297 General discussion process in the lower airways, and in the latter group alterations with impact on the long-term susceptibility to pneumonia. These findings may contribute to ambitions of the critical care community to stratify patients based on pathophysiological features, which is a first crucial step for enrichment of trial populations with patients who are more likely to benefit from an immunomodulatory therapy, thereby paving the way for precision medicine. Future perspectives Future perspectives on the use of biomarkers in pneumonia and sepsis are promising, with ongoing research seeking to identify subgroups of patients with more homogeneous host response aberrations that might respond better to treatments targeted at specific pathophysiological mechanisms. In this context, the integration of multi-omics approaches, including genomics, proteomics, and metabolomics, is expected to yield more comprehensive and accurate biomarker panels. Advanced computational methods are essential for analysing complex biomarker data and the development of personalized treatment approaches. This, together with point-of-care tests for rapid biomarker measurements, is likely to significantly improve early diagnosis and management of individual patients with pneumonia and/or sepsis. Major future challenges lie in the standardization of easy-to-use biomarker assays with quick turnaround times and the real time computational analysis of complex host response data, ideally together with physiological data on for example circulation and oxygenation. The incorporation of complex, multi-faceted data into user-friendly clinical decision support systems at the bedside may pave the way for the long-sought goal of tailored, individualized treatment of patients with severe pneumonia and sepsis. Intermezzo: the microbiome Although antibiotics are crucial and frequently life-saving interventions for patients with sepsis, they may inadvertently lead to harm by disrupting the gut microbiome. Disruptions of the microbiome during early development, such as caused by the frequent use of antibiotics at infancy, are known to have lasting effects on microbiome composition far into adulthood [14]. Chapter 6 is a narrative review in which we discuss the effect of sepsis and the antibiotics used as empiric treatment on the gut microbiota. Many studies show that antibiotics, sometimes in as little as a single dose, disrupt the microbiome, which can take weeks for recovery [15]. But this weighs, understandably, only little in the acute phase of treating fatal infections. Withholding or interrupting early antibiotic therapy for patients displaying signs and symptoms of sepsis is potentially lethal and therefore not advisable. However, there should be endeavours to minimize unnecessary exposure to these agents. A focus on optimizing the balance between efficacy and negative effects on the microbiota should be applied to antibiotic interventions in sepsis patients. Much is still unknown about the mechanisms by which the microbiome influences systemic or pulmonary immunity. Murine studies suggest the existence of the so-called gut-lung-axis - a hypothesized interaction between the gut microbiota and the lungs 12
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