Deciphering the Role of Skin Surface Microbiome in Skin Health: An Integrative Multiomics Approach Reveals Three Distinct Metabolite‒Microbe Clusters.

The advent of 16S RNA profiling and shotgun metagenomics has enabled a holistic approach to the study of the skin microbiome composition. Despite the interesting findings in this rapidly developing scientific area, the big question remains: What role does the microbiome play in skin physiology? To begin answering this question, we employed an integrative methodology for microbiome and metabolome analysis of skin surface samples collected from the volar forearm of healthy infants aged 3-6-months. Whereas the infant skin metabolome was dominated by amino acids, lipids, and xenobiotics, the primary phyla of the microbiome were Firmicutes, Actinobacteria, and Proteobacteria. Zooming in on the species level revealed a large contribution of commensals belonging to the Cutibacterium and Staphylococcus genera, including Cutibacterium acnes, Staphylococcus epidermidis, and S. aureus. This heterogeneity was further highlighted when combining the microbiome with metabolome data. Integrative analyses delineated the coexistence of three distinct metabolite‒microbe clusters: one dominated by Cutibacterium linked to hydrophobic elements of the skin barrier, one associating Staphylococcus genus with amino acids relevant to the water holding capacity and pH regulation of the skin surface, and one characterized by Streptococcus and independent of any particular metabolomic profile.

Postprandial triglyceride-rich lipoproteins promote invasion of human coronary artery smooth muscle cells in a fatty-acid manner through PI3k-Rac1-JNK signaling.

SCOPE: The aim was to investigate the effect of postprandial triglyceride-rich lipoproteins (TRLs) with different fatty acid compositions on human coronary artery smooth muscle cell (hCASMC) invasion and to identify the molecular pathways involved. METHODS AND RESULTS: TRLs were isolated from the plasma of healthy volunteers after the ingestion of single meals enriched in MUFAs, saturated fatty acids (SFAs), or PUFAs. hCASMC invasion was analyzed using transwell chambers with Matrigel. TRLs-SFAs provoked the highest invasion, followed by TRLs-MUFAs and TRLs-PUFAs. Inhibition studies with Orlistat showed that invasion was dependent on the fatty acid composition of the TRLs. Fatty acids incorporated into the cell membranes strongly associated with cell invasion. Pull-down assays showed that TRLs-SFAs were able to increase Rac1 activity via inhibition of RhoA-dependent signaling. Chemical inhibition and siRNA studies showed that Rac1, PI3k, JNK, and MMP2 regulates TRL-SFA-induced hCASMC invasion. CONCLUSION: We demonstrate for the first time that TRLs induce hCASMCs invasion in a fatty acid dependent manner. This effect in TRLs-SFAs is mediated by the PI3k-Rac1-JNK, RhoA, and Rac1-MMP2 pathways. The ingestion of MUFA, compared to other dietary fatty acids such as SFA, could be considered as a nutritional strategy to reduce the atherosclerotic plaque formation.