Microbial volatile organic compounds and olfactory receptors in wound malodor

Wound odor is a common symptom in patients with chronic wounds. Malodorous wounds can result in embarrassment, anxiety, and, therefore, in social isolation of the patient. Current treatment options are limited and focused on masking the odor. Current approaches to wound odor management have notable limitations and fail to adequately address existing therapeutic needs. Wound odor is multifactorial, with a major contribution from volatile organic compounds (VOCs) emitted by microorganisms and necrotic tissue. Several VOCs have been identified as key drivers of malodor, such as short-chain fatty acids, dimethyl-trisulfide, specific alcohols, ketones, and aldehydes. These compounds are detected by the human olfactory system, including olfactory receptors (ORs) expressed on olfactory sensory neurons (OSNs). The human olfactory system comprises more than 400 ORs, which enable the detection of a vast array of odorants, however only a small fraction of these receptors has been deorphanized. This systematic review will evaluate therapeutic clinical strategies addressing malodor and compile current knowledge on VOCs that cause wound odor and the ORs associated with their detection. It summarizes the existing evidence on deorphanized ORs that detect these VOCs in malodorous wounds and outlines experimental mechanisms of deorphanization. Identifying wound-odor-associated VOCs and their corresponding ORs provides a framework for novel therapeutic strategies, such as antagonizing the OR to suppress odor perception. This may directly improve the quality of life of patients with chronic malodorous wounds, particularly in malignant wounds and palliative care.