Mechanism of intact-protein enteral nutrition formula improving intestinal injury and metabolic disorders in sepsis

Abstract:

Objective To investigate the metabolic disorders induced by intact-protein enteral nutrition formula in sepsis through metabolomics methods，and to provide new theoretical and experimental bases for the clinical treatment of sepsis.Methods Male mice，aged 8-12 weeks，were randomly divided into sham-operation group（Sham group），sepsis group（CLP），and sepsis+intact-protein enteral nutrition group（CLP+IPEN group），with 6 mice in each group. The mice in the CLP group were treated with cecal ligation and puncture to induce sepsis，while those in the Sham group were given laparotomy alone without ligation and puncture. The mice in the CLP+IPEN group received additional intact-protein enteral nutrition formula after surgery. Daily weight changes were monitored for 7 days，and samples were collected after 3 days of modeling and feeding. Staining was used to observe the histopathological changes of the ileum，and quantitative real-time PCR was used to measure the expression of different proteins. Differentially expressed metabolites in the treatment of sepsis with intact-protein enteral nutrition formula were identified based on specific criteria.Results There were 15 differentially expressed metabolites between the CLP group and the CLP+IPEN group. Compared with the CLP group，the CLP+IPEN group had significant increases in the content of five metabolites including dimethyl 3-hydroxy-3-methylpentane-1，5-dioate，malonic acid，and L-Serine，N-（methoxycarbonyl）-methyl ester（P<0.05）. Throughout the experiment，all three groups of mice showed a gradual reduction in body weight，and the CLP group showed the most significant weight loss on day 4（P<0.05），suggesting that intact-protein enteral nutrition formula could alleviate weight loss in mice with sepsis. The CLP+IPEN group had a significantly lower Chiu score than the CLP group（P<0.05），indicating a notable reduction in intestinal mucosal injury. Both the CLP group and the Sham group had significant increases in the expression of occludin，zonula occludens-1（ZO-1），and MUC2，suggesting that sepsis caused impairment of intestinal barrier function. Compared with the CLP group，the CLP+IPEN group had significant reductions in the expression of occludin，ZO-1，and MUC2（P<0.05）.Conclusion This study investigates the metabolic disorders induced by intact-protein enteral nutrition formula in sepsis through metabolomics methods，and the results show that intact-protein enteral nutrition formula can alleviate metabolic disorders in sepsis-related intestinal injury by regulating linoleic acid metabolism，biosynthesis of unsaturated fatty acids，biosynthesis of fatty acids，and metabolism of cytochrome P450 substances. In addition，such formulas have the potential in enhancing intestinal barrier function，mitigating weight loss in mice，and reducing the severity of intestinal injury，thereby laying a foundation for strengthening the efficacy of sepsis treatment.