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The progress of the microbe-gut-brain axis in sepsis-associated encephalopathy

Summary

Sepsis can cause brain dysfunction called sepsis-associated encephalopathy, leading to memory problems and confusion in about one-third to two-thirds of sepsis patients. The bacteria in your gut communicate with your brain through multiple pathways, and when sepsis disrupts this communication, it causes harmful inflammation in the brain. Treatments like probiotics and transplanting healthy gut bacteria from donors show promise in animal studies and early human trials for improving memory and cognitive function after sepsis.

Background

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction occurring in 30-70% of sepsis patients, characterized by cognitive impairments and behavioral changes. The microbiota-gut-brain axis (MGBA) is a bidirectional communication network that regulates host behavior and cognitive function through multiple pathways. Understanding the relationship between SAE and gut microbiota alterations is crucial for developing targeted therapeutic interventions.

Objective

This review consolidates interdisciplinary insights to evaluate the mechanistic contribution of the MGBA to cognitive impairment relief in SAE. The aim is to unify perspectives from immunology, microbiology, neuroendocrine signaling, and neural pathophysiology to formulate MGBA-targeted therapeutic strategies for preventing or enhancing SAE-related neurological dysfunction.

Results

The review identifies multiple mechanisms through which MGBA influences SAE, including neural pathways via the vagus nerve, neuroendocrine pathways involving the HPA axis and hormones like GLP-1, immune pathways through Th17 cells and microglia polarization, and microbiological regulation via short-chain fatty acids and neurotransmitter precursors. Therapeutic approaches including probiotics, fecal microbiota transplantation, and targeted therapies show promise in animal models and clinical studies.

Conclusion

MGBA dysregulation in SAE drives systemic inflammatory responses and neuroinflammation through multiple integrated pathways. Current therapeutic strategies targeting MGBA show potential, though clinical application faces challenges regarding precision and safety. Future research should focus on biomarker screening, multi-omics technology, and individualized treatment regimens based on disease progression stages.
  • Published in:Frontiers in Cellular and Infection Microbiology,
  • Study Type:Review,
  • Source: PMC12106472, PMID: 40433666, DOI: 10.3389/fcimb.2025.1587463
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