PracticalDermatology

What is the microbiome?

As dermatologists, we may tend to use the term “microbiome” casually to refer to what is specifically the cutaneous or skin microbiome—just a limited swath of the vast human microbiome. While we are increasingly aware of the importance of the microbiome and its influence on health, there remains much to learn. We are still relatively early in uncovering how the microbiome influences dermatologic diseases and understanding how to potentially modulate the skin microbiome in efforts to improve skin health.

This Q&A format article is intended to navigate this complex and rapidly evolving field.

Microbial cells outnumber human cells by about 10 to one. While the microbiome has been known for some time, the significance of this vast system came to prominence in 2007 when the NIH Common Fund launched the Human Microbiome Project (HMP). In its own words, the “project sought to ascertain the influence of human-associated microbes on human development, physiology, immunity, and nutrition almost entirely unknown.”

The first phase of the HMP resulted in the development of DNA sequence datasets, along with computational tools. As a consequence of this and related study, researchers and clinicians now have improved knowledge about the microorganisms that coexist with humans. The Human Microbiome Project in 2010 published an analysis of 178 genomes from microbes that live in or on the human body. This analysis included novel genes and proteins that serve functions in human health and disease. HMP researchers have, in fact, discovered 29,693 previously undiscovered, unique proteins. This figure represents more proteins than there are estimated genes in the human genome. The HMP reference collection is expected to eventually include a total of approximately 900 microbial genomes of bacteria, viruses, and fungi.

Research has confirmed that genes and proteins unique to individual microbial strains directly modulate human health. Consider that previously unknown proteins produced by bacteria in the stomach are now implicated in gastric ulceration.

What are characteristics of the skin microbiome?

Medical science has for some time focused on the role of pathogenic microbes in causing or exacerbating skin disease. We now understand that the role of microbes is complex and that a healthy microbiota can support skin health. In fact, the skin microbiome has recently been described as a component of the epidermal barrier, playing a crucial role in protecting the body and modulating overall human health, in addition to cutaneous health.¹

Initial research from the HMP that looked at the skin identified impressive microbial diversity: more than 112,000 bacterial gene sequences belonging to 19 different phyla of bacteria and 205 different genera.

There is considerable variation in the number of bacteria species at different anatomic sites. Greatest diversity is seen on the forearm (44 species on average), and the least diversity is found behind the ear (19 species on average). Not surprisingly the type and density of bacteria differs based on the environment, where it may be dry, mucosal, or sebaceous. (Figure 1)

Figure 1

Characteristics of the skin microbiome may differ between sexes and across age groups. The healthy skin microbiota is fairly stable, and commensal organisms predominate.¹ Healthy, balanced populations of these beneficial organisms are thought to keep pathogenic species from over-proliferating.

Dysbiosis of the skin microbiome has been extensively linked to atopic dermatitis.^1-3 In fact, Kong et al serially analyzed AD patients to show that lower cutaneous bacterial diversity is associated with worsening of disease severity and that shifts in bacterial load are largely localized to sites of disease activity. Furthermore, the team found that increases in the proportion of Staphylococcus and reductions in microbial diversity preceded worsening of AD.²

A connection between the health of the skin microbiota and cutaneous health is intuitive, and there is also research suggesting links between dysbiosis and acne, psoriasis, and vitiligo. When researchers studied the microbiome of patients with acne, they found alterations in microbial diversity relative to healthy skin; the skin of severe acne patients was significantly more altered than that of those with mild to moderate disease.⁴

Does the gut microbiome affect the skin?

The gut microbiome is now thought to mediate overall health and wellness and to potentially influence a host of diseases. The critical influence of the gut microbiome is evident even in infancy, where it has been linked to conditions as diverse as obesity, inflammatory bowel disease, cancer, necrotizing enterocolitis, neurodevelopment, and asthma.⁵

There are similarities between the skin and gut as organ systems. They are both heavily vascularized and innervated, and both have neuroendocrine and immune functions. In fact, it is now thought that the two organs have a bidirectional connection; multiple studies link intestinal health to skin homeostasis and allostasis, as Lee et al recently outlined.⁶ The so-called Western diet has been shown to modulate the intestinal flora and promotes inflammation, suggesting a possible mechanism for the observed association between diet and acne.⁶

While potential connections between the gut and the skin are complex, the role for short chain fatty acids (SCFAs) to modulate a gut/skin connection warrants consideration. SCFAs are produced in the gut through the fermentation of carbohydrates. All SCFAs inhibit Histone deacetylases activity and suppress the activity of regulatory T cells (Treg) cells, thereby disrupting immunologic homeostasis.⁶

Can we modify skin health and disease by modifying the skin microbiome?

Use of specific skincare products has been shown to modify bacterial communities at the site of use. Researchers recently employed a multi-omics approach integrating metabolomics and microbiome data to assess skin samples of 11 healthy human individuals to determine the influence of certain topical products. In addition to showing that many compounds from beauty products persist on the skin for weeks following their application, the research showed that topical beauty products modify both the microbiome as well as local skin chemistry, including hormones and pheromones.⁷ These findings provide context for understanding the potential influence of topical skincare for modulating the microbiota.

Topical application of a cream containing Streptococcus thermophiles has been shown to improve AD symptoms, while a cream containing lysate of Vitroscilla filioformis led to clinical improvement of AD.⁸ Recent research in acne has shown that topical application of a bacteriocin (named ESL5) of E. faecalis SL-5 in patients with mild to moderate acne significantly reduced inflammatory lesions compared to placebo.⁹

Barrier function support is an established strategy in medical management of AD and other dermatoses. In light of new conceptualization of the skin microbiome as part of the epidermal barrier, the role of modulation of the microbiome to support barrier function warrants consideration. Topical formulations may offer ingredients, such as prebiotics to modulate growth of desirable bacteria. Additionally, long-used ingredients, such as shea butter, niacinamide, and thermal spring waters have been demonstrated to support bacterial diversity.¹

Can we modify skin health and disease by modifying the gut microbiome?

Modulation of the gut microbiome has been associated with improvements in skin diseases, and reportedly has induced remission in rosacea.¹⁰ Similarly, studies of oral probiotic supplementation to treat or prevent AD have shown promise.⁸ A nutraceutical product containing Lactobacillus spp. (L. casei, L. rhamnosus , L. plantarum ), Bacillus lactis, fructooligosaccharide, galactooligosaccharide, and biotin reportedly improved AD symptoms in a small sample of children with good safety and tolerability.¹¹

After two months of consumption of Bifidobacterium infantis, patients with psoriasis had significantly decreased measures of all proinflammatory parameters.¹¹

In one study, supplementation with Lactobacillus extract was effective in reducing skin erythema, repairing skin barrier, and reducing skin microflora, and was associated with reduction in acne lesion size and erythema. Benefit was seen with a 5%, but not 1% concentration.¹²

Importantly, in these generally small studies, the effects of supplements appear to be strain-, species-, or concentration-dependent.^8,11 We require additional studies to ascertain best practices.

What are implications for care of dermatologic disease?

The accumulating data offers tantalizing evidence that modulation of the skin or gut microbiome may have beneficial effects on skin diseases. However, it remains to be seen which strategies for modulation offer the most promise. Note that no current guidelines for care for dermatologic diseases currently endorse microbiome modulation, specifically.

Oral supplementation may be a worthwhile option for some patients with dermatologic concerns like hair loss, psoriasis, and rosacea. Each patient requires counseling regarding what is known and not known about supplementation and should be an active participant in the decision to pursue supplementation as adjunctive to standard medical interventions.

In the case of topical products, dermatologists may shift their recommendations toward products with documented or suspected effects on the skin microbiota. Some of the most commonly used topical skincare ingredients have been shown to exert effects on local microbe populations, and it appears we may have inadvertently been modulating the microbiota through use of skin care products for some time. Products that support function of both the chemical, physical, immune, and microbiome levels of the epidermal barrier may provide optimal benefit for patients.¹

For further reading: J Drug Dermatol 2017;16(1):12-18

1. Strugar TL, Kuo A, Seité S, Lin M, Lio P. Connecting the Dots: From Skin Barrier Dysfunction to Allergic Sensitization, and the Role of Moisturizers in Repairing the Skin Barrier. J Drugs Dermatol. 2019 Jun 1;18(6):581.

2. Kong HH, Oh J, Deming C, Conlan S, Grice EA, Beatson MA, Nomicos E, Polley EC, Komarow HD; NISC Comparative Sequence Program, Murray PR, Turner ML, Segre JA. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 2012 May;22(5):850-9.

3. Paller AS, Kong HH, Seed P, Naik S, Scharschmidt TC, Gallo RL, Luger T, Irvine AD. The microbiome in patients with atopic dermatitis. J Allergy Clin Immunol. 2019 Jan;143(1):26-35.

4. Li CX, You ZX, Lin YX, Liu HY, Su J. Skin microbiome differences relate to the grade of acne vulgaris. J Dermatol. 2019 Sep;46(9):787-790.

5. Schoch JJ, Monir RL, Satcher KG, Harris J, Triplett E, Neu J. The infantile cutaneous microbiome: A review. Pediatr Dermatol. 2019 Jul 23.

6. Lee YB, Byun EJ, Kim HS. Potential Role of the Microbiome in Acne: A Comprehensive Review. J Clin Med. 2019 Jul 7;8(7).

7. Yu Y, Dunaway S, Champer J, Kim J, Alikhan A. Changing our microbiome: probiotics in dermatology. Br J Dermatol. 2019 May 3.

8. Kang BS, Seo JG, Lee GS, Kim JH, Kim SY, Han YW, Kang H, Kim HO, Rhee JH, Chung MJ, Park YM. Antimicrobial activity of enterocins from Enterococcus faecalis SL-5 against Propionibacterium acnes, the causative agent in acne vulgaris, and its therapeutic effect. J Microbiol. 2009 Feb;47(1):101-9.

9. Yu Y, Dunaway S, Champer J, Kim J, Alikhan A. Changing our microbiome: probiotics in dermatology. Br J Dermatol. 2019 May 3.

10. Catinean A, Neag MA, Mitre AO, Bocsan CI, Buzoianu AD. Microbiota and Immune-Mediated Skin Diseases-An Overview. Microorganisms. 2019 Aug 21;7(9).

11. Muizzuddin N, Maher W, Sullivan M, Schnittger S, Mammone T. Physiological effect of a probiotic on skin. J Cosmet Sci. 2012 Nov-Dec;63(6):385-95.

12. Strugar TL, Kuo A, Seité S, Lin M, Lio P. Connecting the Dots: From Skin Barrier Dysfunction to Allergic Sensitization, and the Role of Moisturizers in Repairing the Skin Barrier. J Drugs Dermatol. 2019 Jun 1;18(6):581.

13. Kong HH, Oh J, Deming C, Conlan S, Grice EA, Beatson MA, Nomicos E, Polley EC, Komarow HD; NISC Comparative Sequence Program, Murray PR, Turner ML, Segre JA. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 2012 May;22(5):850-9.

14. Paller AS, Kong HH, Seed P, Naik S, Scharschmidt TC, Gallo RL, Luger T, Irvine AD. The microbiome in patients with atopic dermatitis. J Allergy Clin Immunol. 2019 Jan;143(1):26-35.

15. Li CX, You ZX, Lin YX, Liu HY, Su J. Skin microbiome differences relate to the grade of acne vulgaris. J Dermatol. 2019 Sep;46(9):787-790.

16. Schoch JJ, Monir RL, Satcher KG, Harris J, Triplett E, Neu J. The infantile cutaneous microbiome: A review. Pediatr Dermatol. 2019 Jul 23.

17. Lee YB, Byun EJ, Kim HS. Potential Role of the Microbiome in Acne: A Comprehensive Review. J Clin Med. 2019 Jul 7;8(7).

18. Yu Y, Dunaway S, Champer J, Kim J, Alikhan A. Changing our microbiome: probiotics in dermatology. Br J Dermatol. 2019 May 3.

19. Kang BS, Seo JG, Lee GS, Kim JH, Kim SY, Han YW, Kang H, Kim HO, Rhee JH, Chung MJ, Park YM. Antimicrobial activity of enterocins from Enterococcus faecalis SL-5 against Propionibacterium acnes, the causative agent in acne vulgaris, and its therapeutic effect. J Microbiol. 2009 Feb;47(1):101-9.

20. Yu Y, Dunaway S, Champer J, Kim J, Alikhan A. Changing our microbiome: probiotics in dermatology. Br J Dermatol. 2019 May 3.

21. Catinean A, Neag MA, Mitre AO, Bocsan CI, Buzoianu AD. Microbiota and Immune-Mediated Skin Diseases-An Overview. Microorganisms. 2019 Aug 21;7(9).

22. Muizzuddin N, Maher W, Sullivan M, Schnittger S, Mammone T. Physiological effect of a probiotic on skin. J Cosmet Sci. 2012 Nov-Dec;63(6):385-95.