“Roses are red, violets are blue, bad hair days are okay, but bad air days will screw you.”
Abhijit Naskar. Neuroscientist and International Bestselling Author
Air quality and health
Back in September 2016, I chaired the in-cosmetics Formulation Summit on the theme of ‘Protection’, which featured air pollution as a key topic.
I was fortunate enough to have Dr Julia Fussel join as a speaker, who was then a senior research fellow at Kings College London and an expert on the health effects of air pollution. Dr Fussel told delegates how city atmospheres are rich in tiny airborne damaging particulate matter (PM) and toxic gases, such as nitrogen dioxide and ozone. At that point, most studies investigating the damaging effects of polluted air had been on lung tissue; however, the few studies that involved the skin had shown that exposure to city atmospheres increased the physical changes that we associate with aging, such as age spots, fine lines and weakened skin barrier function. Dr Fussel cautioned that, although skin is an excellent protective barrier, its defensive capacity is limited .
A Pegasor air quality meter (lent to the summit by Air Monitors Ltd) was running during the presentations, meaning that delegates had the disturbing experience of learning about the adverse health effects of polluted air while also seeing the quality of the air they were breathing. The summit was held in central London, close to the busy and traffic-heavy Marble Arch area, so unsurprisingly the Pegasor meter gave some disconcerting real-time data. Air quality was also headlining in the London papers during the week of the conference, with headlines proclaiming 40,000 premature deaths due to air pollution (see Fig. 1).
Figure 1 | Air pollution is the news. Reproduced from the article ‘Morally and legally, the UK government has failed us on air pollution’ in The Guardian (2016) .
In a more recent paper on the toxicity of airborne particles, Dr Fussel points out that PM can be carcinogenic and references the estimated 9 million deaths globally per year that can be attributed to airborne particles less than 2.5 µm in diameter. She goes on to discuss the results of several studies, where human volunteers were exposed to whole diesel exhausts. This exposure triggered antioxidant and redox-signalling pathways, followed by inflammatory cascades in healthy lung tissue. It has now been indisputably shown that PM, especially when derived from combusted materials, damages cardio-respiratory tissue .
Air pollution and skin damage
At the summit, Dr Gabrielle Sore, then Scientific Communication Director at L’Oréal, gave a keynote speech on how pollution is overwhelming the skin’s defences. Her review of published research highlighted China and India as countries where the connection between skin damage and air pollution had already been made. Airborne PM contributes to premature skin aging, while ozone rapidly depletes the skin’s antioxidants. The adverse effects of air pollution had been observed on both diseased skin and healthy skin, supporting the argument that the skin’s natural defences, even when the skin is healthy, cannot cope with the levels of air pollution found in cities .
Marc-André Lefebvre and his L’Oréal colleagues’ landmark paper ‘Evaluation on the impact of urban pollution on the quality of skin: a multicentre study in Mexico’ won the International Journal of Cosmetics Science prize for best paper of 2015 . The study involved 96 subjects living in Mexico City (exposed to high pollution) and 93 subjects living in Cuernavaca (less exposed to pollution) and reinforced the previously reported damaging effects of air pollution on skin. The researchers showed that sebum secretion increased, and that the sebum contained less vitamin E and squalene, in subjects exposed to the highest level of pollution. They also noted that those living in Mexico City had more lactic acid on their skin, greater facial redness and more carbonylated proteins in the upper skin layers. In addition, the skin of those subjects had lower interleukin 1α (IL-1α) levels, ATP concentrations and chymotrypsin-type activity; and greater occurrence of atopic and urticarial skins, and higher frequency of red dermographism and seborrheic conditions, were observed on foreheads.
Aryl hydrocarbon receptor – city pollution, diet and the gut microbiome
Dr Sore also mentioned that the aryl hydrocarbon receptor (AhR) had been recognized as a target for skin-damaging air pollution . The transcription factors necessary for the skin’s immune response are produced when the AhR is activated. Activating the AhR receptor also triggers transcription factors to support skin barrier function and the body’s coping mechanism for foreign toxic substances (xenobiotics), including those found in polluted air . A fascinating study by Haas and colleagues in 2016 showed that AhR ligands speed up keratinocyte differentiation in mice, which consequently would have increased the synthesis of desmosomes and other components necessary for barrier function. AhR-deficient mice were observed to have higher transepidermal water loss (TEWL), and so weakened barrier function. They also had ”higher interdividual differences in their skin microbiome”.
The authors went on to point out that removing AhR-activating molecules from the diet of the mice resulted in impaired barrier function, which could then be reversed when plant-derived AhR-activating molecules (derived from dietary indol-3-carniol) became available in the diet .
A more recent paper on the regulation of AhR-responsive (AhRR) gene expression in intestinal immune cells by dietary AhR-activating molecules discusses, in greater detail, indole-3-carbinol metabolites acting as AhR activators in the gut . It is interesting that the mouse gut microbiome produces substances that activate AhR and, as a result, the AhR-directed immune response influences the intestinal microbiota population, helping to keep it balanced .
Aryl hydrocarbon receptor – skin microbiome
Could bacterial metabolites from the skin microbiome also activate AhR, and so influence skin barrier function and control the composition of the skin microbiome? Could city air pollution cause skin damage by disrupting those interactions? Or are the toxins in city air directly damaging AhR, leading to weaker damaged skin? Or is skin being damaged by a ‘blanket’ poisoning of both the skin microbiome and the skin’s own barrier?
These are difficult questions to answer. The question of bacteria activating the human AhR system and influencing the skin microbiome was answered in part by Rademacher et al., in 2019 . They reported that Staphylococcus epidermidis, which is known to induce antimicrobial peptides and strengthen skin defences, secretes substances less than 2 kDa in weight that activate human AhRR genes in vitro, including S. epidermidis-mediated induction of IL-1β expression. They also showed that when AhR was inhibited in the skin explants, S. epidermidis growth increased.
Revealing the effects of city atmospheres on the skin microbiome’s dynamic and mostly interdependent microbial ecology requires quite complex mathematics. Network analysis is one statistical approach that is being used successfully. Graphical representations of relationships (edges) between variables (nodes) are analysed, revealing the core complex patterns. A recent paper by Wang and colleagues uses network analysis to visualize the strength of interactions between the different species living on skin . By analysing the data from individual subjects (Microbiome Network of Individual (MNI)) then subtracting group effects, the researchers revealed the effect of pollution on the facial microbiome. Working with 16S sequencing data from facial skin samples, they showed that the connectivity and fragility of MNIs is significantly damaged and worsened by city pollution. These effects were even greater in individuals who smoked.
In the same publication, they also assessed the responses of the subjects’ skin to pollution. They determined the stratum corneum’s levels of tryptic enzyme, total antioxidant capacity and catalase activity, and quantified cholesterol, squalene and vitamin E. They concluded that it is the weakening of the skin microbiome that causes these biochemical changes in skin. They go on to present further data in support of pollution causing skin microbiota-mediated biochemical and biophysical changes in facial skin. They conclude that skin microbiota is the first to respond to air pollution and that measurable skin benefits come from maintaining a stable, strong skin microbiota with good connectivity.
City atmospheres vary but those with high levels of PM, nitrogen dioxide and ozone are damaging the skin and general health of those exposed and causing millions of premature deaths. The ligand-activated AhR triggers the genes responsible for strengthening the skin’s defences (AhRR genes) and dealing with pollutants. AhR-deficiency leads to changes in skin microbiome composition, and experiments using mice indicate a fascinating link between AhR ligands in gut-microbiome-transformed digested food and skin barrier integrity. At least one prominent member of the human skin microbiome (S. epidermidis) produces molecules that activate AhRR genes. Network analysis on the facial skin microbiome indicates that it is damage to the skin microbiome’s interconnectivity and not changes in its composition or diversity that is the root cause of some observed changes in the skin physiology of city dwellers. In the two-way interaction between microbes and skin, evidence suggests that it is the fragility of the skin microbiome ecology in response to city air pollution – more than pollution directly damaging receptors such as AhR – that is mostly responsible for skin damage. Further studies are needed to fully understand the implications of city pollution damaging the skin microbiome; however, it does appear that skincare that maintains and restores a healthy skin microbiome may be the best route to protecting skin, and even reversing skin damage due to city pollution.
1. Whitehouse, L. What’s the science behind anti-pollution skin care? Cosmetic Design Europe (2016); www.cosmeticsdesign-europe.com/Article/2016/10/18/Anti-pollution-skin-care-the-science
2. Thorton, J. Morally and legally, the UK government has failed us on air pollution. The Guardian (2016); https://www.theguardian.com/environment/2016/oct/17/morally-and-legally-the-uk-government-has-failed-us-on-air-pollution
3. Kelly, F. & Fussell, J., Toxicity of airborne particles – established evidence, knowledge gaps and emerging areas of importance. Phil. Trans. R. Soc. A: Math. Phys. Engineer. Sci. 378, 1–15 (2020).
4. Krutmann, J. et al. Pollution and skin: from epidemiological and mechanistic studies to clinical implications. J. Dermatol. Sci. 76, 163–168 (2014).
5. Lefebvre, M. A. et al. Evaluation of the impact of urban pollution on the quality of skin: a multicentre study in Mexico. Int. J. Cosmet. Sci. 37, 329–338 (2015).
6. Rothhammer, V. & Quintana, F. J. The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease. Nat. Rev. Immunol. 19, 184–197 (2019).
7. Haas, K. et al. Aryl Hydrocarbon receptor in keratinocytes is essential for murine skin barrier integrity. J. Invest. Dermatol. 136, 2260–2269 (2016).
8. Schanz, O. et al. Dietary AhR ligands regulate AhRR expression in intestinal immune cells and intestinal microbiota composition. Int. J. Mol. Sci. 21, 3189 (2020).
9. Ji, J. & Qu, H. Cross-regulatory circuit between AhR and microbiota. Curr. Drug Metab. 20, 4–8 (2019).
10. Rademacher, F. et al. Staphylococcus epidermidis activates aryl hydrocarbon receptor signaling in human keratinocytes: implications for cutaneous defense. J. Innate Immun. 11, 125–135 (2019).
11. Wang, L. et al. Facial skin microbiota-mediated host response to pollution stress revealed by microbiome networks of individual. mSystems https://doi.org/10.1128/mSystems.00319-21 (2021).
Air quality is considered unhealthy at 100–150 µg m–3 and very poor when PM10 reaches 201–300 µg m–3 (or when the annual mean concentration of PM2.5 is between 25–35 µg m–3). The European Environment Agency (EEA) has a useful online air quality viewer, where 330 cities across the EEA member countries are ranked from the cleanest city to the most polluted, on the basis of average levels of PM2.5 over the past two calendar years (see https://www.eea.europa.eu/themes/air/urban-air-quality/european-city-air-quality-viewer). Other cities report air quality using the daily Air Quality Index (AQI), derived from the highest concentration of the following five pollutants: nitrogen dioxide, sulphur dioxide, ozone, PM10 and PM2.5. The AQI for London, at the time that this article was written, was a moderate 50, whereas Mexico City was 76 and Cuernavaca was 39, and Beijing was an unhealthy 153. Note that these values are taken from https://www.iqair.com/, and to be ranked as ‘Hazardous’ the AQI needs to be 300–500.