肠道微生物与自闭症研究进展

Gut microbiota and autism

自闭症是一种严重的神经发育障碍,其患病率急剧上升,不符合哈迪-温伯格平衡,表明环境因素对其影响远大于遗传因素.自闭症与肠道微生物失衡及肠-脑轴异常密切相关.由于肠脑发育与头脑发育同步,因而在婴幼儿发育的关键期肠道微生物发育异常可增加自闭症风险.肠道微生物可通过代谢产物、免疫、神经内分泌以及迷走神经等途径影响自闭症.特定有益微生物菌株主要通过微生物-肠-脑轴、调节微生态平衡和抗感染、调节宿主代谢和吸收、改善肠漏等方式改善和治疗自闭症.益生菌以肠道菌群为靶点或可成为自闭症有效辅助治疗方法.本文对近年来与肠道微生物相关的自闭症研究进行综述,为我国今后全面防治自闭症提供人体共生微生物领域的参考.

Autism spectrum disorder（ASD） is one of the most severe neurodevelopmental disorders in the world, and it has brought tremendous burden for family and society. However, there is still no effective method clinically to cure this disorder. The morbidity of the disorder has increased rapidly in recent decades, which does not correspond with Hardy-Weinberg Equilibrium, indicating the disorder is more involved in some environmental factors than genes. Maternal disturbances, poor diet, and leaky gut are remarkable risk factors for autism, all of which can induce gut microbiota dysbiosis. More and more studies have indicated that autism is closely related to imbalanced gut microbiota and abnormal gut-brain axis. Autistic children have different gut microbiota including bacteria and fungi from healthy children, and gut microbiota modulation using either antibiotics, probiotics, or fecal microbiota transplantation may change autistic symptoms. Due to the synchronization of gut brain development and brain development, factors that affect the gut microbiota development of infants during the critical period will increase the incidence rate of autism. Gut microbiota can influence brain development and brain function like behavior and cognition through gut-brain axis/microbiota-gut-brain axis. The microbiota-gut-brain axis mainly include four pathways, which are metabolism, immune system, neuroendocrine system, and vagus nervous system. Abnormal microbiota can increase the harmful metabolites including 3-（3-hydroxyphenyl）-3-hydroxypropionic acid（HPHPA） and 4-ethylphenylsulfate（4 EPS） to induce autistic-like behaviors. Gut microbiota regulates the development and function of immune system, and microbiota dysbiosis can result in chronic inflammation to impair the normal development of brain and mentality. Abnormal microbiota can induce autistic symptoms through neuroendocrine pathway, it probably disturbs the development and function of hypothalamus-pituitary-adrenal（HPA） axis, influence the activity of serotonergic system and oxytocin system, and increase the content of harmful gas neurotransmitters such as hydrogen sulfide（H2 S） and ammonia（NH3）. Microbiota dysbiosis can also lead to autistic-like behaviors through vagus nervous system. Gut microbiota dysbiosis will possibly be the effective target of autism treatment. Increasing studies have shown that gut microbiota restoration including probiotics supplementation alleviates autism symptoms. Certain beneficial microbial strains can recover normal microbiota, prevent pathogen infection, alleviate gut barrier leakiness, prompt gastrointestinal function, and improve behavior and cognition development. These beneficial bacteria probably alleviate autism through regulating the microbiota-gut-brain axis function. They can improve brain function via vagus nervous systems, alleviate brain inflammation through immune response regulation, and restore normal brain neurotransmitters and neurogenesis through HPA function recovery and neurotransmitters metabolism regulation. The new intervention is different from traditional interventions which usually focus on one or two symptoms of autism, it not only restores normal gut microbiota but also improve the whole microbiota-gut-brain axis function including the gut brain and the great brain. Certain symbiotic microorganism intervention will probably become promising auxiliary treatment for autism. In the present paper, we review and summarize some valuable related researches between autism and gut microbiota, to provide an important reference for comprehensive prevention and treatment of autism in China.