肠道微生态在结直肠癌诊断中的研究进展

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。     

微生态调节剂对大负荷运动下肠道微生物群调节作用的研究进展

大负荷运动不仅会使运动系统如骨骼、骨骼肌等受到影响，还可导致消化系统出现功能障碍，包括肠道微生物群失调、微生物多样性降低、肠屏障功能损伤等问题。而益生菌、益生元等微生态调节剂则可以对肠屏障功能、肠道微生物群等起到积极的调节作用，降低大负荷运动所引起的不良影响，提高恢复能力，进而提高运动表现。这提示微生态调节剂作为营养补剂在运动营养领域中具有重要的应用前景。该文对大负荷运动影响肠道微生物群及其作用机制进行介绍，并梳理益生菌、益生元等微生态调节剂对肠道微生物群的调节作用。     

益生菌在结直肠癌患者中的应用

结直肠癌(colorectal cancer,CRC)的发病率及病死率在多国多年居高不下,肠道微生态的失衡在CRC的发生发展中所起的作用被许多学者所证实。专家一致认为,积极纠正肠道微生态失衡是可取的。CRC患者术前肠道菌群已经出现改变,术后肠道菌群失衡加重,化疗会进一步加重这种失衡状态。肠道微生态的稳态对机体肠道功能和免疫功能等起着重要作用。益生菌作为一种可调节肠道菌群的微生态制剂,已显现出在CRC患者治疗中的应用价值,现对益生菌在CRC患者中的应用进展作一综述。     

肠道微生态与白血病的研究进展

微生物群与人体的健康密切相关,约20%的恶性肿瘤与微生态失调有关。研究显示肠道微生物可以调节造血,其与血液系统疾病的关系逐渐得到研究者的关注,肠道微生物参与白血病的发生发展,影响白血病的治疗效果。较早的暴露于微生物群是儿童白血病的保护性因素,化疗会引起肠道微生物紊乱,肠道微生物可以改变化疗药物的疗效和毒性,其多样性和组成能够预测化疗相关的并发症,通过微生态制剂和粪菌移植可以减少化疗相关的并发症。本文从肠道微生态与白血病及其并发症的关系,以及调节肠道微生态对白血病的影响两个方面的最新进展进行综述。     

母乳糖复合物对新生儿肠道菌群的影响

母乳是新生儿最理想的营养来源。母乳喂养不仅维持婴儿的发育,也促进有益的肠道微生物增殖。母乳中的糖复合物,包括游离的低聚糖、糖蛋白和糖脂,因在肠道健康和菌群调节方面起着重要作用而被越来越多的人所重视。这些糖类物质不仅能预防传染病,也可作为益生元调节肠道微生态。新生儿出生时肠道是不成熟的,复杂的母乳成分确保了肠道微环境成熟。婴儿的肠道微生物群的构成在出生后会发生连续变化。出生后的细菌定植是肠道发育和免疫系统成熟的必要条件。本文将母乳中糖物质及对婴儿肠道菌群的影响作一综述。     

肠道微生物群在人类健康衰老中的作用机制研究进展北大核心

衰老的特征是组织器官的功能衰退以及衰老相关疾病风险的增加,这给维护和促进健康长寿带来一系列新的挑战。尽管进行了广泛的衰老相关研究,但进展有限。人们越来越意识到肠道微生物群的结构和功能积极参与了衰老过程。肠道微生物群紊乱表现为许多与年龄相关的肠外器官轴的衰老。肠道微生物群可以被调节,这暗示了通过肠道微生物群抗衰老是一个可以实现的重要目标。本综述总结了肠道微生物群在不同年龄段中的动态演替,这种动态的肠道微生物群从胎儿到出生和婴儿期开始迅速发展,从断奶期到幼儿期迅速变化,然后建立稳定的成年人菌群,直到随着年龄增长最后发生衰退;肠道微生物群与肠外器官轴(大脑、心脏、肝脏、胰腺、肌肉、皮肤和骨骼)衰老相关疾病,以及通过饮食、粪菌移植和微生态制剂调节肠道微生物群靶向抗衰老的研究进展,以期为调控肠道微生物群抗衰老研究提供参考。     

肠道微生物群对肺部免疫微环境稳态影响的研究进展

肠道微生物群是与宿主共生的最大的微生态系统的重要组成部分,它们通过调节宿主的内分泌、代谢、神经和免疫微环境影响人体的多种基本功能。近年来,肠道微生物群对机体局部和远端免疫器官的影响引起了科学家们的广泛关注。肠道微生物和肺之间的相互作用被称为“肠-肺轴”,对肺部免疫微环境稳态的维持至关重要。研究表明,肠道微生物群失调与哮喘、肺炎和囊性纤维化等多种肺部疾病密切相关。本文将对肠道微生物群对肺部免疫微环境稳态的影响及在多种肺部疾病中的作用进行阐述,为临床通过调整肠道微生物群来治疗肺部疾病和维持肺部免疫微环境稳态提供理论依据。     

慢性腹泻患者肠道微生物群失调的调查及应用微生态学治疗的意义

本室对57例慢性腹泻患者肠道微生态的菌群变化作了初步探讨,现将结果与52例健康人的材料作了比较。实验中我们挑选肠道微生物群中具有代表性的需氧和厌氧菌10种做了定性和定量分析。健康人组10种细菌的检出率为94％～100％;病人组的检出率则为75％～96％。二组间“t”检验的结果:说明包括肠杆菌科,葡萄球菌,类杆菌、双歧杆菌、消化球菌和真杆菌属在内都表现有非常显著性差异(P<0.01),梭菌也有显著性差异(P<0.05)实验结果表明慢性腹泻患者的肠道微生物群发生了显著失调。本文从4个方面讨论了微生态失调发生的原因:1.慢性腹泻与肠道微生物群间的相互关系;2.慢性腹泻影响了肠道微生物群的生长、繁殖、以及它们的定植受阻;3.肠粘膜牯液丢失可使肠道微生物群发生紊乱;4.抗生素与肠道内微生物群的微生态失调有关。我们认为发生肠道微生物群失调时应尽快重建其间关系的平衡。治疗时不宜使用以抗生素为主的方案,而应尽可能地使用生物制剂,此外,还应减少肠道蠕动,避免肠粘膜粘液的大量排出。     

肠道微生物群与药物相互作用的研究进展

药物的代谢是机体对药物处置过程的关键步骤,而肠道作为机体中重要的微生态系统,其在药物代谢方面的作用至关重要。肠道微生物群能够对各种药物等外源化合物进行生物转化、积累,并改变这些物质的活性和毒性,从而影响宿主机体对它们的反应。肠道微生物群与药物之间的相互作用相当复杂,亟待更多更加深入、全面的发掘和研究。近年来,随着人们对肠道微生物群代谢及其与药物互作关系,肠道菌-宿主共代谢认知的不断深化,越来越多的研究表明肠道微生物在药代动力学中扮演重要角色。本文通过调研、整理、归纳和总结国内外相关文献资料,对机体肠道微生物的分类、功能,几种常用药物对肠道微生物的影响以及肠道菌群对药物的代谢作用效果与几个主要的机制进行了梳理和综述,并讨论了微生物和药物之间的双向互作。有利于增进对微生物群影响药物疗效及其代谢途径和机制的了解,提高调控肠道微生物改善治疗的可能性,为指导临床合理用药、精准用药、个体化治疗、药物的评价和新药研发等提供科学参考。     

脆弱拟杆菌在炎症性肠病、结直肠癌促进、调控及防治中的作用

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。     

Gut microbiome in tumorigenesis and therapy of colorectal cancer

Colorectal cancer (CRC) is the malignant tumor with the highest incidence in the digestive system, and the gut microbiome plays a crucial role in CRC tumorigenesis and therapy. The gastrointestinal tract is the organ harboring most of the microbiota in humans. Changes in the gut microbiome in CRC patients suggest possible host–microbe interactions, thereby hinting the potential tumorigenesis, which provides new perspective for preventing, diagnosing, or treating CRC. In this review, we discuss the effects of gut microbiome dysbiosis on CRC, and reveal the mechanisms by which gut microbiome dysbiosis leads to CRC. Gut microbiome modulation with the aim to reverse the established gut microbial dysbiosis is a novel strategy for the prevention and treatment of CRC. In addition, this review summarizes that probiotic antagonize CRC tumorigenesis by protecting intestinal barrier function, inhibiting cancer cell proliferation, resisting oxidative stress, and enhancing host immunity. Finally, we highlight clinical applications of the gut microbiome, such as gut microbiome analysis-based biomarker screening and prediction, and microbe modulation-based CRC prevention, treatment enhancement, and treatment side effect reduction. This review provides the reference for the clinical application of gut microbiome in the prevention and treatment of CRC.     

Mice with dysfunctional TGF-β signaling develop altered intestinal microbiome and colorectal cancer resistant to 5FU

Emerging data show a rise in colorectal cancer (CRC) incidence in young men and women that is often chemoresistant. One potential risk factor is an alteration in the microbiome. Here, we investigated the role of TGF-β signaling on the intestinal microbiome and the efficacy of chemotherapy for CRC induced by azoxymethane and dextran sodium sulfate in mice. We used two genotypes of TGF-β-signaling-deficient mice (Smad4^+/? and Smad4^+/?Sptbn1^+/?), which developed CRC with similar phenotypes and had similar alterations in the intestinal microbiome. Using these mice, we evaluated the intestinal microbiome and determined the effect of dysfunctional TGF-β signaling on the response to the chemotherapeutic agent 5-Fluoro-uracil (5FU) after induction of CRC. Using shotgun metagenomic sequencing, we determined gut microbiota composition in mice with CRC and found reduced amounts of beneficial species of Bacteroides and Parabacteroides in the mutants compared to the wild-type (WT) mice. Furthermore, the mutant mice with CRC were resistant to 5FU. Whereas the abundances of E. boltae, B.dorei, Lachnoclostridium sp., and Mordavella sp. were significantly reduced in mice with CRC, these species only recovered to basal amounts after 5FU treatment in WT mice, suggesting that the alterations in the intestinal microbiome resulting from compromised TGF-β signaling impaired the response to 5FU. These findings could have implications for inhibiting the TGF-β pathway in the treatment of CRC or other cancers.     

Towards the human colorectal cancer microbiome

Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC). To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions.     

Recent advancements in the exploitation of the gut microbiome in the diagnosis and treatment of colorectal cancer

Over the last few decades it has been established that the complex interaction between the host and the multitude of organisms that compose the intestinal microbiota plays an important role in human metabolic health and disease. Whilst there is no defined consensus on the composition of a healthy microbiome due to confounding factors such as ethnicity, geographical locations, age and sex, there are undoubtably populations of microbes that are consistently dysregulated in gut diseases including colorectal cancer (CRC). In this review, we discuss the most recent advances in the application of the gut microbiota, not just bacteria, and derived microbial compounds in the diagnosis of CRC and the potential to exploit microbes as novel agents in the management and treatment of CRC. We highlight examples of the microbiota, and their derivatives, that have the potential to become standalone diagnostic tools or be used in combination with current screening techniques to improve sensitivity and specificity for earlier CRC diagnoses and provide a perspective on their potential as biotherapeutics with translatability to clinical trials.     

The Human Intestinal Microbiome: A New Frontier of Human Biology

To analyze the vast number and variety of microorganisms inhabitingthe human intestine, emerging metagenomic technologies are extremelypowerful. The intestinal microbes are taxonomically complexand constitute an ecologically dynamic community (microbiota)that has long been believed to possess a strong impact on humanphysiology. Furthermore, they are heavily involved in the maturationand proliferation of human intestinal cells, helping to maintaintheir homeostasis and can be causative of various diseases,such as inflammatory bowel disease and obesity. A simplifiedanimal model system has provided the mechanistic basis for themolecular interactions that occur at the interface between suchmicrobes and host intestinal epithelia. Through metagenomicanalysis, it is now possible to comprehensively explore thegenetic nature of the intestinal microbiome, the mutually interactingsystem comprising the host cells and the residing microbialcommunity. The human microbiome project was recently launchedas an international collaborative research effort to furtherpromote this newly developing field and to pave the way to anew frontier of human biology, which will provide new strategiesfor the maintenance of human health.     

The potential for probiotic manipulation of the gastrointestinal microbiome

Multiple internal and external sites of the healthy human body are colonized by a diversity of symbiotic microbes. The microbial assemblages found in the intestine represent some of the most dense and diverse of these human-associated ecosystems. Unsurprisingly, the enteric microbiome, that is the totality of microbes, their combined genomes, and their interactions with the human body, has a profound impact on physiological aspects of mammalian function, not least, host immune response. Lack of early-life exposure to certain microbes, or shifts in the composition of the gastrointestinal microbiome have been linked to the development and progression of several intestinal and extra-intestinal diseases, including childhood asthma development and inflammatory bowel disease. Modulating microbial exposure through probiotic supplementation represents a long-held strategy towards ameliorating disease via intestinal microbial community restructuring. This field has experienced somewhat of a resurgence over the past few years, primarily due to the exponential increase in human microbiome studies and a growing appreciation of our dependence on resident microbiota to modulate human health. This review aims to review recent regulatory aspects related to probiotics in food. It also summarizes what is known to date with respect to human gastrointestinal microbiota - the niche which has been most extensively studied in the human system - and the evidence for probiotic supplementation as a viable therapeutic strategy for modulating this consortium.     

Analyzing the Secretome of Gut Microbiota as the Next Strategy For Early Detection of Colorectal Cancer

Dysbiosis of gut microbiome can contribute to inflammation, and subsequently initiation and progression of colorectal cancer (CRC). Throughout these stages, various proteins and metabolites are secreted to the external environment by microorganisms or the hosts themselves. Studying these proteins may help enhance our understanding of the host–microorganism relationship or they may even serve as useful biomarkers for CRC. However, secretomic studies of gut microbiome of CRC patients, until now, are scarcely performed. In this review article, the focus is on the roles of gut microbiome in CRC, the current findings on CRC secretome are highlighted, and the emerging challenges and strategies to drive forward this area of research are addressed.     

植物多糖对肠道微生态的作用研究进展

近年来,随着微生态学的发展,越来越多的学者认识到肠道微生态平衡对人体健康的重要意义。许多研究表明植物多糖作为肠道微生态调节剂,具有调节肠道菌群比例、促进肠黏膜修复、增强肠黏膜分泌型免疫球蛋白表达及调节细胞因子水平等作用。除此以外,植物多糖具有来源广泛、成本低廉、作用效果好等优势。本文归纳了近年来报道的具有肠道微生态调节功能的植物多糖及其研究方法和作用机制等,希望为今后的研究重点和发展方向提供参考。