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Objective: To investigate the protective effect of Dahuang Fuzi Decoction (DHFZD),a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods: Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups: normal control group (NCG,n =10),model control group (MCG,n =15) and DHFZD-treated group (DHFZDG,n =15).NCG rats were sham operated on and used as the controls,whereas MCG and DHFZDG rats were used to replicate the rat sepsis model using cecal ligation and puncture (CLP).The DHFZDG rats received DHFZD by gavage (4.5 mg/g of body weight) 2 h prior to CLP and after its successful induction,while the NCG and MCG rats received equivalent amounts of sterilized water by gavage.All rat groups were starved and had free access to water.At 24 h post-experimental set up,the mortality of rats in each group was recorded,and peritoneal inflammation assessment and pathological changes related to the intestinal mucosal injury index (IMII) in the surviving rats were evaluated.D-lactic acid,tumor necrosis factor (TNF)-α,interleukin (IL)-6 and IL-10 peripheral blood concentrations,along with secretory immunoglobulin A (slgA) in the intestinal mucosa were evaluated by enzyme-linked immunosorbent assays.Gut microbes were detected using 16S rRNA gene sequencing.Results: DHFZD reduced sepsis-related mortality in the rats.Moreover,it alleviated peritoneal inflammation and pathological changes according to the IMII.DHFZD reduced serum procalcitonin,TNF-α and IL-6 concentrations,but not the IL-10 concentration.It also reduced serum D-lactic acid and increased sIgA concentrations in intestinal mucosa.Notably,DHFZDG restored gut microbiota diversity and regulated the decrease in Bacteroidetes induced by sepsis,compared with the MCG rats.Conclusion: DHFZDG may play a protective role in sepsis by alleviating sepsis-induced inflammation and gut barrier damage in rats.