Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Clin Rev Allergy Immunol. 2019 Dec;57(3):350-363. doi: 10.1007/s12016-018-8719-7.
Over the last few decades, advances in our understanding of microbial ecology have allowed us to appreciate the important role of microbial communities in maintaining human health. While much of this research has focused on gut microbes, microbial communities in other body sites and from the environment are increasingly recognized in human disease. Here, we discuss recent advances in our understanding of host-microbiota interactions in the development and manifestation of asthma focusing on three distinct microbial compartments. First, environmental microbes originating from house dust, pets, and farm animals have been linked to asthma pathogenesis, which is often connected to their production of bioactive molecules such as lipopolysaccharide. Second, respiratory microbial communities, including newly appreciated populations of microbes in the lung have been associated with allergic airway inflammation. Current evidence suggests that the presence of particular microbes, especially Streptococcus, Haemophilus, and Morexella species within the airway may shape local immune responses and alter the severity and manifestations of airway inflammation. Third, the gut microbiota has been implicated in both experimental models and clinical studies in predisposing to asthma. There appears to be a "critical window" of colonization that occurs during early infancy in which gut microbial communities shape immune maturation and confer susceptibility to allergic airway inflammation. The mechanisms by which gut microbial communities influence lung immune responses and physiology, the "gut-lung axis," are still being defined but include the altered differentiation of immune cell populations important in asthma and the local production of metabolites that affect distal sites. Together, these findings suggest an intimate association of microbial communities with host immune development and the development of allergic airway inflammation. Improved understanding of these relationships raises the possibility of microbiota-directed therapies to improve or prevent asthma.
在过去的几十年中,我们对微生物生态学的理解的进步使我们能够认识到微生物群落在维持人类健康方面的重要作用。虽然这项研究的大部分重点都放在了肠道微生物上,但其他身体部位和环境中的微生物群落也越来越被认为与人类疾病有关。在这里,我们讨论了近年来在宿主-微生物群相互作用方面的进展,这些进展在哮喘的发生和表现中重点关注了三个不同的微生物区室。首先,来自房屋灰尘、宠物和农场动物的环境微生物已与哮喘发病机制有关,这通常与它们产生生物活性分子(如脂多糖)有关。其次,呼吸道微生物群落,包括肺部新发现的微生物种群,与过敏性气道炎症有关。目前的证据表明,特定微生物的存在,特别是呼吸道中的链球菌、嗜血杆菌和莫拉克斯菌,可能会影响局部免疫反应,并改变气道炎症的严重程度和表现。第三,肠道微生物群在实验模型和临床研究中都与哮喘易感性有关。在婴儿早期,可能存在一个“关键定植窗”,在此期间,肠道微生物群塑造免疫成熟并赋予对过敏性气道炎症的易感性。肠道微生物群影响肺部免疫反应和生理学的机制,即“肠道-肺部轴”,仍在定义中,但包括对哮喘中重要的免疫细胞群的分化改变和影响远端部位的代谢物的局部产生。总之,这些发现表明微生物群落与宿主免疫发育和过敏性气道炎症的发展密切相关。对这些关系的更好理解提高了通过微生物群导向的疗法来改善或预防哮喘的可能性。