生酮饮食调控肠道菌群在疾病治疗中的研究进展

Research progress of ketogenic diet regulating intestinal microbiome in the treatment of diseases

生酮饮食是一种高脂肪、极低碳水化合物、适量蛋白质和其他营养素的饮食模式,最早被用于治疗儿童癫痫。随着医学的不断发展,生酮饮食被逐渐用于其他疾病的辅助治疗,但其具体作用机制尚不明确。最近的研究发现,生酮饮食可影响肠道菌群的多样性和数量,对宿主的健康有着重要的意义。研究表明,生酮饮食可以增加小鼠肠道中的嗜黏蛋白阿克曼菌(Akkermansia muciniphila,A.muciniphila)和副拟杆菌的丰度,导致γ-谷氨酰氨基酸生成减少、海马体中γ-氨基丁酸/谷氨酸比值升高,从而降低癫痫的发作频率;A.muciniphila丰度增加还可以改善脑血管功能,降低阿尔茨海默病的发生风险。另外,生酮饮食还可降低小鼠肠道双歧杆菌的丰度,导致肠道乳酸水平下降,从而改善认知和记忆功能;同时,该丰度的下降还可导致具有促炎作用的辅助性T细胞17水平的下降,从而治疗肥胖。基于此,该文就生酮饮食调控肠道菌群在神经系统疾病(包括癫痫、阿尔茨海默病、多发性硬化症、孤独症)、代谢性疾病(包括糖尿病、肥胖)及肿瘤中的治疗作用及可能的机制进行综述。

Ketogenic diet is a high-fat,very low-carbohydrate,appropriate amount of protein and other nutrients diet.It was first used to treat children’s epilepsy.With the continuous development of medicine,ketogenic diet has been gradually used in the adjuvant treatment of other diseases,but its specific mechanism is not clear.Recent studies have shown that ketogenic diet can affect the diversity and quantity of intestinal flora,which is of great significance to the health of the host.Studies have also shown that ketogenic diet can increase the abundance of Akkermansia muciniphila(A.muciniphila)and Parabacteroides in mouse intestine,resulting in decreased subset of gamma-glutamylated amino acids and increased ratio of hippocampal gammaaminobutyric acid and glutamate,which could reduce the frequency of seizures.Elevated abundance of A.muciniphila can also improve cerebrovascular function,and then reduce the risk of Alzheimer’s disease.Besides,ketogenic diet can also decrease the abundance of Bifidobacterium in mouse intestine,resulting in the decrease of intestinal lactic acid level and pro-inflammatory T helper 17 cell(Th17 cell)level,which could improve cognitive and memory function and treat obesity,respectively.This article reviews the therapeutic effects and possible mechanisms of ketogenic diet on the regulation of intestinal flora in neurological diseases(epilepsy,Alzheimer’s disease,multiple sclerosis and autism),metabolic diseases(diabetes mellitus and obesity),and tumors.