Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, leading to organ dysfunction and high mortality. Increasing evidence indicates that the gut microbiota plays a significant role in the pathophysiology of sepsis, influencing immune homeostasis, intestinal barrier integrity, and systemic inflammation. This review aimed to provide a comprehensive overview of the role of gut microbiota in the development, progression, and clinical outcomes of sepsis, with particular emphasis on underlying mechanisms and potential therapeutic strategies. Intestinal dysbiosis, characterized by reduced microbial diversity, depletion of commensal bacteria, and expansion of opportunistic pathogens, is associated with increased intestinal permeability and bacterial translocation, which may amplify systemic inflammatory responses. Microbiota-derived metabolites, including short-chain fatty acids and tryptophan-derived compounds, play a key role in maintaining epithelial integrity and modulating immune responses. Disruption of these pathways in sepsis leads to impaired barrier function and immune dysregulation. Clinical studies demonstrate that alterations in gut microbiota composition are associated with disease severity, organ dysfunction, and mortality, suggesting its potential utility as a prognostic marker. At the same time, standard therapeutic interventions, particularly broad-spectrum antibiotics, further exacerbate dysbiosis and may negatively affect clinical outcomes. Emerging microbiota-targeted strategies, such as fecal microbiota transplantation, probiotics, prebiotics, and postbiotics, offer promising adjunctive approaches aimed at restoring microbial balance and improving host responses. However, current evidence remains limited and heterogeneous. In conclusion, the gut microbiota represents an important contributor to sepsis pathophysiology and a potential target for innovative therapeutic interventions. Further research is required to establish clinically effective microbiome-based strategies and to integrate microbiota profiling into personalized approaches to sepsis management.
Citation: Bartosz Ziółkowski, Kamila Gorczyca, Dorota Siwicka, Wojciech Dąbrowski. The gut microbiota as a key modulator of sepsis: Mechanisms, clinical implications, and therapeutic perspectives[J]. AIMS Microbiology, 2026, 12(4): 840-874. doi: 10.3934/microbiol.2026036
Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, leading to organ dysfunction and high mortality. Increasing evidence indicates that the gut microbiota plays a significant role in the pathophysiology of sepsis, influencing immune homeostasis, intestinal barrier integrity, and systemic inflammation. This review aimed to provide a comprehensive overview of the role of gut microbiota in the development, progression, and clinical outcomes of sepsis, with particular emphasis on underlying mechanisms and potential therapeutic strategies. Intestinal dysbiosis, characterized by reduced microbial diversity, depletion of commensal bacteria, and expansion of opportunistic pathogens, is associated with increased intestinal permeability and bacterial translocation, which may amplify systemic inflammatory responses. Microbiota-derived metabolites, including short-chain fatty acids and tryptophan-derived compounds, play a key role in maintaining epithelial integrity and modulating immune responses. Disruption of these pathways in sepsis leads to impaired barrier function and immune dysregulation. Clinical studies demonstrate that alterations in gut microbiota composition are associated with disease severity, organ dysfunction, and mortality, suggesting its potential utility as a prognostic marker. At the same time, standard therapeutic interventions, particularly broad-spectrum antibiotics, further exacerbate dysbiosis and may negatively affect clinical outcomes. Emerging microbiota-targeted strategies, such as fecal microbiota transplantation, probiotics, prebiotics, and postbiotics, offer promising adjunctive approaches aimed at restoring microbial balance and improving host responses. However, current evidence remains limited and heterogeneous. In conclusion, the gut microbiota represents an important contributor to sepsis pathophysiology and a potential target for innovative therapeutic interventions. Further research is required to establish clinically effective microbiome-based strategies and to integrate microbiota profiling into personalized approaches to sepsis management.
The author acknowledges the valuable contributions of the scientific community in advancing the understanding of gut microbiota and sepsis. No specific funding was received for this work.
The authors declare that they have no competing interests.
Conceptualization: B.Z.; K.G.; Methodology: B.Z.; K.G.; Literature search: B.Z; Data curation: B.Z.; K.G.; Writing—original draft preparation: B.Z.; K.G.; Writing—review and editing: B.Z.; K.G.; Supervision: W.D.; D.S. All authors have read and agreed to the published version of the manuscript.
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Figures(4) / Tables(2)
Bartosz Ziółkowski, Kamila Gorczyca, Dorota Siwicka, Wojciech Dąbrowski. The gut microbiota as a key modulator of sepsis: Mechanisms, clinical implications, and therapeutic perspectives[J]. AIMS Microbiology, 2026, 12(4): 840-874. doi: 10.3934/microbiol.2026036
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