I had the privilege of crafting a scientific literature review for Cg Magazine©, a publication by the Dutch Society of Cosmetic Medicine NVCG-SOCG. This article delves into the current scientific data on the impact of microbiomes on skin aging. Additionally, insights from my clinical practice are shared, discussing potential interventions.
This article consolidates the current body of evidence on how human microbiomes impact skin ageing and a novel concept called the skin interactome which has emerged, emphasizing the integration of the “genome-microbiome-exposome” in the ageing process.
Moreover, it explores potential interventions related to human microbiomes that can be utilized to modulate skin health and ageing.
Ageing Process
Ageing is a universal and irreversible process that occurs at the cellular and molecular levels, resulting in the deterioration of organ systems [1]. While genetic factors determine the lifespan of a species, extrinsic factors such as physical activity, diet, environment, and diseases can accelerate or delay the ageing process [2]. Mechanisms driving ageing include genetic and epigenetic alterations, accumulation of abnormal proteins, oxidative stress, mitochondrial dysfunction, and cellular senescence [3].
Figure 1: Molecular mechanism of ageing. Abbreviation: RNA; ribonucleic acid, ROS; reactive oxygen species. [41]
DNA damage, mutations, and telomere shortening occur due to oxidative stress and cell replication. Intrinsic DNA repair systems decline with age, leading to the accumulation of defects and cellular dysfunction [4]. Epigenetic phenomena, such as histone modification and DNA methylation, protect DNA and regulate gene expression [5]. Environmental pollution, an imbalanced diet, and toxic substances generated by microbiota can disrupt epigenetic factors, contributing to cellular dysfunction [5,6].
The accumulation of abnormal proteins is a key factor in age-related degenerative diseases, including dementia and Parkinson's disease. Abnormal protein synthesis or post-translational modifications due to oxidative stress and impaired proteostasis system contribute to their pathogenesis [7].
Mitochondrial dysfunction leads to the production of reactive oxygen species (ROS), causing damage to DNA and proteins, and promoting cellular aging. Pathways related to energy and nutrient metabolism, such as insulin signalling, the TOR pathway, and sirtuin activity, influence gene expression, protein modification, and mitochondrial function, emphasizing the role of dietary patterns and caloric intake in ageing [3, 8].
Cellular senescence, characterized by permanent cell cycle arrest, naturally occurs with ageing due to the absence of telomerase enzyme. However, DNA damage and oxidative stress accelerate cellular senescence. Senescent cells not only lose their regenerative capacity but also contribute to chronic inflammation through the release of proinflammatory cytokines [9].
Skin Ageing and Gut Microbiome
As individuals age, the gut microbiota undergoes significant changes, including a decline in microbial diversity and altered composition [44]. Microbiome composition has been linked to the rate of ageing, with certain bacterial species associated with longevity [10,11,13]. The gut microbiota of centenarians exhibits a distinct composition compared to other age groups, with a higher abundance of beneficial bacteria and increased diversity [13,14]. However, conflicting findings exist, and it is suggested that microbiota differences may be influenced by overall health status rather than solely by ageing [12,13]. Dysbiosis in the gut microbiota with age can contribute to inflammation, frailty, and compromised health [12,15].
The gut microbiota produces bioactive metabolites, including short-chain fatty acids (SCFAs) like butyrate, propionate, and acetate, which have anti-inflammatory and immunomodulatory effects [16,17,18,19]. Age-related dysbiosis, characterized by changes in the Firmicutes-to-Bacteroidetes (F/B) ratio, can impact SCFA production and contribute to ageing, inflammation, and frailty [20,21]. Dysbiosis has also been associated with cellular senescence and the senescence-associated secretory phenotype (SASP), implicating microbial dysbiosis in senescence processes [22]. Prebiotics and probiotics show promise in preventing pathological conditions in the elderly by reducing chronic inflammation and enhancing immune responses [23,24].
Gut dysbiosis in ageing individuals can lead to increased intestinal permeability, allowing pro-inflammatory microbial products to enter the bloodstream and contribute to systemic effects [15]. Microbial metabolites promote SASP damage and upregulate inflammatory molecules, resulting in chronic inflammation or inflammaging [15]. This dysbiosis-induced inflammaging and compromised immune surveillance can impair the removal of senescent cells, further contributing to the ageing process [15].
The human microbiome, which undergoes dynamic changes throughout life, plays a bidirectional role in health and disease. Alterations in microbiome composition, such as a high proportion of Bacteroides and low biological diversity, have been associated with decreased survival in older adults [10, 11].
Figure 2: Age-related intestinal dysbiosis [41]
Possible Interventions to Modulate Skin Health and Aging
The skin interactome, consisting of the genome, microbiome, and exposome, plays a significant role in skin aging and health [29].
Probiotics, specifically Lactobacillus and Bifidobacterium strains, have shown promise in mitigating signs of skin aging such as pH imbalance, oxidative stress, photodamage, and impaired skin barrier function [26]. Examples include Bifidobacterium breve strain YaKult, which protects the skin from UV-induced damage and oxidative stress [30], Lactobacillus plantarum, which inhibits MMP-1 expression and prevents UV-induced photoaging [31], and Lactobacillus reuteri DSM 17,938, which secretes lactic acid to suppress pro-inflammatory cytokines and protect against UVB damage [32]. Clinical trials have demonstrated that daily intake of Lactobacillus plantarum HY7714 improves skin hydration, elasticity, gloss, and reduces wrinkles [28]. The exopolysaccharide (EPS) produced by Lactobacillus plantarum HY7714 regulates the gut-skin axis and affects dermal cell properties [27]. Probiotics may restore the balance between free radicals and scavengers.
Combining probiotics and prebiotics can benefit skin health by increasing hydration, enhancing keratinocyte differentiation, and reducing phenol production [33]. In a trial involving Japanese women, the daily intake of Bifidobacterium breve strain Yakult and galacto-oligosaccharides (GOS) improved skin hydration, cathepsin L-like activity, and decreased phenol levels [33].
Skincare formulations incorporating prebiotics, probiotics, or microbiome-friendly ingredients are gaining interest. Hylocereus undatus fruit extract, rich in antioxidants, may impact the skin microbiome balance [34]. Topical formulations containing bacterial extracts, including various Lactobacillus strains, have been studied for their effects on the skin microbiota [25]. A range of interventions targeting the skin microbiota in ageing has been summarized [25].
Emerging evidence suggests that age-related epigenetic changes can be targeted for future interventions [35,36]. Manipulating epigenomic pathways has the potential to reverse the epigenetic abnormalities associated with ageing [37]. Microbiome analyses and genetic ageing tests, some of which are currently available commercially, can provide valuable information about an individual's ageing status, guiding clinicians in determining appropriate interventions [38,39]. Similar to drugs targeting the microbiome, there are commercially available drugs targeting epigenetic enzymes, with others being investigated in clinical trials. However, large confirmatory trials and long-term effectiveness studies are still needed [37].
Figure 3: Possible microbiome-targeted intervention to prevent skin aging [41]
How to find out more about your gut health?
I work with the metagenomic shotgun/ whole genome sequencing to assess my patient's complete gut microbiome as well as its potential function. Metagenomics is considered the gold standard method to study the gut microbiota. [40]
This gut test detects bacteria, fungi, protists, and archaea amounting to over 28,000 species. Each person's microbiome contains over 200 species, all listed in the personalized report.
Includes identification of species that may confer pathogenic potential, such as Bacteroides fragilis and the fragilysin toxin;
It assesses all methane-producing organisms, including Methanobrevibacter smithii;
It assesses the genetic potential to form unique metabolites such as hexa-LPS, TMA, histamine, vitamin production, branched-chain amino acids, urease, GABA, hydrogen sulfide and many others
Many metabolites can be transported across the intestinal barrier and into the body's circulation.
Figure 4: Overview of results obtained from GI EffectsTM Comprehensive Stool profile.
Gut 5R Framework
In my clinical practice, I employ the Gut "5R" framework, meticulously clinically designed, which aims at tackling an array of gastrointestinal ailments and imbalances within the gut microbiota. Utilizing a comprehensive assessment of the patient's gut microbiome composition and overall gut health, I employ this compounds reference table to discern the appropriate nutraceutical or herbal formulation tailored to address specific conditions.
Nonetheless, it is imperative to emphasize that dietary choices and lifestyle modifications constitute the fundamental pillars of this framework. While these compounds have undergone rigorous research and demonstrated efficacy, it is crucial to consider the individualized nature of each patient's circumstances, as numerous factors must be considered and factored into the treatment approach.
#GutMicrobiota #SkinInteractome #ProbioticsForSkin #PrebioticsAndSkin #EpigeneticsAndAging #SkinCareScience #MicrobiomeInterventions #HealthyAging
#GutHealth #MetagenomicSequencing #SkinMicrobiota #DietAndAging #NutritionForSkinHealth #Inflammaging #Gut5RFramework
References
1. Britannica E. Old Age. 2018. [(accessed on 19 March 2022)]. Available online: https://www.britannica.com/science/old-age
2. Lemoine M. The Evolution of the Hallmarks of Aging. Front. Genet. 2021;12:1511. doi: 10.3389/fgene.2021.693071.[PMC free article] [PubMed] [CrossRef] [Google Scholar]
3. Pyo I.S., Yun S., Yoon Y.E., Choi J.-W., Lee S.-J. Mechanisms of Aging and the Preventive Effects of Resveratrol on Age-Related Diseases. Molecules. 2020;25:4649. doi: 10.3390/molecules25204649. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
4. Lord C.J., Ashworth A. The DNA damage response and cancer therapy. Nature. 2012;481:287–294. doi: 10.1038/nature10760. [PubMed] [CrossRef] [Google Scholar]
5. López-Otín C., Blasco M.A., Partridge L., Serrano M., Kroemer G. The Hallmarks of Aging. Cell. 2013;153:1194–1217. doi: 10.1016/j.cell.2013.05.039. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
6. Rider C.F., Carlsten C. Air pollution and DNA methylation: Effects of exposure in humans. Clin. Epigenet. 2019;11:1–15. doi: 10.1186/s13148-019-0713-2. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
7. Yu G., Hyun S. Proteostasis-associated aging: Lessons from a Drosophila model. Genes Genom. 2020;43:1–9. doi: 10.1007/s13258-020-01012-9. [PubMed] [CrossRef] [Google Scholar]
8. Giorgi C., Marchi S., Simoes I.C., Ren Z., Morciano G., Perrone M., Patalas-Krawczyk P., Borchard S., Jędrak P., Pierzynowska K., et al. Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases. Int. Rev. Cell Mol. Biol. 2018;340:209–344. doi: 10.1016/bs.ircmb.2018.05.006. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
9. Di Micco R., Krizhanovsky V., Baker D., di Fagagna F.D. Cellular senescence in ageing: From mechanisms to therapeutic opportunities. Nat. Rev. Mol. Cell Biol. 2020;22:75–95. doi: 10.1038/s41580-020-00314-w. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
10. Candela M., Biagi E., Brigidi P., O’Toole P., De Vos W.M. Maintenance of a healthy trajectory of the intestinal microbiome during aging: A dietary approach. Mech. Ageing Dev. 2014;136:70–75. doi: 10.1016/j.mad.2013.12.004.[PubMed] [CrossRef] [Google Scholar]
11. Saraswati S., Sitaraman R. Aging and the human gut microbiota—From correlation to causality. Front. Microbiol. 2015;5:764. doi: 10.3389/fmicb.2014.00764. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
12. Claesson M.J., Jeffery I.B., Conde S., Power S.E., O’Connor E.M., Cusack S., Harris H.M.B., Coakley M., Lakshminarayanan B., O’Sullivan O., et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488:178–184. doi: 10.1038/nature11319. [PubMed] [CrossRef] [Google Scholar]
13. O’Toole P.W., Jeffery I.B. Gut microbiota and aging. Science. 2015;350:1214–1215. doi: 10.1126/science.aac8469.[PubMed] [CrossRef] [Google Scholar]
14. Kim B.-S., Choi C.W., Shin H., Jin S.-P., Bae J.-S., Han M., Seo E.Y., Chun J., Chung J.H. Comparison of the Gut Microbiota of Centenarians in Longevity Villages of South Korea with Those of Other Age Groups. J. Microbiol. Biotechnol. 2019;29:429–440. doi: 10.4014/jmb.1811.11023. [PubMed] [CrossRef] [Google Scholar]
15. Biragyn A., Ferrucci L. Gut dysbiosis: A potential link between increased cancer risk in ageing and inflammaging. Lancet Oncol. 2018;19:e295–e304. doi: 10.1016/S1470-2045(18)30095-0. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
16. Krautkramer K.A., Fan J., Bäckhed F. Gut microbial metabolites as multi-kingdom intermediates. Nat. Rev. Genet. 2020;19:77–94. doi: 10.1038/s41579-020-0438-4. [PubMed] [CrossRef] [Google Scholar]
17. Maslowski K.M., Vieira A.T., Ng A., Kranich J., Sierro F., Yu D., Schilter H.C., Rolph M.S., Mackay F., Artis D., et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461:1282–1286. doi: 10.1038/nature08530. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
18. Keenan M.J., Marco M.L., Ingram D.K., Martin R.J. Improving healthspan via changes in gut microbiota and fermentation. AGE. 2015;37:1–10. doi: 10.1007/s11357-015-9817-6. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
19. Rivière A., Selak M., Lantin D., Leroy F., De Vuyst L. Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut. Front. Microbiol. 2016;7:979. doi: 10.3389/fmicb.2016.00979. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
20. Vaiserman A., Romanenko M., Piven L., Moseiko V., Lushchak O., Kryzhanovska N., Guryanov V., Koliada A. Differences in the gut Firmicutes to Bacteroidetes ratio across age groups in healthy Ukrainian population. BMC Microbiol. 2020;20:1–8. doi: 10.1186/s12866-020-01903-7. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
21. Fernandes J.J.D.R., Su W., Rahat-Rozenbloom S., Wolever T.M.S., Comelli E. Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans. Nutr. Diabetes. 2014;4:e121. doi: 10.1038/nutd.2014.23. [PMC free article][PubMed] [CrossRef] [Google Scholar]
22. Saccon T.D., Nagpal R., Yadav H., Cavalcante M.B., Nunes A.D.D.C., Schneider A., Gesing A., Hughes B., Yousefzadeh M., Tchkonia T., et al. Senolytic Combination of Dasatinib and Quercetin Alleviates Intestinal Senescence and Inflammation and Modulates the Gut Microbiome in Aged Mice. J. Gerontol. Ser. A. 2021;76:1895–1905. doi: 10.1093/gerona/glab002.[PMC free article] [PubMed] [CrossRef] [Google Scholar]
23. Martínez G.P., Bäuerl C., Collado M. Understanding gut microbiota in elderly’s health will enable intervention through probiotics. Benef. Microbes. 2014;5:235–246. doi: 10.3920/BM2013.0079. [PubMed] [CrossRef] [Google Scholar]
24. Lowry C.A., Smith D.G., Siebler P.H., Schmidt D., Stamper C.E., Hassell J.E., Yamashita P.S., Fox J.H., Reber S.O., Brenner L.A., et al. The Microbiota, Immunoregulation, and Mental Health: Implications for Public Health. Curr. Environ. Heal. Rep. 2016;3:270–286. doi: 10.1007/s40572-016-0100-5. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
25. Boxberger M., Cenizo V., Cassir N., La Scola B. Challenges in exploring and manipulating the human skin microbiome. Microbiome. 2021;9:1–14. doi: 10.1186/s40168-021-01062-5. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
26. Sharma D., Kober M.-M., Bowe W.P. Anti-Aging Effects of Probiotics. J. Drugs Dermatol. 2016;15:9–12. [PubMed] [Google Scholar]
27. Lee K., Kim H., Kim S., Park S.-D., Shim J.-J., Lee J.-L. Exopolysaccharide from Lactobacillus plantarum HY7714 Protects against Skin Aging through Skin–Gut Axis Communication. Molecules. 2021;26:1651. doi: 10.3390/molecules26061651. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
28. Lee D.E., Huh C.-S., Ra J., Choi I.-D., Jeong J.-W., Kim S.-H., Ryu J.H., Seo Y.K., Koh J.S., Lee J.-H., et al. Clinical Evidence of Effects of Lactobacillus plantarum HY7714 on Skin Aging: A Randomized, Double Blind, Placebo-Controlled Study. J. Microbiol. Biotechnol. 2015;25:2160–2168. doi: 10.4014/jmb.1509.09021. [PubMed] [CrossRef] [Google Scholar]
29. Khmaladze I., Leonardi M., Fabre S., Messaraa C., Mavon A. The Skin Interactome: A Holistic “Genome-Microbiome-Exposome” Approach to Understand and Modulate Skin Health and Aging. Clin. Cosmet. Investig. Dermatol. 2020;13:1021–1040. doi: 10.2147/CCID.S239367. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
30. Ishii Y., Sugimoto S., Izawa N., Sone T., Chiba K., Miyazaki K. Oral administration of Bifidobacterium breve attenuates UV-induced barrier perturbation and oxidative stress in hairless mice skin. Arch. Dermatol. Res. 2014;306:467–473. doi: 10.1007/s00403-014-1441-2. [PubMed] [CrossRef] [Google Scholar]
31. Kim H.M., Lee D.E., Park S.D., Kim Y.-T., Kim Y.J., Jeong J.W., Jang S.S., Ahn Y.-T., Sim J.-H., Huh C.-S., et al. Oral Administration of Lactobacillus plantarum HY7714 Protects Hairless Mouse Against Ultraviolet B-Induced Photoaging. J. Microbiol. Biotechnol. 2014;24:1583–1591. doi: 10.4014/jmb.1406.06038. [PubMed] [CrossRef] [Google Scholar]
32. Khmaladze I., Butler É., Fabre S., Gillbro J.M. Lactobacillus reuteri DSM 17938—A comparative study on the effect of probiotics and lysates on human skin. Exp. Dermatol. 2019;28:822–828. doi: 10.1111/exd.13950. [PubMed] [CrossRef] [Google Scholar]
33. Mitsuyoshi K., Masuoka N., Chiaki K., Sugimoto S., Iizuka R., Manabe K., Toshiro S., Kazutoshi O., Nonaka C., Miyazaki K., et al. Consecutive intake of fermented milk containing Bifidobacterium breve strain yakult and galacto-oligosaccharides benefits skin condition in healthy adult women. Biosci. Microbiot. Food Health. 2013;32:33–39. [PMC free article] [PubMed] [Google Scholar]
34. Som A., Ahmat N., Hamid H.A.A., Azizuddin N. A comparative study on foliage and peels of Hylocereus undatus (white dragon fruit) regarding their antioxidant activity and phenolic content. Heliyon. 2019;5:e01244. doi: 10.1016/j.heliyon.2019.e01244. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
35. Pagiatakis C., Musolino E., Gornati R., Bernardini G., Papait R. Epigenetics of aging and disease: A brief overview. Aging. 2019;33:737–745. doi: 10.1007/s40520-019-01430-0. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
36. Saul D., Kosinsky R.L. Epigenetics of Aging and Aging-Associated Diseases. Int. J. Mol. Sci. 2021;22:401. doi: 10.3390/ijms22010401. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
37. Heerboth S., Lapinska K., Snyder N., Leary M., Rollinson S., Sarkar S. Use of Epigenetic Drugs in Disease: An Overview. Genet. Epigenet. 2014;6:GEG.S12270. doi: 10.4137/GEG.S12270. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
38. Zhang J., Fu H., Xu Y. Age Prediction of Human Based on DNA Methylation by Blood Tissues. Genes. 2021;12:870. doi: 10.3390/genes12060870. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
39. Ratiner K., Abdeen S.K., Goldenberg K., Elinav E. Utilization of Host and Microbiome Features in Determination of Biological Aging. Microorganisms. 2022;10:668. doi: 10.3390/microorganisms10030668. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
40. Amrane, Sophie & Hocquart, Marie & Afouda, Pamela & Kuete, Edmond & Pham, Thi Phuong Thao & Niokhor, Dione & Ngom, Issa & Valles, Camille & Bachar, Dipankar & Raoult, Didier & Lagier, Jean-Christophe. (2019). Metagenomic and culturomic analysis of gut microbiota dysbiosis during Clostridium difficile infection. Scientific Reports. 9. 10.1038/s41598-019-49189-8.
41. Ratanapokasatit, Y., Laisuan, W., Rattananukrom, T., Petchlorlian, A., Thaipisuttikul, I., & Sompornrattanaphan, M. (2022). How Microbiomes Affect Skin Aging: The Updated Evidence and Current Perspectives. Life (Basel, Switzerland), 12(7), 936. https://doi.org/10.3390/life12070936
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