Bacteriophages are the most numerous entities on the planet. From high in the sky to the bottom of the ocean, phages are everywhere. (1) Phages surround us — in the air, water, and soil. As such, it should be no surprise that we have phages throughout our bodies as essential microbiome members.

Your microbial “other half”

You have probably heard about the human microbiome – the collection of bacteria, fungi, archaea, and viruses that call your body home. Influenced by a person’s genetics, age, environment, and lifestyle, everyone has a bustling microbiome with billions of microbes. These microorganisms inhabit the entire body, including the digestive system (mouth, stomach, intestines), the respiratory tract (nose, lungs), eyes, ears, blood, skin, and more. In total, it is estimated that nearly HALF of the cells in your body are not human; microbes are the other half of you. (2,3)

The skin as an ecosystem

The skin’s primary function is to act as a physical barrier from the outside world. In addition to keeping water in and harmful substances out, the skin is also a complex ecosystem with microbial life across its entirety, including individuals from 200 genera from 19 different phyla. (5)

A mixture of microbes occupies the skin, creating a patchwork quilt of diverse microbial populations that wraps the body’s surface. The largest organ with nearly 25 square meters of surface area, the skin is a vast and varied environment for microbes to occupy. The outermost stratum corneum is decorated with appendage structures, such as hair follicles, sebaceous glands, and sweat glands, that can all provide refuge for your microbiota.

The types of microbes on the skin vary depending on the area’s unique characteristics or biogeography. (4,5) For example, sebum-rich areas of the forehead harbor oil -loving Cutibacterium and Staphylococcus bacterial species and Malassezia fungus. Proteobacteria and Flavobacteriales prefer dry areas (such as the inner forearm or palm), while Corynebacterium and some Staphylococcus species live in moist environments (armpits and nostrils). Interestingly, dry sites generally have the widest diversity of microorganisms. Sebaceous sites on the face tend to be very stable, while the hands and feet seem to have the most dynamic microbial populations. Each diverse microenvironment on the skin provides its microbial constituents with conditions to thrive. 

Getting to know the “virome”

While bacteria tend to get the most attention, viruses are also a significant component of the human microbiota, known as the “virome”. (6) Over the past decade or so, the methods to detect viruses have advanced, facilitating the characterization of the human virome. Viruses seem to inhabit every location on the body, from the cerebrospinal fluid surrounding the brain to the skin’s surface. (3)

Remarkably, very few viruses found throughout the human body can infect human cells (less than 10%). (7) Instead, the human virome is dominated by phages, the prokaryotic viruses that infect bacteria and other nonhuman cells.

Caudovirales (tailed phages) are most common on the skin, accounting for over 50% of viruses, and Microviridae (non­tailed phages) are also numerous. (3,6,9) A core collection of phages is nearly universal on the skin, including phages targeting Propionibacterium, Staphylococcus, and Streptococcus. (9)

What do phages want from us?

Our body serves as a “hunting ground” where phages prey on their preferred strains of bacteria. Researchers have found that phages are distributed on the skin based on the bacteria in each environment. (6,9) For example, the phages that target Cutibacterium (previously known as Propionibacterium) are significantly more abundant at the sebaceous sites that Cutibacterium bacteria love. (6) 

What’s more, phages help to shape microbial communities through their predation. (6,10,11) Scientists have discovered an inverse relationship between phages and bacteria, meaning that the more Cutibacterium-targeting phages at a location, the fewer Cutibacterium bacteria there. (9) This naturally occurring antagonism between the lytic phages and their host bacteria demonstrates the phages’ ability to impact the skin’s microbial content.

More than microbial hitchhikers

A growing body of scientific evidence supports the microbiome as a fundamental component of human health. A balanced, healthy microbiome contributes to overall wellness. For example, the cutaneous microbiota helps contribute to the skin’s natural processes and characteristics. Specifically, metabolically active microbes secrete enzymes necessary for desquamation and stratum corneum renewal. The microorganisms also produce free fatty acids that help maintain the skin’s pH. Additionally, the skin microbiome has been found to interface with our immune system to promote pathogen defense, control inflammation, and train adaptive immunity.

A balancing act

The microbes on our skin form intricate communities that promote and preserve diversity. Various mechanisms are in place to ensure that no species dominate the others.

In cases of infection or other skin disorders, some resident microbes can become pathogenic and contribute to excessive inflammation, tissue damage, and other painful symptoms. This dysbiosis plays a role in several cutaneous disorders, including acne, atopic dermatitis (eczema), psoriasis, rosacea, dandruff, and chronic wounds.

Here we explore examples of dysbiosis, highlighting the intricate interactions that are fundamental for the stability of the microbiome.

Act I: Blemished skin lacking some phages

While Cutibacterium acnes is a predominant resident species on all skin, blemish-prone skin is often overpopulated with “acneic” C. acnes strains that drive excessive production of immune-stimulating molecules (such as porphyrin compounds associated with acne severity). (13-15) In parallel, active lytic C. acnes phages are sometimes diminished on acne patients’ skin. (16) Notably, reintroducing C. acnes-targeting bacteriophages can help to reestablish homeostasis and reduce the appearance of blemishes on acne-prone skin. The C. acnes population also seems to be maintained through competitive interactions with S. epidermidis in sebaceous areas. Stable communities containing both C. acnes and S. epidermidis contribute to healthy skin with imbalances of strain diversity and relative abundance in blemished skin. (17) Taken together, C. acnes interactions illustrate the complexity of the microbiome crosstalk and its impact on skin health.

Act II: Psoriasis associated with depleted phages

Studies of psoriatic skin demonstrate the strong ties between the phage and bacterial communities on the skin. For example, scientists found that psoriatic skin has lower levels of the phages that target Acinetobacter and Pseudomonas compared to healthy skin of the same individual or other people without psoriasis. (12) Most notably, skin with fewer phages has concurrent blossoms of host bacteria with an overall loss of microbial diversity. These findings reinforce the link between a balanced microbiome and healthy skin.

References

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