Da Yuan Yin Regulates Gut Microbiota and Improves Intestinal Injury in Sepsis

ABSTRACT Sepsis is a common disease, which is a life‐threatening organ dysfunction caused by the host's dysfunctional response to infection. Da Yuan Yin (DYY) is a traditional Chinese medicine that has anti‐inflammatory and purgative effects. Sepsis mouse model was conducted by lipopolysaccharide induction to explore the effects of DYY in vivo. Hematoxylin–eosin staining was performed to observe mouse ileum tissue. ELISA and western blot were carried out to measure the levels of inflammatory factors and tight junction proteins. Moreover, proliferation and apoptosis were measured by immunohistochemistry (Ki67) and TUNEL staining. 16S rRNA sequencing was implemented to predict the effects of DYY on gut microbiota in sepsis. Metabolic function was predicted by PICRUSt2 and experimentally validated by measuring short‐chain fatty acids (SCFAs) and β‐glucuronidase activity. A fecal microbiota transplantation (FMT) experiment was performed to establish causality. In this study, DYY alleviated sepsis‐induced intestinal injury. Additionally, DYY inhibited inflammation (TNF‐α, IL‐1β, and IL‐6), cell apoptosis, and promoted proliferation in sepsis, as well as the promotion of tight junction proteins (claudin‐1, occludin, and ZO‐1). 16S rRNA sequencing revealed that DYY could regulate the alteration in the abundance of gut microbiota in sepsis and promote the growth of bacilli, such as Lactobacillales and Enterobacteriaceae. Functionally, DYY increased protective SCFA levels and suppressed β‐glucuronidase activity. Crucially, FMT from DYY‐treated donors replicated these protective effects in septic recipients, directly demonstrating the mediatory role of gut microbiota. Collectively, DYY can mitigate intestinal injury and modulates gut microbiota in sepsis; the protective role of DYY on sepsis was mediated through the regulation of gut microbiota, which may be a promising therapeutic strategy for sepsis.