Progress in the study of the correlation between sepsis and intestinal microecology

Abstract

Sepsis, a disease with high incidence, mortality, and treatment costs, has a complex interaction with the gut microbiota. With advances in high-throughput sequencing technology, the relationship between sepsis and intestinal dysbiosis has become a new research focus. However, owing to the intricate interplay between critical illness and clinical interventions, it is challenging to establish a causal relationship between sepsis and intestinal microbiota imbalance. In this review, the correlation between intestinal microecology and sepsis was summarized, and new therapies for sepsis intervention based on microecological target therapy were proposed, and the shortcomings of bacterial selection and application timing in clinical practice were addressed. In conclusion, current studies on metabolomics, genomics and other aspects aimed at continuously discovering potential probiotics are all providing theoretical basis for restoring intestinal flora homeostasis for subsequent treatment of sepsis.

Keywords: gut microbiota; high-throughput sequencing; immune suppression; inflammatory response; sepsis.

Figure 1

The antigen in the mucosa is transported and presented to antigen-presenting cells (macrophages and dendritic cells), at which point naïve B cells are first activated into IgA+ plasma cells and finally differentiate into IgA-secreting cells that can produce J chain polymers with the help of various factors, followed by further differentiation into IgA-secreting plasma cells. IgA binds to the secretory component SC secreted by intestinal epithelial cells to form SIgA. In the early stage of sepsis, pathogenic substances enter the blood, appropriately activate the inflammatory response, and combine with innate immune cells to produce cytokine IL-22 through the IL-23/IL-23R pathway, promoting the expression of IEC antimicrobial peptides and reducing the number of symbiotic Enterobacteriaceae. As the disease progresses, catecholamines and inflammatory factors are released to directly affect the intestine. Intestinal blood perfusion is reduced, resulting in ischemia and hypoxia, mitochondrial membrane depolarization, and the transformation of intracellular ATP into hypoxanthine. During reperfusion, hypoxanthine reacts with O₂, under the action of xanthine oxidase, to produce cytotoxic superoxide anions. Pathogen-related molecular patterns bind to TLR and nucleotide-bound oligomeric domain receptors on the surface of host immune cells, inducing the release of pro-inflammatory and anti-inflammatory cellular mediators, triggering the formation of extensive thrombi in the coagulation and complement systems, and aggravating intestinal mucosal microcirculation disorders.

Figure 2

The destruction of intestinal flora reduces the growth and development of intestinal villi, the formation of neovascularization, the ability to shape the intestinal epithelium, and the integrity of the intestinal mucosal barrier function, leading to the colonization and excessive growth of pathogenic microorganisms. Intestinal probiotics also participate in host immune regulation, stimulating related pathways through the flora and metabolites to trigger intestinal innate and adaptive immune cells to respond to intestinal damage. They play a vital role in curbing the colonization and growth of pathogenic microorganisms. The imbalance of intestinal environment combined with the excessive release of inflammatory cell mediators initiates the inflammatory response, which induces an increase of inflammation-related microorganisms in the intestinal cavity, the change of pathogenicity leads to decreased intestinal colonization resistance.