Dynamic gut responses to sepsis uncovered by multi-omics profiling in a rodent model.

Sepsis reflects an immune dysregulation in response to infection, and the intestine functions as the largest immune organ in the human body. However, the multidimensional dynamic changes within the gut environment during the progression of sepsis remain incompletely understood. Here, we show the alterations in the gut over the course of pneumonia-induced sepsis through the analysis of cellular, microbial, metabolic, and protein profiles over time. We demonstrate that subsets of immune cells, including mononuclear phagocytes and T cells, undergo compositional and transcriptional shifts. Simultaneously, specific structural cells and mucus-producing cells exhibit adapted roles in antigen presentation and the regulation of intestinal homeostasis. Furthermore, we detail alterations in the gut microbiome composition, metabolite levels, and colonic protein expression, identifying shared fluctuation patterns across these biological dimensions. These findings outline the interactions among the gut microbiome, cellular activity, and immune responses, providing potential therapeutic targets for future sepsis management.