(1414) Shenfu Injection Alleviates Gut Dysfunction in Sepsis via Improving Crypt and Gut Microbiota

Introduction: Shenfu injection (SFI) is widely used in clinical severe conditions due to its pharmacological effects of invigorating qi and reviving yang for resuscitation. This study aimed to assess the protective effects of SFI on sepsis-induced intestinal injury in mice and to investigate the regulatory role of SFI in mucosal regeneration and gut microbiota in sepsis.

Methods: 48 male C57/B6 mice were randomly divided into four groups: control, sepsis induced by lipopolysaccharide intraperitoneal injection, sepsis treated with low dose of SFI (10 ml/kg) and high dose of SFI (20 ml/kg). Blood and intestinal tissue samples were collected from different groups at 48h after LPS challenge.The proliferation and migration of crypts/enterocytes were assessed by 5-Ethynyl-2’- deoxyuridine (EdU) staining. Moreover, the composition of gut microbiota was analyzed by 16S rRNA sequencing.

Results: Compared to the control mice, sepsis induced severe mucosal damage in the intestine, including the decrease of the villus length and the number of crypts. The plasma levels of diamine oxidase and lactate were significantly increased in septic mice. These changes induced by sepsis were effectively diminished by SFI administration at both low and high doses. In addition, the number of EdU+ cells representing cell proliferation and migration respectively was significantly reduced in the intestinal tissues of septic mice. SFI treatment was found to greatly increase the proliferation of crypts/enterocytes as well as the migration of enterocytes. Moreover, the gut microbiota composition in septic mice was modulated by SFI administration. In particular, high dose of SFI treatment was found to decrease the proportion of harmful bacteria including Proteobacteria and Escherichia-Shigella, while increase the abundance of beneficial bacteria such as Alloprevotella and Butyricimonas in septic mice.

Conclusions: Our findings reveal that SFI protects against sepsis-induced intestinal injury in mice through promoting crypt/enterocyte proliferation and migration and increasing the expressions of tight junction proteins. The regulation of the gut microbiota composition by high dose of SFI may also contribute to the beneficial effects of SFI on sepsis-related intestinal dysfunction.