“HAVE you been bitten?”, an older woman asks me, gesturing to my spotty temple. It isn’t the first time this has happened. Normally, I go along with it to save enquirers the embarrassment, but today I have had enough. “It’s acne,” I tell her. Clearly uncomfortable, she reassures me it makes me look younger, presumably based on the notion that only teenagers have acne. Perhaps a passer-by in the street sees my pimples and pegs me at a youthful 17, rather than my actual 32 years. There’s a silver lining.
Acne affects to some degree, often arising during puberty. As a teenager with blemish-free skin, I assumed I had escaped the danger zone relatively unscathed – since I didn’t have acne during my adolescence, surely my adult years were safe? My breakouts, however, took hold in my mid-20s, and I am not alone. It turns out acne can strike at any age.
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Hormones undoubtedly play a part, but they are far from the only culprit: diet, lifestyle and genetics have been implicated too. There is one offender, however, whose contribution to acne has long been suspected, but has proved difficult to pin down. I am talking about our microbiome – microbes that reside in our gut, on our skin and in our hair follicles.
Now, a flurry of new evidence and a leap in the technology that lets us study this microscopic community have led to a shift in our understanding of acne. For the first time, we can actually see what is happening on our skin during a breakout, and these insights are offering up targets for much-needed new treatments.
Teenage acne
Some people consider adult and teenage acne to be separate conditions. Teenage acne primarily affects the forehead, nose and chin, also known as the T-zone. Adult acne, meanwhile, is more likely to cause spots – particularly pus-filled whiteheads – on the lower chin, jaw and neck. But beyond the spots’ locations, there isn’t good evidence to support adult and teenage acne being all that different, says at Pennsylvania State University.
Whatever age someone develops acne, it can affect their quality of life. Acne has been linked to , particularly among those . It also varies between individuals. “You can have two pimples and think you have acne; you can have two pimples and think you don’t have acne,” says at Harvard Medical School. This makes it difficult to define or measure, he says. Adding to the problem is that what we consider to be “normal” skin may have shifted over time. These days, “everyone feels like they need to be a movie star, with the Instagram filters and whatnot”, says Barbieri.
What causes acne?
Regardless of your beauty standards, most people have seen a spot on their face and wondered what caused it. The main issue is the overproduction of sebum, an oily substance that keeps skin hydrated, but can also clog pores. This acts as food for a bacterium called Cutibacterium acnes, which is abundant in our hair follicles and can to cause inflammation in the skin, erupting as acne.
“They all feed off each other,” says Nelson. “The sebum uptick causes more of an inflammatory response in the follicle. So, the follicle closes off, which leads to a build-up of sebum, which causes more inflammation, so C. acnes increases, which feeds off the sebum, which causes more irritation.”
Also involved are skin cells called keratinocytes, which can clog the skin’s pores. Keratinocytes make up the vast majority of our skin, helping to protect against invasion by microbes and keeping the skin hydrated. But in acne, they start to divide abnormally and shed more rapidly, which could be a cause or consequence of inflammation.
Hormone levels
What we don’t know is what drives the initial shift to more sebum production, especially in adults. “Why it happens is an uncertain question,” says Barbieri. “It probably has to do with hormones, as they make us develop acne in our teenage years.” These include higher levels of the hormones (IGF-1) and androgens, which may boost our production of sebum. than men, with fluctuating hormone levels often causing breakouts during pregnancy or at different stages of the menstrual cycle.
Our genetics also plays a part, with , even if my parents say they never experienced acne. and 100 genetic variants are implicated in people with Asian and European ancestry, with the main culprits seeming to be the TNF gene, which influences our inflammatory responses, and the CYP17A1 and FST genes, which affect our sebum-producing glands.
When it comes to our lifestyle, . Feeling frazzled has been linked to the increased release of hormones such as glucocorticoids and adrenal androgens, which can worsen acne, possibly by inducing increased sebum production. However, reaching for chocolate or carbs during stressful situations could also make things worse, as foods like these quickly increase our blood sugar level, altering hormone levels. Even has been implicated, perhaps because its and possibly fuel sebum production, according to Bodo Melnik at the University of Osnabrück in Germany. I, for one, have seen an improvement to the acne on my back, but not my face, since switching to oat milk.
Gut microbiome
It isn’t just hormones that are influenced by our diet, of course. The food we consume also affects the community of bacteria, fungi and viruses that reside in our gut, collectively known as our gut microbiome. Until recently, studying this was challenging because it was difficult – and expensive – to tease apart the different species present. Now, though, technological advances are allowing us to overcome both hurdles. This has resulted in the discovery of links between the gut microbiome and numerous health conditions, including depression, anxiety and even Parkinson’s disease. It was only a matter of time before these insights told us more about acne, too.
For instance, in 2018, at Southwest Medical University in Luzhou, China, and colleagues compared stool samples from 43 people with acne with those from 43 people who didn’t have the condition. They found a : those with acne had much lower microbial diversity in their gut compared with the control group. They also had depleted levels of bacteria belonging to the taxa Clostridia, Clostridiales, Lachnospiraceae and Ruminococcaceae, which suggests they may help prevent the condition.
One way to change your gut microbiota is to change your diet. “The gut microbiome could be a reflection of diet,” says Barbieri. “It can secrete short-chain fatty acids that modulate inflammation, which may influence your acne.” Indeed, the 2018 study noted that those volunteers with acne ate more dairy, fried and fatty foods than those without, and suggested that this may be contributing to the differences seen in gut microbiota and acne.
Another approach that might change the gut microbiota is to eat probiotics – microbes that may help restore a healthy gut microbiome. To see if this would help with acne, in 2022, Fabio Rinaldi at pharmaceutical company Giuliani SpA, based in Milan, Italy, and his colleagues gave 30 people with mild to moderate acne an oral mix of probiotics and botanical extracts to take once a day. After eight weeks, the volunteers had , lower sebum production and lower C. acnes levels on their skin than participants who had been given a placebo. Two similar trials have also recently been completed, but we don’t yet know their results.
The difficulty is that what constitutes an optimal gut microbiome, and how this may vary from person to person, hasn’t yet been defined, says Nelson. Without knowing this, doctors can’t easily guide a gut microbiome away from causing acne, she says. “It’s very early,” says at the University of California, San Diego. “We need to figure out which bacteria are a little more beneficial and then try to promote that colonisation or isolate what they’re secreting.”
Skin microbiome
While researchers continue to puzzle over the gut microbiome, others are looking at the skin itself. It is, after all, a bacterium on the skin – C. acnes – that is directly implicated in acne. Indeed, for moderate and severe acne already target skin bacteria, including benzoyl peroxide, which acts as an antiseptic, and antibiotics. If the problem is too many bacteria, the idea goes, then removing them could break the endless cycle of excess sebum production boosting bacteria numbers, which increases inflammation and acne.
These approaches have a problem, however: they are indiscriminate, taking out all bacteria on the skin as well as C. acnes. In addition, antibiotics can usually only be taken for a short period to prevent the development of antibiotic resistance.
In a bid to target only C. acnes, researchers cast their net wider. For example, one group turned to a seemingly unlikely, and yet surprisingly fruitful, source: faeces. In 2009, people with mild to moderate acne were given a lotion to apply that contained the Petri dish liquid that Enterococcus faecalis – a bacterium isolated from human faeces that showed antimicrobial activity against C. acnes – was grown in. After eight weeks, the lotion did. Perhaps unsurprisingly, this hasn’t caught on.
Despite all these efforts, however, developments stalled until technology improved enough to allow scientists to get a closer look at what was happening on the skin. What they found was surprising: the problem isn’t simply that there is too much C. acnes, but that there is too much of one strain.
Increased inflammation
It turns out that more than one strain of C. acnes lives on our skin. Ordinarily, the strains live alongside each other just fine, but if they and one – called strain IA1 – starts to dominate while another – strain II – starts to fall, then acne may result. “A disbalance between these strains increases the inflammation, which will increase sebum excretion,” says Joan Attia-Vigneau at Lucas Meyer Cosmetics in Toulouse, France.
Surprisingly, one drug prescribed for severe and treatment-resistant acne since 1982, isotretinoin, already targets this unbalanced microbiome. Earlier this year, it was found to affect the , increasing its overall diversity and selectively altering the balance of C. acnes strains, probably by influencing sebum production. Volunteers in the study who took isotretinoin but didn’t see a reduction in their spots didn’t see any changes in their microbiome.
However, isotretinoin has a drawback: its potential to cause congenital conditions makes it unsuitable for use during pregnancy or for those who are hoping to conceive. It also comes with many side effects, including the drying out of the body’s mucous membranes due to decreased sebum production, which can irritate the eyes, lips and nose.
To find an alternative, the hunt is on for other ways to rebalance the bacteria on our skin. Attia-Vigneau and her team have been investigating a compound called G2 dendrimer, which they discovered could attack strain IA1 C. acnes and leave strain II unaffected. When the researchers created a lotion that included G2 dendrimer and gave it to 20 volunteers for 28 days, they found that the , balancing IA1 and II, compared with a placebo lotion.
However, the study didn’t look at whether it had an effect on acne. So, earlier this year, some members of the team asked 16 people with acne to apply a lotion containing G2 dendrimer to one side of their face and one containing 10 per cent benzoyl peroxide to the other side. After 28 days, the G2 dendrimer lotion by 21 per cent and the number of pus-filled spots by 72 per cent, while no statistically significant change was seen on the side of the face that received benzoyl peroxide. The researchers also found that G2 dendrimer didn’t have any negative effect on other skin bacteria when they tested it on cells in the lab.
“By working on the microbiota, we are decreasing the inflammation and the sebum secretion, and then reducing papules and pustules at the end,” says Attia-Vigneau. Lucas Meyer Cosmetics has patented G2 dendrimer as , and it is already available as an ingredient in some skincare products.
Despite these promising findings, it remains early days. “We’re still trying to define what a normal skin microbiome is, and then it’s going to be even harder to modulate it,” says Nelson. “Your skin microbiome is pretty stable as an adult. Those bugs and those actives [ingredients in skincare] would have to take up root and force out what is already living there.”
Bespoke treatments
As in every field of medicine, the ideal outcome would be bespoke treatments tailored to the individual. “Could we get to the point where you go to a dermatologist and they take a skin scan, a blood test, a swab of your skin and get your profile that says you need drug X?” asks Nelson. “That’s the goal for every medication.”
So, what can we do while we wait? “People want the ‘What do I do?’ answer,” says Barbieri. “But often it’s genetics and things you can’t control. A lot of the time, there’s not a satisfying answer.”
My approach, at least for now, is to use oil-free moisturisers and gentle exfoliators to help prevent keratinocytes from clogging my skin. I know that covering my blemishes with make-up is probably counterproductive, but I am not comfortable enough with my skin to let it be seen freely by all. As for my microbiome, I have already ditched cow’s milk and I am eating a healthy diet filled with the fruit and veg that beneficial gut microbes are thought to love. Maybe I will go nuclear and cut back on chocolate, too, to keep them a bit happier until acne researchers find a way for me to rebalance my gut microbiome more precisely.
Consult a doctor before starting any new treatments.
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