Centre for Clinical Microbiology, UCL (University College London), Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK,
Adv Exp Med Biol. 2014;817:319-56. doi: 10.1007/978-1-4939-0897-4_15.
Regulation of the immune system is an important function of the gut microbiota. Increasing evidence suggests that modern living conditions cause the gut microbiota to deviate from the form it took during human evolution. Contributing factors include loss of helminth infections, encountering less microbial biodiversity, and modulation of the microbiota composition by diet and antibiotic use. Thus the gut microbiota is a major mediator of the hygiene hypothesis (or as we prefer, "Old Friends" mechanism), which describes the role of organisms with which we co-evolved, and that needed to be tolerated, as crucial inducers of immunoregulation. At least partly as a consequence of reduced exposure to immunoregulatory Old Friends, many but not all of which resided in the gut, high-income countries are undergoing large increases in a wide range of chronic inflammatory disorders including allergies, autoimmunity and inflammatory bowel diseases. Depression, anxiety and reduced stress resilience are comorbid with these conditions, or can occur in individuals with persistently raised circulating levels of biomarkers of inflammation in the absence of clinically apparent peripheral inflammatory disease. Moreover poorly regulated inflammation during pregnancy might contribute to brain developmental abnormalities that underlie some cases of autism spectrum disorders and schizophrenia. In this chapter we explain how the gut microbiota drives immunoregulation, how faulty immunoregulation and inflammation predispose to psychiatric disease, and how psychological stress drives further inflammation via pathways that involve the gut and microbiota. We also outline how this two-way relationship between the brain and inflammation implicates the microbiota, Old Friends and immunoregulation in the control of stress resilience.
免疫系统的调节是肠道微生物群的一个重要功能。越来越多的证据表明，现代生活条件导致肠道微生物群偏离了人类进化过程中所采取的形式。促成因素包括寄生虫感染的丧失、接触到较少的微生物多样性，以及饮食和抗生素使用对微生物群落组成的调节。因此，肠道微生物群是卫生假说（或者我们更喜欢称之为“老朋友”机制）的主要介导者，该假说描述了我们共同进化的、需要耐受的生物体的作用，这些生物体对于免疫调节至关重要。至少部分由于接触到免疫调节的“老朋友”减少，许多但不是所有这些老朋友都存在于肠道中，高收入国家正在经历广泛的一系列慢性炎症性疾病的大量增加，包括过敏、自身免疫和炎症性肠病。抑郁症、焦虑症和应激反应能力下降与这些疾病并存，或者在没有明显外周炎症性疾病的情况下，个体持续存在循环炎症生物标志物升高时也会发生。此外，怀孕期间炎症调节不当可能导致自闭症谱系障碍和精神分裂症的一些病例的大脑发育异常。在本章中，我们解释了肠道微生物群如何驱动免疫调节，错误的免疫调节和炎症如何导致精神疾病，以及心理压力如何通过涉及肠道和微生物群的途径进一步引发炎症。我们还概述了大脑和炎症之间的这种双向关系如何使微生物群、老朋友和免疫调节参与到应激反应能力的控制中。
