Impact of a 7-day short peptide diet on gut microbiota and metabolomics in septic mice

Dan Zuo ¹ yu Bin Zuo ^2* yang Liu Wang ^3* bi Da Hu ^1* Yang Yang ^3* Biao Huang ^1* Yong Chen ^1*

• ¹ The Dazu District People's Hospital, Chongqing, China
• ² Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Region, China
• ³ First Affiliated Hospital of Chongqing Medical University, Chongqing, Chongqing Municipality, China

Objective: Our study aim is to explore the action agents of short peptide passages on intestinal dysfunction in septic mice utilizing a metabolomics approach, which provides a new scientific basis for the clinical study of sepsis.Mices were allocated at random into four groups: control (Con), cecal ligation and puncture + Short-peptide-based enteral nutrition group one (CLP + SPEN1), CLP + SPEN3 and CLP + SPEN7 groups. The CLP group was replicated in a mice model of sepsis utilizing cecal ligation and puncture. The ileal tissues and contents were collected and analyzed at the end of the experiment on days one, three, and seven. Mice in the CLP + SPEN1, CLP + SPEN3, CLP + SPEN7 groups were allowed to eat ad libitum for 1-7 days after surgery, and 4 g of short peptide enteral nutrition preparation was added to the drinking water. A liquid chromatography-mass spectrometry-based metabolomics method was used to analyze changes in serum metabolites in septic mice.Results: Short peptides showed effectiveness in reducing symptoms, mucosal inflammation, and intestinal function damage scores in septic mice. The 16sRNA analysis showcased significant variances in the distribution of bacterial communities between the CLP + SPEN1, CLP + SPEN3, and CLP + SPEN7 groups. At the phylum level, statistically significant variances in the relative abundance of Proteobacteria, Firmicutes, and Bacteroidetes were recognized. The metabolomics analysis results showed significant separation of metabolites between the CLP + SPEN1 and CLP + SPEN3 groups, as well as significant differences in metabolite profiles between the CLP + SPEN3 and CLP + SPEN7 groups. Utilizing a differential Venn diagram, four metabolites were commonly different; 10-heptadecanoic and dodecanoic acids had statistical significance. The abundance of both dodecanoic and lactic acid bacteria was negatively associated at the genus level.Conclusion: a short peptide diet enhanced intestinal function in septic mice. Analysis of intestinal microbial sequencing data suggested that the short peptide diet promoted intestinal health by modulating flora-mediated effects. The results showed a decrease in beneficial bacteria abundance on the third day, which gradually recovered by the seventh day. Correlation analysis with metabolites revealed significant associations with 10-heptadecenoic and dodecanoic acids.