Mechanism Study Of Huang Lian Jie Du Tang For Sepsis Treatment Based On Metagenomic And Metabolomics Investigation

Sepsis is a disorder of the host’s response to infection,leading to life-threatening organ dysfunction.Cecal ligation and perforation（CLP）is the gold standard for sepsis animal models.In this study,the therapeutic effects of Huang Lian Jie Du Tang on sepsis at different time points after administration were investigated from the perspectives of immunity,intestinal flora and metabolism by using a combination of flow cytometry,16 S r DNA sequencing technology and metabolomics approach.The results showed that Huang Lian Jie Du Tang could ameliorate excessive inflammatory response in sepsis by reducing IL-1β and IL-6 levels to avoid severe damage to the organism,and could regulate the immune disorder state of the organism by reducing the apoptosis of CD4+T cells and CD8+T cells during sepsis;the abundance of Bacteroidetes in the intestinal flora of sepsis rats was increased and that of Firmicutes was decreased.At the genus level,it was found that the content of beneficial bacteria such as Akkermansia spp.decreased,while the content of conditionally pathogenic bacteria such as Bacteroides spp.increased,and the structure of flora tended to be back towards the sham group after treatment with Huanglian Jie Du Tang.The shift of intestinal flora and the increase of conditionally pathogenic bacteria may exacerbate the symptoms of sepsis,while the alteration of these conditionally pathogenic bacteria and other bacteria can be used to denote sepsis;the metabolomic results showed that Huang Lian Jie Du Tang exerted anti-inflammation,energy supply amelioration and protection of intestinal barrier by affecting the metabolism of shortchain fatty acids in sepsis rats and the decrease of short-chain fatty acids such as propionic acid after 18 h may be beneficial to reduce the intensity of the anti-inflammatory response and prevent the organism from falling into the immune paralysis stage,which may lead to serious complications.This study suggests that Huang Lian Jie Du Tang may exert protection and increase survival in sepsis rats by regulating immuninflammation,intestinal flora and metabolism.