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Long term management of ulcerative colitis with Faecal Microbiota Transplantation 粪便菌群移植治疗溃疡性结肠炎的长期治疗
Q2 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.medmic.2020.100026
Arshdeep Singh , Ramit Mahajan , Dina Kao , Vandana Midha , Ajit Sood

Gut microbiota has emerged a major player in the pathogenesis of ulcerative colitis (UC). Targeting dysbiotic microbiota with the aim to restore intestinal homoeostasis and alleviate disease is an attractive approach in patients with UC. Results with microbiota targeted therapies including probiotics, prebiotics, and antibiotics have however been inconsistent and lack reproducibility. Faecal Microbiota Transplantation (FMT) is a novel microbiota centered therapy that has shown promise (in both efficacy and safety) with its short term use in UC. FMT appears to have bright prospects for long term management of UC due to its multi-pronged attack on the pathophysiological mechanisms involved in pathogenesis of UC. However, only limited data is available on its long term use in UC. We discuss important unsettled issues concerning use of FMT as a long term therapy. Various attributes related to FMT procedure, namely preparation of fecal slurry, frequency and duration of intervention, acceptability and safety, are analysed. Additionally we also explore the issues concerning patient and donor selection and the impact of habitual diet on results with FMT.

肠道微生物群在溃疡性结肠炎(UC)的发病机制中发挥了重要作用。针对益生菌群,旨在恢复肠道平衡和减轻疾病是UC患者的一个有吸引力的方法。然而,包括益生菌、益生元和抗生素在内的微生物群靶向治疗的结果不一致,缺乏可重复性。粪便微生物群移植(FMT)是一种以微生物群为中心的新型治疗方法,在短期内用于UC已显示出希望(在有效性和安全性方面)。由于FMT多管齐下地研究UC发病机制的病理生理机制,因此在UC的长期治疗中具有光明的前景。然而,只有有限的数据可用于UC的长期使用。我们讨论了关于使用FMT作为长期治疗的重要悬而未决的问题。分析了与粪浆处理有关的各种属性,即粪浆的制备、干预的频率和持续时间、可接受性和安全性。此外,我们还探讨了有关患者和供体选择以及习惯性饮食对FMT结果的影响的问题。
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引用次数: 3
Fecal microbiota transplantation: Uses, questions, and ethics 粪便微生物群移植:用途、问题和伦理
Q2 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.medmic.2020.100027
Zoya Grigoryan , Michael J. Shen , Shaina W. Twardus , Marc M. Beuttler , Lea Ann Chen , Alison Bateman-House

Fecal microbiota transplantation (FMT) has rapidly grown in notoriety and popularity worldwide as a treatment for both recurrent and refractory C. difficile infection (CDI), as well as for a myriad of other indications, with varying levels of evidence to justify its use. At present, FMT use in the U.S. has not received marketing approval from the U.S. Food and Drug Administration (FDA), but is permitted under “enforcement discretion” for CDI not responding to standard therapy. Meanwhile, the rising interest in the gut microbiome throughout mainstream media has paved the way for “do-it-yourself” (DIY) adaptations of the procedure. This access and unregulated use, often outside any clinical supervision, has quickly outpaced the medical community's research and regulatory efforts. While some studies have been able to demonstrate the success of FMT in treating conditions other than CDI—studies on ulcerative colitis have been particularly promising—little is still known about the treatment's mechanism of action or long-term side effects. Likewise, screening of donor stool is in its early stages in terms of protocol standardization. In this paper, we explore the regulatory and ethical concerns that arise from the need to balance access to a nascent but promising innovative treatment with the need for research into its efficacy, risk profile, and long-term impact.

粪便微生物群移植(FMT)作为一种治疗复发性和难治性艰难梭菌感染(CDI)以及无数其他适应症的方法,在世界范围内迅速臭名昭著和普及,有不同程度的证据证明其使用是合理的。目前,FMT在美国的使用尚未获得美国食品和药物管理局(FDA)的上市许可,但在CDI对标准治疗无反应的“强制裁量权”下是允许的。与此同时,主流媒体对肠道微生物组的兴趣日益浓厚,为“自己动手”(DIY)适应该程序铺平了道路。这种获取和不受管制的使用,往往在任何临床监督之外,已经迅速超过了医学界的研究和监管努力。虽然一些研究已经能够证明FMT在治疗cdi以外的疾病方面取得了成功-溃疡性结肠炎的研究尤其有希望-但对于治疗的作用机制或长期副作用仍然知之甚少。同样,供体粪便的筛查在方案标准化方面处于早期阶段。在本文中,我们探讨了监管和伦理问题,这些问题是由于需要平衡获得一种新兴但有前途的创新治疗与研究其疗效、风险状况和长期影响的需要而产生的。
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引用次数: 19
Methodology, efficacy and safety of fecal microbiota transplantation in treating inflammatory bowel disease 粪便菌群移植治疗炎症性肠病的方法学、疗效和安全性
Q2 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.medmic.2020.100028
Xiao Ding , Xiaozhong Yang , Honggang Wang

Fecal microbiota transplantation (FMT), as an emerging therapy, can be used to treat microbiota related diseases. Progresses in donor screening, washed microbiota preparation, microbiota delivery routes, clinical administrative strategies, and long-term safety are moving FMT forward. Increasing clinical studies, especially those randomized controlled trials about ulcerative colitis and pilot real-word studies about serious inflammatory bowel disease (IBD), have been conducted. This review presents the latest findings about the efficacy, safety and methodology of FMT in treating IBD.

粪便微生物群移植作为一种新兴的治疗方法,可用于治疗微生物群相关疾病。供体筛选、洗涤菌群制备、菌群输送途径、临床管理策略和长期安全性方面的进展正在推动FMT向前发展。越来越多的临床研究,特别是关于溃疡性结肠炎的随机对照试验和关于严重炎症性肠病(IBD)的试点实际研究已经开展。本文综述了FMT治疗IBD的有效性、安全性和方法学方面的最新发现。
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引用次数: 3
Anti-tubercular modelling, molecular docking simulation and insight toward computational design of novel compounds as potent antagonist against DNA gyrase receptor 抗结核模型,分子对接模拟和新化合物作为DNA旋切酶受体有效拮抗剂的计算设计见解
Q2 Medicine Pub Date : 2020-09-01 DOI: 10.1016/j.medmic.2020.100020
Shola Elijah Adeniji , Olajumoke Bosede Adalumo , Faith Omeyi Ekoja

Tuberculosis continue to be a critical health problem causing death and illness among millions of people yearly and ranked the second leading cause of mortality among the communicable infections in the world. Therefor this work accessed the application of modelling technique to predict the inhibition activity of some prominent compounds which been reported to be efficient against Mycobacterium tuberculosis. To accomplish the purpose of this work, multiple regression and genetic function approximation were adopted to create the model. The established model was swayed with topological descriptors; AATS7s, GATS4v, nHBint3 and RDF90i which have been tested validated. More also, interactions between the compounds and the target ‘‘DNA gyrase’’ was evaluated via docking approach utilizing the PyRx and discovery studio simulated software. Meanwhile, compounds 5, 7, 10, 11, 12, 20, 25, 26, 27 and 28 were revealed to have significant bind affinities of (−6.3 to −16.5 kcal/mol) whereas, compound 12 has the most perceptible binding affinity of −16.5 kcal/mol. This implies that compound 12 could be used as a structural template when the pharmacist or the medicinal chemists aim to design new proposed drugs with more efficient activities.

结核病仍然是一个严重的健康问题,每年造成数百万人死亡和生病,是世界上传染性感染中第二大死亡原因。因此,这项工作进入了应用建模技术来预测一些突出的化合物的抑制活性,这些化合物被报道对结核分枝杆菌有效。为了达到本工作的目的,采用多元回归和遗传函数近似建立模型。用拓扑描述符对所建立的模型进行摇摆;AATS7s, GATS4v, nHBint3和RDF90i已经过测试验证。此外,利用PyRx和discovery studio模拟软件通过对接方法评估化合物与目标“DNA gyrase”之间的相互作用。化合物5、7、10、11、12、20、25、26、27和28的结合亲和力为−6.3 ~−16.5 kcal/mol,而化合物12的结合亲和力为−16.5 kcal/mol。这意味着当药剂师或药物化学家打算设计具有更有效活性的新药物时,化合物12可以用作结构模板。
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引用次数: 3
Cell free bacterial DNAs in human plasma provide fingerprints for immune-related diseases 人血浆中游离细胞细菌dna为免疫相关疾病提供指纹图谱
Q2 Medicine Pub Date : 2020-09-01 DOI: 10.1016/j.medmic.2020.100022
Tingting Zhao , Shien Zou , Maoping Chu , Jun Chen , Jie Zhong , Yamao Chen , Jiangao Fan , Ji Qi , Qijun Wang

Microbiota is increasingly being recognized as an important factor in human health. Alterations in the bacterial community structure have been implicated in a wide range of human diseases. Most therapeutic strategies targeting microbiota, such as probiotics, prebiotics and fecal transplantation, aim to modulate the bacterial community. Herein we demonstrate that the cell free bacterial DNAs (cfbDNAs) are extensively observed in human bloodstreams and gradually arise along with growth. Moreover, patients with immune-related diseases, e.g. inflammatory bowel disease (IBD), kawasaki disease (KD) and HIV, own higher amounts of cfbDNAs with lower microbial biodiversity compared with healthy individuals by using real-time PCR measurement and high-throughput 16S rDNA sequences analyses. Further comparisons reveal that 173 genera exhibit preferential abundance in either healthy individuals or patients, providing “molecular phenotypes” of the corresponding diseases in a manner of microbiome, especially in those IBD patients post/pre-therapy. Although the origination and function of these cfbDNAs in human circulating bloodstreams remain unclear, their taxonomic variations offer fingerprints for potential applications in noninvasive and safe pre-diagnosis or prognosis, and provide clues for further understanding of the host-microbiota interactions.

微生物群越来越被认为是人类健康的一个重要因素。细菌群落结构的改变与许多人类疾病有关。大多数针对微生物群的治疗策略,如益生菌、益生元和粪便移植,旨在调节细菌群落。本文表明,游离细胞细菌dna (cfbdna)在人体血液中广泛存在,并随着生长逐渐出现。此外,通过实时荧光定量PCR和高通量16S rDNA序列分析发现,炎症性肠病(IBD)、川崎病(KD)和HIV等免疫相关疾病患者的cfbdna含量高于健康人群,但微生物多样性较低。进一步比较发现,173个属在健康个体或患者中表现出优先丰度,以微生物组的方式提供了相应疾病的“分子表型”,特别是在治疗后/前的IBD患者中。尽管这些cfbdna在人类循环血液中的起源和功能尚不清楚,但它们的分类变异为无创和安全的预诊断或预后的潜在应用提供了指纹,并为进一步了解宿主-微生物群相互作用提供了线索。
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引用次数: 1
Bacterial contamination screening and interpretation for biological laboratory environments 生物实验室环境的细菌污染筛选和解释
Q2 Medicine Pub Date : 2020-09-01 DOI: 10.1016/j.medmic.2020.100021
Xue Zhu , Xi Li , Wenjie Wang, Kang Ning

Advances in microbiome researches have led us to the realization that the compositions of bacterial communities of indoor environment is profoundly affected by the function of buildings, and they in turn may bring detrimental effects to the indoor environment and the occupants. These phenomena are common in biological product manufacturing, which might seriously compromise the analytical results. Thus, investigation is warranted for a deeper understanding of the potential impact of the indoor bacterial communities. Among these environments, the biological laboratories stand out because they are relatively clean and yet are highly susceptible to bacterial contaminants. However, few studies have examined the bacterial compositions of biological laboratories. In this study, we assessed the bacterial compositions of samples from the surfaces of various sites across different types of biological laboratories. We have qualitatively assessed these possible bacterial contaminants, and found distinct differences in their bacterial community composition. We also found that the types of laboratories had a larger influence than the sampling sites in shaping the bacterial community, in terms of both structure and richness. On the other hand, the public areas of the different types of laboratories shared very similar sets of bacteria. Tracing the main sources of these bacteria, we identified both environmental and human factors that are important factors in shaping the diversity and dynamics of these possible bacterial contaminations in biological laboratories. These possible bacterial contaminants that we have identified will be helpful for people who aim to eliminate them from samples.

微生物组研究的进展使我们认识到室内环境细菌群落的组成受到建筑物功能的深刻影响,进而可能给室内环境和居住者带来不利影响。这些现象在生物制品生产中很常见,可能会严重影响分析结果。因此,为了更深入地了解室内细菌群落的潜在影响,有必要进行调查。在这些环境中,生物实验室脱颖而出,因为它们相对清洁,但极易受到细菌污染物的影响。然而,很少有研究检查生物实验室的细菌组成。在这项研究中,我们评估了来自不同类型生物实验室不同地点表面的样品的细菌组成。我们对这些可能的细菌污染物进行了定性评估,并发现它们的细菌群落组成存在明显差异。我们还发现,在形成细菌群落的结构和丰富度方面,实验室的类型比采样地点有更大的影响。另一方面,不同类型实验室的公共区域共享非常相似的细菌组。追踪这些细菌的主要来源,我们确定了环境和人为因素,这些因素是塑造生物实验室中这些可能的细菌污染的多样性和动态的重要因素。我们已经确定的这些可能的细菌污染物将有助于人们从样品中消除它们。
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引用次数: 5
Adherence patterns of Escherichia coli in the intestine and its role in pathogenesis 大肠杆菌在肠道中的粘附模式及其在发病机制中的作用
Q2 Medicine Pub Date : 2020-09-01 DOI: 10.1016/j.medmic.2020.100025
Deenadayalan Karaiyagowder Govindarajan , Nandhini Viswalingam , Yogesan Meganathan , Kumaravel Kandaswamy

Gut microbiota plays an important role in maintaining a healthy intestine. Escherichia coli (E.coli) is a commensal bacteria colonizes the mucous membranes of the gut, intestine, and urinary tract. However, these strains incorporate genetic elements to become pathotype and affected in hundreds of millions of people worldwide. Seven pathotypes have been categorized such as Entero-Hemorrhagic E.coli (EHEC), Entero-Aggregative E.coli (EAEC), Entero-Pathogenic E.coli (EPEC), Entero-Toxigenic E.coli (ETEC), Diffusely Adherent E.coli (DAEC), Entero-Invasive E.coli (EIEC) and Adherent-Invasive E.coli (AIEC), and each pathotype possess distinct virulence mechanism and virulence factors to disrupt the host intestinal epithelial cells that cause diarrhea and other intestinal inflammation. This review highlights the various fimbrial and afimbrial adherence mechanisms of E.coli pathovars, and how it competes with commensal bacteria in achieving pathogenicity in the host. Such adherence mechanisms are mediated by virulence proteins that have a significant impact on the outcome of intestinal inflammation.

肠道菌群在维持肠道健康方面起着重要作用。大肠杆菌(E.coli)是一种寄生于肠道、肠道和泌尿道粘膜的共生细菌。然而,这些菌株结合遗传因素成为致病型,并影响到全世界数亿人。目前已将大肠杆菌分为肠出血性大肠杆菌(EHEC)、肠聚集性大肠杆菌(EAEC)、肠致病性大肠杆菌(EPEC)、肠产毒性大肠杆菌(ETEC)、弥漫性粘附性大肠杆菌(DAEC)、肠侵袭性大肠杆菌(EIEC)和粘附性侵袭性大肠杆菌(AIEC)等7种病原型,每种病原型具有不同的毒力机制和毒力因子,可破坏宿主肠上皮细胞,引起腹泻和其他肠道炎症。本文综述了大肠杆菌病原菌的各种缘状和缘状粘附机制,以及它如何与共生菌竞争以在宿主中实现致病性。这种粘附机制是由毒力蛋白介导的,对肠道炎症的结果有重大影响。
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引用次数: 24
Analysis of the intestinal microbiota in COVID-19 patients and its correlation with the inflammatory factor IL-18 COVID-19患者肠道菌群分析及其与炎症因子IL-18的相关性
Q2 Medicine Pub Date : 2020-09-01 DOI: 10.1016/j.medmic.2020.100023
Wanyin Tao , Guorong Zhang , Xiaofang Wang , Meng Guo , Weihong Zeng , Zhihao Xu , Dan Cao , Aijun Pan , Yucai Wang , Kaiguang Zhang , Xiaoling Ma , Zhengxu Chen , Tengchuan Jin , Lianxin Liu , Jianping Weng , Shu Zhu

The ongoing global pandemic of COVID-19 disease, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly infect lung epithelial cells, and spread mainly through respiratory droplets. However, recent studies showed potential intestinal infection of SARS-CoV-2, implicated the possibility that the intestinal infection of SARS-CoV-2 may correlate with the dysbiosis of gut microbiota, as well as the severity of COVID-19 symptoms. Here, we investigated the alteration of the gut microbiota in COVID-19 patients, as well as analyzed the correlation between the altered microbes and the levels of intestinal inflammatory cytokine IL-18, which was reported to be elevated in the serum of in COVID-19 patients. Comparing with healthy controls or seasonal flu patients, the gut microbiota showed significantly reduced diversity, with increased opportunistic pathogens in COVID-19 patients. Also, IL-18 level was higher in the fecal samples of COVID-19 patients than in those of either healthy controls or seasonal flu patients. Moreover, the IL-18 levels were even higher in the fecal supernatants obtained from COVID-19 patients that tested positive for SARS-CoV-2 RNA than those that tested negative in fecal samples. These results indicate that changes in gut microbiota composition might contribute to SARS-CoV-2-induced production of inflammatory cytokines in the intestine and potentially also to the onset of a cytokine storm.

由严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)引起的COVID-19疾病正在全球大流行,主要感染肺上皮细胞,主要通过呼吸道飞沫传播。然而,最近的研究表明,SARS-CoV-2的肠道感染可能与肠道菌群失调以及COVID-19症状的严重程度有关。在这里,我们研究了COVID-19患者肠道微生物群的改变,并分析了微生物改变与肠道炎症细胞因子IL-18水平的相关性,据报道,IL-18在COVID-19患者的血清中升高。与健康对照组或季节性流感患者相比,肠道微生物群的多样性显著降低,COVID-19患者的机会致病菌增加。此外,COVID-19患者粪便样本中的IL-18水平高于健康对照组或季节性流感患者。此外,从SARS-CoV-2 RNA检测为阳性的COVID-19患者的粪便上清液中获得的IL-18水平甚至高于粪便样本中检测为阴性的患者。这些结果表明,肠道微生物群组成的变化可能有助于sars - cov -2诱导的肠道炎症细胞因子的产生,也可能导致细胞因子风暴的发生。
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引用次数: 95
Comparative study of classifiers for human microbiome data 人类微生物组数据分类器的比较研究。
Q2 Medicine Pub Date : 2020-06-01 DOI: 10.1016/j.medmic.2020.100013
Xu-Wen Wang , Yang-Yu Liu

Accumulated evidence has shown that commensal microorganisms play key roles in human physiology and diseases. Dysbiosis of the human-associated microbial communities, often referred to as the human microbiome, has been associated with many diseases. Applying supervised classification analysis to the human microbiome data can help us identify subsets of microorganisms that are highly discriminative and hence build prediction models that can accurately classify unlabeled samples. Here, we systematically compare two state-of-the-art ensemble classifiers: Random Forests (RF), eXtreme Gradient Boosting decision trees (XGBoost) and two traditional methods: The elastic net (ENET) and Support Vector Machine (SVM) in the classification analysis of 29 benchmark human microbiome datasets. We find that XGBoost outperforms all other methods only in a few benchmark datasets. Overall, the XGBoost, RF and ENET display comparable performance in the remaining benchmark datasets. The training time of XGBoost is much longer than others, partially due to the much larger number of hyperparameters in XGBoost. We also find that the most important features selected by the four classifiers partially overlap. Yet, the difference between their classification performance is almost independent of this overlap.

积累的证据表明,共生微生物在人类生理和疾病中发挥着关键作用。人类相关微生物群落的失调,通常被称为人类微生物组,与许多疾病有关。将监督分类分析应用于人类微生物组数据可以帮助我们识别具有高度鉴别力的微生物子集,从而建立能够准确分类未标记样本的预测模型。在这里,我们系统地比较了两种最先进的集成分类器:随机森林(RF)、极限梯度提升决策树(XGBoost)和两种传统方法:弹性网(ENET)和支持向量机(SVM),用于29个基准人类微生物组数据集的分类分析。我们发现XGBoost仅在少数基准数据集中优于所有其他方法。总体而言,XGBoost、RF和ENET在剩余的基准数据集中显示出相当的性能。XGBoost的训练时间比其他方法长得多,部分原因是XGBoost中的超参数数量要多得多。我们还发现,四个分类器选择的最重要的特征部分重叠。然而,它们的分类性能之间的差异几乎与这种重叠无关。
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引用次数: 31
Role of skin and gut microbiota in the pathogenesis of psoriasis, an inflammatory skin disease 皮肤和肠道微生物群在银屑病(一种炎症性皮肤病)发病机制中的作用
Q2 Medicine Pub Date : 2020-06-01 DOI: 10.1016/j.medmic.2020.100016
Daniel K. Hsu , Maxwell A. Fung , Hung-Lin Chen

Psoriasis is a chronic inflammatory skin disease associated with epidermal keratinocyte hyperplasia and epidermal immune cell over-activation. Compositions of both local skin and gut microbiome are linked to modulation of inflammation and disease severity in psoriasis. Owing to the situation that different bacteria may elicit differential immune or inflammatory responses from epidermal immune cells and keratinocytes, and to-date no single pathogen was highlighted to be responsible for psoriasis, disruption of homeostasis (dysbiosis) in the original microbial ecosystems may create a disease-promoting environment, and as a whole may be a primary causal factor. Several studies have provided evidence that the dominant IL-23/IL-17 pathogenesis pathway is regulated by metabolites produced by gut and skin microbiota. This review summarizes the approaches commonly used for functional characterization of the microbiome compositions associated with development of clinical phenotypes of psoriasis. The underlying mechanisms by which microbiota modulate immune cells and keratinocytes are also proposed.

银屑病是一种慢性炎症性皮肤病,与表皮角化细胞增生和表皮免疫细胞过度活化有关。局部皮肤和肠道微生物组的组成与银屑病炎症和疾病严重程度的调节有关。由于不同的细菌可能会引起表皮免疫细胞和角质形成细胞的不同免疫或炎症反应,并且迄今为止没有单一病原体被强调为银屑病的原因,原始微生物生态系统中稳态的破坏(生态失调)可能会产生促进疾病的环境,并且作为一个整体可能是主要原因。一些研究已经提供证据表明,显性的IL-23/IL-17发病途径是由肠道和皮肤微生物群产生的代谢物调节的。本文综述了与银屑病临床表型发展相关的微生物组组成的功能表征的常用方法。微生物群调节免疫细胞和角质形成细胞的潜在机制也被提出。
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引用次数: 30
期刊
Medicine in Microecology
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