The interplay between gastrointestinal dysfunction and gut microbiota dynamics in sepsis

Area of Science:

• Gastroenterology and Hepatology
• Microbiology
• Immunology
• Critical Care Medicine

Background:

• Sepsis-induced gastrointestinal dysfunction involves intestinal barrier breakdown and microbiota dysbiosis, amplifying inflammation and multi-organ failure.
• The gut actively drives sepsis pathology via epithelial injury, immune dysregulation, ischemia-reperfusion, and impaired motility, promoting microbial translocation.
• Sepsis remodels the gut microbiome, reducing diversity and altering metabolites, compromising mucosal integrity and host immunity.

Purpose of the Study:

• To review the bidirectional gut barrier-microbiota interaction in sepsis.
• To elucidate mechanistic links across epithelial, immune, and metabolic pathways, including gut-liver and gut-brain axes.
• To discuss therapeutic strategies targeting the gut-microbiota axis in sepsis.

Main Methods:

• Narrative review synthesizing experimental, translational, and clinical findings.
• Analysis of mechanistic links in sepsis-associated organ dysfunction.
• Evaluation of emerging gut-microbiota-targeted therapies.

Main Results:

• Gut barrier dysfunction and dysbiosis are central to sepsis pathogenesis and multi-organ failure.
• The gut-microbiota axis influences systemic immune deviation and sepsis-associated encephalopathy.
• Therapeutic strategies like enteral nutrition and microbial interventions show promise but have limitations.

Conclusions:

• The gut-microbiota axis is a critical factor in sepsis progression and outcomes.
• Targeting this axis presents potential therapeutic avenues for sepsis management.
• Further research is needed to address causality, variability, and safety for precision microbiome-based sepsis treatments.