Citizen Science for Skin Microbiome Research—A 'Microbiome-friendly' Case Study

Read the full feature in the May 2022 digital edition here. . .

Something is “off” with consumers’ skin and they know it. The search terms hormonal acne and sensitive skin have been trending upward on Google for at least the past five years (see Figure 1). Dermatologists echo that these issues have become more prevalent year over year, especially in adult females.^1-6 The pathophysiology of inflammatory skin conditions from acne to rosacea to seborrheic dermatitis is commonly accepted as microbially mediated, while in autoimmune disorders, microbes may be more of a trigger than causative agent (e.g., chronic eczema). In addition, newer research shows microbial shifts may be an important factor even in the development of “sensitive skin,”^7-11 which is disruptive for sufferers yet relies purely on patient perception, has no defined pathophysiology, and therefore has no treatment.

Unfortunately, research into the skin microbiome, especially the white whale Acne vulgaris, has led to few actionable insights and innovations, with most standards of care being serendipitous discoveries, e.g., doxycycline and retinoids, or harsh broad-spectrum antimicrobials such as benzoyl peroxide, salicylic acid and antibiotics.^12-16 As may be expected, skin microbiome studies have tended to raise more questions than they answer, but without the necessary follow-up to prove causation or the translational research to develop targeted therapies.

With a more connected and more educated consumer base,^{17, 18} companies are attempting to address these increasingly prevalent microbially mediated skin conditions and market gaps with probiotic and prebiotic products. But until the skin microbiome is better understood, the ability to truly solve these issues is limited.

Developing an in-house clinical research unit to answer these questions and move the field and a business forward would generally be deemed cost-prohibitive; consider hiring a small team of researchers with this niche expertise, as well as renting or building the laboratory space and outfitting it with the appropriate equipment, and this is easily a million-dollar investment just to get started. This also does not offer the perceived quality, rigor or reduction in bias that academic research does; though it does promise complete control of resultant data.

Sponsoring academic research is typically less costly, can be engaged intermittently, and is historically the gold standard but often results in small cohorts for clinical studies and demographically restricted participants, e.g., university students. However, this model is usually at odds with data and intellectual property ownership.

Citizen science, as an alternative, affords the opportunity to reach a large population and broad demographic of study subjects who are often willing to offset or even absorb the cost of their own participation.^19-22 In fact, if current products and research are not satisfying the need to improve users’ skin or quality of life, participants are excited to contribute to the next generation of science-driven innovation, hoping to benefit from it.²¹

Citizen science is accruing successes, scientifically and commercially. For example, 23andMe developed its first drug based on consumer genomic data.²³ Also, Project Acari, by working with thousands of citizen scientists, discovered novel microbe associations in ticks colonized with the Lyme disease agent Borrelia burgdorferi, and that almost 2/3 of ticks in the Northwestern United States are colonized with this pathogen.²⁴ The American Gut Project, Viome, and various academic groups have produced crowd-sourced data connecting microbiomes to geography, health and even foods,^25-28 realizing the promise of personalized medicine.

The sheer number of participants is the power of this research, with the number of subjects routinely in the thousands. Building datasets with few inclusions or exclusion criteria, however, greatly reduces the relevant sample size for any particular question asked post-hoc. Also, while citizen science enables much larger cohorts than in-house or traditional academic research, there are challenges in collecting accurate and actionable data—primarily, ensuring that the metadata collected is accurate and providing subject training/education for replicable and aseptic sampling.

Studying the skin microbiome innately requires extra technical precautions, compared with oral, fecal and vaginal microbiomes. Specifically, low yields continue to be a primary hurdle in skin microbiome studies, leading to over-representation by any contaminants. And, like the vaginal microbiome, nearly all bacteria, e.g., Cutibacterium, Staphylococcus, Streptococcus, Micrococcus, etc., on the face are Gram-positive, exacerbating low yields due to their difficulty to lyse during DNA isolation—a challenge that sequencing cores at universities and even in published methods address inadequately; e.g., not using lysostaphin; not killing cells before incubation; etc.

To assess the potential of a citizen science approach to skin microbiome research, the work described herein utilized a consumer test kit deployed in a pilot study of 59 participants, including a wide age range and representing various skin conditions, to collect and assess skin microbiome data. The validity of this approach, learnings for skin microbiome research, results of a case study, and potential value of this approach in skin care innovation are outlined.

. . .Read more in the May 2022 digital edition here. . .

References

1. Addor, F.A.S. and Schalka (2010). S. Acne in adult women: epidemiological, diagnostic and therapeutic aspects. An Bras Dermatol 85 789-795.
2. Anaba, E.L. and Oaku, I.R. (2020). Adult female acne: A cross-sectional study of diet, family history, body mass index and premenstrual flare as risk factors and contributors to severity. Int J Womens Dermatol 7 265-269.
3. Bagatin, E., Rocha, M.A.D. da, Freitas, T.H.P. and Costa, C.S. (2021). Treatment challenges in adult female acne and future directions. Expert Rev Clin Pharmacol 14 687-701.
4. Bagatin, E., et al. (2019). Adult female acne: A guide to clinical practice. An Bras Dermatol 94 62-75.
5. Yentzer, B.A., et al. (2010). Acne vulgaris in the United States: A descriptive epidemiology. Cutis 86 94-99.
6. Di Landro, A. et al. (2016). Adult female acne and associated risk factors: Results of a multicenter case-control study in Italy. J Amer Acad Derm 75 1134-1141.e1.
7. Bai, Y., Wang, Y., Zheng, H., Tan, F. and Yuan, C. (2021). Correlation between facial skin microbiota and skin barriers in a Chinese female population with sensitive skin. Infect Drug Resist 14 219-226.
8. Qiao, Z., et al. (2021). Analysis of the bacterial flora of sensitive facial skin among women in Guangzhou. Clin Cosmet Investig Dermatol 14, 655-664.
9. Keum, H.L., et al. (2020). Structures of the skin microbiome and mycobiome depending on skin sensitivity. Microorganisms 8 E1032.
10. Zheng, Y., Liang, H., Li, Z., Tang, M. and Song, L. (2020). Skin microbiome in sensitive skin: The decrease of Staphylococcus epidermidis seems to be related to female lactic acid sting test sensitive skin. J Dermatol Sci 97, 225-228.
11. Seite, S. and Misery, L. (2018). Skin sensitivity and skin microbiota: Is there a link? Exp Dermatol 27 1061-1064.
12. Del Rosso, J.Q. (2015). Oral Doxycycline in the management of Acne vulgaris: Current perspectives on clinical use and recent findings with a new double-scored small tablet formulation. J Clin Aesthetic Dermatol 8 19-26.
13. Melnik, B., Kinner, T. and Plewig, G. (1988). Influence of oral isotretinoin treatment on the composition of comedonal lipids. Implications for comedogenesis in Acne vulgaris. Arch Dermatol Res 280, 97-102.
14. Ochsendorf, F. (2006). Systemic antibiotic therapy of Acne vulgaris. JDDG J Dtsch Dermatol Ges 4 828-841.
15. AAD (accessed 2022, Apr 6). Acne clinical guideline. Available at https://www.aad.org/practicecenter/quality/clinical-guidelines/acne/systemic-antibiotics
16. Whitney, K.M. and Ditre, C.M. (2011), Management strategies for Acne vulgaris. Clin Cosmet Investig Dermatol 4, 41-53.
17. Adler, B.L., Harter, N., Park, C. and DeLeo, V. (2021). YouTube as a source of information on contact dermatitis. Dermat Contact Atopic Occup Drug 32 e43-e44.
18. Winstone, L., Mars, B., Haworth, C.M.A. and Kidger, J. (2021). Social media use and social connectedness among adolescents in the United Kingdom: A qualitative exploration of displacement and stimulation. BMC Public Health 21 1736.
19. Afshinnekoo, E., Ahsanuddin, S. and Mason, C.E. (2016). Globalizing and crowdsourcing biomedical research. Br Med Bull 120, 27-33.
20. Bates, M. (2018). Direct-to-consumer genetic testing: Is the public ready for simple, at-home DNA tests to detect disease risk? IEEE Pulse 9 11-14.
21. Del Savio, L., Prainsack, B. and Buyx, A. (2017). Motivations of participants in the citizen science of microbiomics: Data from the British Gut Project. Genet Med 19, 959-961.
22. Grieneisen, L.E. and Blekhman, R. (2018). Crowdsourcing our national gut. mSystems 3, e00060-18.
23. Abbasi, J. (2020). 23andMe develops first drug compound using consumer data. JAMA 323 916.
24. Chauhan, G., et al. (2020). Combining citizen sScience and genomics to investigate tick, pathogen and commensal microbiome at single-tick resolution. Front Genet 10 1322.
25. Hatch, A., et al. (2019). A robust metatranscriptomic technology for population-scale studies of diet, gut microbiome, and human health. Int J Genomics e1718741.
26. Klimenko, N.S., et al. (2018). Microbiome responses to an uncontrolled short-term diet intervention in the frame of the Citizen Science Project. Nutrients 10 576.
27. McDonald, D., et al. (2018). American gut: An open platform for citizen science microbiome research. mSystems 3 e00031-18.
28. Tily, H., et al. (2022). Gut microbiome activity contributes to prediction of individual variation in glycemic response in adults. Diabetes Ther 13 89-111.