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1、The genomics of probiotic intestinal microorganismsSeppoSalminen1, JussiNurmi2 and MiguelGueimonde1(1) Functional Foods Forum, University of Turku, FIN-20014Turku, Finland(2) Department of Biotechnology, University of Turku, FIN-20014Turku, FinlandSeppoSalminenEmail: seppo.salminenutu.fiPublished on
2、line: 29June2005AbstractAn 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 bact
3、eria 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
4、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 mic
5、robiota 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
6、harmful food components 46. 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 infants gastrointestinal tract is originally created through
7、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 suc
8、cession 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
9、 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 heal
10、th. 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 alteratio
11、n 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, an
12、d 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 hosts energy metabolism 10, 11. Key microbial groups in the intestinal microb
13、iota 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, 1114, the effects of species compositio
14、n and microbial diversity and their potential compensatory functions are still not understood.Probiotics and healthA 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
15、 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
16、 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
17、 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 o
18、f 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
19、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
20、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 sequ
21、enced, and others are under way 21. Table 1 lists 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 facili
22、tates a healthy and relatively stable but adaptable gut environment. Table 1 Probiotic bacteria with completed genome sequencesStrainSize (Mb)ReferenceBifidobacterium longum NCC 27052.2512Lactobacillus plantarum WCFS13.3018Lactobacillus johnsonii NCC 5332.0223Lactobacillus acidophilus NCFM1.9922Less
23、ons from genomesLactic-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 co
24、mpletely 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 microorgani
25、sms. 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
26、, 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
27、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 geno
28、me 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 bi
29、le-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 sequenc
30、ed 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 th
31、e 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 inhabi
32、t 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
33、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 oligosacchari
34、des 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 enhance
35、the growth of beneficial commensals in the colon 25.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An intestinal population of beneficial commensal microorganisms helps maintain human health, and some of the
36、se 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
37、.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。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.
38、 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
39、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 46. It has al
40、so 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.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
41、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。The indigenous microbiota of an infants gastrointestinal tract is originally created through contact with the diverse microbiota of the parents and the immediate
42、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. T
43、he 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
44、genetic background of the individual.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。Current research into the intestinal microbiome is focused on obtai
45、ning 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
46、 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 foo
47、d 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 deli
48、very of products of carbohydrate breakdown to the hosts 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 i
49、mportant details about the impact of the intestinal microbiota on specific processes 3, 1114, the effects of species composition and microbial diversity and their potential compensatory functions are still not understood.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
