Approaches and gaps in skin microbiome engineering

As one of the body’s largest organs, the skin offers a variety of surface environments, harboring a wide range of microbes. These microbes constitute the skin microbiome and play an important role in maintaining skin barrier integrity, immune function, and overall host health. Advances in skin microbiome research point to applications for wound healing, infection resistance, and metabolic processes. Despite the ongoing research on the skin microbiome, gaps still remain in understanding what mechanisms drive microbe–human interactions. In this review, we discuss the importance of the skin and its microbiome, as well as current research techniques and engineered therapeutics. Methods to evaluate and engineer the skin microbiome include sequencing-based techniques, culture-based methods, in silico modeling, and experimental platforms (in vitro and in vivo). Some limitations of these methods include, respectively, sequencing and sampling bias, limited culture success, loss of complexity in modeling, and differences between organisms in animal models. Therapeutic engineering strategies and methods include probiotics, prebiotics, antimicrobial peptides, and synthetic biology tools. However, environmental, genetic, and host-specific factors can significantly influence microbiome composition, complicating predictive modeling and intervention design. Even after technological advancements in microbial characterization, the limited level of mechanistic insights delays translational progress. A multidisciplinary approach integrating experimental, computational, and engineering strategies is essential to advance the field of skin microbiome engineering and realize its full therapeutic potential. Resolving current methods’ limitations and improving understanding of microbial interactions will elevate the rational design of microbiome-based therapeutics, ultimately enhancing human health through prebiotic and probiotic therapeutics.