How Does the Microbiome Control Our Skin's Genes?
Bacteria may influence our genetics
The microbiome is the collection of microorganisms (bacteria, fungi, viruses) and their metabolic byproducts that live within and on our bodies. There are different microbiomes associated with different parts of the body, including the respiratory system, the digestive system, the reproductive system, and the skin. The types and numbers of organisms present in the microbiome change with our age, our nutrition, our health, and with additional environmental factors (weather and pets). The skin microbiome is composed of many different organisms and varies from person to person. It also varies by different sites on the body. For example, the moist regions of the body (armpits and bottom of the feet) have different types of bacteria compared to the dry regions of the body (forearms and palms of the hands). Most of these organisms pose little harm to us and live in harmony within and on humans. But the microbiome does more for us than we realize, and one question is how it affects our skin’s genes.
The naturally occurring bacteria in our microbiome often prevent the overgrowth of other bad bacteria, preventing infection from developing. Studies have shown that these curious creatures impact our own inner workings in different ways, altering our immune systems or development.[2,4] Several skin conditions are associated with changes in the skin microbiome. The most notable are atopic dermatitis, acne, and psoriasis. But how do bacteria, fungi, and viruses do this? They alter the way our cells read our skin’s genes through a process called epigenetics. Several skin diseases appear to have an interaction between the microbiome and epigenetics.
What Is Epigenetics?
DNA is the building block that contains our genes passed down to us from our parents. Scientists thought that the sequence of our DNA was the only factor in determining who we are. But research has shown that our body actually modifies the expression of our DNA. There are 3 major ways our bodies do this: methylation, chromatin modification, and noncoding RNAs.
- Methylation turns genes off by adding methyl groups, and demethylation (removing the methyl groups) turns genes on.
- Chromatin is the large package that contains the DNA in each and every cell in the body. Within chromatin are histones, which are large proteins that can spool and wrap DNA. Once DNA wraps around a histone, many histones come together to create a tight package considered chromatin. Chromatin modification usually involves adding or subtracting groups to and from the histones. Modifying the histones makes the package easier or harder to open, making DNA more or less accessible to be read and translated.
- Noncoding RNAs are small pieces of DNA that can cover up and hide parts of DNA to turn the skin’s genes off or make genes more visible to turn them on.
All of these changes in DNA expression are collectively called epigenetics. How our cells know when and which of the skin’s genes should be turned on or off is still under investigation. Our internal genetic programming and certain external environmental factors play a role in the way our microbiome and epigenetics are influenced.
Acne and Propionibacterium acnes
There are four causes of acne: excessive skin cell development, overproduction of sebum (a product from oil glands), the bacterium Propionibacterium acnes, and inflammation. Propionibacterium acnes is present in the pores of the majority of people but can lead to inflammation in some. This bacterium has been shown to produce short-chain fatty acids (SCFAs). The SCFAs inhibit enzymes within skin cells that are responsible for making chromatin less accessible by removing acetyl groups (HDAC8 and HDAC9), thereby turning genes off. This results in a double negative, where the SCFAs turn off the “off-switch.” What results is an increase in inflammation where the skin cell receptors that detect bad bacteria, called toll-like receptor (TLR2 and TLR3), are overstimulated. Once TLR2 is stimulated, it creates a domino effect to eventually produce signals of inflammation.
Our microbiome even helps prevent the development of acne with a common skin bacterium, Staphylococcus epidermidis. One study found that this organism produced a specific type of noncoding RNA called miR-143 that stopped the production of TLR2, one of the skin cell receptors that causes inflammation. It did this by preventing the code for this protein from being read to create the complete receptor. So Staphylococcus epidermidis prevents Propionibacterium acnes from causing inflammation. When it comes to the microbiome and epigenetics, our microbiome can both cause and prevent acne depending upon the bacterium present.
Seborrheic Dermatitis and Malassezia
Seborrheic dermatitis is a very common condition and affects people in very different ways. Some people have very severe reactions, resulting in significant reddening and flaking of parts of their face, while others may only experience minor dandruff. We know that seborrheic dermatitis is associated with the yeast species, Malassezia, and the inflammation caused by its presence. Malassezia is a type of yeast that exists on the majority of people’s skin. But in certain people, it can cause problems. There is still ongoing debate regarding the absolute cause of seborrheic dermatitis, but the yeast is a major factor. Malassezia causes problems on the skin like plugging up pores and breaking down oils into inflammation, inducing chemicals, but the yeast definitely affects our genes to produce inflammation.
One of the specific types of fungus, Malassezia furfur (M. furfur), has been shown in research studies to stimulate HBD-2, a compound that combats microorganisms and a known component of our immune system. In one study, M. furfur was shown to increase the production of HBD-2 through the increased expression of its genes within skin cells. The presence of M. furfur on skin cells increased the levels of an enzyme, LSD1, which modifies histones. Histones are proteins that package DNA. DNA that is tightly packed by histones cannot be read. However, LSD1 modifies the histones holding the HBD-2 genes and causes them to open up that portion of the DNA so that the HBD-2 proteins can be made from the DNA.
Atopic Dermatitis (Eczema) and Staphylococcus Aureus
Staphylococcus is a commonly found group of bacteria, but people with eczema have abnormal amounts of some of the species within the Staphylococcus group. In 90% of patients with chronic eczema, their skin is inhabited by Staphylococcus aureus (S. aureus). This is very different from the 5% of people without eczema that has S. aureus on their skin. It is not yet known if S. aureus is a contributing cause of eczema or if the bacterium is present in the lesions of patients because of eczema. We do know from a study in skin cells outside the body, however, that S. aureus increases the reading of the gene for IL-17, an inflammation signal known to be associated with eczema. It does this by stimulating a receptor inside cells called NOD2 that then moves to the DNA and tells the cell to read the IL-17 gene. This turns on the gene and causes inflammation. S. aureus has been shown to alter our DNA through chromatin modification and noncoding RNAs in different cell types. Research will be needed to determine if S. aureus can do the same in skin cells and impact eczema.
Many more conditions are related to the microbiome, and the relationship between our microbiome and us is becoming clearer with time. Although we know that microscopic organisms have the ability to impact our skin’s genes through epigenetics, the question remains whether these possible interactions between the microbiome and epigenetics are the cause or just the result of a disease. And if they are the cause, perhaps there are ways we can change the way that our skin’s genes are read and the course of the disease by changing our microbiome. With so many organisms in our skin microbiome, there is still much to uncover.
- Zeeuwen PL, Kleerebezem M, Timmerman HM, et al. Microbiome and skin diseases. Curr Opin Allergy Clin Immunol.2013;13(5):514-520; PMID: 23974680 Link to research.
- Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol.2011;9(4):244-253; PMID: 21407241 Link to research.
- Wanke I, Steffen H, Christ C, et al. Skin commensals amplify the innate immune response to pathogens by activation of distinct signaling pathways. J Invest Dermatol.2011;131(2):382-390; PMID: 21048787 Link to research.
- Li K, Bihan M, Yooseph S, et al. Analyses of the microbial diversity across the human microbiome. PLoS One.2012;7(6):e32118; PMID: 22719823 Link to research.
- Lu Q. The critical importance of epigenetics in autoimmunity. J Autoimmun.2013;41:1-5; PMID: 23375849 Link to research.
- Sanford JA, Zhang LJ, Williams MR, et al. Inhibition of HDAC8 and HDAC9 by microbial short-chain fatty acids breaks immune tolerance of the epidermis to TLR ligands. Sci Immunol.2016;1(4)PMID: 28783689 Link to research.
- Skabytska Y, Biedermann T. Staphylococcus epidermidis Sets Things Right Again. J Invest Dermatol.2016;136(3):559-560; PMID: 26902125 Link to research.
- Dessinioti C, Katsambas A. Seborrheic dermatitis: etiology, risk factors, and treatments: facts and controversies. Clin Dermatol.2013;31(4):343-351; PMID: 23806151 Link to research.
- Borda LJ, Wikramanayake TC. Seborrheic Dermatitis and Dandruff: A Comprehensive Review. J Clin Investig Dermatol.2015;3(2)PMID: 27148560 Link to research.
- Donnarumma G, Paoletti I, Buommino E, et al. Malassezia furfur induces the expression of beta-defensin-2 in human keratinocytes in a protein kinase C-dependent manner. Arch Dermatol Res.2004;295(11):474-481; PMID: 14963722 Link to research.
- Angrisano T, Pero R, Paoletti I, et al. Epigenetic regulation of IL-8 and beta-defensin genes in human keratinocytes in response to Malassezia furfur. J Invest Dermatol.2013;133(8):2101-2104; PMID: 23519334 Link to research.
- Powers CE, McShane DB, Gilligan PH, et al. Microbiome and pediatric atopic dermatitis. J Dermatol.2015;42(12):1137-1142; PMID: 26388516 Link to research.
- Roth SA, Simanski M, Rademacher F, et al. The pattern recognition receptor NOD2 mediates Staphylococcus aureus-induced IL-17C expression in keratinocytes. J Invest Dermatol.2014;134(2):374-380; PMID: 23892590 Link to research.
- Modak R, Das Mitra S, Vasudevan M, et al. Epigenetic response in mice mastitis: Role of histone H3 acetylation and microRNA(s) in the regulation of host inflammatory gene expression during Staphylococcus aureus infection. Clin Epigenetics.2014;6(1):12; PMID: 25075227 Link to research.