Title : Immunorestoration and microbial reconfiguration after sepsis: An integrative approach to dysbiosis immunology
Abstract:
During sepsis, the intestinal microbiome undergoes profound dysbiosis, characterized by a significant loss of microbial diversity and a predominance of pathobionts, particularly gram-negative bacilli. This microbial imbalance is accompanied by functional damage to the intestinal barrier, associated with epithelial apoptosis, hypoperfusion, and systemic inflammatory mediators, which facilitate the translocation of microbial products into the bloodstream, exacerbating immune dysregulation.
This dysbiosis has important immunological consequences. The depletion of protective commensal organisms such as Bifidobacterium and Faecalibacterium is associated with systemic immune dysfunction, impaired innate responses, increased risk of nosocomial infections, and worse clinical outcomes. At the cellular level, sepsis survivors frequently exhibit hypofunctional neutrophils, persistent lymphopenia, and cytokine imbalance, contributing to either chronic sterile inflammation or adaptive immunosuppression.
Post-sepsis immunorestoration involves more than resolving inflammation; it requires active reprogramming of the intestinal microbial ecosystem as a platform for immune recovery. Interventions such as probiotics, prebiotics, synbiotics, postbiotic metabolites, selective digestive decontamination, and fecal microbiota transplantation have shown promise in restoring immunomicrobial homeostasis.
Specific microbial profiles have been linked to distinct immunological signatures, including elevated anti-inflammatory cytokines, increased CD8+ T cell counts, enhanced NK cell activity, and improved immunoglobulin levels. These correlations suggest a bidirectional relationship between microbial composition and immune functionality in the post-septic state. From a clinical perspective, identifying patients with persistent dysbiosis, epithelial barrier dysfunction, or acquired immunosuppression allows for targeted therapeutic interventions. Monitoring of intestinal permeability markers and microbiome profiling through molecular techniques offers tools for risk stratification and personalized immune-nutritional strategies.
Dysbiosis immunology thus proposes an integrative model in which immune recovery after sepsis depends not only on overcoming the critical phase but also on restoring the gut–microbiota–immune axis. This approach promotes the reactivation of innate and adaptive immune functions, reduces the incidence of secondary infections, and improves overall clinical progression in critically ill patients. In summary, microbial reconfiguration after sepsis emerges as a crucial component of modern immunomodulatory strategies, with direct implications for precision medicine and the comprehensive management of patients recovering from critical illness.
