Caenorhabditis elegans as an In Vivo Model for the Discovery and Development of Natural Plant-Based Antimicrobial Compounds.

Antimicrobial resistance (AMR) due to the prevalence of multidrug-resistant (MDR) pathogens is rapidly increasing worldwide, and the identification of new antimicrobial agents with innovative mechanisms of action is urgently required. Medicinal plants that have been utilised for centuries with minor side effects may hold great promise as sources of effective antimicrobial products. The free-living nematode Caenorhabditis elegans (C. elegans) is an excellent live infection model for the discovery and development of new antimicrobial compounds. However, while C. elegans has widely been utilised to explore the effectiveness and toxicity of synthetic antibiotics, it has not been used to a comparable extent for the analysis of natural products. By screening the PubMed database, we identified articles reporting the use of the C. elegans model for the identification of natural products endowed with antibacterial and antifungal potential, and we critically analysed their results. The studies discussed here provide important information regarding "in vivo" antimicrobial effectiveness and toxicity of natural products, as evaluated prior to testing in conventional vertebrate models, thereby supporting the relevance of C. elegans as a highly proficient model for their identification and functional assessment. However, their critical evaluation also underlines that the characterisation of active phytochemicals and of their chemical structure, and the unravelling of their mechanisms of action represent decisive challenges for future research in this area.

Immunomodulatory Properties of Vitamin D in the Intestinal and Respiratory Systems.

Vitamin D plays a crucial role in modulating the innate immune response by interacting with its intracellular receptor, VDR. In this review, we address vitamin D/VDR signaling and how it contributes to the regulation of intestinal and respiratory microbiota. We additionally review some components of the innate immune system, such as the barrier function of the pulmonary and intestinal epithelial membranes and secretion of mucus, with their respective modulation by vitamin D. We also explore the mechanisms by which this vitamin D/VDR signaling mounts an antimicrobial response through the transduction of microbial signals and the production of antimicrobial peptides that constitute one of the body's first lines of defense against pathogens. Additionally, we highlight the role of vitamin D in clinical diseases, namely inflammatory bowel disease and acute respiratory distress syndrome, where excessive inflammatory responses and dysbiosis are hallmarks. Increasing evidence suggests that vitamin D supplementation may have potentially beneficial effects on those diseases.