In 2020, one of the most rapidly expanding acne realms is the world of skin bacteria.
There’s lactobacilli, staphylococcus epidermidis, ammonia oxidising bacteria; the complexity keeps growing. Just as we’ve unmasked one mysterious player, twenty more outlines of shadowy figures pop up in the distance.
Meanwhile, a more ancient riddle is stress causing acne, which dermatologists have long denied, but deep down everybody knows to be true. Several specific connections are known, like vitamin C depletion, but stress is still mysterious…
…and now the moment has come: two worlds are colliding head on. We have a fresh study on p.acnes bacteria, the number one strain inhabiting clogged skin pores.
It turns out that p.acnes has special receptors which detect your stress and anxiety, beaming in like a satellite dish, whether from a frustrating commute to work or important college exams. In response, they increase their nefarious acne-causing activities.
A fresh link to oily skin
Our study, released in December 2019, involves an eerie anomaly first detected during the gloomy Depression years. In 1930, French scientists noticed that mental stress caused a renewed burst of illness in patients already infected with bacteria.
The data gathered dust in the vast archives of science until the 1990s, when it transpired that E. coli could accelerate its growth by absorbing adrenaline into newly formed DNA. In the gut, mental stress helped the vicious pseudomonas aeruginosa to weaken gut barrier permeability (important for vitamin absorption), and stick to the small intestine using adhesins, thereby explaining the nausea from stress.
In the skin, stress hormones made the hospital-stalking staphylococcus aureus more infectious and vicious. Thus, the road had logically arrived at acne bacteria, and in our study, two strains of p.acnes were selected, the harmless RT6 and the acne causing RT4. They were both treated with the stress hormones epinephrine (adrenaline), norepinephrine or left alone.
Every acne actor under the sun was tested, and the results weren’t uniformly positive; p.acnes didn’t mutate into giga acnes instantly. The numbers of bacteria cells barely changed at all. Despite peering into the most intense microscopes, no strengthening of the cell membrane or alteration of the p.acnes’ shape could be seen.
What did increase was persistence. Namely, p.acnes’ biofilms, when bacteria forms a tightly assembled structure like superglue which resists all attempt to remove it.
In RT4, the acne-causing strain, norepinephrine increased average biofilm thickness by 215% and epinephrine by 65%. Maximum biofilm thickness didn’t increase because there was massive variation to start with, but average biofilm biomass rose by 230% and 70%.
Two of the classic stress hormones, the hormones which inform you that hugging a crocodile is probably a bad idea, allow the deadliest acne bacteria to dominate your skin pores.
Next, oily skin was tested, and after adding norepinethrine and epinephrine, the sebum (oil) stimulated by strain 4 increased by 11% and 7% respectively. In the friendly strain 6, norepinephrine achieved nothing, whereas epinephrine increased oiliness by 4%.
It’s only a small increase, but it’s enough to counteract 6 weeks of applying topical turmeric, enough to keep p.acnes fed and thriving through the winter. Sebum is p.acnes’ primary energy source; they stimulate its production to stay alive, and apparently, stress hormones help them in their quest. In a self fulfilling acne spiral, the sebum further clogs your pores, reducing the oxygen which the species is intolerant to.
The players in the study
So is this study a revolution for acne, or an interesting yet overly technical lab experiment which will never impact the real world? It’s somewhere in between.
For one thing, the hormones tested aren’t obscure. They affect workers, commuters and stock market wizards daily. They’re flowing through your body right now:
Epinephrine – formerly called adrenaline, it’s the hormone which gives you the addictive rush when you ski off a cliff and only survive by landing on a random bouncy castle. It’s responsible for a pounding heartbeat when you swerve an absentminded deer. It’s responsible for a sudden burst of energy when bar brawl o’clock arrives, increasing bloodstream glucose. Epinephrine is sometimes injected into nearly dead patients to restart their heart. Norepinethrine and epinephrine are called catecholamines, released by the adrenal glands. In chronic stress, the two are chronically elevated, alongside cortisol.
Norepinephrine – not the cousin, not the godfather, but definitely the brother of epinephrine, because its bodily functions are almost identical. Norepinethrine also increases heartbeat, energy, and the mad fight or flight rush.
The main difference is increasing your blood pressure during stress, by narrowing your arteries. Remember when your furious schoolteacher stood with his eye twitching and a bulging red vein on his temple? That was probably norepinephrine. It’s actually used an emergency drug to restore blood pressure.
Both hormones are triggered directly from mental stress; it all starts with worrying thoughts in your brain. Epinephrine makes up 80% of the body’s stress-related catecholamines, versus 20% for norepinethrine. The body has both alpha and beta receptors for catecholamines and epinephrine is more active on the alpha ones.
You also need to understand…
The two p.acnes strains – p.acnes has thousands of strains, but 4 broad families. Groups 2 and 3 are safer, while group 1b is common in acne patients and group 1a is linked to severe acne. For example, your immune system targets bacteria by identifying neuraminidases within their cell membrane, like a thermal vision rocket seeing a red glow. 1a and 1b have more neuraminidases and therefore stimulate inflammatory chemicals like interleukin-8 particularly strongly.
In this study, p.acnes 1a and 1b increased the inflammatory human beta defensin (hBD) fivefold after 3 hours, whereas group 2 did nothing. This is the tip of the iceberg, but anyway, our study today chose one deadly strain and one friendly one. RT4 from group 1a, and RT6 from group 2. Because their genomes are fully explored, these strains are the gold standard in studies.
A direct mental channel
Chronic inflammation, a hyperactive immune system, was barely affected. In the deadly strain 4, epinephrine increased inflammatory interleukin 8 slightly, but norepinephrine decreased it slightly; neither alteration was significant. It’s the same story for strain 6. It’s not like the bacteria was unusually inert either, because strain 4 stimulated plenty of IL-8 in healthy skin cells.
Next, however, the fully explored genome came in use: the scientists found special receptors which epinephrine could bind to.
A catecholamine receptor in e. coli was already known, and an exact replica wasn’t found in p.acnes, but they found a similarly shaped, mutated version, logically for a different species. In fact, this nor/epinephrine receptor was larger than in e. coli. The link between mental stress and p.acnes was staring them in the face.
Based on the amino acids in epinephrine, the scientists calculated a high binding affinity to this receptor. The study provided “a first indication that C. acnes expresses a membrane sensor for catecholamines” (note that p.acnes is now renamed c. acnes)
We have a mixed bag of results. Inflammation, p.acnes cell numbers, and their shape were unaffected, but sebum rose, biofilm glue rose, and a specific receptor exists.
A strengthening biofilm yet unchanging shape is very unusual. For example, the deadly staphylococcus species grows more infectious as its membrane strengthens under a microscope. The scientists had a few theories up their sleeves, speculating that adhesins may have strengthened, special proteins which p.acnes uses to glue to skin cells.
Generally, strain 6 from p.acnes group 2 reacted far less. Supposedly, this is because it lies on the vast plains of your cheeks, whereas the 1a group is buried in the oxygen deprived skin pores, where the two hormones are much more concentrated. Group 2 is only exposed to them through sweat, and therefore hasn’t evolved to react to them. Regardless of why, it gives us one last nugget of acne knowledge: that different p.acnes strains react to stress differently.
Stress – a new power finally emerges
For years, the exact connection between stress and acne has been wrapped in mystery. Teenagers and adults alike have sworn that pimples burst into being after a long commute, but even chocolate or eggs are more explained.
Milk is actually fully explained; it’s packed with IGF-1 which stimulates oily skin and proteins like casein which people’s guts are genetically unable to tolerate. Milk is probably the classic acne food/event which is best researched.
With stress, we know that the stress hormone cortisol slows wound healing, and depletes acne-clearing nutrients like vitamin C and magnesium. It also weakens your digestive system, fuelling inflammatory gut bacteria – just witness the butterflies in your stomach on your first date.
However, it always felt like something was missing, something more focused, a direct channel between the brain and acne. This study is no revolution, but it opens up a whole new dimension.
P.acnes and catecholamines could explain a big chunk of pimples from stress. Again, these hormones aren’t obscure, they surge in chronic and acute stress alike.
If true, it would explain why stress simply bounces of some people’s skin. Everyone has p.acnes, but acne patients have more, giving them a deeper reservoir of potential stress-fuelled pimple warriors. The study could have strategical benefits; chronically stressed people could knuckle down hard on antibacterial remedies.
Above all, it’s fascinating to finally shine a light on this age-old acne riddle. Avalanche-threatened medieval farmers, or Aztec warriors waiting tensely on outposts probably had the same fears (not caring that arrows were firing past their head).
The oily skin increase was tested over 18 hours, mimicking a real life stressful situation perfectly, like two consecutive college exams, a job interview, or commuting to work on a rusty unicycle. All experiments, whether for inflammation or biofilms, were conducted 3 to 5 times, bolstering the reliability.
The failures of the study
The flaws, meanwhile, are common to lots of bacteria studies. The skin’s biosphere is so rich in competing, interacting microorganisms that when you test one in isolation, it might not be representative of its true results.
This recent lactobacilli study was a classic example; the three strains reduced acne when transplanted from the gut, but in the long term, p.acnes could easily evolve to target them. Here, p.acnes strengthened in response to stress, but if healthy species like staphylococcus epidermidis strengthen too? In fact, what if healthy species of p.acnes strengthen? Some strains in group 3 wipe out vicious group 1a members using antibacterial peptides; strain RT6 was unreactive to stress, but others might be.
The oily skin increase was tested for 18 hours, and could taper off as the skin adjusts. In 3 days, the bacteria multiverse could enter a new equilibrium. If so, the stress shock could still explain short term stress pimples, but would shrink in importance for chronic stress.
Then there’s a huge question: its role in stress overall. Assuming the bacteria connection is real, it might still pale compared to delayed wound healing, digestive havoc, and nutrient depletion. Interesting, perhaps, but ultimately obscure and irrelevant. Sebum increased, but not massively. Inflammation didn’t increase at all.
Meanwhile, the unaffected friendly strain proves that variation exists, so what if with strain 4, scientists accidentally chose a loose cannon, the single most sensitive strain to stress? What if these results are totally misleading?
It’s possible the reverse is true – that RT4 is a rare strain which doesn’t become more inflammatory. However, group 1a is the supervillain society of the acne world, even darker and more twisted than 1b. A Danish study spelt it out perfectly, where scientists collected 125 different strains of p.acnes. 39 were from healthy skin, 42 from mild acne, and 25 from severe acne skin samples. 22 strains from severe acne belonged to group 1a. Our study would have been superior if 5 different malicious stains were tested.
The verdict!
So where do we stand? My guess is that ultimately, when fully researched, the alliance with p.acnes won’t be the main role of stress in acne. However, it will still be a decent contributor which presents opportunity.
The special receptors for epinephrine and norepinephrine say it all. It shows a direct channel from the brain to a red and fiery pimple. It cuts of a chunk of potential interference from immune system actors and other bacteria.
The evil RT4 is tested precisely because it’s so representative of unhealthy p.acnes strains, so its minor yet significant changes will probably translate well into other species.
This connection also hints at other obscure stress powers. For example, when eaten, the antioxidants like lycopene in tomatoes are eventually built into human skin; what if stress makes this construction less efficient? What if stress alters the proportions of fatty acids like squalene in your skin’s oil? Roll 3 small time connections into one and you have a big chunk of stress-induced acne to target.
The connection between stress and p.acnes won’t be revolutionary, but it’s one to watch.
Thanks for reading!