并介导免疫逃逸,导致结直肠癌的发生;还可以通过调控信号通路,营造适合肿瘤生存的肿瘤微环境等促进结直肠癌发展。将其作为生物标志物用于结直肠癌的早期筛查或作为治疗靶点,对于尽早干预结直肠癌或开发治疗肿瘤新策略具有潜在临床意义。 相似文献
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目的 探究二甲双胍抑制肠癌的生长及调控肠道菌群的作用。 方法 20只C57BL/6J小鼠通过AOM DSS诱导结直肠癌发生,分成2组每天分别灌胃生理盐水及二甲双胍溶液,12周后处死小鼠,收集结直肠组织及粪便,比较2组小鼠肠道肿瘤个数及大小并进行H&E染色分析,运用16S rRNA基因测序技术检测小鼠肠道菌群组成,使用QIIME软件分析菌群物种分类、物种多样性指数及组间显著性差异。 结果 2组小鼠体质量随周龄增加均呈现增长趋势,且实验结束时体质量差异无统计学意义(t=0.743 1,P=0.469 7)。与对照组相比,接受二甲双胍灌胃的实验组小鼠结直肠肿瘤数量减少(t=2.260 0,P=0.040 3)且尺寸偏小(t=2.570 0,P=0.014 4)。粪便菌群测序结果显示实验组小鼠肠道菌群丰富度增加(P0.05)。在属水平上,实验组Akkermansia、Ruminococcus及Clostridium Ⅹa和Ⅳ等细菌的丰富度增加。 结论 二甲双胍能够调控肠道菌群的组成,增加肠道内产SCFAs细菌的定植,并抑制肠癌的发生发展。 相似文献
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目的应用PCR-DGGE技术对结直肠癌患者肠道黏膜局部菌群多样性进行研究,为结直肠病变的防治提供微生态调节思路。方法收集正常对照组、结直肠息肉组及结直肠癌组患者各30例,采集结直肠黏膜局部肛拭子,提取细菌基因组DNA,采用PCR-DGGE对肠道黏膜局部菌群进行指纹图谱分析。结果正常对照组、结直肠息肉组和结直肠癌组患者PCR-DGGE指纹图谱分析显示3组肠道黏膜局部菌群多样性发生了显著的变化,3组肠道黏膜局部菌群发生了显著的菌群变迁。结论 PCR-DGGE分析结直肠癌患者肠道黏膜局部菌群多样性变化对监测肠道局部微生态变化在结直肠癌的发生过程中的作用具有重要价值。 相似文献
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Tingting Wang Guoxiang Cai Yunping Qiu Na Fei Menghui Zhang Xiaoyan Pang Wei Jia Sanjun Cai Liping Zhao 《The ISME journal》2012,6(2):320-329
Despite a long-suspected role in the development of human colorectal cancer (CRC), the composition of gut microbiota in CRC patients has not been adequately described. In this study, fecal bacterial diversity in CRC patients (n=46) and healthy volunteers (n=56) were profiled by 454 pyrosequencing of the V3 region of the 16S ribosomal RNA gene. Both principal component analysis and UniFrac analysis showed structural segregation between the two populations. Forty-eight operational taxonomic units (OTUs) were identified by redundancy analysis as key variables significantly associated with the structural difference. One OTU closely related to Bacteroides fragilis was enriched in the gut microbiota of CRC patients, whereas three OTUs related to Bacteroides vulgatus and Bacteroides uniformis were enriched in that of healthy volunteers. A total of 11 OTUs belonging to the genera Enterococcus, Escherichia/Shigella, Klebsiella, Streptococcus and Peptostreptococcus were significantly more abundant in the gut microbiota of CRC patients, and 5 OTUs belonging to the genus Roseburia and other butyrate-producing bacteria of the family Lachnospiraceae were less abundant. Real-time quantitative PCR further validated the significant reduction of butyrate-producing bacteria in the gut microbiota of CRC patients by measuring the copy numbers of butyryl-coenzyme A CoA transferase genes (Mann–Whitney test, P<0.01). Reduction of butyrate producers and increase of opportunistic pathogens may constitute a major structural imbalance of gut microbiota in CRC patients. 相似文献
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Colorectal cancer(CRC)and hepatocellular carcinoma(HCC)are the second and third most common causes of death by cancer,respectively.The etiologies of the two cancers are either infectious insult or due to chronic use of alcohol,smoking,diet,obesity and diabetes.Patho-logical changes in the composition of the gut microbiota that lead to intestinal inflammation are a common factor for both HCC and CRC.However,the gut microbiota of the cancer patient evolves with disease pathogenesis in unique ways that are affected by etiologies and envi-ronmental factors.in this review,we examine the chan-ges that occur in the composition of the gut microbiota across the stages of the HCC and CRC.Based on the idea that the gut microblota are an additional\"lifeline\"and contribute to the tumor microenvironment,we can observe from previously published literature how the microbiota can cause a shift in the balance from normal→ inflammation → diminished inflammation from early to later disease stages.This pattern leads to the hypothesis that tumor survival depends on a less pro-inflammatory tumor microenvironment.The differences observed in the gut microbiota composition between different disease etiologies as well as between HCC and CRC suggest that the tumor microenvironment is unique for each case. 相似文献
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Despite the success of colonoscopy screening and recent advances in cancer treatment, colorectal cancer (CRC) still remains one of the most commonly diagnosed and deadly cancers, with a significantly increased incidence in developing countries where people are adapting to Western lifestyle. Diet has an important impact on risk of CRC. Multiple epidemiological studies have suggested that excessive animal protein and fat intake, especially red meat and processed meat, could increase the risk of developing CRC while fiber could protect against colorectal tumorigenesis. Mechanisms have been investigated by animal studies.Diet could re-shape the community structure of gut microbiota and influence its function by modulating the production of metabolites. Butyrate, one of the short-chain fatty acids (SCFAs), which act as a favorable source for colonocytes, could protect colonic epithelial cells from tumorigenesis via anti-inflammatory and antineoplastic properties through cell metabolism, microbiota homeostasis, antiproliferative, immunomodulatory and genetic/epigenetic regulation ways. In contrast, protein fermentation and bile acid deconjugation, which cause damage to colonic cells through proinflammatory and proneoplastic ways, lead to increasedriskofdevelopingCRC.In conclusion, abalanced diet with an increased abundance of fiber should be adopted to reduce the risk and prevent CRC. 相似文献
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Gang Wang Yang Yu Yu-Zhu Wang Jun-Jie Wang Rui Guan Yan Sun Feng Shi Jing Gao Xing-Li Fu 《Journal of cellular physiology》2019,234(10):17023-17049
Increased risk of colorectal cancer (CRC) is associated with altered intestinal microbiota as well as short-chain fatty acids (SCFAs) reduction of output The energy source of colon cells relies mainly on three SCFAs, namely butyrate (BT), propionate, and acetate, while CRC transformed cells rely mainly on aerobic glycolysis to provide energy. This review summarizes recent research results for dysregulated glucose metabolism of SCFAs, which could be initiated by gut microbiome of CRC. Moreover, the relationship between SCFA transporters and glycolysis, which may correlate with the initiation and progression of CRC, are also discussed. Additionally, this review explores the linkage of BT to transport of SCFAs expressions between normal and cancerous colonocyte cell growth for tumorigenesis inhibition in CRC. Furthermore, the link between gut microbiota and SCFAs in the metabolism of CRC, in addition, the proteins and genes related to SCFAs-mediated signaling pathways, coupled with their correlation with the initiation and progression of CRC are also discussed. Therefore, targeting the SCFA transporters to regulate lactate generation and export of BT, as well as applying SCFAs or gut microbiota and natural compounds for chemoprevention may be clinically useful for CRCs treatment. Future research should focus on the combination these therapeutic agents with metabolic inhibitors to effectively target the tumor SCFAs and regulate the bacterial ecology for activation of potent anticancer effect, which may provide more effective application prospect for CRC therapy. 相似文献
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《Cell host & microbe》2021,29(10):1573-1588.e7
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Singh N Shirdel EA Waldron L Zhang RH Jurisica I Comelli EM 《International journal of biological sciences》2012,8(2):171-186
The intestinal messenger RNA expression signature is affected by the presence and composition of the endogenous microbiota, with effects on host physiology. The intestine is also characterized by a distinctive micronome. However, it is not known if microbes also impact intestinal gene expression epigenetically. We investigated if the murine caecal microRNA expression signature depends on the presence of the microbiota, and the potential implications of this interaction on intestinal barrier function. Three hundred and thirty four microRNAs were detectable in the caecum of germ-free and conventional male mice and 16 were differentially expressed, with samples from the two groups clustering separately based on their expression patterns. Through a combination of computational and gene expression analyses, including the use of our curated list of 527 genes involved in intestinal barrier regulation, 2,755 putative targets of modulated microRNAs were identified, including 34 intestinal barrier-related genes encoding for junctional and mucus layer proteins and involved in immune regulation. This study shows that the endogenous microbiota influences the caecal microRNA expression signature, suggesting that microRNA modulation is another mechanism through which commensal bacteria impact the regulation of the barrier function and intestinal homeostasis. Through microRNAs, the gut microbiota may impinge a much larger number of genes than expected, particularly in diseases where its composition is altered. In this perspective, abnormally expressed microRNAs could be considered as novel therapeutic targets. 相似文献
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近年来人们越来越重视肠道菌群在肠源性疾病的发生、发展及防治中所发挥的作用。脆弱拟杆菌(Bacteroides fragilis,BF)是定殖于人体肠道中的共生菌,对肠道健康有多种影响,是健康人群及腹泻、腹膜炎、腹内脓肿、败血症、炎症性肠病等临床病例最常见的肠道微生物。随着人们对脆弱拟杆菌的深入研究,发现脆弱拟杆菌与炎症性肠病(inflammatory bowel disease,IBD)、结直肠癌(colorectal cancer,CRC)有密切关系。通过对脆弱拟杆菌与IBD、CRC之间的关系进行综述,探究脆弱拟杆菌在IBD、CRC促进、调控及防治中的作用,为IBD、CRC的早期干预和治疗提供新思路,为开发基于脆弱拟杆菌的药物提供数据与思路。 相似文献