益生菌肠道微生物的基因组学英文论文及翻译

The genomics of probiotic intestinal microorganisms

Seppo Salminen1 , Jussi Nurmi2 and Miguel Gueimonde1

(1) Functional Foods Forum, University of Turku, FIN-20014 Turku, Finland

(2) Department of Biotechnology, University of Turku, FIN-20014 Turku, Finland

Seppo Salminen

Email: seppo.salminen@utu.fi

Published online: 29 June 2005

Abstract

An intestinal population of beneficial commensal microorganisms helps maintain human health, and some of these bacteria have been found to significantly reduce the risk of gut-associated disease and to alleviate disease symptoms. The genomic characterization of probiotic bacteria and other commensal intestinal bacteria that is now under way will help to deepen our understanding of their beneficial effects.

While the sequencing of the human genome [1, 2] has increased our

understanding of the role of genetic factors in health and disease, each human being harbors many more genes than those in their own genome. These belong to our commensal and symbiotic intestinal microorganisms - our intestinal 'microbiome' - which play an important role in maintaining human health and well-being. A more appropriate image of ourselves would be drawn if the genomes of our intestinal microbiota were taken into account. The microbiome may contain more than 100 times the number of genes in the human genome [3] and provides many functions that humans have thus not needed to develop themselves. The indigenous intestinal microbiota provides a barrier against pathogenic bacteria and other harmful food components [4–6]. It has also been shown to have a direct impact on the morphology of the gut [7], and many intestinal diseases can be linked to disturbances in the intestinal microbial population [8].

The indigenous microbiota of an infant's gastrointestinal tract is originally created through contact with the diverse microbiota of the parents and the immediate environment. During breast feeding, initial microbial colonization is enhanced by galacto-oligosaccharides in breast milk and contact with the skin microbiota of the mother. This early colonization process directs the microbial succession until weaning and forms the basis for a healthy microbiota. The viable microbes in the adult

intestine outnumber the cells in the human body tenfold, and the composition of this microbial population throughout life is unique to each human being. During adulthood and aging the composition and diversity of the microbiota can vary as a result of disease and the genetic background of the individual.

Current research into the intestinal microbiome is focused on obtaining genomic data from important intestinal commensals and from probiotics, microorganisms that appear to actively promote health. This genomic information indicates that gut commensals not only derive food and other growth factors from the intestinal contents but also influence their human hosts by providing maturational signals for the developing infant and child, as well as providing signals that can lead to an alteration in the barrier mechanisms of the gut. It has been reported that colonization by particular bacteria has a major role in rapidly providing humans with energy from their food [9]. For example, the intestinal commensal Bacteroides thetaiotaomicron has been shown to have a major role in this process, and whole-genome transcriptional profiling of the bacterium has shown that specific diets can be associated with selective upregulation of bacterial genes that facilitate delivery of products of carbohydrate breakdown to the host's energy metabolism [10, 11]. Key microbial groups in the intestinal microbiota are highly flexible in adapting to changes in diet, and thus detailed prediction of their actions and effects may be difficult. Although genomic studies have revealed important details about the impact of the intestinal microbiota on specific processes [3, 11–14], the effects of species composition and microbial diversity and their potential compensatory functions are still not understood.

Probiotics and health

A probiotic has been defined by a working group of the International Life Sciences Institute Europe (ILSI Europe) as "a viable microbial food supplement which beneficially influences the health of the host" [15]. Probiotics are usually members of the healthy gut microbiota and their addition can assist in returning a disturbed microbiota to its normal beneficial composition. The ILSI definition implies that safety and efficacy must be scientifically demonstrated for each new probiotic strain and product. Criteria for selecting probiotics that are specific for a desired target have been developed, but general criteria that must be satisfied include the ability to adhere to intestinal mucosa and tolerance of acid and bile. Such criteria have proved useful but cumbersome in current selection processes, as there are several adherence mechanisms and they influence gene upregulation differently in the host. Therefore, two different adhesion studies need to be conducted on each strain and their

predictive value for specific functions is not always good or optimal. Demonstration of the effects of probiotics on health includes research on mechanisms and clinical intervention studies with human subjects belonging to target groups.

The revelation of the human genome sequence has increased our understanding of the genetic deviations that lead to or predispose to gastrointestinal disease as well as to diseases associated with the gut, such as food allergies. In 1995, the first genome of a free-living organism, the bacterium Haemophilus influenzae, was sequenced [16]. Since then, over 200 bacterial genome sequences, mainly of pathogenic microorganisms, have been completed. The first genome of a mammalian lactic-acid bacterium, that of Lactococcus lactis, a microorganism of great industrial interest, was completed in 2001 [17]. More recently, the genomes of numerous other lactic-acid bacteria [18], bifidobacteria [12] and other intestinal microorganisms [13, 19, 20] have been sequenced, and others are under way [21]. Table 1lists the probiotic bacteria that have been sequenced. These great breakthroughs have demonstrated that evolution has adapted both microbes and humans to their current state of cohabitation, or even symbiosis, which is beneficial to both parties and facilitates a healthy and relatively stable but adaptable gut environment.

Table 1

Lessons from genomes

Lactic-acid bacteria and bifidobacteria can act as biomarkers of gut health by giving early warning of aberrations that represent a risk of specific gut diseases. Only a few members of the genera Lactobacillus and Bifidobacterium, two genera that provide many probiotics, have been completely sequenced. The key issue for the microbiota, for probiotics, and for their human hosts is the flexibility of the microorganisms in coping with a changeable local environment and microenvironments.

This flexibility is emphasized in the completed genomes of intestinal and probiotic microorganisms. The complete genome sequence of the probiotic Lactobacillus acidophilus NCFM has recently been published by Altermann et al. [22]. The genome is relatively small and the bacterium appears to be unable to synthesize several amino acids, vitamins and cofactors. It

also encodes a number of permeases, glycolases and peptidases for rapid uptake and utilization of sugars and amino acids from the human intestine, especially the upper gastrointestinal tract. The authors also report a number of cell-surface proteins, such as mucus- and fibronectin-binding proteins, that enable this strain to adhere to the intestinal epithelium and to exchange signals with the intestinal immune system. Flexibility is guaranteed by a number of regulatory systems, including several transcriptional regulators, six PurR-type repressors and nine

two-component systems, and by a variety of sugar transporters. The genome of another probiotic, Lactobacillus johnsonii [23], also lacks some genes involved in the synthesis of amino acids, purine nucleotides and numerous cofactors, but contains numerous peptidases, amino-acid permeases and other transporters, indicating a strong dependence on the host.

The presence of bile-salt hydrolases and transporters in these bacteria indicates an adaptation to the upper gastrointestinal tract [23], enabling the bacteria to survive the acidic and bile-rich environments of the stomach and small intestine. In this regard, bile-salt hydrolases have been found in most of the sequenced genomes of bifidobacteria and lactic-acid bacteria [24], and these enzymes can have a significant impact on bacterial survival. Another lactic-acid bacterium, Lactobacillus plantarum WCFS1, also contains a large number of genes related to carbohydrate transport and utilization, and has genes for the production of exopolysaccharides and antimicrobial agents [18], indicating a good adaptation to a variety of environments, including the human small intestine [14]. In general, flexibility and adaptability are reflected by a large number of regulatory and transport functions.

Microorganisms that inhabit the human colon, such as B. thetaiotaomicron and Bifidobacterium longum [12], have a great number of genes devoted to oligosaccharide transport and metabolism, indicating adaptation to life in the large intestine and differentiating them from, for example, L. johnsonii [23]. Genomic research has also provided initial information on the relationship between components of the diet and intestinal microorganisms. The genome of B. longum [12] suggests the ability to scan for nutrient availability in the lower gastrointestinal tract in human infants. This strain is adapted to utilizing the oligosaccharides in human milk along with intestinal mucins that are available in the colon of breast-fed infants. On the other hand, the genome of L. acidophilus has a gene cluster related to the metabolism of fructo-oligosaccharides, carbohydrates that are commonly used as prebiotics, or substrates to

肠道微生物益生菌的基因组学

塞波萨米宁，尤西鲁米和米格尔哥尔摩得

（1）功能性食品论坛，图尔库大学，FIN-20014芬兰图尔库

（2）土尔库大学生物技术系，FIN-20014芬兰图尔库

塞波萨米宁

电子邮件：seppo.salminen utu.fi

线上发表于2005年6月29日

摘要

肠道有益的共生微生物有助于维护人体健康，一些这些细菌被发现显着降低肠道疾病的风险和减轻疾病的症状。现在正在进行的益生菌和其他肠道共生细菌的基因组特性的研究，将有助于加深我们理解他们的有益的影响。

虽然人类基因组的测序[ 1，2 ]增加了我们对健康和疾病的遗传因素的作用的理解，每个人都有着着比自己的基因组更多的基因。这是属于我们的共生，共生的肠道微生物-我们的肠道的微生物”在维持人体健康和幸福上发挥了重要的作用。如果考虑到了我们的肠道菌群的基因组，将得出一个更合适的自我形象。微生物可能包含超过人类基因组中[ 3 ]基因的数量的100倍的基因，并提供了许多功能，因此，人类已经不需要发展自己。土著肠道菌群提供了一种对致病性细菌和其他有害的食物成分[ 6 ] 4–的屏障。它也被证明有对肠道[ 7 ]的形态有着直接影响，许多肠道疾病可使肠道菌群紊乱。一个土著婴儿胃肠道的微生物最初是通过与父母不同的微生物，和周围的环境联系了。哺乳期间，最初的微生物定植的低聚半乳糖在母乳和母亲的皮肤菌群接触增强。这种早期的殖民过程指示微生物在婴儿体内演替形成一个健康的菌群直到婴儿断奶。在成人的肠道微生物的数量是人体细胞的十倍，对于整个生命的微生物种群组成，每个人独特的，成年和老龄化的微生物群落的组成及多样性的变化由于疾病和个体的遗传背景的不同而出现差异。

电流进入肠道微生物的研究重点是重要的肠道共生和益生菌微生物基因组数据的获取，出现积极促进健康。该基因组的信息表明，肠道共生不仅从肠内容物获得食品和其他生长因子也为人类宿主的婴儿和儿童的发展提供了成熟的信号，并且提供的信号可以导致在肠道的屏障机制的改变。据报道，由特定的细菌定植在快速提供人类从食物中获取能量起主要作用[ 9 ]。例如，肠道共生多形拟杆菌已被证明在这个过程中是一个重要的角色，和全基因组的细菌转录谱对比表明，细菌显示特定的饮食可以与细菌的基因，促进糖分解的产品交付到宿主的能量代谢的选择性上调相关[ 10，11 ]。在肠道菌群的主要微生物类群适应饮食的变化是非常灵活的，因此详细预测他们的行为和作用可能是困难的。虽然基因组研究揭示肠道菌群的影响特定的进程有关的重要细节11–14 ] ，但微生物的多样性和潜在的代偿功能的物种组成的影响仍不清楚。

益生菌和健康

益生菌已由国际生命科学学会的欧洲工作组定义（ILSI欧洲）为"；一个可行的微生物食品添加剂影响宿主健康；[ 15 ]。益生菌通常是健康的肠道菌群及添加成员可以协助返回

到其正常干扰微生物的有益成分。ILSI定义暗示了每一个新的益生菌产品的安全性和有效性必须科学地证明。选择益生菌，目标是具体的标准已经制定，但一般标准，必须满足包括肠粘膜及耐酸、耐胆盐的能力。这些标准已被证明是有用的但在当前选择的过程繁琐，存在一些粘附机制和他们的影响在不同的宿主基因表达上调。因此，两个不同的粘附的研究在每个应变和对具体功能进行的预测值不一定是好的或最优的。对益生菌对健康的影响包括对示范机制和临床干预研究人类受试者属于目标群体的研究。

应变的大小（MB）参考

长双歧杆菌NCC 2705 2.25 [ 12 ]

植物乳杆菌WCFS1 3.30 [ 18 ]

乳杆菌johnsonii NCC 533 2.02 [ 23 ]

嗜酸乳杆菌1.99 [ 22 ]

从基因组

乳酸菌和双歧杆菌可通过像差，代表一个特定的肠道疾病风险预警的肠道健康的生物标志。只有少数成员的乳酸杆菌和双歧杆菌属，这两个属提供的多种益生菌，已完全测序。肠道菌群中的益生菌的问题是它们的人类宿主是在应对多变的当地环境和微环境微生物。这种灵活性是强调完成的肠道和益生菌微生物基因组。益生菌嗜酸乳杆菌的全基因组序列最近已由奥尔特曼等人发表。22。基因组相对较小，细菌似乎无法合成的多种氨基酸，维生素和辅助因子。它也编码的通透，glycolases和肽从人类的肠道快速摄取糖和氨基酸并利用，尤其是上消化道。作者还指出了大量的细胞表面蛋白，如粘液和纤连蛋白结合蛋白，使这株坚持肠上皮细胞和肠道免疫系统交换信号。灵活性是由多个监管系统保证的，包括几个转录调节因子，六呼噜型抑制，九双组分系统，并通过各种糖转运蛋白。另一个基因组的益生菌，乳酸菌菌[ 23 ]，也缺乏一些参与氨基酸合成基因，嘌呤核苷酸和众多的辅助因子，但包含许多肽，氨基酸通透酶和转运蛋白，指示主机上的强依赖性。

在这些细菌中胆盐水解酶和转运的存在表明它们在上消化道上的适应性 [ 23 ]，使细菌在酸性和胆胃和小肠的丰富的环境中生存。在这方面，胆盐水解酶在大多数的基因组测序的双歧杆菌和乳酸菌中被发现 [ 24 ]，这些酶可以对细菌的生存有一个显着的影响。另一种乳酸菌，植物乳杆菌WCFS1，还含有大量的碳水化合物运输和利用相关的基因，并且基因的胞外多糖和抗菌剂[ 18 ]生产，能很好的适应各种环境，包括人类小肠[ 14 ]。一般来说，灵活性和适应性是由大量的监管和运输功能体现。微生物存在于人的结肠，如B. thetaiotaomicron 双歧杆菌[ 12 ]，有大量的基因用于寡糖的转运和代谢，表明在大肠中生活的适应性能区分他们，例如，L.逊[ 23 ]。基因组学研究提供了组成的饮食和肠道微生物之间的关系初步的信息。B. longum [ 12 ]基因组显示扫描在下消化道的人类婴儿的养分供应能力。该菌株在利用人乳随肠粘蛋白低聚糖在母乳喂养的婴儿的结肠中是可用的。另一方面，嗜酸乳杆菌基因组中有一个对低聚果糖的代谢相关的基因群，碳水化合物，是能提高结肠[ 25 ]有益的共生生长的常用的益生元。

微生物与人类健康2018

伤寒与细菌性痢疾 1 【单选题】（B）是细菌性痢疾的主要传播渠道。 A、唾液 B、食物 C、水源 D、体液 2 【单选题】通过（B）传播有可能会感染伤寒沙门氏菌。 A、空气 B、水源 C、唾液 D、接触 3 【单选题】伤寒可能首先出现的症状是引起（A）出血和穿孔。 A、肠道 B、胃 C、肾 D、肺 4 【判断题】采用抗生素治疗后，伤寒病死率可以降低到1%以下。（对）

【判断题】任意一种细菌与志贺氏菌结合都可以感染伤寒。（错） 1.2 霍乱与破伤风 1 【单选题】下列选项中，哪些不是霍乱可能引起的结果？（D） A、酸中毒 B、腹泻 C、反射性呕吐 D、血压上升 2 【单选题】下列不是关于破伤风杆菌说法的是（A）。 A、经飞沫传播感染 B、棒槌状 C、广泛分布与环境、土壤 D、厌氧细菌 3 【单选题】霍乱从1817年到1923年在世界范围内流行了（A）次。 A、6次 B、5次

C、4次 D、3次 4 【判断题】几乎不引起局部炎症症状，煮沸即可使之失活是破伤风感染。（错）5 【判断题】分泌外毒素，造成末端神经系统急性中毒的症状是破伤风感染。（错） 1.3 梅毒与幽门螺杆菌 1 【单选题】梅毒在不治疗的情况下，死亡率约达（D）。 A、50% B、30% C、40% D、20% 2 【单选题】由幽门螺杆菌引起的病症，（C）是十二指肠溃疡。 A、95% B、85% C、90% D、80%

3 【单选题】梅毒根据现有资料推测，（B）是其原发地。 A、亚洲 B、美洲 C、欧洲 D、大洋洲 4 【判断题】 梅毒病毒可能通过胎盘直接传染给胎儿。（对） 5 【判断题】存在于胃的上半部分幽门附近的病菌是幽门螺杆菌。（错） 1.4 黑死病 1 【单选题】通过（A）传播最容易得结核病。 A、空气 B、食物 C、水源 D、唾液 2

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Inventory management Inventory Control On the so-called "inventory control", many people will interpret it as a "storage management", which is actually a big distortion. The traditional narrow view, mainly for warehouse inventory control of materials for inventory, data processing, storage, distribution, etc., through the implementation of anti-corrosion, temperature and humidity control means, to make the custody of the physical inventory to maintain optimum purposes. This is just a form of inventory control, or can be defined as the physical inventory control. How, then, from a broad perspective to understand inventory control? Inventory control should be related to the company's financial and operational objectives, in particular operating cash flow by optimizing the entire demand and supply chain management processes (DSCM), a reasonable set of ERP control strategy, and supported by appropriate information processing tools, tools to achieved in ensuring the timely delivery of the premise, as far as possible to reduce inventory levels, reducing inventory and obsolescence, the risk of devaluation. In this sense, the physical inventory control to achieve financial goals is just a means to control the entire inventory or just a necessary part; from the perspective of organizational functions, physical inventory control, warehouse management is mainly the responsibility of The broad inventory control is the demand and supply chain management, and the whole company's responsibility. Why until now many people's understanding of inventory control, limited physical inventory control? The following two reasons can not be ignored: First, our enterprises do not attach importance to inventory control. Especially those who benefit relatively good business, as long as there is money on the few people to consider the problem of inventory turnover. Inventory control is simply interpreted as warehouse management, unless the time to spend money, it may have been to see the inventory problem, and see the results are often very simple procurement to buy more, or did not do warehouse departments . Second, ERP misleading. Invoicing software is simple audacity to call it ERP, companies on their so-called ERP can reduce the number of inventory, inventory control, seems to rely on their small software can get. Even as SAP, BAAN ERP world, the field of

人体肠道微生物群落与疾病

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