1. Interplay of human ABCC11 transporter gene variants with axillary skin microbiome functional genomics.
- Author
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Stevens BR and Roesch LFW
- Subjects
- Humans, Female, Male, Haplotypes, Genomics methods, Axilla microbiology, Adult, Pedigree, Microbiota genetics, Polymorphism, Single Nucleotide, Skin microbiology, Skin metabolism, ATP-Binding Cassette Transporters genetics, ATP-Binding Cassette Transporters metabolism
- Abstract
The human armpit microbiome is metabolically entangled with skin cell physiology. This "meta-organism" symbiotic mutualism results in sweat either with or without odor (osmidrosis), depending on host ABCC11 gene haplotypes. Apocrine metabolism produces odorless S-glutathione conjugate that is transferred by ABCC11 transporters into secretory vesicles, deglutamylated to S-Cys-Gly-3M3SH thiol, and exuded to skin surface. An anthropogenic clade of skin bacteria then takes up the thiol and bioconverts it to malodorous 3-methyl-3-sulfanylhexan-1-ol (3M3SH). We hypothesized a familial meta-organism association of human ABCC11 gene non-synonymous SNP rs17822931 interplaying with skin microbiome 3M3SH biosynthesis. Subjects were genotyped for ABCC11 SNPs, and their haplotypes were correlated with axilla microbiome DNA sequencing profiles and predicted metagenome functions. A multigeneration family pedigree revealed a Mendelian autosomal recessive pattern: the C allele of ABCC11 correlated with bacterial Cys-S-conjugate β-lyase (PatB) gene known for Staphylococcus hominis biosynthesis of 3M3SH from human precursor; PatB was rescinded in hosts with homozygous TT alleles encoding ABCC11 loss-of-function mutation. We posit that a C allele encoding functional ABCC11 is key to delivering host conjugate precursors that shape heritable skin niche conditions favorable to harboring Staphylococcus having genomics of odor thiol production. This provides existential insights into human evolution and global regional population ancestries., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics declaration of IRB approval for human subjects The project protocol was approved as a non‑intervention observational study of samples obtained from human subjects by the Institutional Review Board of the University of Florida, in accordance with the guidelines and regulations of the Declaration of Helsinki. Signed informed consent to participate and consent to publish deidentified data was obtained from all subjects., (© 2024. The Author(s).)
- Published
- 2024
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