In September, Dr. Martin Pagac from dsm-firmenich presented new findings at the IFSCC (International Federation of Societies of Cosmetic Chemists) Congress on what impact menopause might have on the facial skin microbiome. Today, Martin discusses these new results with us.
An overview of our study
It is well understood that our skin microbiota is affected by age. It has been shown by several studies that elderly subjects exhibit an increased microbial diversity on their skin compared to their younger counterparts [5, 14, 16]. However, these same studies also imply that menopausal status can relate to changes in skin microbial compositions, and, despite this, no studies have yet been published that investigate the direct influence of menopausal status on the skin microbiome.
Because menopausal status is inherently linked to age, in such studies it is necessary to minimize the impact of chronological age as well as the underlying changes in biophysical properties of the skin. We therefore decided to perform an observational study on female volunteers who were all a similar age but had different defined self-declared pre- and post-menopausal statuses. We used bacterial 16S rRNA gene sequencing of skin samples and skin elasticity measurements to study their facial skin.
We found that while facial skin microbiomes differed significantly between the pre- and post-menopausal groups, aging-associated skin elasticity was unaffected. These results showed, for the first time, that there is a direct and significant association between facial skin microbiomes and menopausal status, while removing aging-associated skin biophysical properties from the equation. These findings have the potential to open the door to development of treatments for menopause-associated skin disorders that target the microbiome.
Why we did it
The skin is the largest human organ, serving as a natural barrier against the external environment. It is a diverse ecosystem that consists of many distinct microenvironments, which can be dry, moist, or oily. The skin is composed of a variety of specialized cell types, as well as appendages such as hair follicles, sebaceous and sweat glands. As a result, the skin offers a diverse and rich habitat for a myriad of microorganisms adapted to inhabit any of its many niches .
As regular readers of this blog will be aware, the skin microbiome, consisting of bacteria, archaea, fungi, and arthropods, including viruses, contributes actively to skin homeostasis and health . Skin health is impacted by both environmental and intrinsic factors, such as UV irradiation, pollution, climate, the microbiota, genetic background, and chronological age. Sometimes these factors can trigger skin inflammation and consequently impair epidermal barrier function, causing irritating skin symptoms such as pruritus, an itchy and painful skin sensation [3, 4].
It is known that changes in skin structure and function in post-menopausal women are accompanied by dropping estradiol levels and increasing luteinizing and follicle-stimulating hormone levels , and are inherently linked to aging. The skin’s sebaceous glands are significantly less active in post- versus pre-menopausal women . The decreased secretion of sebaceous lipids, concomitant with the post-menopausal state, leads to drier, more sensitive skin, which is more susceptibility to infection. We also believed that it would affect the composition of the skin microbiome due to limited availability of sebaceous lipids as a nutritional source .
These changes in skin microbiome diversity and composition at different taxonomic levels have been described previously in relation to ageing . The more lipid-rich skin regions of pre-menopausal individuals preferentially support colonization by lipophilic skin microbes such as Malassezia , Cutibacteria, and Corynebacteria . However, although previous studies revealed clear correlations between chronological age and skin microbiome profiles, the links to menopausal status were only implied. We therefore wanted to investigate whether changes in the composition of the human skin microbiome can be directly associated with menopausal status.
What we did
To conduct our study, we obtained samples from Caucasian female volunteers aged 40-65, who were either pre- (n=14, average age 48.1 years) or post-menopausal (n=30, average age 60.8 years) status, defined based on whether their last menstrual period occurred at least 12 months ago. Peri-menopausal and menopausal individuals were excluded from the study.
To investigate the compositions of their facial skin microbiomes, microbial DNA was collected from our volunteers by swabbing their forehead and cheek skin, and this was sequenced according to dedicated protocols. The protocols for generation and sequencing of the 16S rRNA gene amplicon libraries are described in detail here .
To evaluate any aging-associated changes in the biophysical properties of our volunteers’ facial skin, Cutometer measurements were performed according to standardized guidelines. The viscoelastic properties of the skin were determined, in vivo, using a Cutometer™ – a device that measures the deformation and recovering power of a cutaneous area submitted to mechanical suction.
Data was analysed using the statistical and visual analysis software MicrobiomeAnalyst .
What we found
To be able to attribute any potential change in the composition of the skin microbiome to menopausal status, rather than skin aging and the associated biophysical properties, we chose volunteers who were all similar ages, within the range close to menopausal transition. The average age difference between the pre- and post-menopausal groups was only 12.7 years. We were therefore not surprised that the Cutometer readings revealed no significant differences in aging-associated skin elasticity and tiring effects between the groups. Consequently, if the main selective determinant for microbial population was the age-dependent biophysical conditions of the skin, we would also not expect to see a significant change in the compositions of the skin microbiomes between the groups.
To determine whether this was the case, we performed 16S rRNA gene sequencing of the bacterial DNA isolated from the forehead and cheek skin of our volunteers. We found that the relative abundances of several skin bacteria were different between the pre- and post-menopausal groups. For example, the proportional abundance of the lipophilic Cutibacterium acnes species was significantly higher on pre-menopausal facial skin. These findings are in agreement with the theory that skin sites that are enriched with sebaceous lipids attract more lipophilic microorganisms [7, 8].
The alpha-diversity (Shannon index) and beta-diversity (Bray-Curtis index), assessed at the genus taxonomic level, differed significantly between the pre- and post-menopausal groups at sampled facial skin sites (Kruskal-Wallis p-value < 0.02 and PERMANOVA p-value < 0.001, respectively).
Overall, the study revealed an increased bacterial diversity on the facial skin sites of post-menopausal subjects. We did not measure the sebum concentrations and skin hydration levels of the volunteers. However, this finding was in line with previous studies that reported a broader variety of microbes on aging skin, which is characterized by dry and moist properties, rather than oiliness .
The skin microbial community is characterized by being longitudinally stable . Previous reports only detected changes in the composition of the skin microbiome when comparing healthy groups with broad age differences [8, 14-17]. Our results, describing menopausal status-dependent changes in skin microbial diversity and composition, are substantiated by these prior studies – the average age difference between the pre- and post-menopausal groups was only 12.7 years, which did not significantly impact the ageing-associated skin biophysical properties.
We therefore propose that the differentiating factor between our two examined groups with regards to skin microbial profiles was not chronological age, but rather a sudden hormonal-driven impact associated with the menopausal states of our volunteers. Alternatively, microbes may have adapted rapidly to changes in the availability of sebum lipids on post-menopausal skin.
What are the next steps?
Our study revealed that the differences in the composition of the skin microbiome in pre- and post-menopausal subjects are independent of the aging-associated properties of the skin. Cutometer measurements did not detect any significant differences in the signs of aging skin between the pre- and post-menopausal groups. This suggests that the change in the skin microbiome in response to altered skin conditions is not causatively linked to age.
Further research will be required to understand the mechanisms by which menopause-associated physiological parameters interact with the skin microbiota. We hypothesize that an increased bacterial diversity and associated skin microbiome dysbiosis will be found to contribute to the development of skin disorders experienced by post-menopausal women.
Current commercial skincare products aim to reduce symptoms of inflammation by using soothing, cooling, moisturizing, or hydrating ingredients. Targeted microbiome-based interventions aimed at rebalancing the composition of the skin microbiome could provide valuable alternative approaches to these traditional approaches.
- A. L. Byrd, Y. Belkaid, and J. A. Segre, “The human skin microbiome,” Nature Reviews Microbiology, vol. 16, no. 3, pp. 143-155, 2018/03/01 2018.
- R. Sfriso, M. Egert, M. Gempeler, R. Voegeli, and R. Campiche, “Revealing the secret life of skin – with the microbiome you never walk alone,” (in eng), Int J Cosmet Sci, vol. 42, no. 2, pp. 116-126, Apr 2020.
- S. Song et al., “Acute health effects of urban fine and ultrafine particles on children with atopic dermatitis,” (in eng), Environ Res, vol. 111, no. 3, pp. 394-9, Apr 2011.
- B. Eberlein-König et al., “Influence of airborne nitrogen dioxide or formaldehyde on parameters of skin function and cellular activation in patients with atopic eczema and control subjects,” (in eng), J Allergy Clin Immunol, vol. 101, no. 1 Pt 1, pp. 141-3, Jan 1998.
- P. E. Pochi, J. S. Strauss, and D. T. Downing, “Age-related changes in sebaceous gland activity,” (in eng), J Invest Dermatol, vol. 73, no. 1, pp. 108-11, Jul 1979.
- J. Oh, S. Conlan, E. C. Polley, J. A. Segre, and H. H. Kong, “Shifts in human skin and nares microbiota of healthy children and adults,” Genome Medicine, vol. 4, no. 10, p. 77, 2012/10/10 2012.
- W. Zhou et al., “Skin microbiome attributes associate with biophysical skin aging,” bioRxiv, p. 2023.01.30.526239, 2023.
- J. H. Jo et al., “Diverse Human Skin Fungal Communities in Children Converge in Adulthood,” (in eng), J Invest Dermatol, vol. 136, no. 12, pp. 2356-2363, Dec 2016.
- J. Oh, S. Conlan, E. C. Polley, J. A. Segre, and H. H. Kong, “Shifts in human skin and nares microbiota of healthy children and adults,” (in eng), Genome Med, vol. 4, no. 10, p. 77, 2012.
- S. Deyaert et al., “Development of a reproducible small intestinal microbiota model and its integration into the SHIME®-system, a dynamic in vitro gut model,” (in English), Frontiers in Microbiology, Original Research vol. 13, 2023-March-17 2023.
- J. Chong, P. Liu, G. Zhou, and J. Xia, “Using MicrobiomeAnalyst for comprehensive statistical, functional, and meta-analysis of microbiome data,” (in eng), Nat Protoc, vol. 15, no. 3, pp. 799-821, Mar 2020.
- E. A. Grice and J. A. Segre, “The skin microbiome,” (in eng), Nat Rev Microbiol, vol. 9, no. 4, pp. 244-53, Apr 2011.
- J. Oh, A. L. Byrd, M. Park, H. H. Kong, and J. A. Segre, “Temporal Stability of the Human Skin Microbiome,” (in eng), Cell, vol. 165, no. 4, pp. 854-66, May 5 2016.
- B. Howard et al., “Aging-Associated Changes in the Adult Human Skin Microbiome and the Host Factors that Affect Skin Microbiome Composition,” (in eng), J Invest Dermatol, vol. 142, no. 7, pp. 1934-1946.e21, Jul 2022.
- H.-J. Kim et al., “Aged related human skin microbiome and mycobiome in Korean women,” Scientific Reports, vol. 12, no. 1, p. 2351, 2022/02/11 2022.
- R. Jugé et al., “Shift in skin microbiota of Western European women across aging,” (in eng), J Appl Microbiol, vol. 125, no. 3, pp. 907-916, Sep 2018.
- P. A. Dimitriu, B. Iker, K. Malik, H. Leung, W. W. Mohn, and G. G. Hillebrand, “New Insights into the Intrinsic and Extrinsic Factors That Shape the Human Skin Microbiome,” mBio, vol. 10, no. 4, pp. e00839-19, 2019.