Intrinsic and extrinsic factors affecting axillary odor variation. A comprehensive review.

Humans produce odorous secretions from multiple body sites according to the microbiomic profile of each area and the types of secretory glands present. Because the axilla is an active, odor-producing region that mediates social communication via the sense of smell, this article focuses on the biological mechanisms underlying the creation of axillary odor, as well as the intrinsic and extrinsic factors likely to impact the odor and determine individual differences. The list of intrinsic factors discussed includes sex, age, ethnicity, emotions, and personality, and extrinsic factors include dietary choices, diseases, climate, and hygienic habits. In addition, we also draw attention to gaps in our understanding of each factor, including, for example, topical areas such as the effect of climate on body odor variation. Fundamental challenges and emerging research opportunities are further outlined in the discussion. Finally, we suggest guidelines and best practices based on the factors reviewed herein for preparatory protocols of sweat collection, data analysis, and interpretation.

The molecular basis of thioalcohol production in human body odour.

Body odour is a characteristic trait of Homo sapiens, however its role in human behaviour and evolution is poorly understood. Remarkably, body odour is linked to the presence of a few species of commensal microbes. Herein we discover a bacterial enzyme, limited to odour-forming staphylococci that are able to cleave odourless precursors of thioalcohols, the most pungent components of body odour. We demonstrated using phylogenetics, biochemistry and structural biology that this cysteine-thiol lyase (C-T lyase) is a PLP-dependent enzyme that moved horizontally into a unique monophyletic group of odour-forming staphylococci about 60 million years ago, and has subsequently tailored its enzymatic function to human-derived thioalcohol precursors. Significantly, transfer of this enzyme alone to non-odour producing staphylococci confers odour production, demonstrating that this C-T lyase is both necessary and sufficient for thioalcohol formation. The structure of the C-T lyase compared to that of other related enzymes reveals how the adaptation to thioalcohol precursors has evolved through changes in the binding site to create a constrained hydrophobic pocket that is selective for branched aliphatic thioalcohol ligands. The ancestral acquisition of this enzyme, and the subsequent evolution of the specificity for thioalcohol precursors implies that body odour production in humans is an ancient process.

Structural basis of malodour precursor transport in the human axilla.

Mammals produce volatile odours that convey different types of societal information. In Homo sapiens, this is now recognised as body odour, a key chemical component of which is the sulphurous thioalcohol, 3-methyl-3-sulfanylhexan-1-ol (3M3SH). Volatile 3M3SH is produced in the underarm as a result of specific microbial activity, which act on the odourless dipeptide-containing malodour precursor molecule, S-Cys-Gly-3M3SH, secreted in the axilla (underarm) during colonisation. The mechanism by which these bacteria recognise S-Cys-Gly-3M3SH and produce body odour is still poorly understood. Here we report the structural and biochemical basis of bacterial transport of S-Cys-Gly-3M3SH by Staphylococcus hominis, which is converted to the sulphurous thioalcohol component 3M3SH in the bacterial cytoplasm, before being released into the environment. Knowledge of the molecular basis of precursor transport, essential for body odour formation, provides a novel opportunity to design specific inhibitors of malodour production in humans.

Identification of axillary Staphylococcus sp. involved in the production of the malodorous thioalcohol 3-methyl-3-sufanylhexan-1-ol.

The production of malodour by humans is mediated by bacterial transformation of naturally secreted, non-odorous molecules. Specifically in the underarm (axilla), malodour arises due to biotransformation by the microbiota of dipeptide-conjugated thioalcohols, particularly S-[1-(2-hydroxyethyl)-1-methylbutyl]-(L)-cysteinylglycine (Cys-Gly-3M3SH). This molecule, secreted by the axilla, has a well-established role in malodour when metabolized to free thioalcohol by bacteria. We present Cys-Gly-3M3SH biotransformation data from a library of skin-isolated corynebacteria and staphylococci and report a significant variation in thioalcohol generation across individual bacterial species. Staphylococcus hominis, Staphylococcus haemolyticus and Staphylococcus lugdunensis were particularly efficient Cys-Gly-3M3SH transformers. In contrast, Staphylococcus epidermidis and Corynebacterium tuberculostearicum, both highly prevalent axillary commensals, are low producers of 3M3SH. We also identify significant differences between the ability of several isolates to biotransform Cys-Gly-3M3SH compared to S-benzyl-L-Cys-Gly, a dipeptide-linked version of a commonly used malodour precursor substrate. Finally, using traditional biochemical assays we subsequently establish that Cys-Gly-3M3SH is actively transported into S. hominis, rather than passively diffusing across the membrane. This work significantly enhances our knowledge of Cys-Gly-3M3SH biotransformation by physiologically important bacteria in the axillary microbiota.

Metingear: a development environment for annotating genome-scale metabolic models.

UNLABELLED: Genome-scale metabolic models often lack annotations that would allow them to be used for further analysis. Previous efforts have focused on associating metabolites in the model with a cross reference, but this can be problematic if the reference is not freely available, multiple resources are used or the metabolite is added from a literature review. Associating each metabolite with chemical structure provides unambiguous identification of the components and a more detailed view of the metabolism. We have developed an open-source desktop application that simplifies the process of adding database cross references and chemical structures to genome-scale metabolic models. Annotated models can be exported to the Systems Biology Markup Language open interchange format. AVAILABILITY: Source code, binaries, documentation and tutorials are freely available at http://johnmay.github.com/metingear. The application is implemented in Java with bundles available for MS Windows and Macintosh OS X.

Microbiological and biochemical origins of human axillary odour.

The generation of malodour on various sites of the human body is caused by the microbial biotransformation of odourless natural secretions into volatile odorous molecules. On the skin surface, distinctive odours emanate, in particular, from the underarm (axilla), where a large and permanent population of microorganisms thrives on secretions from the eccrine, apocrine and sebaceous glands. Traditional culture-based microbiological studies inform us that this resident microbiota consists mainly of Gram-positive bacteria of the genera Staphylococcus, Micrococcus, Corynebacterium and Propionibacterium. Among the molecular classes that have been implicated in axillary malodour are short- and medium-chain volatile fatty acids, 16-androstene steroids and, most recently, thioalcohols. Most of the available evidence suggests that members of the Corynebacterium genus are the primary causal agents of axillary odour, with the key malodour substrates believed to originate from the apocrine gland. In this article, we examine, in detail, the microbiology and biochemistry of malodour formation on axillary skin, focussing on precursor-product relationships, odour-forming enzymes and metabolic pathways and causal organisms. As well as reviewing the literature, some relevant new data are presented and considered alongside that already available in the public domain to reach an informed view on the current state-of-the-art, as well as future perspectives.

Metabolic analysis of the cutaneous fungi Malassezia globosa and M. restricta for insights on scalp condition and dandruff.

Dandruff is a global consumer problem, characterized by flaking and scaling of the scalp, accompanied by itch and irritancy. However, the aetiology of the condition remains poorly understood, although there is a strong consensus that the cutaneous fungi Malassezia globosa and M. restricta are a major contributory factor. Although there is a paucity of understanding on how these commensal microorganisms adopt a pathogenic phenotype, a rich source of potential insights now exists in the shape of the recently published whole-genome sequence of M. globosa, a functional annotation and metabolic reconstruction of which is freely accessible via the integrated microbial genomes (IMG) online community resource (http://www.hmpdacc-resources.org/cgi-bin/imgm_hmp/main.cgi). In these studies, we have taken a combined in-silico and in-vitro approach to investigate aspects of lipid and amino acid metabolism by M. globosa and M. restricta that have the potential to impact on scalp condition and dandruff. The IMG platform was employed to analyse the metabolism of triacylglycerols and fatty acids, as well as the aromatic amino acid tryptophan, by M. globosa, to investigate pro-inflammatory pathways linked in the literature to dandruff and pityriasis versicolour, respectively. Results were equivocal, leaving question marks over the ability of M. globosa to fully degrade unsaturated fatty acids and metabolize tryptophan to indole-3-pyruvic acid. In-vitro assay systems were then developed to study the biotransformation of these metabolites by both M. globosa and M. restricta, as well as their effect on human keratinocytes, and the results here indicated that neither unsaturated fatty acids nor indole derivatives are likely to be major aetiological factors in dandruff.