microRNA 对宿主和肠道微生物互作的调控

摘要:肠道内环境是宿主和肠道微生物菌群互作的结果,肠道菌群一方面通过抗原物质调节肠道组织的免疫稳定,另一方面,肠道菌群参与糖、脂、蛋白质代谢,产生的代谢产物能够调控细菌营养代谢、群体结构和肠道组织的营养吸收等。microRNA是宿主细胞内调控基因表达的重要因子,肠道微生物菌群不仅调控宿主mRNA的转录,同时也影响某些基因的转录后修饰。研究表明,肠道菌群通过与宿主肠道组织互作,调节肠上皮组织内某些参与炎症应答和屏障功能的microRNA 的表达。本文介绍了肠道微生物与宿主互作的基本内容,对microRNA在肠道微生物与宿主互作和肠道健康中的调节进行综述。     

基于肠道菌群的免疫调节策略用于结直肠癌联合治疗研究的进展

肠道菌群可形成特殊的免疫微环境,通过免疫调节机制影响结直肠癌的发生、发展和治疗。本文综述了肠道菌群用于结直肠癌免疫调节治疗的研究进展,回顾了肠道菌群与宿主免疫、肿瘤免疫的关系,重点分析了相关动物实验和临床试验的结果,总结了基于肠道菌群免疫调节联合疗法用于结直肠癌治疗的机制和策略,期望为结直肠癌的治疗提供新的参考。     

结直肠癌患者肠道黏膜菌群多样性变化研究

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。     

具核梭杆菌与结直肠癌关系的研究进展

结直肠癌(Colorectal cancer,CRC)是世界第三大癌症,涉及因素众多,而肠道菌群失调、菌群致病性与结直肠癌的发生、发展有着密不可分的关系。近期的研究发现具核梭杆菌(Fusobacterium nucleatum,F.nucleatum)与结直肠癌的发生存在显著的相关性。具核梭杆菌为革兰阴性厌氧菌,广泛存在于人体肠道中。分子机制研究发现,其能影响宿主细胞因子水平,促进血管生成、巨噬细胞M2极化和抑制机体免疫调节能力,进而增强肿瘤细胞增殖、侵袭及转移。本文就具核梭杆菌与结直肠癌相关机制研究进展作一综述。     

结直肠癌与肠道微生物群研究进展

肠道微生物群是人体内环境的重要组成部分,与宿主共进化、共代谢、共发育,并与宿主之间相互调控,影响宿主健康。近年研究显示,肠道微生物群参与了结直肠癌的发生和发展。了解肠道微生物群的特征性变化及其诱发结直肠癌的机制对于结直肠癌的防治有着重要意义。目前以肠道微生物群为靶点的干预性基础研究也取得了一些突破性的研究进展。本文主要对结直肠癌患者肠道微生物群的变化、其可能的致病机制及临床相关研究进展等进行综述。     

肠道菌群稳态与结直肠癌研究进展

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。     

肠道菌群失调引起类风湿关节炎发病的研究进展

肠道菌群大多与宿主共生进化,菌群结构、数量恒定形成稳态,能有效预防有害病菌的入侵和炎性疾病的发生。目前多项研究结果显示,肠道菌群失调可能与多种疾病相关联,包括2型糖尿病、肥胖症、肝硬化、结直肠癌和类风湿关节炎。有研究表明,肠道菌群是影响类风湿关节炎(rheumatoid arthritis, RA)发病的环境因素,其中涉及的机制有肠道菌群-黏膜稳态的失衡,其不利于肠道适应性免疫的形成,使得免疫系统不能识别常驻菌与致病菌,引起黏膜紊乱;另一种机制是肠道菌群失调激活免疫因子,引起全身免疫反应。由此可见,肠道菌群参与类风湿关节炎的发生、发展,既有肠道黏膜与菌群的局部调节,也有全身性免疫因子的共同参与。本文主要对肠道菌群失调诱导类风湿关节炎发病的相关性研究予以综述,为进一步研究关节炎早期预防及病因治疗提供理论依据。     

老年结直肠癌患者肠道菌群变化与机体免疫炎症营养相关性

目的探讨老年结直肠癌患者肠道菌群变化与机体免疫、炎症、营养指标的相关性,为结直肠癌的防治提供参考。方法纳入2016年1月至2018年6月在我院接受治疗的老年结直肠癌患者30例和同期健康查体的老年人群30例,收集粪便标本,采用FloraCheck~(TM)高通量测序技术对粪便样本中所有细菌的16S rRNA V3-V4区进行DNA测序,序列通过MiSeq 16S宏基因组APP及QIIME软件,分析两组人群间属水平上显著差异性菌群。比较两组人群炎性指标(TNF-α、IL-6、IL-1、IL-12)、营养指标(总蛋白、白蛋白、前白蛋白、转铁蛋白)和免疫指标(CD3~+、CD4~+、CD8~+、NK)的差异。分析老年结直肠癌患者肠道菌群变化与营养、炎症、免疫的内在联系。结果老年结直肠癌组和老年健康组人群免疫指标CD3~+、CD4~+、CD8~+、NK和CD4~+/CD8~+比较差异无统计学意义;炎性指标老年结直肠癌组TNF-α含量较对照组明显增高(t=3.769,P=0.001),两组人群IL-1、IL-6、IL-12比较差异无统计学意义;营养指标老年结直肠癌组白蛋白、前白蛋白较对照组明显下降(t=-4.107,P=0.001;t=-4.366,P=0.001),两组人群总蛋白、转铁蛋白比较差异无统计学意义。老年结直肠癌组肠道差异性菌属变化,包括Eubacterium、Ruminococcaceae_UCG-002、Peptostreptococcus、Porphyromonas和部分炎症指标、营养指标、免疫指标有明显相关性。结论老年结直肠癌患者肠道菌群结构和功能异常,可能是导致患者机体免疫损伤、炎症反应、营养不佳的主要原因之一。有针对性地对肠道菌群结构进行优化,改善肠道菌群对宿主的影响,是一种帮助老年结直肠癌患者促进健康的策略。     

基于16S rRNA和非靶向代谢组测序分析结直肠癌患者肠道菌群及代谢物的变化

目的 采用16S rRNA和非靶向代谢组测序分析的方法探讨结直肠癌患者肠道菌群和其代谢产物的变化。方法 新鲜粪便为实验样品,收集10个结直肠癌患者组样本和6个正常对照组样本进行16S rRNA测序,分析肠道菌群的组成、多样性和物种差异,并对预测差异肠道菌群代谢功能;取8个结直肠癌组样本和6个正常对照组样本进行LC-MS非靶向代谢组学测序,分析代谢产物变化情况并进行功能预测。结果 结直肠癌组的菌群多样性较正常对照组无显著差异（P>0.05）。结直肠癌组的优势菌群为疣微菌门,结直肠癌组葡萄球菌、嗜冷杆菌属、毛螺菌科NK4A136、梭状芽孢杆菌vadinBB60和CAG-56相对丰度增加（P<0.05）,CAG-352、瘤胃球菌属、粪球菌属和挑剔真杆菌相对丰度降低（P<0.05）。KEGG富集分析发现,差异菌群在环境信息处理、遗传信息处理和新陈代谢等通路中发挥重要作用。非靶向代谢组学测序检测出两组样本有367种代谢物存在显著差异,对差异代谢物进行功能预测发现与咖啡因、嘌呤、氨基糖和核苷酸糖和生物素等的代谢相关。结论 结直肠癌患者的肠道菌群和代谢物与健康个体存在差异,结直肠癌...     

MicroRNA通过肠道菌群对绝经后骨质疏松症影响的机制探讨

胃肠道是营养和矿物质高效吸收的重要部位。研究显示胃肠道微生物群通过肠-骨轴对骨质量具有调节作用,其作用机制十分复杂,主要通过矿物质吸收、激素控制和免疫调节来实现。中药可以调节肠道菌群,起到治疗绝经后骨质疏松症的作用。近期研究发现,microRNA通过调节肠道微生物基因,改变肠道微生物的生理功能,从而调节骨代谢,影响绝经后骨质疏松症的发生与发展。本文就microRNA调节肠道菌群的研究现状作一综述,探讨绝经后骨质疏松症的调节机制,为绝经后骨质疏松症的肠道微生态研究提供一定的理论依据。     

The Effects and Mechanisms of Flavonoids on Cancer Prevention and Therapy: Focus on Gut Microbiota

Flavonoids are a group of polyphenolic compounds which are ubiquitously found in plants and are consumed as part of the human diet in substantial amounts. The verification of flavonoids'' cancer chemopreventive benefits has led to a significant interest in this field. Gut microbiota includes a diverse community of microorganisms and has a close relationship with cancer development. Increasing evidence has indicated that flavonoids exert anticarcinogenic effects by reshaping gut microbiota. Gut microbiota can convert flavonoids into bioactive metabolites that possess anticancer activity. Here, we present a brief introduction to gut microbiota and provide an overview of the interplay between gut microbiota and cancer pathogenesis. We also highlight the crucial roles of flavonoids in preventing cancer based on their regulation of gut microbiota. This review would encourage research on the flavonoid-intestinal microbiota interactions and clinical trials to validate the chemotherapeutic potentials of targeting gut microbiota by dietary bioactive compounds.     

后生元缓解胃肠道疾病的研究进展及其潜在机制

胃肠道是全身代谢最活跃的器官之一，也是人体内最大的细菌库。人体胃肠道中含有丰富的微生物群，其与宿主健康存在着错综复杂的关系。肠道菌群处于一种动态平衡的状态，当这种平衡被打破时会引起便秘、腹泻、肠易激综合征、炎症性肠病和结直肠癌等胃肠道疾病的发生。近年来，关于后生元的研究越来越多，其对肠道屏障的保护作用与益生菌类似甚至效果更佳。本文重点介绍了当前后生元在动物实验和临床中改善胃肠道疾病的相关研究，探讨了后生元在胃肠道中的作用及其在增强上皮屏障、调节免疫系统、肠道菌群和神经系统4个方面的潜在作用机制。     

Human Gut Microbiota and Gastrointestinal Cancer

Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.     

Beneficial modulation of the gut microbiota

The human gut microbiota comprises approximately 100 trillion microbial cells and has a significant effect on many aspects of human physiology including metabolism, nutrient absorption and immune function. Disruption of this population has been implicated in many conditions and diseases, including examples such as obesity, inflammatory bowel disease and colorectal cancer that are highlighted in this review. A logical extension of these observations suggests that the manipulation of the gut microbiota can be employed to prevent or treat these conditions. Thus, here we highlight a variety of options, including the use of changes in diet (including the use of prebiotics), antimicrobial-based intervention, probiotics and faecal microbiota transplantation, and discuss their relative merits with respect to modulating the intestinal community in a beneficial way.     

Gut microbiome in gastrointestinal cancer: a friend or foe?

The impact of the gut microbiome on host health is becoming increasingly recognized. To date, there is growing evidence that the complex characteristics of the microbial community play key roles as potential biomarkers and predictors of responses in cancer therapy. Many studies have shown that altered commensal bacteria lead to cancer susceptibility and progression in diverse pathways. In this review, we critically assess the data for gut microbiota related to gastrointestinal cancer, including esophageal, gastric, pancreatic, colorectal cancer, hepatocellular carcinoma and cholangiocarcinoma. Importantly, the underlying mechanisms of gut microbiota involved in cancer occurrence, prevention and treatment are elucidated. The purpose of this review is to provide novel insights for applying this understanding to the development of new therapeutic strategies in gastrointestinal cancer by targeting the microbial community.     

The gut microbiota in the metagenomics era: sometimes a friend, sometimes a foe

The normal intestinal microflora (microbiota) represents a complex, dynamic, and diverse collection of microorganisms, which usually inhabit the gastrointestinal tract. Normally, between this flora and the human host a mutually beneficial long-term symbiotic relationship is established, where the host contributes essential nutrients necessary for the survival of the microbiota and the latter fulfils multiple roles in host nutrition and development. Several achievements have recently converged to renew interest in studying the normal gut microbiota: the development of molecular methods of studying the microbial communities, the improved understanding of host-microbe interactions in health and disease, and the potential for therapeutic manipulation of the microbiota. We present recent data concerning the molecular technologies of studying the microbiota and new findings regarding the composition of the normal flora. We underline the beneficial activities of the gut flora on the human host. We emphasize the recent findings in the alterations of the microbiota in various medical conditions (celiac disease, irritable bowel syndrome, obesity, colorectal cancer, allergic disorders, and especially inflammatory bowel diseases). The results of these new studies suggest that changes of the microbiota could be linked to the etiopathogenesis of these diseases. These outstanding findings could be used for further diagnostic tools and/or therapy.     

Interplays between human microbiota and microRNAs in COVID-19 pathogenesis: a literature review

[Purpose]Recent studies have shown that COVID-19 is often associated with altered gut microbiota composition and reflects disease severity. Furthermore, various reports suggest that the interaction between COVID-19 and host-microbiota homeostasis is mediated through the modulation of microRNAs (miRNAs). Thus, in this review, we aim to summarize the association between human microbiota and miRNAs in COVID-19 pathogenesis.[Methods]We searched for the existing literature using the keywords such “COVID-19 or microbiota,” “microbiota or microRNA,” and “COVID-19 or probiotics” in PubMed until March 31, 2021. Subsequently, we thoroughly reviewed the articles related to microbiota and miRNAs in COVID-19 to generate a comprehensive picture depicting the association between human microbiota and microRNAs in the pathogenesis of COVID-19.[Results]There exists strong experimental evidence suggesting that the composition and diversity of human microbiota are altered in COVID-19 patients, implicating a bidirectional association between the respiratory and gastrointestinal tracts. In addition, SARS-CoV-2 encoded miRNAs and host cellular microRNAs modulated by human microbiota can interfere with viral replication and regulate host gene expression involved in the initiation and progression of COVID-19. These findings suggest that the manipulation of human microbiota with probiotics may play a significant role against SARS-CoV-2 infection by enhancing the host immune system and lowering the inflammatory status.[Conclusion]The human microbiota-miRNA axis can be used as a therapeutic approach for COVID-19. Hence, further studies are needed to investigate the exact molecular mechanisms underlying the regulation of miRNA expression in human microbiota and how these miRNA profiles mediate viral infection through host-microbe interactions.     

Human activity can influence the gut microbiota of Darwin's finches in the Galapagos Islands

The gut microbiota of animal hosts can be influenced by environmental factors, such as unnatural food items that are introduced by humans. Over the past 30 years, human presence has grown exponentially in the Galapagos Islands, which are home to endemic Darwin's finches. Consequently, humans have changed the environment and diet of Darwin's finches, which in turn, could affect their gut microbiota. In this study, we compared the gut microbiota of two species of Darwin's finches, small ground finches (Geospiza fuliginosa) and medium ground finches (Geospiza fortis), across sites with and without human presence, where finches prefer human‐processed and natural food, respectively. We predicted that: (a) finch microbiota would differ between sites with and without humans due to differences in diet, and (b) gut microbiota of each finch species would be most similar where finches have the highest niche overlap (areas with humans) compared to the lowest niche overlap (areas without humans). We found that gut bacterial community structure differed across sites and host species. Gut bacterial diversity was most distinct between the two species at the site with human presence compared to the site without human presence, which contradicted our predictions. Within host species, medium ground finches had lower bacterial diversity at the site with human presence compared to the site without human presence and bacterial diversity of small ground finches did not differ between sites. Our results show that the gut microbiota of Darwin's finches is affected differently across sites with varying human presence.     

How informative is the mouse for human gut microbiota research?

The microbiota of the human gut is gaining broad attention owing to its association with a wide range of diseases, ranging from metabolic disorders (e.g. obesity and type 2 diabetes) to autoimmune diseases (such as inflammatory bowel disease and type 1 diabetes), cancer and even neurodevelopmental disorders (e.g. autism). Having been increasingly used in biomedical research, mice have become the model of choice for most studies in this emerging field. Mouse models allow perturbations in gut microbiota to be studied in a controlled experimental setup, and thus help in assessing causality of the complex host-microbiota interactions and in developing mechanistic hypotheses. However, pitfalls should be considered when translating gut microbiome research results from mouse models to humans. In this Special Article, we discuss the intrinsic similarities and differences that exist between the two systems, and compare the human and murine core gut microbiota based on a meta-analysis of currently available datasets. Finally, we discuss the external factors that influence the capability of mouse models to recapitulate the gut microbiota shifts associated with human diseases, and investigate which alternative model systems exist for gut microbiota research.KEY WORDS: Gut microbiota, Humanized mouse models, Mouse core gut microbiota, Mouse models, Mouse pan-gut microbiota