The dual role of the microbiome in sepsis: A complex interplay between pathogenicity and protection.

Sepsis is an infection-induced syndrome characterized by systemic immune dysregulation and has traditionally been treated primarily with antibiotics. Although antibiotics remain essential for pathogen control, they rarely reverse immune dysfunction, barrier disruption, or microbial ecological imbalance in sepsis, suggesting that a purely anti-infective paradigm may be insufficient. In such phenotypes, microbiome-centered approaches may complement conventional anti-infective strategies by supporting microbial ecological restoration, host immune recalibration and disease tolerance. There is increasing evidence that the microbiome plays an important role in sepsis pathogenesis and immune modulation, both as a byproduct of immune perturbation and as a context-dependent mediator of immune maladaptation. Such insights underpin therapeutic strategies that integrate immune reprogramming with ecological restoration beyond infection control. Recent progress in single-cell omics, spatial transcriptomics and metabolomics is starting to uncover the complex interactions between microbial communities and the host immune system, providing new conceptual and translational pathways. Precise microbiome modulation combined with targeted immune recalibration may help shape future sepsis therapy, centered on restoring immune-microbial homeostasis rather than simply suppressing inflammation.