Date of Award
8-2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Bioengineering
Committee Chair/Advisor
Dr. David K. Karig
Committee Member
Dr. Jordon A. Gilmore
Committee Member
Dr. Anna M. Seekatz
Committee Member
Dr. Vincent P. Richards
Committee Member
Dr. Sarah W. Harcum
Abstract
The skin microbiome is the collection of microorganisms that live on and in skin, including bacteria, fungi, and viruses. While correlations have been established with numerous factors, including host genetics, age, and diseases, the mechanisms that drive the complex interactions between host and microbes are not well understood. In order to more effectively leverage the skin microbiome as a therapeutic tool, the methods of interaction used by the skin and microbiome must be characterized. A better understanding of how microbe-host interaction occurs will allow for precise targeting to improve skin health and issues. A three-pronged strategy was implemented here to investigate these interaction mechanisms: characterization of microbial resource utilization, evaluation of microbes’ effects on human skin equivalents, and computational analysis of gene function and metabolism.
Recognizing which host skin compounds specific microbes can use as nutrient sources allows for a deeper knowledge of the metabolite communication between skin and microorganisms, as well as potential prebiotic identification. Therefore, a novel, high-throughput assay was developed to screen skin microbes for the ability to grow using a defined carbon source. The expectation was that only a small percentage of tested microbes would be able to grow on a single compound of interest; thus, the goal was to develop a protocol to identify bacteria that can utilize the compounds of interest. For initial protocol development, the amino acid glutamine and hormone melatonin were selected since these are known to be found in the skin. Using this assay, 703 isolates were evaluated, identifying three that were able to grow with the amino acid glutamine; however, none were found with the hormone melatonin. Screening to identify nutrient sources for desired microbes could improve a gentle and targeted approach to microbiome modification with targeted prebiotics.
Full-thickness skin equivalents, collagen gels embedded with human skin cells, provided a controllable environment to test the effects of skin microbes. Optical coherence tomography (OCT) allowed for non-invasive, time-series data collection of skin equivalents co-cultured with eight individual bacterial isolates as well as a mixed community. The purpose of this experiment is to validate the use of OCT technology to image and quantify the response of skin equivalents to skin microbes. Eight individual bacteria and a mixed community containing all eight bacteria were placed on the skin equivalents’ surfaces to simulate the interaction between the skin microbiome and human skin. Significant skin thinning was observed with Micrococcus luteus. The novel application of OCT imaging to evaluate skin microbiome interactions provides longitudinal data and images, allowing for a more complete understanding of how and when skin changes occur. This experiment has potential applications in screening for age- and disease-related skin thinning probiotic therapies.
Bioinformatics and modeling tools were leveraged to maximize insights extracted from microbe-host experiments. Ultimately, the goal of this analysis method was to explore the possibility of evaluating the functions a microbiome community can offer based on sequencing data. Genomes from 12 isolates were sequenced and analyzed to infer gene functions and construct metabolic models. Data from previously published microbe-host experiments were then analyzed to associate potential connections between host outcomes and the functions of present microbes. Several functional groups were associated with significant changes in skin thickness and cell proliferation, including the absence of L-asparaginase associated with skin thinning. A list of potential metabolites was produced with metabolic modeling and compared to preliminary metabolomics results, finding that Micrococcus luteus may be able to produce forms of urocanic acid. Trans-urocanic acid may absorb ultraviolet (UV) energy, which offers the potential of a probiotic-produced sunscreen to protect against sun damage. This innovative screening approach has the potential for bespoke therapeutic recommendations, offering precise analysis of a host’s microbiome potential and identifying gaps where specific probiotics can improve health.
The nutrient use of host-signals, effects of defined skin microbiome on skin equivalents, as well as production of proteins and metabolites, all provide insight into the mechanisms microbes use to affect hosts. Through modeling various aspects of the skin and microbiome environment, a better understanding was gained of how interaction occurs. These experiments have potential leading to improved therapies for skin health and diseases. For example, bioinformatics can allow for pre- and probiotic screening to identify therapies to improve skin health and address symptoms. Further exploration into host-microbe interaction mechanisms can improve the use of the skin microbiome as a therapeutic tool to improve skin health.
Recommended Citation
Rentz, Lauren Elizabeth J.F., "Mechanistic Investigation Into Host-Microbe Interactions of the Human Skin Microbiome" (2026). All Dissertations. 4290.
https://open.clemson.edu/all_dissertations/4290
Author ORCID Identifier
https://orcid.org/0009-0001-1020-5267