肠道微生物可作为慢性肝病发生及治疗的靶位点

Title：
Review article: the gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease

DOI：
10.1111/apt.14397

Abstract：
Mortality from chronic liver disease is rising exponentially. The liver is intimately linked to the gut via the portal vein, and exposure to gut microbiota and their metabolites translocating across the gut lumen may impact upon both the healthy and diseased liver. Modulation of gut microbiota could prove to be a potential therapeutic target. To characterise the changes in the gut microbiome that occur in chronic liver disease and to assess the impact of manipulation of the microbiome on the liver. We conducted a PubMed search using search terms including 'microbiome', 'liver' and 'cirrhosis' as well as 'non-alcoholic fatty liver disease', 'steatohepatitis', 'alcohol' and 'primary sclerosing cholangitis'. Relevant articles were also selected from references of articles and review of the ClinicalTrials.gov website. Reduced bacterial diversity, alcohol sensitivity and the development of gut dysbiosis are seen in several chronic liver diseases, including non-alcoholic fatty liver disease, alcohol-related liver disease and primary sclerosing cholangitis. Perturbations in gut commensals could lead to deficient priming of the immune system predisposing the development of immune-mediated diseases. Furthermore, transfer of stool from an animal with the metabolic syndrome may induce steatosis in a healthy counterpart. Patients with cirrhosis develop dysbiosis, small bowel bacterial overgrowth and increased gut wall permeability, allowing bacterial translocation and uptake of endotoxin inducing hepatic and systemic inflammation. Manipulation of the gut microbiota with diet, probiotics or faecal microbiota transplantation to promote the growth of "healthy" bacteria may ameliorate the dysbiosis and alter prognosis.

All Authors：
C A Woodhouse,V C Patel,A Singanayagam,D L Shawcross

First Authors：
C A Woodhouse

Correspondence：
D L Shawcross

内容要点：

肝脏与肠道通过门静脉相连，密不可分，在大多数慢性肝病中，可见肠道菌群失调。肝脏作为机体主要代谢器官，其功能受损也会影响到神经和免疫系统。 受损的肠道菌群会触发免疫介导性疾病，将代谢综合征动物模型的粪便移植到健康个体，可见肝脏脂肪变性。肝硬化患者的菌群失调，小肠细菌过度生长且肠壁通透性增加，引发造成肝脏和全身炎症的细菌易位及内毒素吸收。通过饮食、粪菌移植等手段来调控肠道菌群组成，对治疗肝病有潜在益处。