抑郁症研究的发展和趋势——从菌-肠-脑轴看抑郁症

The development and tendency of depression researches: Viewed from the microbiota-gut-brain axis

抑郁症是现代社会最常见的心理疾病,该病不仅降低个人的生活质量,还给家庭和社会带来巨大的经济负担.但由于经济文化和医疗资源等因素限制,目前大部分抑郁症患者并没有进行过任何治疗,已有疗法效果的有限性又进一步加剧了这种困境.研究发现,抑郁症患者的大脑、内分泌、免疫和肠脑功能都出现异常,脑-肠轴功能失常可能是抑郁症的主要病理机制.以往的抑郁症治疗主要针对大脑,如药物治疗和心理治疗,而忽视了患者的其他症状.近年来,全世界范围随生活水平的提高抑郁症患病率也随之升高的现象提示,食品添加剂、药物、环境压力及不良饮食等均可为肠道菌群异常的直接诱因,而肠道菌群改变导致菌-肠-脑轴功能异常更可能促进抑郁症发生;通过益生菌、益生元、健康饮食以及粪便菌群移植等方式重建肠道菌群平衡,改善菌-肠-脑轴功能则能减轻甚至治疗抑郁.通过调节肠道微生物来改变抑郁焦虑等心理疾病已成为神经科学和心理学的热点,维护良好的肠道菌群可能是未来抑郁症预防和治疗的重要方向.

Depressive disorder is the most prevalent mental disease, not only it has impaired the life and wellbeing of patients, but also brought great economic burden for family and society. Yet depressive disorder is widely undiagnosed and untreated because of stigma, inadequate mental-health resources, complex comorbidities, and lack of effective therapies. Increasing researches indicate that depressive disorder is more a physiological disease rather than a psychological illness. For most patients, the brain-gut axis function is impaired, including the imbalances in brain neurotransmitters, the decline in brain neuroplasticity, the dysfunction in hypothalamic-pituitary-adrenal axis, the chronic periphery inflammation and neuro-inflammation, as well as gastrointestinal diseases and the gut microbiota dysbiosis. Traditional treatments for depression have been focusing on the brain itself, and/or also, using variety of medications and psychotherapy. Almost half of the patients have not acquired effective help. New treatment strategies underlining the whole brain-gut axis dysfunction will shed light on the dilemma. In recent years, more and more studies have presented the important role played by gut microbiota in brain and behavior, promoting the appearance of new theories for mental disorders. According to current gut microbiota hypothesis, gut microbiota is a crucial component of gut brain, gut microbiota disruption and the following brain-gut axis dysregulation are the main pathophysiology of depression, and which will be the promising target of future therapies. Patients and model animals with depressive disorder share some similarities in gut microbiota, which are obviously distinctive with their healthy controls, indicating that depression is probably related with certain gut microbiota phenotype. Both the physiological symptoms and behavioral symptoms can transfer to germ-free and microbiota-deficient animals through fecal microbiota transplantation from depressed patients, further confirming the relationship between depression and abnormal microbiota. Various factors like antibiotics use, chronic stress, and long-term unhealthy diet disturb gut microbiota, while the abnormal microbiota probably induce microbiota-gut-brain axis dysfunction and increase the incidence of depression and other mental disorders. Several methods have presented good effects in gut microbiota regulation, including probiotics, prebiotics, healthy diet, and fecal microbiota transplantation, all of which possibly alleviate and treat depression via improving the microbiota-gut-brain axis function. Additionally, traditional adjuvant treatments like diet therapy and exercise therapy also possibly work through microbiota-gut-brain axis regulation. Even the effects of common antidepressants are probably related with gut microbiota, too. And the integrative therapy attempts emphasizing gut microbiota regulation present promising effects. All of the above results indicate that depression is strongly linked with gut microbiota abnormalities, and it may be treated through gut microbiota intervention using effective methods like psychobiotics supplement. Now-a-day the application of gut microbiota interventions has been becoming a hot point in treatment of mental disorders. And maintaining the normal condition of gut microbiota probably play vital part in the prevention and therapy of mental disorders in the future.