肠道菌群与恶性肿瘤的研究进展

人类微生物群是由寄生在人体上皮屏障的细菌和其他微生物组成的，其中大部分位于肠道内，与宿主之间形成共生的关系。机体肠道微生物的组成虽然受到年龄、饮食、生活方式等因素的影响，但在正常生理情况下是相对稳定的。近年来，肠道菌群与恶性肿瘤的关系越来越受到重视。肠道菌群不但能够维持局部稳态，还能调节机体代谢、炎症和免疫等生理过程。有研究表明，微生物群，特别是肠道菌群能够显著调节机体对癌症治疗的反应性以及机体对毒副反应的敏感性。检查肠道菌群中各菌种之间的比例可作为筛查恶性肿瘤的新方法。本文将综述微生物群具有影响肿瘤的发生发展、抗肿瘤治疗疗效以及药物不良反应的证据，以及其中所涉及的微生物种类，从而为恶性肿瘤精准治疗提供证据。     

肠道微生物群衍生的代谢产物调控结直肠癌的新进展

肠道生态系统的改变会影响人类的健康,甚至引发结直肠癌。大量证据表明,在结直肠癌患者的肠道中普遍存在一种病理性微生物群失衡状态,失衡的微生物群衍生的代谢产物也会影响结直肠癌的发生发展。本文综述了由特定肠道微生物群代谢产物触发结直肠癌进程的方式,总结了肠道微生物群代谢产物对结直肠癌贡献的最新进展,并考虑代谢产物的积累效应以及多种代谢产物相结合的方式来预测和预防结直肠癌。     

肠道微生物稳态与肝癌关系的研究进展

[摘要] 肝细胞癌（hepatocellular carcinoma,HCC）是全球发病率和死亡率较高的恶性肿瘤之一。菌群平衡对于维持肠道和全身态的代谢与免疫非常重要,肠道微生物与肝细胞癌的形成密切相关。肠漏、菌群失衡、微生物代谢物及免疫抑制是导致肝细胞癌形成的主要机制。肠漏及微生物相关模式分子-Toll样受体促进肝细胞癌的发生发展;菌群失衡及菌群移位除了能引起晚期肝病的感染性并发症之外,还能使肝脏中产生慢性炎症;肠道菌群及代谢物还可影响细胞的分化;肠道菌群及代谢产物介导的免疫抑制也可促进肝细胞癌的发生。可通过靶向肠道菌群,如使用抗生素杀灭有害菌群,使用益生菌调节菌群平衡,使用药物改善肠漏,使用药物拮抗TLR等策略来抑制肝细胞癌的发生。肠道微生物稳态与肝癌的研究进展为有效预防和治疗肝癌提出了新的策略。     

肠道微生物群在肿瘤中的作用和机制研究进展

肠道微生物群参与人类疾病的调控。随着宏基因组学和代谢组学技术的发展,肠道微生物群在癌症中的作用受到了研究者们的重视。相比于健康人群,不同癌症患者肠道微生物群的种类和丰度及其代谢产物存在差别,这提示我们可以借助肠道微生物群检测为癌症无创诊断提供更加敏感且易于被接受的新方法,以期实现癌症的早期诊断。不同的肠道微生物群和其代谢产物可能对肿瘤起着促进或抑制的作用,并且这一过程可能受到饮食、吸烟等其他因素的影响。相比于健康人群,癌症患者的肠道微生物群发生了变化,而这些变化还可以影响癌症患者对化疗或免疫治疗的反应。靶向肠道微生物群为癌症的诊断和治疗提供了新的思路和方法。本文综述了肠道微生物群在癌症中的作用和机制研究进展。     

肠道微生物在结直肠癌发生发展及诊疗中作用的新进展

肠道生态系统的改变会影响人类的健康，甚至引发结直肠癌。大量证据表明，在结直肠癌患者的肠道中普遍存在一种病理性微生物群失衡状态。本综述从免疫与炎症反应、肠道微生物代谢产物和基因损伤三个方面总结了肠道微生物引发结直肠癌的机制，介绍了肠道微生物群相关的结直肠癌诊断标志物，分析了肠道微生物在结直肠癌放化疗及免疫治疗中的新进展,希望为结直肠癌的防治及诊疗提供新的机会。     

肿瘤患者脂肪酸营养与肠道微环境的关系

我国恶性肿瘤的发病率和死亡率呈逐年上升趋势。恶性肿瘤，尤其是胃肠道肿瘤的发生和发展与肠道微环境失 调即肠道微生物紊乱密切相关；脂肪酸尤其是必需脂肪酸是人体生长发育及维持生命过程的重要营养物质，肠道微生物介 导胃肠道消化和吸收脂肪酸。脂代谢失调和肠道微生物作用密切关联，引发胃肠道炎症，导致肠道通透性增加，毒素进入 体内，最终产生免疫反应。肠道微生物群通过病原微生物和肿瘤抗原之间的交叉反应，形成T细胞储备和（或）微生物产品， 刺激模式识别受体，从而影响免疫反应的类型和强度。通过对免疫的影响， 微生物群有助于对远处肿瘤的免疫控制或逃逸。 微生物源性代谢产物也可以通过直接细胞自主致癌机制来促进局部肿瘤的发展。恶性肿瘤的防治过程中，应重视脂肪酸营 养和肠道微环境的重要作用。脂肪酸也可以根据患者的需要通过肠外通路提供。晚期恶性肿瘤患者往往伴有营养不良或异 质性。补充ω-3 多不饱和脂肪酸可以改善患者的体质，有助于肿瘤的治疗。通过补充益生菌或移植肠道微生物群，可以矫 正肠道微生物群紊乱，在肿瘤的防治中发挥重要作用。     

膳食模式、肠道菌群与结直肠癌

结直肠癌是一种发病率和致死率均极高的肿瘤疾病,其发生和发展由基因、环境、生活方式等多方面因素共同决 定,并往往伴随着肠道微环境的改变。膳食成分是调节肠道微环境的重要因素。现阶段,越来越多的研究关注了饮食模式、膳 食成分和结直肠癌间的关系。本文首先讨论了不同膳食模式对结直肠癌发生风险的影响,证明了西方饮食可能促进结直肠癌 的发生,而地中海饮食、能量限制饮食、素食饮食和生酮饮食对结直肠癌具有一定的预防和干预作用。进一步分析了各类膳食 成分如何通过直接作用或通过调节肠道菌群间接影响了结直肠癌的发生发展。其中,多酚类物质、胡萝卜素、膳食纤维等,可 以维持肠道稳态,改善肠道内炎症及氧化应激等,从而降低结直肠癌的发病风险。而特定膳食成分的缺失或过剩则可以改变 肠道微生物组成,诱导肿瘤相关微生物丰度的升高,造成有毒代谢产物的积累,进而促进肠道炎症和肿瘤的发生。最后,本文 提出了一套针对结直肠癌患者的个性化饮食干预策略思路。利用宏基因组、宏转录组、代谢组等多组学手段,结合人工智能分 析结直肠患者菌群组成及功能上的异常,进一步设计个性化的膳食模式,以实现患者肠道菌群的精准调节,并对结直肠癌患者 进行膳食干预。     

肠道菌群在肿瘤免疫治疗中的作用研究进展

肠道微生物与肿瘤发生、发展关系密切。机体暴露于大量肠道菌群及其代谢产物中,构成机体的生态环境,肠道微生物通过多种途径参与肿瘤的发生与发展。肠道菌群在肿瘤的治疗中发挥重要作用。目前,肿瘤免疫检测点抑制剂在多种恶性肿瘤中的治疗取得重要突破,肠道微生物组对肿瘤免疫治疗,尤其是免疫检测点抑制剂的疗效产生重要影响。本文就近年来肠道菌群对肿瘤免疫治疗中的作用及影响展开综述,为免疫检测点抑制剂在肿瘤治疗中的应用提供参考。      

肠道微生物影响结直肠癌化疗疗效的研究现状

肠道微生物是一个与机体健康密切相关的“生态系统”。一方面,肠道微生物可以为机体提供营养物质、参与机体新陈代谢和免疫调节,抵御病原体、发挥生物屏障功能等。另一方面,肠道微生物及其代谢产物可参与结直肠癌的发生,调节化疗药物及免疫检查点抑制剂作用机制,继而影响化疗及免疫治疗疗效、调节相关不良反应。基于既往大量肠道微生物研究及相关文献,本文将综述肠道微生物影响结直肠癌化疗药物作用机制、疗效的现状,其有望成为提高结直肠癌化疗疗效、降低药物毒副反应的新靶点。     

肠道菌群在肠道屏障功能维护中的作用和机制

胃肠道是重要的消化器官,其表面稳定而具有功能性的黏膜屏障是分隔机体内环境与食物抗原及微生物的生物界面.肠道菌群是定植于人体最大的微生态系统,在维持内外环境稳态中具有重要作用,肠道菌群紊乱主要体现于共生菌及病原菌的生长失衡,并与疾病的进展密切相关.越来越多的证据表明,肠道菌群作为一个完整的生态系统其组成或代谢产物影响肠道黏膜屏障结构和功能的完整性.本文就肠道菌群对肠道黏膜屏障的作用及机制进行介绍,为了解肠道微生物的研究进展提供部分参考.     

Diet,Gut Microbiota,and Colorectal Cancer Prevention: a Review of Potential Mechanisms and Promising Targets for Future Research

Diet plays an important role in the development of colorectal cancer. Emerging data have implicated the gut microbiota in colorectal cancer. Diet is a major determinant for the gut microbial structure and function. Therefore, it has been hypothesized that alterations in gut microbes and their metabolites may contribute to the influence of diet on the development of colorectal cancer. We review several major dietary factors that have been linked to gut microbiota and colorectal cancer, including major dietary patterns, fiber, red meat and sulfur, and obesity. Most of the epidemiologic evidence derives from cross-sectional or short-term, highly controlled feeding studies that are limited in size. Therefore, high-quality large-scale prospective studies with dietary data collected over the life course and comprehensive gut microbial composition and function assessed well prior to neoplastic occurrence are critically needed to identify microbiome-based interventions that may complement or optimize current diet-based strategies for colorectal cancer prevention and management.     

Highlights in the prevention of sporadic colorectal cancer

Colorectal cancer is one of the most often diagnosed malignant tumors in humans. Undoubtedly, dietary patterns and lifestyle are strongly implicated in the pathogenesis of sporadic colorectal cancer. Evidence is emerging for the participation of human gut microflora in the pathogenesis of colorectal cancer. Chemoprevention of colorectal cancer with medications is an attractive opportunity, although the results from clinical trials are inconclusive. This review discusses the association between the colorectal cancer and some of the most important dietary and lifestyle risk factors, as well as the role of gut microbiota and chemoprevention with acetylsalicylic acid in colorectal cancer.     

肠道菌群与免疫检查点抑制剂研究进展

肠道菌群能够通过局部或全身炎性反应影响肿瘤的发生、发展以及治疗。目前,肠道菌群在肿瘤治疗中的作用越来越显著,研究发现,肠道菌群影响实体瘤免疫检查点抑制剂治疗反应,但造成个体间免疫反应差异的机制尚不清楚。有学者认为,肠道菌群在其中可能发挥潜在的调节作用。例如嗜黏蛋白-艾克曼菌、乳酸杆菌及双歧杆菌等都具有调节肿瘤细胞及免疫细胞功能,并促进多种细胞因子的产生,进而提高免疫检查点抑制剂治疗效果。因此,本文就肠道菌群对肿瘤细胞及免疫细胞的影响和目前肠道菌群与免疫检查点抑制剂的研究现状做一阐述。     

Differential susceptibility to colorectal cancer due to naturally occurring gut microbiota

Recent studies investigating the human microbiome have identified particular bacterial species that correlate with the presence of colorectal cancer. To evaluate the role of qualitatively different but naturally occurring gut microbiota and the relationship with colorectal cancer development, genetically identical embryos from the Polyposis in Rat Colon (Pirc) rat model of colorectal cancer were transferred into recipients of three different genetic backgrounds (F344/NHsd, LEW/SsNHsd, and Crl:SD). Tumor development in the pups was tracked longitudinally via colonoscopy, and end-stage tumor burden was determined. To confirm vertical transmission and identify associations between the gut microbiota and disease phenotype, the fecal microbiota was characterized in recipient dams 24 hours pre-partum, and in Pirc rat offspring prior to and during disease progression. Our data show that the gut microbiota varies between rat strains, with LEW/SsNHsd having a greater relative abundance of the bacteria Prevotella copri. The mature gut microbiota of pups resembled the profile of their dams, indicating that the dam is the primary determinant of the developing microbiota. Both male and female F344-Pirc rats harboring the Lewis microbiota had decreased tumor burden relative to genetically identical rats harboring F344 or SD microbiota. Significant negative correlations were detected between tumor burden and the relative abundance of specific taxa from samples taken at weaning and shortly thereafter, prior to observable adenoma development. Notably, this naturally occurring variation in the gut microbiota is associated with a significant difference in severity of colorectal cancer, and the abundance of certain taxa is associated with decreased tumor burden.     

Mechanisms linking dietary fiber,gut microbiota and colon cancer prevention

Many epidemiological and experimental studies have suggested that dietary fiber plays an important role in colon cancer prevention. These findings may relate to the ability of fiber to reduce the contact time of carcinogens within the intestinal lumen and to promote healthy gut microbiota, which modifies the host’s metabolism in various ways. Elucidation of the mechanisms by which dietary fiber-dependent changes in gut microbiota enhance bile acid deconjugation, produce short chain fatty acids, and modulate inflammatory bioactive substances can lead to a better understanding of the beneficial role of dietary fiber. This article reviews the current knowledge concerning the mechanisms via which dietary fiber protects against colon cancer.     

Gut-liver axis-mediated mechanism of liver cancer: A special focus on the role of gut microbiota

Gut microbiota and the mammalian host share a symbiotic relationship, in which the host provides a suitable ecosystem for the gut bacteria to digest indigestible nutrients and produce useful metabolites. Although gut microbiota primarily reside in and influence the intestine, they also regulate liver function via absorption and subsequent transfer of microbial components and metabolites through the portal vein to the liver. Due to this transfer, the liver may be continuously exposed to gut-derived metabolites and components. For example, short-chain fatty acids (SCFA) produced by gut microbiota, through the fermentation of dietary fiber, can suppress inflammation via regulatory T cell induction through SCFA-induced epigenetic mechanisms. Additionally, secondary bile acids (BA), such as deoxycholic acid, produced by gut bacteria through the 7α-dehydroxylation of primary BAs, are thought to induce DNA damage and contribute to the remodeling of tumor microenvironments. Other substances that are also thought to influence liver function include lipopolysaccharides (components of the outer membrane of gram-negative bacteria) and lipoteichoic acid (cell wall component of Gram-positive bacteria), which are ligands of innate immune receptors, Toll-like receptor-4, and Toll-like receptor-2, respectively, through which inflammatory signaling is elicited. In this review, we focus on the role of gut microbiota in the liver microenvironment, describing the anatomy of the gut-liver axis, the role of gut microbial metabolites, and the relationships that exist between gut microbiota and liver diseases, including liver cancer.     

Race,the microbiome and colorectal cancer

In the past decade, more cancer researchers have begun to understand the significance of cancer prevention, which has prompted a shift in the increasing body of scientific literature. An area of fascination and great potential is the human microbiome. Recent studies suggest that the gut microbiota has significant roles in an individual’s ability to avoid cancer, with considerable focus on the gut microbiome and colorectal cancer. That in mind, racial disparities with regard to colorectal cancer treatment and prevention are generally understudied despite higher incidence and mortality rates among Non-Hispanic Blacks compared to other racial and ethnic groups in the United States. A comprehension of ethnic differences with relation to colorectal cancer, dietary habits and the microbiome is a meritorious area of investigation. This review highlights literature that identifies and bridges the gap in understanding the role of the human microbiome in racial disparities across colorectal cancer. Herein, we explore the differences in the gut microbiota, common short chain fatty acids produced in abundance by microbes, and their association with racial differences in cancer acquisition.     

左右半结肠癌研究进展

结直肠癌是最常见的消化道恶性肿瘤之一, 根据肿瘤原发部位的不同, 其发病率、发病机制、临床特征、生存预后、分子生物学特征及肠道菌群等方面均存在差异。本文主要针对结直肠癌原发部位的不同, 阐述了相关分子生物学、肠道菌群以及免疫治疗的最新研究进展。不同的分子生物学特征导致了临床治疗反应的差异, 从而导致了临床预后的差异, 通过总结其中的规律, 可以提高临床对结直肠癌中不同原发部位肿瘤的一系列不同特征的深刻认识, 为提高及完善临床治疗提供进一步理论依据。