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.

Background: to date, there are no specific markers available for diagnosing sepsis. Diagnosis is, indeed, mainly determined by clinical suspicion and the evaluation of the patient’s overall condition. This evaluation involves assessing various inflammatory markers, such as C-reactive protein (CRP) and procalcitonin (PCT), along with markers of tissue hypoxia, such as serum lactate. Additionally, it includes scores that account for complete blood count (CBC), organ function markers, and the patient’s vital parameters, including SOFA, qSOFA, SIRS, and NEWS. Over the years, various potential biomarkers have been studied; among these presepsin appears to offer some significant advantages. Objective: Presepsin, which is the N-terminal fragment of the soluble component of CD14, is primarily elevated in infectious conditions. Its levels rise much earlier in the context of infection compared to currently used biomarkers. As a result, Presepsin shows promise for the early identification of septic patients and could aid in prognostic assessment, allowing clinicians to prioritize care for critically ill individuals. Methods: this study aims to evaluate the role of serum presepsin in the early diagnosis of sepsis in patients who present to the emergency room with a clinical suspicion of sepsis. The secondary objectives include comparing the diagnostic performance of presepsin with traditional biomarkers currently used for sepsis diagnosis and assessing its utility as a prognostic biomarker for mortality risk stratification, in comparison with validated severity prediction scores. Result: Presepsin had valuable diagnostic utility for sepsis (AUC 0.946, p < 0.001) comparable to PCT (AUC 0.905, p < 0.001). Conclusions: the combination of Presepsin, PCT, and EWS yielded the highest diagnostic accuracy for sepsis.

Sepsis is a complex and potentially life-threatening syndrome characterized by an abnormal immune response to an infection, which can lead to organ dysfunction, septic shock, and death. Early diagnosis is crucial to improving prognosis and reducing hospital management costs. This narrative review aims to summarize and evaluate the current literature on the role of monocyte distribution width (MDW) as a diagnostic biomarker for sepsis, highlighting its advantages, limitations, and potential clinical applications. MDW measures the volumetric distribution width of monocytes, reflecting monocytic anisocytosis, and is detected using advanced hematological analyzers. In 2019, it was approved by the FDA as a biomarker for sepsis due to its ability to identify systemic inflammatory response at an early stage. Thirty-one studies analyzed by us have shown that an increased MDW value is associated with a higher risk of sepsis and that its combination with clinical parameters (such as qSOFA) and other biomarkers (CRP, PCT) can enhance diagnostic sensitivity and risk stratification capacity. Despite its high sensitivity, MDW has lower specificity compared to more established biomarkers such as procalcitonin, thus requiring a multimodal integration for an accurate diagnosis. The use of MDW in emergency and intensive care settings represents an opportunity to improve early sepsis diagnosis and critical patient management, particularly when combined with other markers and clinical tools. However, further studies are needed to define a universal cut-off and confirm its validity in different clinical contexts and pathological scenarios.

Background/Objectives: Sepsis is a leading cause of hospital mortality and represents a time-sensitive medical emergency. Current diagnostic strategies rely on clinical assessment, severity scores, biomarkers, and blood cultures. However, blood cultures require 24–72 h for pathogen identification and demonstrate limited sensitivity, while biomarkers such as procalcitonin and C-reactive protein lack optimal specificity. These limitations support the widespread empirical use of broad-spectrum antibiotics and highlight the need for rapid, sensitive, and culture-independent diagnostic tools. Methods: A narrative literature review was conducted using PubMed and Google Scholar, including 28 studies published over the past 10 years, encompassing observational and preclinical investigations. Current evidence on the application of Raman spectroscopy in sepsis was summarized, with a dual focus on pathogen identification and the assessment of the host response. Results: Raman spectroscopy has demonstrated the ability to detect early molecular alterations in circulating immune cells and mitochondrial redox status, potentially preceding conventional biomarkers. For pathogen identification, Raman techniques have achieved diagnostic accuracies comparable to automated systems, but with significantly shorter turnaround times. Integration with microfluidics, optical tweezers, and deep learning algorithms has further enhanced performance, although these applications remain largely experimental. Conclusions: Despite these promising results, the lack of methodological standardization, spectral overlap among phylogenetically related species, limited large-scale validation, and challenges in interpreting certain spectral signatures remain unresolved. Most available evidence originates from preclinical, single-center, and controlled studies, underscoring the need for prospective multicenter trials and harmonized protocols.