粪菌移植治疗中枢神经系统疾病的基础与临床研究

Basic and Clinical Research of Fecal Microbiota Transplantation in The Treatment of Central Nervous System Diseases

粪菌移植(fecal microbiota transplantation,FMT)作为一种微生物治疗方法,近年来备受关注。FMT已被证实是治疗艰难梭菌感染、肠易激综合征、炎症性肠病等胃肠疾病的有效方法。研究显示,FMT可能通过重塑患者肠道菌群从而影响中枢神经系统及其疾病的发生与发展。本文介绍了FMT的发展历程与中国FMT研究现状,重点关注FMT在神经变性疾病(阿尔茨海默病、帕金森病),神经创伤性疾病(脊髓损伤、颅脑损伤)以及脑卒中的基础与临床研究,分别从上述疾病特点、肠道菌群特征、FMT作用与机制等方面进行了综述。

As a microbial therapy method,fecal microbiota transplantation(FMT)has attracted the attention of researchers in recent years.As one of the most direct and effective methods to improve gut microbiota,FMT achieves therapeutic benefits by transplanting functional gut microbiota from healthy human feces into the intestines of patients to reconstruct new gut microbiota.FMT has been proven to be an effective treatment for gastrointestinal diseases such as Clostridium difficile infection,irritable bowel syndrome,and inflammatory bowel disease.In addition,the clinical and basic research of FMT outside the gastrointestinal system is also emerging.It is worth noting that there is bidirectional communication between the gut microbial community and the central nervous system(CNS)through the gut-brain axis.Some gut bacteria can synthesize and release neurotransmitters such as glutamate,gamma-aminobutyric acid(GABA)and dopamine.Imbalanced gut microbiota may interfere with the normal levels of these neurotransmitters,thereby affecting brain function.Gut microbiota can also produce metabolites that may cross the blood-brain barrier and affect CNS function.FMT may affect the occurrence and development of CNS and its related diseases by reshaping the gut microbiota of patients through a variety of pathways such as nerves,immunity,and metabolites.This article introduces the development of FMT and the research status of FMT in China,and reviews the basic and clinical research of FMT in neurodegenerative diseases(Alzheimer’s disease,Parkinson’s disease),neurotraumatic diseases(spinal cord injury,traumatic brain injury)and stroke from the characteristics of three types of nervous system diseases,the characteristics of intestinal flora,and the therapeutic effect and mechanism of fecal microbiota transplantation,summarize the common mechanism of fecal microbiota transplantation in the treatment of CNS diseases and the therapeutic targets.We found that the common mechanisms of FMT in the treatment of nervous system diseases may include the following 3 categories through summary and analysis.(1)Gut microbiota metabolites,such as SCFAs,TMAO and LPS.(2)Inflammatory factors and immune inflammatory pathways such as TLR-MyD88 and NF-κB.(3)Neurotransmitter 5-HT.In the process of reviewing the studies,we found the following problems.(1)In basic researches on the relationship between FMT and CNS diseases,there are relatively few studies involving the autonomic nervous system pathway.(2)Clinical trial studies have shown that FMT improves the severity of patients’symptoms and may be a promising treatment for a variety of neurological diseases.(3)The improvement of clinical efficacy is closely related to the choice of donor,especially emphasizing that FMT from healthy and young donors may be the key to the improvement of neurological diseases.However,there are common challenges in current research on FMT,such as the scientific and rigorous design of FMT clinical trials,including whether antibiotics are used before transplantation or different antibiotics are used,as well as different FMT processes,different donors,different functional analysis methods of gut microbiota,and the duration of FMT effect.Besides,the safety of FMT should be better elucidated,especially weighing the relationship between the therapeutic benefits and potential risks of FMT carefully.It is worth mentioning that the clinical development of FMT even exceeds its basic research.Science and TIME rated FMT as one of the top 10 breakthroughs in the field of biomedicine in 2013.FMT therapy has great potential in the treatment of nervous system diseases,is expected to open up a new situation in the medical field,and may become an innovative weapon in the medical field.