The Gut Microbiome in Sepsis: From Dysbiosis to Personalized Therapy

Abstract

Sepsis is a complex clinical syndrome characterized by an uncontrolled inflammatory response to an infection that may result in septic shock and death. Recent research has revealed a crucial link between sepsis and alterations in the gut microbiota, showing that the microbiome could serve an essential function in its pathogenesis and prognosis. In sepsis, the gut microbiota undergoes significant dysbiosis, transitioning from a beneficial commensal flora to a predominance of pathobionts. This transformation can lead to a dysfunction of the intestinal barrier, compromising the host's immune response, which contributes to the severity of the disease. The gut microbiota is an intricate system of protozoa, fungi, bacteria, and viruses that are essential for maintaining immunity and metabolic balance. In sepsis, there is a reduction in microbial heterogeneity and a predominance of pathogenic bacteria, such as proteobacteria, which can exacerbate inflammation and negatively influence clinical outcomes. Microbial compounds, such as short-chain fatty acids (SCFAs), perform a crucial task in modulating the inflammatory response and maintaining intestinal barrier function. However, the role of other microbiota components, such as viruses and fungi, in sepsis remains unclear. Innovative therapeutic strategies aim to modulate the gut microbiota to improve the management of sepsis. These include selective digestive decontamination (SDD), probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT), all of which have shown potential, although variable, results. The future of sepsis management could benefit greatly from personalized treatment based on the microbiota. Rapid and easy-to-implement tests to assess microbiome profiles and metabolites associated with sepsis could revolutionize the disease's diagnosis and management. These approaches could not only improve patient prognosis but also reduce dependence on antibiotic therapies and promote more targeted and sustainable treatment strategies. Nevertheless, there is still limited clarity regarding the ideal composition of the microbiota, which should be further characterized in the near future. Similarly, the benefits of therapeutic approaches should be validated through additional studies.

Keywords: DAO (diamine oxidase); FMT (fecal microbiota transplantation); I-FABP (intestinal fatty acid-binding protein); SDD (selective digestive decontamination); antibiotics; intestinal barrier; intestinal microbiota; postbiotics; prebiotics; probiotics; sepsis; symbiotics.

Figure 1

Representation of bacterial phyla in the healthy gut microbiota. Created with BioRender.com.

Figure 2

The taxonomic composition of the gut microbiome at the phylum level in healthy volunteers (A), ICU patients dying with severe sepsis (as indicated by black circles on the timeline) (B), and ICU patients who had recovered (as indicated by green circles on the timeline) (C) [16].

Figure 3

Gut microbiota variability according to healthy status (light-blue box) and during sepsis (red box) [77].

Figure 4

Predominant fecal microbiota composition in the donor and patients (case 1 and case 2) at the phyla level (a), the class level (b), the order level (c), the family level (d), and the genus level (e). Variations in the microbiota composition are shown at the representative time points in the days following fecal microbiota transplantation [111].