PAMPs and DAMPs in Sepsis: A Review of Their Molecular Features and Potential Clinical Implications.

Sepsis is a serious organ dysfunction caused by a dysregulated immune host reaction to a pathogen. The innate immunity is programmed to react immediately to conserved molecules, released by the pathogens (PAMPs), and the host (DAMPs). We aimed to review the molecular mechanisms of the early phases of sepsis, focusing on PAMPs, DAMPs, and their related pathways, to identify potential biomarkers. We included studies published in English and searched on PubMed® and Cochrane®. After a detailed discussion on the actual knowledge of PAMPs/DAMPs, we analyzed their role in the different organs affected by sepsis, trying to elucidate the molecular basis of some of the most-used prognostic scores for sepsis. Furthermore, we described a chronological trend for the release of PAMPs/DAMPs that may be useful to identify different subsets of septic patients, who may benefit from targeted therapies. These findings are preliminary since these pathways seem to be strongly influenced by the peculiar characteristics of different pathogens and host features. Due to these reasons, while initial findings are promising, additional studies are necessary to clarify the potential involvement of these molecular patterns in the natural evolution of sepsis and to facilitate their transition into the clinical setting.

Intestinal Fibrogenesis in Inflammatory Bowel Diseases: Exploring the Potential Role of Gut Microbiota Metabolites as Modulators.

Fibrosis, sustained by the transformation of intestinal epithelial cells into fibroblasts (epithelial-to-mesenchymal transition, EMT), has been extensively studied in recent decades, with the molecular basis well-documented in various diseases, including inflammatory bowel diseases (IBDs). However, the factors influencing these pathways remain unclear. In recent years, the role of the gut microbiota in health and disease has garnered significant attention. Evidence suggests that an imbalanced or dysregulated microbiota, along with environmental and genetic factors, may contribute to the development of IBDs. Notably, microbes produce various metabolites that interact with host receptors and associated signaling pathways, influencing physiological and pathological changes. This review aims to present recent evidence highlighting the emerging role of the most studied metabolites as potential modulators of molecular pathways implicated in intestinal fibrosis and EMT in IBDs. These studies provide a deeper understanding of intestinal inflammation and fibrosis, elucidating the molecular basis of the microbiota role in IBDs, paving the way for future treatments.