Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Asian Pac J Allergy Immunol. 2016 Dec;34(4):249-264. doi: 10.12932/AP0803.
Our health and probably also our behaviors and mood depend not only on what we eat or what we do (lifestyle behaviors), but also on what we host. It is well established for decades that all vertebrates including humans are colonized by a wide array of bacteria, fungi, eukaryotic parasites and viruses, and that, at steady state (homeostasis), this community of microbes establishes a friendly mutual relationship with the host. The term microbiota was originally meant to represent an ecological community of commensals and potentially pathogenic microbes that live within our bodies, but it is now used interchangeably with the term microbiome which was initially meant to represent a collective genome of the microbiota. Although the number of microbes that live in or on our body was previously estimated to outnumber that of their hosts by 10 to 1, the latest estimate put the ratio to be closer to 1:1. On the other hand, their collective genomes (microbiome) outnumber those of the host by 100-200 times. It is not surprising therefore that these microbes not only provide the host with a variety of metabolic impact, but can also modulate tissue integrity and immune defense, all of which lead to a healthy ecosystem (symbiosis) that is unfavorable for colonization and invasion of pathogens. Microbiota is well known for its role in development and education of immune system. However, its link with diseases is less known and it is only recently that there is a surge of interest in the potential impact of microbiota on human health and disease. The diversity and composition of microbiota (healthy microbiota profile) are dynamics, depending not only on the host physical status, genotype and immune phenotype, but also on the environmental factors like diet, antibiotic usage and lifestyle behaviors. These environmental factors may adversely alter gut ecosystem (dysbiosis) that is frequently associated with increased susceptibility to infections as well as to non-communicable diseases like obesity, metabolic syndromes (e.g., diabetes and cardiovascular diseases), allergy and other inflammatory diseases. Emerging evidence from more recent studies also demonstrate the existence of a bidirectional communication route linking gut and microbiota with brain, thus suggesting that these microbes may play a role in neurological disorders as well as in host perception, behavior and emotional response. However, whether the observed alteration of the microbiota profile in these diverse conditions is the cause or the consequence of the disease remains to be established. These observations imply that it may be possible to design new strategies for the management of diseases by manipulating gut microbiota. The common practice now available is the use of probiotics to rehabilitate gut ecosystem. The microbiota-based therapeutics like fecal transplantation for the treatment of recurrent antibiotic-resistant Clostridium difficile infection is now under clinical trial and reported to be highly successful. In the next decade, we will probably see even more exciting approaches, for example, using advanced microbiota engineering technologies to create "intelligent" or "smart" bacteria for use in diagnosis, prevention, prediction and treatment of inflammatory diseases and possibly of some gastrointestinal cancers. The microbiota-based therapeutics together with personalized medicine may be the most accurate and optimal strategy for the future treatment of some difficult-to-manage diseases. However, many challenges remain to be solved before the translational potential of this new knowledge can be implemented clinically. In this review, I highlight some important recent developments and advances that contribute to our understanding in the role of microbiota in human health and disease and on how to best manipulate the microbiome to promote greater human health.
我们的健康状况，甚至我们的行为和情绪，不仅取决于我们吃什么或做什么（生活方式行为），还取决于我们体内所携带的微生物。几十年来，人们已经充分认识到，所有脊椎动物，包括人类，都被各种各样的细菌、真菌、真核寄生虫和病毒定植，而且在稳定状态（体内平衡）下，这些微生物群落与宿主建立了友好的互利关系。“微生物组”一词最初是指生活在我们体内的共生菌和潜在致病微生物的生态群落，但现在它与“微生物组”一词可以互换使用，后者最初是指微生物组的集体基因组。虽然以前估计生活在我们体内或体表的微生物数量是宿主数量的 10 到 1 倍，但最新估计表明，这个比例更接近 1:1。另一方面，它们的集体基因组（微生物组）是宿主的 100-200 倍。因此，这些微生物不仅为宿主提供了多种代谢影响，还可以调节组织完整性和免疫防御，所有这些都导致了一个有利于宿主健康的生态系统（共生），不利于病原体的定植和入侵。微生物组在免疫系统的发育和教育方面是众所周知的。然而，它与疾病的联系鲜为人知，直到最近，人们才对微生物组对人类健康和疾病的潜在影响产生了浓厚的兴趣。微生物组的多样性和组成是动态的，不仅取决于宿主的身体状况、基因型和免疫表型，还取决于环境因素，如饮食、抗生素使用和生活方式行为。这些环境因素可能会破坏肠道生态系统（功能紊乱），使宿主更容易受到感染以及非传染性疾病（如肥胖、代谢综合征[如糖尿病和心血管疾病]、过敏和其他炎症性疾病）的影响。最近的研究也提供了新的证据，证明肠道和微生物组与大脑之间存在双向通讯途径，这表明这些微生物可能在神经紊乱以及宿主的感知、行为和情绪反应中发挥作用。然而，在这些不同的情况下，观察到的微生物组谱的改变是疾病的原因还是结果仍有待确定。这些观察结果表明，通过操纵肠道微生物组，可能有可能设计出用于疾病管理的新策略。目前常见的做法是使用益生菌来恢复肠道生态系统。基于微生物组的治疗方法，如粪便移植治疗复发性抗生素耐药性艰难梭菌感染，目前正在临床试验中，据报道成功率很高。在未来十年，我们可能会看到更令人兴奋的方法，例如，使用先进的微生物组工程技术来创建“智能”或“聪明”细菌，用于诊断、预防、预测和治疗炎症性疾病，甚至可能用于某些胃肠道癌症。基于微生物组的治疗方法与个性化医疗相结合，可能是未来治疗某些难以管理疾病的最准确和最佳策略。然而，在将这一新知识的转化潜力付诸临床实践之前，仍有许多挑战需要解决。在这篇综述中，我强调了一些重要的最新进展和发现，这些进展和发现有助于我们理解微生物组在人类健康和疾病中的作用，以及如何最好地操纵微生物组来促进人类健康。
