SARS-CoV-2调控肠道菌群-肠-肝通讯对肝损伤的影响

Effect of microbiota-gut-liver communication during SARS-CoV-2 infection on liver injury

部分新型冠状病毒肺炎(COVID-19)患者出现肝损伤症状,然而肝脏标本免疫染色并未显示出阳性,肝细胞内血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE2)的表达也相对较少,因此严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)进入肝细胞可能不是造成肝损伤的直接原因。COVID-19患者的肠道屏障遭到破坏、肠道菌群生态失衡,抗炎细菌及下调ACE2表达的拟杆菌类丰度下降而机会致病菌的丰度增加。机会性病原体丰度增加可能会加剧肺细胞因子风暴,并导致COVID-19患者的继发性病原体感染,进而引发肝脏炎症。部分患者初级胆汁酸积累,次级胆汁酸代谢受阻,提示肠道菌群调控胆汁酸代谢可能也是促进肝脏感染的因素。除菌体外,肠道菌群的代谢物也是介导肝损伤的重要因素,正常情况下,短链脂肪酸、脱氨基酪氨酸等代谢物可以通过门静脉进入肝脏,保护肝脏免受病毒感染,而COVID-19患者的肠道菌群代谢紊乱则影响了肝脏的功能。本文探讨了微生物群-肠-肝通讯在SARS-CoV-2感染期间的作用,以期通过靶向微生物群的方式缓解COVID-19患者肝损伤的症状。

Some patients with novel coronavirus pneumonia(COVID-19)showed symptoms of liver injury,but the immunostaining of liver samples are not positive,and the expression of angiotensin-converting enzyme 2(ACE2)in liver cells was relatively low,so the entry of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)into liver cells may not be the primary factor of liver injury.The research findings suggest that COVID-19 patients exhibit a disrupted intestinal barrier and an imbalanced gut microbiota,characterized by a decreased abundance of anti-inflammatory bacteria and bacteroides that down-regulate ACE2 expression,as well as an increased abundance of opportunistic pathogens.Increased abundance of opportunistic pathogens may exacerbate the pulmonary cytokine storm and lead to secondary pathogen infection in COVID-19 patients,which in turn triggers liver inflammation.Primary bile acid accumulation and secondary bile acid metabolism were inhibited in some patients,suggesting that intestinal flora regulation of bile acid metabolism may also be a contributing factor to liver infection.In addition to the microbiota,the metabolites of the gut microbiota are also important factors that mediate liver injury,normally,metabolites such as short-chain fatty acids,deaminotyrosine,and other metabolites can enter the liver through the portal vein to protect it from viral infection while the disrupted metabolism of the gut microbiota in COVID-19 patients affects the function of the liver.This review explored the role of microbiota-gut-liver communication during SARS-CoV-2 infection,with a view to alleviating symptoms of liver injury in COVID-19 patients in the future by targeting the microbiota.