Human microbiota: 'the philosophers have only interpreted the world in various ways. The point, however, is to change it'.
Human microbiota: 'the philosophers have only interpreted the world in various ways. The point, however, is to change it'.
复制标题
DOI：
10.1111/1751-7915.12259
复制
发表时间：
2015-01
影响因子：
5.7
通讯作者：
Brüssow H
中科院分区：
文献类型：
--
作者：
Brüssow H
尽管我们仍然不知道世界上细菌种类的最终数量，但随着人类微生物组计划的开展，我们对人类体内细菌的了解大大增加了。这一国际性努力的第一幕（古典戏剧中的博览会）——描述殖民我们身体的东西——现在如果不是结束，就是进入了饱和阶段。科学家已经研究了微生物群组成与健康和疾病状况之间的统计学关联（第二阶段，并发症阶段）。其中许多调查采取病例对照研究的形式，例如引用最近的一个例子，肝硬化患者和匹配的健康对照者的肠道微生物群（Qin et al., 2014）。在接下来的几年里，我们将看到更多这样的病例对照研究。它们将为我们提供人类微生物群失调与疾病或不期望的生理状况有关的数据。这些数据如果在针对不同人群的独立研究中得到证实，将确定与微生物群失衡密切相关的疾病状态。然而，古老的流行病学格言“关联不是因果关系”也适用于这些研究。它已经正确地提到，许多这样的研究遭受反向因果伪像（Hanage, 2014）。因此，在未来，我们将看到更多的前瞻性人类微生物群研究，以确定微生物群的变化是在健康状况恶化之前发生的，还是这种变化的结果，将我们带入第三阶段，即逆转阶段。这种时间上的争论对于微生物群紊乱引起或随后的健康变化是一个强有力的区别。虽然数量还不是很多，但这方面的研究已经开始了：老年人转移到养老院后与年龄相关的微生物群变化的动态研究（Claesson et al., 2012）和营养不良的婴儿就是例子（Subramanian et al., 2014）。然而，前瞻性研究仍然不能保证因果关系。这一论点只能由干预研究提供。事实上，卡尔·马克思（Karl Marx）在19世纪中期对古典哲学的批判中提出的一句话也适用于微生物群领域：“哲学家只是用不同的方式解释世界。”然而，关键是要改变它。我们已经看到了此类干预措施的非常成功的例子：第四阶段，即发育迟缓阶段，已经开始发挥作用。最引人注目的例子是将健康捐赠者处理过的粪便样本应用于艰难梭菌感染患者（van Nood et al., 2013）。这种形式的细菌治疗导致这些患者的临床状况迅速和戏剧性的改善。使用抗生素治疗儿童营养不良是另一个有争议的案例（Trehan et al., 2013）。然而，用处理过的粪便和抗生素进行细菌治疗是相当广泛的干预措施，不太可能取悦监管当局。因此，我们正在等待第五幕，这是经典的戏剧的结束或解决。因此，需要更具体的干预措施来纠正微生物群失衡。针对单一菌种进行噬菌体裂解治疗可能是去除或减少不需要的细菌的一种选择，但证明其价值的对照临床试验仍然很大程度上缺乏。促进健康的益生菌在胃肠病学、阴道健康和过敏等几个明确界定的领域取得了一些成功。然而，将益生菌引入已经高度定植的生态位，如肠道，会遇到来自常驻肠道微生物群的定植抗性，即使不是全部……
Even though we still do not know the ultimate number of bacterial species in the world, our understanding of bacteria populating the human body has increased enormously with the Human Microbiome Project. Act One (the Exposition in classical theatre) of this international effort–in describing what is colonizing our bodies–is now coming if not to an end, then to a saturation phase. Scientists already investigate statistical associations between microbiota composition and health and disease conditions (Act Two, the Complication phase). Many of these investigations took the form of case–control studies, such as gut microbiota in patients with liver cirrhosis and matched healthy controls, to quote a recent example (Qin et al., 2014). In the next years, we will see many more of such case–control studies. They will provide us data where a human microbiota dysbiosis is associated with a disease or an undesired physiological condition. Such data, if confirmed in independent studies with different human populations, will identify disease states that are strongly associated with microbiota disequilibria. However, the old epidemiological dictum that association is not causation also applies to these studies. It has rightly been mentioned that many such studies suffer from reverse causation artefacts (Hanage, 2014). In the future, we will therefore see more prospective human microbiota studies defining whether the microbiota change precedes the development of the deteriorating health condition or is a consequence of this change, bringing us to Act Three, the Reversal phase. This temporal argument is a strong discriminator for health changes induced or followed by microbiota upsets. Although still not very numerous, this research is already on the stage: dynamic studies on age-related microbiota changes in elderly people transferred to residence homes (Claesson et al., 2012) and infants suffering from malnutrition are examples (Subramanian et al., 2014). However, prospective studies are still no guarantee for causal relationships. This argument can only be provided by intervention studies. In fact, a sentence that was formulated by Karl Marx as a mid-19th century critique of classical philosophy also applies to the microbiota field:‘The philosophers have only interpreted the world in various ways. The point, however, is to change it’. We have already seen very successful examples for such interventions: Act Four, the Retardation phase, is already being played. The most striking example is the application of processed stool samples from healthy donors to patients suffering from Clostridium difficile infections (van Nood et al., 2013). This form of bacteriotherapy led to rapid and dramatic ameliorations of the clinical condition in these patients. Antibiotics in treating malnutrition in children is another, although more controversial case(Trehan et al., 2013). Bacteriotherapy with processed faeces and antibiotics are, however, rather broad spectrum interventions unlikely to please regulatory authorities. We are therefore waiting for Act Five, which classically brings the Lysis or Resolution of the drama. More specific interventions correcting microbiota disequilibria are thus needed. Phage therapy targeting a single bacterial species for lysis might be an option to remove or decrease undesired bacteria, but controlled clinical trials proving its value are still largely lacking. Health-promoting probiotic bacteria have shown some success in a few well-defined areas of gastroenterology, vaginal health and allergy. However, introducing probiotic bacteria into an already highly colonized niche, such as the intestine, meets colonization resistance from the resident gut microbiota, even if not all …
登录
查看更多内容
影响因子：
64.8
作者：
Subramanian, Sathish;Huq, Sayeeda;Yatsunenko, Tanya;Haque, Rashidul;Mahfuz, Mustafa;Alam, Mohammed A.;Benezra, Amber;DeStefano, Joseph;Meier, Martin F.;Muegge, Brian D.;Barratt, Michael J.;VanArendonk, Laura G.;Zhang, Qunyuan;Province, Michael A.;Petri, William A., Jr.;Ahmed, Tahmeed;Gordon, Jeffrey I.
通讯作者：
Gordon, Jeffrey I.
影响因子：
64.8
作者：
Claesson, Marcus J.;Jeffery, Ian B.;O'Toole, Paul W.
通讯作者：
O'Toole, Paul W.
DOI：
10.1056/nejmoa1202851
发表时间：
2013-01-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Trehan I;Goldbach HS;LaGrone LN;Meuli GJ;Wang RJ;Maleta KM;Manary MJ
通讯作者：
Manary MJ
影响因子：
8.9
作者：
Smilowitz JT;Lebrilla CB;Mills DA;German JB;Freeman SL
通讯作者：
Freeman SL
DOI：
10.1073/pnas.1000083107
发表时间：
2011-03-15
影响因子：
11.1
作者：
Zivkovic, Angela M.;German, J. Bruce;Mills, David A.
通讯作者：
Mills, David A.