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Tetracycline-like resistome of ancient human guts 古代人类肠道中类似四环素的抵抗组
Q1 Medicine Pub Date : 2018-12-01 DOI: 10.1016/j.humic.2018.07.001
Tasha M. Santiago-Rodriguez , Gino Fornaciari , Stefania Luciani , Gary A. Toranzos , Isolina Marota , Valentina Giuffra , Naseer Sangwan , Raul J. Cano

Tetracyclines were discovered over 70 years ago and their use resulted in the emergence of tetracycline-resistance microorganisms; however, it has been hypothesized that tetracycline-resistance may have originated in the environment, and that determinants were transferred to the human gut microbiota. Ancient microbiomes represent an opportunity to explore the transmission of tetracycline-resistance determinants from the environment to humans. In the present study, tetracycline-like resistomes of three pre-Inca/Inca (10–15th centuries), and five Italian nobility (15–16th centuries) mummies were characterized using high-throughput sequencing. Sequences exhibited low homology to present-day determinants. Results may aid in the understanding of the evolution of tetracycline-resistance.

四环素是在70 年前发现的,它们的使用导致了四环素耐药微生物的出现;然而,据推测,四环素耐药性可能起源于环境,并将决定因素转移到人类肠道微生物群。古代微生物群为探索四环素耐药决定因素从环境向人类的传播提供了机会。本研究利用高通量测序技术对3具前印加/印加木乃伊(10 - 15世纪)和5具意大利贵族木乃伊(15 - 16世纪)的四环素样抗性组进行了鉴定。序列显示低同源性,以今天的决定因素。结果可能有助于了解四环素耐药性的演变。
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引用次数: 4
New microbe genomic variants in patients fecal community following surgical disruption of the upper human gastrointestinal tract 上消化道手术中断后患者粪便群落中新的微生物基因组变异
Q1 Medicine Pub Date : 2018-12-01 DOI: 10.1016/j.humic.2018.10.002
Ranjit Kumar , Jayleen Grams , Daniel I. Chu , David K. Crossman , Richard Stahl , Peter Eipers , Kelly Goldsmith , Michael Crowley , Elliot J. Lefkowitz , Casey D. Morrow

Recent studies have shown that microbe strains in normal individuals fecal microbe community are relatively stable over time. Given the role the gut microbe community plays in human health, it is important to understand if disruption of the gastrointestinal tract environment results in emergence of new genomic variants. To address this, we have used a new technique called Window-based single nucleotide similarity (WSS) to analyze the impact of several surgical procedures of the human gastrointestinal tract on the stability of the fecal microbes. Previously, we established a WSS boundary score cutoff to determine if microbe genomic variants were similar. Based on analysis of normal individuals from the Human Microbiome Project, 93% of microbes in paired fecal samples up to 1 year apart were above the cutoff, indicating similar (stable) microbes. For the current study, we analyzed fecal samples from 18 patients undergoing Roux-en-Y gastric bypass (RYGB) or 6 patients undergoing gastric sleeve for extreme obesity. From comparison of the pre-RYGB versus 1–2 year post RYGB samples from the same patients, 65% of the WSS were above the boundary cutoff, while for pre versus 1–2 year samples post surgery for patients undergoing sleeve gastrectomy, 75% of the WSS were above the cutoff. In contrast, analysis of fecal samples from 5 patients pre and post removal of segments of the sigmoid colon revealed that 97% of WSS scores were above the cutoff. Our study establishes emergence of new microbe genomic variants in the fecal community following alteration of the upper gastrointestinal environment.

最近的研究表明,随着时间的推移,正常个体粪便微生物群落中的微生物菌株相对稳定。鉴于肠道微生物群落在人类健康中的作用,了解胃肠道环境的破坏是否会导致新的基因组变异的出现是很重要的。为了解决这个问题,我们使用了一种称为基于窗口的单核苷酸相似性(WSS)的新技术来分析人类胃肠道的几种外科手术对粪便微生物稳定性的影响。之前,我们建立了一个WSS边界评分截止值来确定微生物基因组变异是否相似。根据人类微生物组计划对正常个体的分析,在相隔1 年的配对粪便样本中,93%的微生物高于临界值,表明微生物相似(稳定)。在目前的研究中,我们分析了18例接受Roux-en-Y胃旁路术(RYGB)或6例接受胃套管术治疗的极度肥胖患者的粪便样本。通过比较来自同一患者的RYGB前和RYGB后1-2 年的样本,65%的WSS高于边界截断,而对于接受袖胃切除术的患者,术前和术后1-2 年的样本,75%的WSS高于边界截断。相比之下,对5例乙状结肠切除前后患者的粪便样本分析显示,97%的WSS评分高于临界值。我们的研究表明,随着上消化道环境的改变,粪便群落中出现了新的微生物基因组变异。
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引用次数: 9
Microbiome and the immune system: From a healthy steady-state to allergy associated disruption 微生物组和免疫系统:从健康的稳定状态到过敏相关的破坏
Q1 Medicine Pub Date : 2018-12-01 DOI: 10.1016/j.humic.2018.10.001
Soraya Mezouar , Yannick Chantran , Justin Michel , Alexandre Fabre , Jean-Christophe Dubus , Marc Leone , Youssouf Sereme , Jean-Louis Mège , Stéphane Ranque , Benoît Desnues , Pascal Chanez , Joana Vitte

Microbiome and the immune system are constantly shaping each other, in a mutual aim to thrive, defining the unstable equilibrium of the healthy individual. Microbiome is growingly involved in dysimmune conditions such as allergy, asthma, autoimmunity, and primary or acquired immune deficiencies. The current epidemics of allergic diseases and asthma has long been linked to the microbial environment through the hygiene hypothesis. Progress in the understanding of the microbiome-immune system crosstalk has unraveled a tight connection between microbial communities and the development of allergic diseases and asthma. Disruption of the microbiome affects the immune response of the host and paves the way for disease pathogenesis. Conversely, disease and therapeutic interventions affect microbial communities. We aimed at providing the reader with a view of the state-of-the art of microbiome – immune system crosstalk, with special focus on the loopholes giving potential grip to the pathogenesis of microbiome-related dysimmunity.

微生物群和免疫系统不断地相互塑造,共同的目标是茁壮成长,定义了健康个体的不稳定平衡。微生物组越来越多地参与免疫功能障碍,如过敏、哮喘、自身免疫和原发性或获得性免疫缺陷。目前流行的过敏性疾病和哮喘早就通过卫生假说与微生物环境联系在一起。对微生物组-免疫系统串扰的理解取得了进展,揭示了微生物群落与过敏性疾病和哮喘发展之间的紧密联系。微生物群的破坏会影响宿主的免疫反应,为疾病的发病机制铺平道路。相反,疾病和治疗干预会影响微生物群落。我们旨在为读者提供最新的微生物组-免疫系统串扰的观点,特别关注微生物组相关免疫障碍发病机制的潜在控制漏洞。
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引用次数: 42
Linking gut redox to human microbiome 将肠道氧化还原与人类微生物群联系起来
Q1 Medicine Pub Date : 2018-12-01 DOI: 10.1016/j.humic.2018.07.002
Matthieu Million, Didier Raoult

Uncontrolled oxidative stress has been associated with many diseases and aging. We previously report an increased gut redox and depletion of the anaerobic microbiome in severe acute malnutrition. Here, we extended the analysis to test if this link could be generalized by including individuals with various age and dietary status. Seventy individuals (children and adults, French and African, healthy individuals and teenagers with anorexia nervosa, marasmus and kwashiorkor) were included. Fecal redox potential was measured using a simple redox probe. v3v4 16S gene targeted metagenomics was used to characterize the microbiota. The Metagenomic Aerotolerant Predominance Index (MAPI) was defined as the natural logarithm of the ratio of the relative abundance of aerotolerant on strict anaerobic species. This index is easily understandable (MAPI > 0: aerotolerant predominance, MAPI < 0: anaerobic predominance), can be calculated for any metagenome and follows a normal distribution among our 70 included individuals. Fecal redox potential (mV) and the Metagenomic Aerotolerant Predominance Index were dose-dependently related (linear regression, p < .001). This link, if confirmed, will allow humans to take care of their microbiome and prevent, treat and/or alleviate gut redox associated chronic diseases by (i) controlling the concentration of reactive species in the gut by avoiding behavior associated with uncontrolled oxidative stress (alcoholism,…) in the gut and using reduced water, and (ii) by improving gut anti-oxidant capacities by an adequate diet rich in nutrients allowing the human gut to maintain a very low redox potential in the gut as a key for homeostasis.

不受控制的氧化应激与许多疾病和衰老有关。我们之前报道了严重急性营养不良中肠道氧化还原和厌氧微生物群消耗的增加。在这里,我们扩展了分析,以测试这种联系是否可以通过包括不同年龄和饮食状况的个体来推广。70人(儿童和成人、法国人和非洲人、健康个体和患有神经性厌食症、消瘦症和营养不良症的青少年)被纳入研究。使用简单的氧化还原探针测量粪便氧化还原电位。采用v3v4 16S基因靶向宏基因组学对菌群进行表征。宏基因组耐氧优势指数(MAPI)定义为严格厌氧菌中耐氧菌相对丰度比值的自然对数。该指数很容易理解(MAPI > 0:耐氧优势,MAPI < 0:厌氧优势),可以计算任何宏基因组,并在我们纳入的70个个体中遵循正态分布。粪便氧化还原电位(mV)与宏基因组耐氧优势指数呈剂量依赖关系(线性回归,p < .001)。这种联系如果得到证实,将使人类能够照顾他们的微生物群,并通过以下方式预防、治疗和/或减轻肠道氧化还原相关的慢性疾病:(i)通过避免肠道中与不受控制的氧化应激(酗酒等)相关的行为和使用减少的水来控制肠道中反应性物种的浓度;(ii)通过营养丰富的饮食来提高肠道抗氧化能力,使人体肠道保持极低的氧化还原电位,作为体内平衡的关键。
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引用次数: 57
Early colonization of the gut microbiome and its relationship with obesity 肠道微生物群的早期定植及其与肥胖的关系
Q1 Medicine Pub Date : 2018-12-01 DOI: 10.1016/j.humic.2018.08.002
Jena L. Dreyer , Andrea L. Liebl

Adult and childhood obesity rates are increasing. Childhood obesity, in particular, is a complicated, multifactorial condition that is not always explained by overeating. To address rising rates of obesity, researchers have begun to address how the composition of the gastrointestinal microbiome influences metabolism, energy absorption, and weight regulation. Colonization of the gut begins in early life and is highly influenced by method of birth (vaginal versus Caesarean), method of feeding (formula feeding versus breastfeeding), and exposure to antibiotics. Not surprisingly, an infant’s gut microbiome is very likely to resemble that of its mother. However, this means that aberrant bacteria characterized by an obese microbiome can also get passed on from an obese mom to child. To promote the colonization of a healthy infant gut microbiome, the optimal strategy generally is to have a vaginal delivery followed by exclusive breastfeeding until 6 months of age with minimal exposure to antibiotics. However, this is not always possible and overweight or obese mothers risk passing on aberrant bacteria to her children. In such cases, in conjunction with medical professionals, women can consider adding pre- and probiotics to their diets during pregnancy and lactation as well as other mitigation strategies. The colonization of an infant’s gut with optimal bacteria may help reduce the risk of obesity later in life.

成人和儿童肥胖率正在上升。特别是儿童肥胖,是一种复杂的、多因素的疾病,并不总是用暴饮暴食来解释。为了解决肥胖率上升的问题,研究人员已经开始研究胃肠道微生物群的组成如何影响新陈代谢、能量吸收和体重调节。肠道的定植始于生命早期,受分娩方式(阴道还是剖腹产)、喂养方式(配方奶还是母乳喂养)和抗生素暴露的高度影响。毫不奇怪,婴儿的肠道微生物群很可能与母亲的相似。然而,这意味着以肥胖微生物群为特征的异常细菌也可以从肥胖的母亲传给孩子。为了促进健康婴儿肠道微生物群的定植,最佳策略通常是阴道分娩,然后进行纯母乳喂养,直到6 个月大,并尽量减少抗生素的接触。然而,这并不总是可能的,超重或肥胖的母亲有可能把异常细菌传给她的孩子。在这种情况下,与医疗专业人员一起,妇女可以考虑在怀孕和哺乳期间在饮食中添加益生菌和益生菌,以及其他缓解策略。在婴儿肠道中定植最佳细菌可能有助于降低以后肥胖的风险。
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引用次数: 31
Human microbiomes and antibiotic resistance 人类微生物组和抗生素耐药性
Q1 Medicine Pub Date : 2018-12-01 DOI: 10.1016/j.humic.2018.08.005
Sophie A Baron , Seydina M Diene , Jean-Marc Rolain

Human microbiomes are complex ecosystems involving bacteria, viruses, archaea or eukaryotes that are co-evolving in an environment subject to various selective pressures, such as antibiotic administration, diet and/or lifestyle. In this sympatric lifestyle, competition is hard and the synthesis of antibiotic molecules and/or antibiotic resistance genes (ARGs) is one solution that was developed by the organisms to survive. This environment becomes a large source of ARGs for pathogenic bacteria, leading to the risk of infection due to multidrug resistant bacteria. Culture and metagenomics are two complementary methods developed to study these microbiomes in order to better understand the type of bacteria and ARGs present in the human body, as well as the factors that modulate the abundance and variety of these ARGs. The objective of this review was to identify factors that influence the colonization and propagation of multidrug resistant bacteria and/or ARGs, and to define resistance genes and multidrug resistant bacteria that have already been isolated from the human microbiota using culturomics and metagenomics techniques.

人类微生物群是复杂的生态系统,涉及细菌、病毒、古生菌或真核生物,它们在受各种选择压力(如抗生素施用、饮食和/或生活方式)影响的环境中共同进化。在这种同域生活方式中,竞争是艰难的,抗生素分子和/或抗生素抗性基因(ARGs)的合成是生物体为生存而开发的一种解决方案。这种环境成为致病菌ARGs的一大来源,导致多重耐药菌感染的风险。培养和宏基因组学是研究这些微生物组的两种互补方法,目的是更好地了解人体内存在的细菌和ARGs的类型,以及调节这些ARGs丰度和多样性的因素。本综述的目的是确定影响多药耐药细菌和/或ARGs定植和繁殖的因素,并利用培养组学和宏基因组学技术确定已经从人类微生物群中分离出的耐药基因和多药耐药细菌。
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引用次数: 75
Potential clinical usefulness of gut microbiome testing in a variety of clinical conditions 肠道微生物组检测在多种临床条件下的潜在临床用途
Q1 Medicine Pub Date : 2018-12-01 DOI: 10.1016/j.humic.2018.08.003
Karl J. Morten , Eleonora Staines-Urias , Julian Kenyon
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引用次数: 2
Comparative therapeutic efficacy study of Lactobacilli probiotics and citalopram in treatment of acute stress-induced depression in lab murine models 乳酸杆菌益生菌与西酞普兰治疗小鼠急性应激性抑郁症的疗效比较研究
Q1 Medicine Pub Date : 2018-12-01 DOI: 10.1016/j.humic.2018.08.001
Abdalla M. Abdrabou, Enass Y. Osman, Osama A. Aboubakr

A relationship between Microbiome and its effect on depression has been suspected in earlier studies. Here we examined whether the addition of Lactobacillus probiotics which flourishes the gut-microbiota will have a beneficial adjuvant therapeutic effect on treatment of depression or even considering it as a main treatment line in the future for treatment of depression or anxiety like behavior after further studies. Mice receiving probiotics in their diet exhibited mostly similar anxiolytic and anti-depressive effects of the mice that received SSRI anti-depressant citalopram and displayed enhanced outcomes which were shown in the Tail Suspension test – which is considered a high output tool in assessing anti-depression medications –, Super oxidase dismutase concentration in the brain tissue and HPLC analysis of Kynurenine biomarker in the brain. Taken together these data support the link between healthy gut microbiome and its effect on depression-like behavior and suggest that probiotics may even have a similar therapeutic effect of anti- depressants in treatment of depression.

在早期的研究中,人们怀疑微生物组与其对抑郁症的影响之间存在关系。在这里,我们进一步研究了益生菌乳杆菌的添加是否会对治疗抑郁症有有益的辅助治疗作用,甚至在未来的研究中考虑将其作为治疗抑郁或焦虑样行为的主要治疗方法。在饮食中服用益生菌的小鼠表现出与服用SSRI抗抑郁药西酞普兰的小鼠相似的抗焦虑和抗抑郁效果,并在Tail Suspension测试(被认为是评估抗抑郁药物的高输出工具)、脑组织超氧化酶歧化酶浓度和大脑中犬尿氨酸生物标志物的HPLC分析中显示出增强的结果。综上所述,这些数据支持健康的肠道微生物群与其对抑郁样行为的影响之间的联系,并表明益生菌在治疗抑郁症方面甚至可能具有与抗抑郁药相似的治疗效果。
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引用次数: 11
Metagenomic and clinical microbiology 宏基因组学和临床微生物学
Q1 Medicine Pub Date : 2018-08-01 DOI: 10.1016/j.humic.2018.06.001
Sophie Amrane, Jean-Christophe Lagier

As a result of Next Generation Sequencing methods, metagenomic studies have become increasingly widespread. After being first applied to microbiome description, metagenomics is currently proposed as a diagnostic tool in clinical microbiology, although this application remains confined to the field of research. In this review, we will discuss the application of metagenomics to the detection of bacterial pathogens and demonstrate that the interpretation of the metagenomic results may fluctuate depending on the type of sample analyzed. However, we propose a view of metagenomic application to the evaluation of antimicrobial resistance, epidemic investigations and forensic medicine. Secondly, we present the many limits of metagenomic interpretation and application in routine clinical microbiology. From our perspective, metagenomics is not yet reliable enough for general use in clinical microbiology.

由于新一代测序方法的出现,宏基因组研究变得越来越广泛。在首次应用于微生物组描述之后,宏基因组学目前被提议作为临床微生物学的诊断工具,尽管这种应用仍然局限于研究领域。在这篇综述中,我们将讨论宏基因组学在细菌病原体检测中的应用,并证明宏基因组学结果的解释可能会根据分析样本的类型而波动。然而,我们提出了宏基因组在抗菌药物耐药性评估、流行病调查和法医学方面的应用观点。其次,我们提出了宏基因组在常规临床微生物学中的解释和应用的许多局限性。从我们的角度来看,宏基因组学在临床微生物学中的普遍应用还不够可靠。
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引用次数: 18
Intestinal microbiota and antibiotic resistance: Perspectives and solutions 肠道菌群和抗生素耐药性:观点和解决方案
Q1 Medicine Pub Date : 2018-08-01 DOI: 10.1016/j.humic.2018.05.002
Climent Casals-Pascual , Andrea Vergara , Jordi Vila

The intestinal commensal microbiota provides a myriad of benefits to the healthy host, including colonisation resistance against pathogens. Perturbations of the intestinal microbiota (dysbiosis) may adversely affect the health status of an individual and prevent protection against colonisation. The whole range of antibiotic resistance genes (resistome) in a specific microbiota is found in pathogenic and non-pathogenic bacteria. The administration of antibiotics may cause dysbiosis, contributing to the loss of colonisation resistance followed by an increment of the resistome in the intestinal microbiota. Treatments to control the current increase of multi drug-resistant (MDR) bacteria are extremely limited. In this context, the administration of healthy faecal microbiota to restore colonisation resistance and displace MDR bacteria emerges as a promising therapeutic alternative.

This brief review describes the role of the intestinal microbiota as a reservoir of MDR bacteria, the impact of different groups of antibiotics in the selection of MDR bacteria and crucially, the potential use of faecal microbiota transplantation using “healthy” or “MDR-free microbiota” to displace MDR bacteria and restore colonisation resistance.

肠道共生微生物群为健康的宿主提供了无数的好处,包括对病原体的定植抗性。肠道微生物群的扰动(生态失调)可能对个体的健康状况产生不利影响,并阻止对定植的保护。特定微生物群中的全部抗生素抗性基因(抗性组)存在于致病性和非致病性细菌中。抗生素的施用可能导致生态失调,导致肠道微生物群中定植抗性的丧失,随后是抗性组的增加。控制当前多重耐药(MDR)细菌增加的治疗非常有限。在这种情况下,健康的粪便微生物群的管理,以恢复定植耐药和取代耐多药细菌成为一个有前途的治疗方案。这篇简短的综述描述了肠道微生物群作为耐多药细菌储存库的作用,不同抗生素组对耐多药细菌选择的影响,以及至关重要的是,使用“健康”或“无耐多药微生物群”的粪便微生物群移植取代耐多药细菌并恢复定植抗性的潜在用途。
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引用次数: 56
期刊
Human Microbiome Journal
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