肠道菌群与多发性骨髓瘤相关研究进展

肠道是营养成分消化吸收的主要场所, 肠道菌群参与了机体的能量存储、代谢、免疫等活动, 在维持机体健康及诱导肿瘤发生等方面具有重要作用。多发性骨髓瘤(MM)是一种恶性浆细胞疾病, 其发病机制尚未阐明。近年来, 随着对肠道菌群研究的深入, 肠道菌群在MM的发生、发展方面的机制逐渐被探索发现。不同疾病状态下, MM患者肠道菌群的组成和丰度均可发生变化, 同时肠道菌群可通过调控其代谢物进而在机体发挥作用, 肠道菌群可能是未来MM治疗新的潜在靶点。现就肠道菌群与MM疾病的相关性作一综述。     

肠道菌群及其代谢产物在胶质瘤中的调控机制研究进展

胶质瘤是成人颅内最常见的恶性肿瘤,占原发性颅脑恶性肿瘤的81%,并且其进展快、恶性程度高,预后极差。胶质瘤的肿瘤微环境较复杂,与机体的免疫应答和代谢密切相关。近年来随着肠道菌群及脑肠轴研究的相继开展,菌群及其代谢产物与中枢神经系统之间的相互作用机制越来越受到重视。然而,目前肠道菌群与胶质瘤之间的相关性仍不明确;故本文着重探讨肠道菌群及其代谢物与胶质瘤之间的联系,并对其参与肿瘤微环境中免疫及代谢的调控机制进行综述,为胶质瘤治疗新靶点的发现和进一步探究其机制提供思路。     

肠道菌群在肿瘤进程中的作用及其临床研究进展

肠道菌群在调控宿主的生长、发育、营养代谢以及免疫稳态方面具有重要的作用.近年来研究发现,肿瘤患者,特别是结直肠癌患者的肠道菌群多呈现失调的状态,而肠道菌群失调能够通过影响肠道代谢、肠道稳态以及肠道免疫等方面促进或者抑制肿瘤的发生发展.目前,通过干预肠道菌群来进行肿瘤治疗的临床实践已经显示出了良好的疗效和巨大的潜能.本文主要论述肠道菌群在肿瘤发生发展进程中的作用及其机制,以及目前利用肠道菌群治疗肿瘤的相关临床研究进展.     

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。     

肠道菌群与甲状腺相关疾病的研究进展

肠道菌群是由大量需氧菌、厌氧菌、病毒等组成,参与了机体许多生理功能的维持,与营养物质的消化吸收、 免疫系统的调节、内分泌系统的激素代谢平衡有着至关重要的联系,二者相互作用,使宿主机体保持稳定。其与机体相关 作用需要的信号物质可能是细菌相互作用的部分或其产生的代谢物,可作用于外源作用以及内生作用等。当肠道菌群出现 紊乱时,机体可能出现一系列疾病。经研究许多内分泌及免疫相关疾病如1 型糖尿病、2 型糖尿病、炎症性肠炎、类风湿 性关节炎等与肠道菌群紊乱多存在一定相关性。甲状腺作为机体重要的内分泌腺体,对于机体激素环境调节极其重要,作 用复杂,同时甲状腺疾病种类多,发病过程中症状多较为复杂,机制尚不明确,如Graves 病、桥本甲状腺炎、亚急性甲状 腺炎等。本文通过对甲状腺相关疾病与肠道菌群紊乱之间的关联性研究进展作一综述,探究肠道菌群对于甲状腺疾病的预防、 诊断以及治疗的指导意义。     

肠道菌群、癌症防治与益生菌(一)

人体健康与稳态的菌群结构密切相关.肠道菌群、营养物质和宿主细胞的相互作用及其稳态决定着机体的健康状况.正常生理状态下,肠道内菌群在种类、数量和生态功能等方面相互影响,维持在一个相对平衡的状态,在体内发挥营养消化吸收、机体免疫防御、器官功能正常等多项生物学功能.但由于年龄、饮食、药物等各种外界因素均会引起肠道菌群失调,进而导致肠炎、肠癌、肝癌、肺癌等疾病的发生发展.因此,近年临床科学家已经把目光聚焦于肠道菌群及其代谢产物在人类健康维护中的作用及其机理上.     

肠道菌群与肺癌关系的研究进展

人类胃肠道系统内的肠道菌群在正常情况下保持动态平衡,具有促进代谢、增强免疫等功能.多项研究证明,肠道菌群失衡与肺癌的发生发展密切相关,肺癌患者肠道菌群的多样性及相对丰度明显不同于对照组.本文总结肠道菌群可能的关联途径,如调节代谢、炎症及免疫等促进肿瘤的发展、转移,也根据中医脏腑及五行相生理论,通过养护脾胃之气和调节肠道菌群平衡等方式抑制肿瘤的中药和方剂,旨在探讨调节肠道菌群联合靶向治疗和化疗成为未来治疗肺癌的常规疗法的可能性.     

肠道菌群通过脑肠轴影响肿瘤的发生发展

正常情况下,人体肠道内菌群保持相对稳定的状态,共生菌、益生菌和病原菌的比例维持相对稳定。肠道菌群失调可改变肠道内的生理环境,还能通过各种途径引起人体肠外组织器官生理状态的改变,甚至影响肿瘤的发生发展。脑肠轴是其中一条通路,由免疫、代谢、神经内分泌和迷走神经等途径构成。本文旨在讨论肿瘤和肠道菌群之间的关系以及肠道菌群通过脑肠轴的4条途径改变机体的应激水平,从而影响肿瘤发生发展的相关机制,同时就肠道菌群调控在肿瘤治疗中的作用进行了探讨。      

肠道菌群干预肿瘤负性免疫调控机制的研究进展

肠道菌群不仅在人体的营养代谢、免疫稳态中扮演重要角色,还与恶性肿瘤进展密切相关.近年来,肠道菌群参与肿瘤免疫调控备受研究者关注,肠道菌群通过干预负性免疫调控网络影响肿瘤发生发展.然而,目前针对肠道菌群与肿瘤免疫调控关系的研究多停留于关联性分析,其分子作用机制尚未完全阐明.本文从肠道菌群干预肿瘤负性免疫调节细胞、负性免疫调节分子及负性免疫调节细胞因子等方面阐述肠道菌群干预肿瘤恶性进程的机制,以期为肿瘤治疗提供新的思路和策略.     

肠道菌群影响肿瘤对免疫检查点抑制剂的应答及其机制

人类肠道菌群种类超过1000种,是人体内最庞大的微生物群,被称为"被遗忘的器官"。肠道菌群易受多种因素影响。已有多项研究证明肠道菌群及其代谢产物参与宿主免疫构建和影响肿瘤微环境,与肿瘤对免疫检查点抑制剂(immune checkpoint inhibitor,ICI)的应答和ICI治疗相关不良反应的发生有关。随着人类微生物组计划的开展和测序分析技术的进步,肠道菌群的相关研究逐步深入,基因功能注释和代谢组学分析的成熟和推广丰富了肠道菌群与宿主免疫及免疫治疗间的探索维度,干预和塑造肠道菌群为提高肿瘤免疫治疗效果提供了新的思路。然而,微生物制品的食源性添加、粪菌移植等研究尚未获得足够证据,肠道菌群的免疫调控机制尚不完全清楚。本文就近年来肠道菌群影响肿瘤对ICI应答机制的研究进展作一综述。     

Colorectal carcinogenesis in germ-free and conventionally reared rats: different intestinal environments affect the systemic immunity

Intestinal microbiota are considered to play an important role both in colorectal tumor development and in the modulation of mucosal immunity. Studies on animals reared in germ-free (GF, without intestinal microbiota) versus conventional (CV, with regular microbiota colonization of the bowel) conditions can aid in clarifying the influence of bacteria on carcinogenesis and the anticancer immune response. The capability of the intestinal environment to modulate anticancer immunity not only at the mucosal but also at the systemic level is still an open question. In our study we found that, following the same protocol of colorectal cancer induction, GF rats developed less and smaller tumors than CV rats. The GF rats that did not develop cancer also presented a better anticancer immune response with an increase in NK, NKT, CTL, B cells and cytotoxicity in peripheral blood. We hypothesize that the lower antigenic challenge and the absence of the 'physiological inflammation', caused by the commensal microbiota in the gut of CV rats, may enhance the capability of the GF rats to develop more efficacious anticancer immune responses. The different levels of tolerance/regulatory mechanisms in GF versus the CV animals may modulate the anticancer response not only at the mucosal but also at the systemic immunity level.     

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。     

肠道菌群与肿瘤免疫治疗疗效及不良反应关系的研究进展

肠道菌群是寄生于肠道内微生物的总称。肠道菌群受到宿主饮食和药物等多种因素影响,同时,肠道菌群也可以参与调控宿主免疫状态。目前,已有一些研究证实了肠道菌群与抗肿瘤免疫治疗疗效及不良反应具有相关性,且调节肠道菌群可以提升免疫治疗疗效,但是具体的机制尚不清楚。本文对肠道菌群与肿瘤免疫治疗现有的研究进展及不足进行了系统综述。     

肠道微生物与乳腺癌发生发展关系及作用机制的研究进展

人体共生肠道微生物是一个动态系统,在宿主生理的各方面起到至关重要的作用,包括免疫成熟、新陈代谢、组织发展等,但同时也能诱发或促进乳腺癌等恶性肿瘤的发生发展。乳腺癌是世界范围内女性最常见的恶性肿瘤之一,且呈迅速增长的趋势。近年来乳腺癌与肠道微生物的研究逐渐成为热点,本文基于肠道屏障、炎症反应和免疫应答及脂质代谢三个方面对肠道微生物在乳腺癌发生发展中的作用机制进行阐述,以把握乳腺癌的发展动向,为乳腺癌的预防和治疗提供理论支持。     

Inflammation-Modulating Effect of Butyrate in the Prevention of Colon Cancer by Dietary Fiber

The intestinal microbiota plays key roles in human health, and adverse dysbiosis shifts of the microbiota have been associated with chronic diseases, including large bowel cancer. High-fiber diets may reduce the risk for large bowel cancer in association with gut microbiota modulation and butyrate production. Butyrate can inhibit histone deacetylases and associated signaling pathways in cultured cancer cells, promoting cancer cell apoptosis. However, butyrate has prevented colon cancer through the regulation of immune homeostasis rather than histone deacetylases inhibition. It could be important to further examine the pathways of how butyrate encourages immune system changes. We posited that butyrate-activated T-regulatory cells block proinflammatory T cells and thus reduce proinflammatory cytokine production; these cytokines increase cell proliferation and cell survival, the 2 most important cancer cell characteristics. Butyrate can exert anticancer effects through inhibition of multiple signaling pathways. It is possible that a low concentration of butyrate could modulate the immune system before other pathways to exert an anticancer effect. Increasing the concentration of butyrate in the intestines may produce a synergistic inhibitory signaling pathway response and an anti-inflammatory effect.     

肿瘤患者肠道菌群特征及益生菌改善其营养不良的应用前景

肿瘤营养不良会增加患者术后并发症、降低生活质量、增加死亡率,根据肿瘤产生部位不同其发生率在40%～80%,改善肿瘤患者营养不良至关重要。肿瘤营养不良与肿瘤自身高代谢、肿瘤相关厌食症以及肿瘤治疗产生的不良反应密切相关。目前肿瘤专用肠内营养制剂并没有完全消除患者的营养不良风险。人体肠道菌群可通过多种机制维持人体健康,健康的肠道微生物多样性高、结构复杂稳定、具有抵抗外部环境压力的能力,在有限的外部干扰时仍能保持菌群结构稳定;而非健康人体则表现为菌群多样性降低,丧失对外部环境压力的抵抗力,发生肠道微生态紊乱等不良状况,如肿瘤患者在疾病进程中往往会伴随肠道菌群总数下降、多样性降低、有益菌比例减少等现象发生,严重影响了机体免疫能力和患者的食欲。益生菌作为一种重要的微生态制剂对人的健康产生有益影响,可预测其调节肿瘤患者肠道菌群结构及组成,细胞因子、胃肠肽等介质分泌改善食物摄入和小肠营养吸收对肿瘤患者发生的营养不良将会产生积极影响。本文就营养不良肿瘤患者的肠道菌群特征及益生菌的潜在作用进行系统论述,并提出应用前景。     

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.     

人体微生态与放疗之间的相互关系

人体微生态,尤其肠道菌群是人体一个新的动态器官,菌群及其代谢物可直接作用于肠道或间接通过菌群-肠-器官轴作用全身组织器官而发挥着重要作用.人体微生态的主要生理作用包括:调节胃肠道运动和消化、肠道屏障,调节免疫稳态和炎症反应、物质代谢、细胞分化和周转,以及认知行为等.肿瘤放疗可引起人体菌群的明显改变,表现为菌群多样性和丰...     

Role of Toll-like receptors in gastrointestinal malignancies

Mounting evidence supports the tenet that innate immune responses to luminal microbes participate in the development of gastrointestinal malignancies. The gastrointestinal tract is relatively unique in that it has evolved in the presence of diverse enteric microflora. Intestinal flora is required to develop a normal adaptive immune response in the periphery. With the characterization of the innate immune system, we have begun to understand the adaptations the intestine has made to the microbiota. The interaction between the microbiota and the intestinal mucosa through Toll-like receptors (TLRs) is required to maintain intestinal homeostasis. In particular, intestinal epithelial cells and lamina propria mononuclear cells such as antigen-presenting cells and T cells must respond to breaches in the mucosal barrier by activating TLR-dependent pathways that result in increased epithelial proliferation, wound healing and recruitment of acute inflammatory cells. In the setting of chronic inflammation such as Helicobacter pylori (H. pylori) infection in the stomach or idiopathic inflammatory bowel disease, the process of repair may eventually result in carcinogenesis. The following review highlights human and animal data that support a role for innate immune responses and TLRs specifically in promoting gastrointestinal malignancies. Candidate pathways linking TLRs to gastrointestinal malignancies include activation of nuclear factor-kappaB and cyclooxygenase-2. Studying the link between innate immune signaling and gastrointestinal malignancies offers the possibility to identify novel ways to both prevent and treat gastrointestinal cancer.