Lipidome–microbiome crosstalk as an outer niche in the skin: regulatory networks in health and disease

The skin is the outermost barrier to organisms from the external environment. This natural role, endowed by evolution, results in a nutrient-poor skin surface that enables microbial nutrition-dependent lipids to shape microbial ecology by survival pressure and nutrient preference. In turn, the skin microbiota produce microorganism-metabolized bioactive molecules (MBMs) to increase molecular diversity. This crosstalk functions as a crucial component of niche-regulating skin properties via multiple mechanisms. Furthermore, the local and remote effects of different barrier sites provide a more comprehensive explanation for the crosstalk from a global perspective. The variable function and mechanism of crosstalk may represent an evolutionary means by which the skin uses fluctuating commensal signals – the highly dynamic MBMs – to calibrate skin status and provide heterologous protection against invasive pathogens. Elucidating the reasons for the differing selectivity and catalytic efficiency of lipid-metabolizing enzymes in microorganisms and revealing the biologic processes and regulatory mechanisms of the ‘co-metabolic systems’ on the skin will advance diagnostic and therapeutic strategies for local cutaneous disorders and comorbid diseases of distant organs.