Abstract
BACKGROUND: The attractiveness of mosquitoes to humans varies among individuals, with human volatile organic compounds (VOCs) playing a pivotal role in the mosquitoes' host-seeking behavior. Differences between human volatiles detected by GC-MS can effectively modulate mosquito host selection. METHODS: Participants were enrolled and then assessed for mosquito attraction via an olfactometer. Their skin volatiles were collected with a stir bar as the sorptive extraction and were analyzed with high-resolution gas chromatography-mass spectrometry (SBSE-HRGC-MS). These data were then integrated with principal component analysis (PCA), volcano plot analysis, and partial least squares discriminant analysis (PLS-DA) to identify differential compounds between high and low mosquito attraction groups. Odorants with repellent properties were screened and evaluated using behavioral bioassays to assess their impact on the attractiveness of Aedes aegypti. RESULTS: From the 30 volunteers, 24 participants (12/12 with high/low attractiveness to mosquitoes) were enrolled. In the group with high mosquito attraction, human skin compounds such as N,N-dibutyl formamide (10.8%), decanoic acid (9.2%), and decanal (5.9%) were detected with high components. Conversely, in the low mosquito attraction group, relatively high levels of indole (0.9%), fury hydroxymethyl ketone (2.2%), and 2-hydroxy-3-methyl-2-cyclopentenone (0.8%) were observed. The results of two pathway analyses indicated that most of these compounds are associated with fatty acid metabolism, respectively. Three compounds-2-hydroxy-3-methyl-2-cyclopentenone, furfuryl hydroxymethyl ketone, and 1,2-cyclopentanedione-were identified as prominent candidates, exhibiting significant repellent efficacy in behavioral bioassays. CONCLUSIONS: In this study, the impact of differences among VOCs emitted by human skin on the host-seeking behavior of Ae. aegypti was investigated, providing insights for the development of novel mosquito baits and repellents.