Role of Lipid Metabolism in Seborrheic Dermatitis (Dandruff)
Yvonne DeAngelis, CVT, Erin MacDonald, BA, and Thomas L. Dawson, Jr. , Ph.D. The Procter & Gamble Company, Cincinnati, OH
Dandruff and seborrheic dermatitis (D/SD) D/SD are chronic scalp conditions characterized by visible flakes induced by rapid turnover of scalp cells1. Seborrheic dermatitis is a severe form of dandruff, resulting from the same etiology2,3. D/SD result from three factors: 1) microbial effects (primarily Malassezia), 2) sebaceous secretions, and 3) unknown individual susceptibility factors4. Oleic acid (C18:1, OA), an unsaturated free fatty acid (FA), has been shown to induce dandruff-like flaking in susceptible individuals4. We hypothesize that oleic acid release from sebum by Malassezia lipases is a mechanism for dandruff induction. However, if Malassezia consume OA, how does it induce dandruff? Malassezia lipid dependence The Malassezia species colonizing humans are lipid-dependent and require specific lipids for growth5,7. The specific lipids supporting Malassezia growth in situ, on human skin, have yet to be elucidated. Significant work, primarily executed prior to the new nomenclature and with commercial grade (relatively impure) FAs as lipid sources, have indicated Malassezia consume oleic acid. We now show Malassezia, in particular M. globosa, require saturated, not unsaturated fatty acids. Sabouraud-Dextrose supplies all nutrients necessary for Malassezia growth except lipids. With this base, specific lipids or combinations can be assayed to determine which can independently support growth.
Compare lipid requirements of the fungus most closely associated with D/SD, M. globosa, with the best studied Malassezia species, M. furfur. Utilize pure free fatty acids to determine the nutritional needs of M. globosa and M. furfur. Evaluate the lipid requirements of human scalp-associated Malassezia species and further define the metabolic pathways by which Malassezia induce D/SD.
The "Tween® Assimilation Assay", from Guillot et al.5, was designed to differentiate Malassezia species. We adapted this assay to investigate lipid effects on growth of M. globosa and M. furfur. Briefly, Sabouraud Dextrose containing low-melt agar was melted, cooled to 38oC, inoculated with Malassezia, and poured into 10cm dishes. After it solidified 6mm holes were punched and 50ml of test compound added. Plates were incubated at 30°C and growth assessed at days 7 and 14. Great care must be taken in the selection of lipid sources. Most commercial lipids are rough mixtures, enriched for the main ingredient. For these studies, the purity is indicated. In the table, the number in parenthesis indicates the number of independent experiments.
M. furfur and M. globosa growth is supported by saturated, not unsaturated fatty acids. Interestingly, neither M. globosa nor M. furfur grew on analytically pure oleic (OA) or ricinoleic (RA) acids, indicating the presence of other necessary materials in the commercial preparations. Both grew well on naturally derived, impure FAs, as well as analytically pure saturated FAs. Analysis of the naturally derived, impure OA confirms it to be 70% oleic, 20% stearic, and the remainder other C16 and C18 fatty acids (NuCheck Prep, Elysian, MN, personal communication).
Malassezia growth is supported by saturated, not unsaturated fatty acids. In all cases, pure, unsaturated FAs were unable to support growth of M. globosa or M. furfur. Interestingly, growth of both species was supported by saturated FAs. This is further evidenced by lard, which is rich in saturated triglycerides. Implications for Dandruff and Seborrheic Dermatitis. Previously, it has been shown that: 1.While number density of M. globosa and M. restricta do not directly correlate to dandruff presence or severity, removal correlates directly with amelioration of flaking. 2.In dandruff susceptible individuals pure OA, an unsaturated FA and Malassezia metabolite, induces flaking in the absence of Malassezia7 by direct effects on the host skin barrier. This finding, that Malassezia require saturated, and not unsaturated FAs, coupled with previous data, supports the following hypothesis:
Malassezia hydrolyze human sebum, releasing a mixture of saturated and unsaturated fatty acids. They take up the required saturated FAs, leaving behind unsaturated FAs. The unsaturated FAs penetrate the stratum corneum and due to their non-uniform structure breach the skins barrier function. This barrier breach induces an irritation response, leading to dandruff and seborrheic dermatitis.
References 1. Orfanos, C. E. and R. Happle (1989). Hair and hair diseases. Berlin, Springer-Verlag. 2.Gupta, A. K., R. Batra, et al. (2004). "Skin diseases associated with Malassezia species." J Am Acad Dermatol 51(5): 785-98. 3.Warner, R., J. Schwartz, et al. (2001). "Dandruff has an altered stratum corneum ultrastructure that is improved with zinc pyrithione shampoo." J Am Acad Dermatol 45(6): 897-903. 4.DeAngelis, Y.M., C.M. Gemmer et al. (2005) Three etiologic facets of dandruff and seborrheic dermatitis: Malassezia fungi, Sebaceous lipids, and Individual sensitivity. J. Invest. Dermatol In press. 5.Guillot, J., E. Gueho, et al. (1996). "Identification of Malassezia Species." Journal of Mycology Medical 6: 103-110. 6.Gupta, A., Y. Kohli, et al. (2000). "Molecular differentiation of seven Malassezia species." J Clin Microbiol 38(5): 1869-75.. 7.DeAngelis, YM et al. (2005) Three etiologic facets of dandruff and seborrheic dermatitis: Malassezia fungi, Sebaceous lipids, and Individual sensitivity. J Invest Dermatol. (in press).