Dinan Timothy G, Cryan John F
APC Microbiome Institute, University College Cork, Cork, Ireland.
Department of Psychiatry & Neurobehavioural Sciences, University College Cork, Cork, Ireland.
Neuropsychopharmacology. 2017 Jan;42(1):178-192. doi: 10.1038/npp.2016.103. Epub 2016 Jun 20.
There is now a large volume of evidence to support the view that the immune system is a key communication pathway between the gut and brain, which plays an important role in stress-related psychopathologies and thus provides a potentially fruitful target for psychotropic intervention. The gut microbiota is a complex ecosystem with a diverse range of organisms and a sophisticated genomic structure. Bacteria within the gut are estimated to weigh in excess of 1 kg in the adult human and the microbes within not only produce antimicrobial peptides, short chain fatty acids, and vitamins, but also most of the common neurotransmitters found in the human brain. That the microbial content of the gut plays a key role in immune development is now beyond doubt. Early disruption of the host-microbe interplay can have lifelong consequences, not just in terms of intestinal function but in distal organs including the brain. It is clear that the immune system and nervous system are in continuous communication in order to maintain a state of homeostasis. Significant gaps in knowledge remain about the effect of the gut microbiota in coordinating the immune-nervous systems dialogue. However, studies using germ-free animals, infective models, prebiotics, probiotics, and antibiotics have increased our understanding of the interplay. Early life stress can have a lifelong impact on the microbial content of the intestine and permanently alter immune functioning. That early life stress can also impact adult psychopathology has long been appreciated in psychiatry. The challenge now is to fully decipher the molecular mechanisms that link the gut microbiota, immune, and central nervous systems in a network of communication that impacts behavior patterns and psychopathology, to eventually translate these findings to the human situation both in health and disease. Even at this juncture, there is evidence to pinpoint key sites of communication where gut microbial interventions either with drugs or diet or perhaps fecal microbiota transplantation may positively impact mental health.
现在有大量证据支持这样一种观点，即免疫系统是肠道与大脑之间的关键沟通途径，它在与压力相关的精神病理学中发挥着重要作用，因此为精神药物干预提供了一个可能富有成效的靶点。肠道微生物群是一个复杂的生态系统，包含各种各样的生物体和复杂的基因组结构。据估计，成年人体内肠道内的细菌重量超过1千克，这些微生物不仅能产生抗菌肽、短链脂肪酸和维生素，还能产生人类大脑中发现的大多数常见神经递质。肠道微生物含量在免疫发育中起关键作用这一点现在已毋庸置疑。宿主与微生物相互作用的早期破坏可能会产生终身影响，不仅涉及肠道功能，还包括包括大脑在内的远端器官。很明显，免疫系统和神经系统持续进行沟通以维持体内平衡状态。关于肠道微生物群在协调免疫 - 神经系统对话方面的作用，仍存在重大知识空白。然而，使用无菌动物、感染模型、益生元、益生菌和抗生素的研究增进了我们对这种相互作用的理解。早年生活压力会对肠道微生物含量产生终身影响，并永久性改变免疫功能。早年生活压力也会影响成人精神病理学这一点在精神病学中早已得到认可。现在的挑战是全面破译在一个影响行为模式和精神病理学的沟通网络中连接肠道微生物群、免疫系统和中枢神经系统的分子机制，最终将这些发现转化到人类健康和疾病的实际情况中。即便在这个阶段，也有证据指出关键的沟通位点，在这些位点上，通过药物、饮食或粪便微生物群移植等肠道微生物干预措施可能会对心理健康产生积极影响。
