便检肠道微生物预测结直肠癌

《自然·医学》杂志在线发表两篇研究报告,研究者从近千份人类粪便样品中找出可用于预测结直肠癌的肠道菌群特征。虽然两项研究选取的样本来自欧洲、亚洲和美洲多个国家不同环境下有不同饮食习惯的人群,但肠道菌群微生物组在结直肠癌发生时有一致的特异性改变。近年来,越来越多的研究证据显示,肠道微生物对人类健康有重要影响,包括肿瘤发生和对治疗的反应等。两项研究中,一项由欧洲分子生物学实验室研究者开展,5项研究对386例结直肠癌患者和392名健康对照者粪便样本进行了宏基因组分析,分析粪便样本中整个微生物群体的遗传物质,找出结直肠癌患者肠道菌群哪些与健康人群有显著差异。     

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。     

便检肠道微生物预测结直肠癌

<正>《自然·医学》杂志上在线发表两篇研究报告,研究者从近千份人类粪便样品中找出可用于预测结直肠癌的肠道菌群特征,尽管两项研究样本来自欧洲、亚洲和美洲多个国家,粪便样本来自生活在不同环境有不同饮食习惯的人群,但肠道菌群微生物组在结直肠癌发生时有一致的特异性改变。近年来,越来越多的研究证据显示,肠道微生物对人类健康有重要影响,包括肿瘤发生和对治疗的反应等。欧洲分子生物学实验室研究者基于5项研究386例结直肠癌患者和392名健康对照者粪便样本进行了宏基因组分析,对粪便样本中     

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。     

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。     

口腔微生物与结直肠癌相关性的研究进展

随着微生物研究的不断深入及微生物组学技术的发展,口腔微生物在疾病发生发展中的作用逐渐显现.口腔微生物与结直肠癌密切相关,该文拟从传播途径、定植机制、肿瘤发生发展等方面对两者相关性进行探讨.此外,口腔微生物在结直肠癌检测中具有一定临床诊断价值,针对口腔微生物的治疗能为结直肠癌治疗提供新的方向.     

微生物群滋养性免疫在结直肠癌发生发展中的作用

摘 要：微生物群滋养性免疫通过抑制肠道有害细菌、真菌的定植和异常扩张，在维持人体肠道微生物稳态、正常肠上皮细胞完整性及重塑宿主免疫系统中发挥了极其重要的作用。肠道微生物稳态的破坏及致病微生物的异常扩张所介导的炎症微环境及免疫功能异常已被反复证实与结直肠癌的发生发展具有紧密的联系。全文就微生物群滋养性免疫在抑制结直肠癌发生发展中的作用进行综述，并解释其中关键的作用机制。     

微生物与结直肠癌的发病机制、早期诊断和治疗的研究进展

结直肠癌是威胁人类健康的重大疾病之一，随着近年来微生物组学技术的发展，很多研究报道了微生物与结直肠癌发生发展的关系，发现了具核梭杆菌、脆弱拟杆菌等微生物促进结直肠癌发生的分子机制以及短链脂肪酸等细菌代谢产物抑制结直肠癌发生发展的作用。利用结直肠癌患者与健康人群之间的差异微生物，可以建立基于微生物标志物的结直肠癌诊断模型，使结直肠癌的早发现、早诊断成为可能。在结直肠癌的治疗领域，微生物可能成为抑制结直肠癌发生发展的药物靶点，并且能够影响化疗药物的疗效与不良反应。本文以微生物与结直肠癌的关系为切入点，结合近年的相关文献及自身研究，对微生物与结直肠癌的发病机制、早期诊断和治疗的研究进展作一综述。     

肠道微生物群调节癌症治疗效果的研究进展

系统生物学为发现肠道微生物群在人类健康几乎所有方面的作用提供了机会。现有证据支持肠道微生物群与化学治疗和新型靶向免疫治疗的药理作用密切相关的假设。肠道微生物群通过以下几个关键机制影响药物的治疗效果:代谢、免疫调节、易位、酶降解、多样性降低和生态变异。因此,肠道微生物群有望成为提高肿瘤治疗效果、降低肿瘤治疗不良反应的新靶点。越来越多的证据表明,癌症治疗扰乱宿主的免疫反应,导致免疫系统失调,进而影响治疗效果。肠道微生物通过调节药物疗效、影响抗癌作用和介导毒性,在肿瘤治疗中发挥重要作用。作者概述了肠道微生物群在癌症治疗中的调节作用,以及其在临床实践中提高化疗和免疫治疗效果的意义。     

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.     

Microbiota regulation in constipation and colorectal cancer

The relevance of constipation to the development and progression of colorectal cancer (CRC) is currently a controversial issue. Studies have shown that changes in the composition of the gut microbiota, a condition known as ecological imbalance, are correlated with an increasing number of common human diseases, including CRC and constipation. CRC is the second leading cause of cancer-related deaths worldwide, and constipation has been receiving widespread attention as a risk factor for CRC. Early colonoscopy screening of constipated patients, with regular follow-ups and timely intervention, can help detect early intestinal lesions and reduce the risks of developing colorectal polyps and CRC. As an important regulator of the intestinal microenvironment, the gut microbiota plays a critical role in the onset and progression of CRC. An increasing amount of evidence supports the thought that gut microbial composition and function are key determinants of CRC development and progression, with alterations inducing changes in the expression of host genes, metabolic regulation, and local and systemic immunological responses. Furthermore, constipation greatly affects the composition of the gut microbiota, which in turn influences the susceptibility to intestinal diseases such as CRC. However, the crosstalk between the gut microbiota, constipation, and CRC is still unclear.     

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.     

The Microbiota: A New Player in the Etiology of Colorectal Cancer

Colorectal cancer is one of the commonest forms of cancer worldwide. Although the molecular pathogenesis of colorectal cancer shares many characteristics with that of other cancers, the tissue environment is unique in that the intestinal mucosal surface is continuously exposed to a vast community of microorganisms. It is increasingly recognized that the intestinal microbiota is a critical component of the tumor environment that contributes to the development of colorectal cancer, and certain members of the commensal microbiota have been identified as critical elements in intestinal carcinogenesis. As sensors of the presence of microbes at mucosal surfaces, pattern-recognition receptors of the innate immune system are equally involved in this process. This review summarizes our current knowledge of the role of the microbiota in colorectal cancer development and provides an overview of the mechanisms involved in the cross talk between intestinal microbial colonization and tumorigenesis.     

The role of gut microbiota in the pathogenesis of colorectal cancer

The human gastrointestinal tract harbors a complex and abundant microbial community that can reach levels as high as 10¹³–10¹⁴ microorganisms in the colon. These microorganisms are essential to a host’s well-being in terms of nutrition and mucosa immunity. However, numerous studies have also implicated members of the colonic microbiota in the development of colorectal cancer (CRC). While CRC involves a genetic component where damaged DNA and genetic instability initiates a malignant transformation, environmental factors can also contribute to the onset of CRC. Furthermore, considering the constant exposure of the colonic mucosa to the microbiome and/or its metabolites, the mucosa has long been proposed to contribute to colon tumorigenesis. However, the mechanistic details of these associations remain unknown. Fortunately, due to technical and conceptual advances, progress in characterizing the taxonomic composition, metabolic capacity, and immunomodulatory activity of human gut microbiota have been made, thereby elucidating its role in human health and disease. Furthermore, the use of experimental animal models and clinical/epidemiological studies of environmental etiological factors has identified a correlation between gut microbiota composition and gastrointestinal cancers. Bacteria continuously stimulate activated immunity in the gut mucosa and also contribute to the metabolism of bile and food components. However, the highest levels of carcinogen production are also associated with gut anaerobic bacteria and can be lowered with live lactobacilli supplements. In this review, evidence regarding the relationship between microbiota and the development of CRC will be discussed, as well as the role for microbial manipulation in affecting disease development.     

Fecal microbiota transplantation in cancer management: Current status and perspectives

The human gut is home to a large and diverse microbial community, comprising about 1,000 bacterial species. The gut microbiota exists in a symbiotic relationship with its host, playing a decisive role in the host's nutrition, immunity and metabolism. Accumulating studies have revealed the associations between gut dysbiosis or some special bacteria and various cancers. Emerging data suggest that gut microbiota can modulate the effectiveness of cancer therapies, especially immunotherapy. Manipulating the microbial populations with therapeutic intent has become a hot topic of cancer research, and the most dramatic manipulation of gut microbiota refers to fecal microbiota transplantation (FMT) from healthy individuals to patients. FMT has demonstrated remarkable clinical efficacy against Clostridium difficile infection (CDI) and it is highly recommended for the treatment of recurrent or refractory CDI. Lately, interest is growing in the therapeutic potential of FMT for other diseases, including cancers. We briefly reviewed the current researches about gut microbiota and its link to cancer, and then summarized the recent preclinical and clinical evidence to indicate the potential of FMT in cancer management as well as cancer-treatment associated complications. We also presented the rationale of FMT for cancer management such as reconstruction of intestinal microbiota, amelioration of bile acid metabolism, and modulation of immunotherapy efficacy. This article would help to better understand this new therapeutic approach for cancer patients by targeting gut microbiota.     

Familial adenomatous polyposis and changes in the gut microbiota: New insights into colorectal cancer carcinogenesis

Patients with familial adenomatous polyposis (FAP), an autosomal dominant hereditary colorectal cancer syndrome, have a lifetime risk of developing cancer of nearly 100%. Recent studies have pointed out that the gut microbiota could play a crucial role in the development of colorectal adenomas and the consequent progression to colorectal cancer. Some gut bacteria, such as Fusobacterium nucleatum, Escherichia coli, Clostridium difficile, Peptostreptococcus, and enterotoxigenic Bacteroides fragilis, could be implicated in colorectal carcinogenesis through different mechanisms, including the maintenance of a chronic inflammatory state, production of bioactive tumorigenic metabolites, and DNA damage. Studies using the adenomatous polyposis coli^Min/+ mouse model, which resembles FAP in most respects, have shown that specific changes in the intestinal microbial community could influence a multistep progression, the intestinal “adenoma-carcinoma sequence”, which involves mucosal barrier injury, low-grade inflammation, activation of the Wnt pathway. Therefore, modulation of gut microbiota might represent a novel therapeutic target for patients with FAP. Administration of probiotics, prebiotics, antibiotics, and nonsteroidal anti-inflammatory drugs could potentially prevent the progression of the adenoma-carcinoma sequence in FAP. The aim of this review was to summarize the best available knowledge on the role of gut microbiota in colorectal carcinogenesis in patients with FAP.     

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.     

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.