Kenneth Timmis1. 1. Environmental Microbiology Laboratory, Helmholtz Centre for Infection Research, and Institute of Microbiology, Technical University of Braunschweig, Braunschweig, Germany.
Personalized medicine, the monitoring, prevention and treatment of disease in an individual, specifically tailored to his or her specific genomic make‐up, is rapidly gaining interest in the medical, scientific and general population, as our understanding of genetic susceptibilities to disease and health‐relevant causal relationships between our individual genetically determined physiologies and environmental factors advances.The current basis of personalized medicine, the genetic diversity of humans and the resulting diversity of susceptibilities of individuals to disease, is of course only part of the equation, because it is well appreciated that we, like all animals and plants, are covered by second outer ‘skins’ of populations of phylogenetically and physiologically diverse microbes, which add and integrate metabolic functions that profoundly influence our physiology and health. We are organized ‘biomes’ of interacting communities of human and microbial cells and tissues. The next level of personalized medicine will therefore integrate the genetic and physiological diversity of our microbial biome partners.Disease is a negative aspect of health and living, and current personalized medicine is principally targeted at disease prevention and treatment, particularly in susceptible individuals. However, personalized medicine will also be applied to the positive side of health and living – lifestyle medicine for healthy people – and will thus be applied to anyone at any time, in most instances over a large part of the lifespan. Just as the treatment of chronic disease is often of more commercial importance than that of acute disease, so chronic health is particularly attractive commercially for personalized lifestyle medicine.Human biome biotechnology will contribute to personalized medicine, including lifestyle medicine, in a variety of spheres; the one I elect to deal with here is our desire to smell nice for personal satisfaction and to please/attract others. The commercial importance of this is reflected in the high value of the odour ingredients (in perfumes, colognes, body lotions, deodorants, scented soaps and the like) that form the core of the body care business.Our smell – the olfactory perception of volatile compounds emitted from our skin, body hair and bodily orifices – is determined by a number of rather variable factors (see Anesti ; Eggert ; Jacob ; Roberts ; Wood and Kelly, 2009; Yamazaki ), and citations therein), such as (i) the ‘personal’ composition of volatiles and non‐volatiles that we secrete onto our skin surface, which depends on our particular physiology (our individual genomic programme), (ii) the age‐related changes in composition of these secretions, (iii) the temporary/periodical secretion of additional chemicals resulting from changes in health/hormonal balance/recent food intake/etc., (iv) the washing of skin with detergents, many of which are perfumed, (v) the application of body care products, many of which are also perfumed (see Wood, 2009), and (vi) the composition and activity of our microbial ‘skin’ that interacts with our natural secretions and applied products, metabolizing and thereby changing their composition, and also creating further volatiles, either metabolites from the secretions, or that are purely microbially derived (see e.g. Anesti ). It is this mix of volatiles of endogenous human secretions, endogenous microbial skin secretions, metabolites resulting from the microbial transformation of human secretions, and perfume supplements, which structures our individual odour profile at any moment in time.It is also this individual diversity of odour‐structuring parameters that leads to the same perfume/cologne on different women/men smelling subtly (or non‐subtly) different (‘Gosh: what is that awful perfume you're wearing today?’‘What do you mean: you said how nice it was on Felicity!’). This has led to the current practice of the empirical testing of the whole range of options in the perfumery in order to find the product that most pleases and matches an individual's preferences and skin odour characteristics. Products that modify our own odour are generally applied daily, usually after showering, and are subject to change – physical, chemical and biological – on the skin surface – over the course of the day, changes that are both generic and individually determined by our particular genome‐determined physiology, skin flora and daily activities, such that the smell created at the time of application changes in time, and differently on different people (Ann Wood: ‘and some disappear much faster than others, making them very expensive odour‐rentals!’).Elucidation of the key interactions and causal relationships that determine personal odour, and how it can be modified to achieve a desired quality, will ultimately allow the development of rational design of enhanced odour profiles. Replacement of the current hit‐and‐miss empiricism of odour selection by human chemistry:microbial ecology‐based procedures to create customized odour profiles, and to optimize their temporal development over the course of the day, may become a significant activity of the lifestyle branch of the personalized medicine industry.The scientific progress necessary to accomplish this will include elucidation of the key human genomic and physiological determinants, the ecological interactions of the skin microbial flora with the epidermal surface and its secretions, the individual variations in these, which underlie personal odour specificity, and the manner in which these interact with and modify relevant personal care products. This will involve not only analysis of the specifics of different anatomical areas of the body surface (axillae, feet, ears, neck, etc.) exhibiting different secretion characteristics, but also different microscopic niches within such areas that characterize the spatial differentiation of the epidermal tissue structure and their diverse ecological chemistries. Functional metagenomics of such micro‐niches will be a key component of this research. At the core of the functional genomics of the skin biome will be the development of ultra‐sensitive analytical procedures to identify and quantify volatiles at odour‐relevant concentrations, namely ‘odouromics’.Such studies will result in major advances in our understanding of physiological and ecological determinants and triggers of production of specific volatiles, and identification of the principal players mediating changes in such volatiles and the agents of regulation of change. This will lead to identification of compounds, microbes and procedures that enable modification of volatile composition. This in turn will lead to the formulation of personalized products (e.g. creams containing volatiles, volatile precursors/metabolites, inducers of volatile formation, inhibitors, prebiotic and/or probiotic microbes, etc.) that modulate skin chemistry and microbial flora such that production/maintenance of production of specific volatiles are favoured and formation of undesirable volatiles by the skin biome are disfavoured, and that, in combination with specific perfumed products, create custom odour profiles in individuals that match their aspirations.Underpinning all of this will be newly developed powerful, but simple to operate and interpret odouromics instrumentation to analyse odour profiles, and skin microbe functionalities, that, in combination with personal genomic profiles, will produce individual assessments for the customization of commercial products.The other aspect of personal odour is, of course, its olfactory perception, which also varies from person to person. As a consequence, self‐perception of one's own smell can be quite different from the perception of the same smell by someone else. This is not an issue if one buys perfume for self‐satisfaction, but may be a major one if the goal is to please or attract others. Thus, a further level in personalizing odour profiles may well be the tuning to a partner's preferences.The aspect of attracting others inevitably leads to another issue, namely that some skin volatiles may act as pheromones: the composition of our volatiles also contributes to our non‐visual sexual attraction to others. This aspect will also undoubtedly be of some interest to the personal care branch of the personalized medicine industry.It is perhaps worth noting that this research may not only result in the ability to custom design personal olfactory images but also lead to a clearer understanding of the fundamental relationships between our volatile emissions and physiological and mental states. This in turn will lead to improved diagnostic procedures in clinical medicine for certain disease states and syndromes (the chemical analysis of volatiles in breath is already used for such purposes: e.g. see Salerno‐Kennedy and Cashman (2005), as well as advances in dermatology itself, but also perhaps for other purposes, such as lie detection (in judicial investigations, job interviews, relationship conflicts, etc.), aptitude assessments; partnership compatibility assessments. And all of this will drive the development of new technology and instrumentation. Only the imagination limits the range of applications. Go to it, biotech!
Authors: Vasiliki Anesti; Jyotsna Vohra; Shalini Goonetilleka; Ian R McDonald; Bettina Sträubler; Erko Stackebrandt; Donovan P Kelly; Ann P Wood Journal: Environ Microbiol Date: 2004-08 Impact factor: 5.491