Malassezia spp. microorganisms also inhabit skin during acne

Most people experience acne at some point in their life, and the AMI has discussed the microbiome’s role in this skin condition many times in our blog and podcasts.  Cutaneous inflammation is observed in people with acne, as well as increased amounts of the Propionibacterium acnes (P. acnes) bacteria.  However, a recent study conducted by dermatologists in Japan quantitatively examined microbiota in follicular skin contents, and providing more evidence that Malassezia spp. fungi may also be present during facial acne episodes in addition to P. acnes. 

15 untreated acne patients were selected for the study, all of whom had not received previous treatments with topical and/or steroid/antibiotic regiments.  A comedo extractor was used to collect follicular contents from inflammatory acne lesions from the cheek and foreheads of patients, and these samples were subject to DNA extraction and subsequent PCR analysis to characterize microbiota species.  Staphylococcus and Propionibacterium were found in follicular contents, but interestingly Malassezia spp. fungi were also observed.  Furthermore, Malassezia spp. fungi in follicular contents were correlated with inflammatory acne and with content on the skin surface, while Staphylococcus and Propionibacterium were not. 

These findings suggest that Propionibacterium acnes may not be the only microbiota skin residents related to acne.  While this was not the first paper to point to Malassezia spp. fungi as implicated in acne, these researchers addressed prior experimental method concerns and utilized advanced quantitation methods such as PCR rather than culture-methods.

Antimicrobial peptide can reduce acne infection in mice

Chances are you have experienced some form of acne, or know someone who has.   Also known as Propionibacterium acnes (P. acnes), these gram-positive bacteria drive the pathogenesis of what we commonly refer to as acne.  The bacteria aggregate in high numbers on the skin in areas such as hair follicles.  When bacteria density gets too high, the innate immune system reacts, resulting in a battery of proinflammatory signals and/or reactions.  Current treatments include both topical and oral antibiotics, but these therapies collectively have shown minimal efficacy at the expense of some side effects.  A recent study conducted by researchers from South Korea and Denver sought to explore the use of a novel and custom made antimicrobial peptide (AMPs) called P5.  AMPs have been previously shown to effectively kill bacterial pathogens while at the same time modulating host immunity.  The aim was to see if this tiny cationic peptide sequence could protect against P. acnes induced immune responses both in vitro and in vivo, and therefore present itself as a potential novel acne treatment. 

The researchers first demonstrated that P5 had antibacterial effects in vitro (administering the peptide to bacteria culture dishes).  In a follow-up in vitro experiment, P5 was shown to disrupt the morphology P. acnes, as displayed by scanning electron microscopy images.  P5 was also able to inhibit proinflammatory signals brought on by P. acnes, including reductions in cytokine signaling and toll-like receptor expression in human skin cells.  Furthermore, P5 reduced the expression of a gene responsible for regulating transcription of these inflammatory signals. 

In the in vivo experiments, mice were inoculated with P. acnes and split into two groups, either receiving the P5 AMP or a vehicle control intradermally (in the skin).  P. acnes growth was visibly reduced in the ears of mice when administered P5.  To demonstrate the effective quantitatively, the researchers measured ear thickness to record differences in swelling.  P5 was able to significantly reduced ear thickness in P. acnes mice that had been given P5.  Importantly, P5 alone– i.e., in mice without the P. acnes infection – did not have any effect on inflammation, suggesting the peptide’s role in modulating immunity specifically with P. acnes. 

Treating bacterial infections at the biological level using unique features of bacteria offers a promising technique to combat common maladies such as acne.  In fact, companies such as AOBiome are already utilizing unique methodologies, as their products are designed to help the skin microbiome.  In light of our previous discussions regarding misuse/overuse of antibiotics, this method could offer a much safer alternative toward treating acne.

Too much vitamin B12 may cause acne

I first paid attention to vitamin B12 when my friend was touting it as a hangover cure. As it turns out, vitamin B12 is a bit more important than just stopping a headache after drinking alcohol. This vitamin is important for proper functioning of the brain, the formation of blood, among many other functions.  A recent study also found that when we have too much vitamin B12, it may be affecting our skin microbiome in a negative way causing acne. Many people have said that taking B12 has given them acne; however, there had been little research into why this happened. Scientists at UCLA investigated this and published their results in Science Translational Medicine. 

The team of investigators studied the skin bacteria of individuals with severe acne and those without and looked at the gene expression patterns. They found that people taking B12 supplements ended up with higher levels of the vitamin in their skin. They found that this resulted in Propionibacterium acnes, the bacteria implicated in acne, to lower its own production of B12, which is important for performing normal functions. This imbalance resulted in the production of porphyrins, a molecule that is implicated in inflammation and possibly resulting in acne formation.

As with all things microbiome and the human body, it’s important to have a positive equilibrium. Just last night I was speaking with a friend who is undergoing significant microbiome troubles since travelling to Africa in March. When she returned she had major stomach problems and was told to take a course of ciprofloxacin that only worsened her symptoms. She now finds herself with severe vitamin B12 deficiency and anecdotally she mentions slight memory loss, a common symptom of B12 deficiency. Like everything in our body, it’s important to find that middle ground and those with acne shouldn’t yet be starving themselves of vitamin B12. This study did not prove that too much B12 causes acne and in fact other studies have shown that the vitamin has anti-inflammatory effects. More work will be needed to show if this is in fact causal and if new treatments for acne can be designed using this new information about vitamin B12. 

Understanding the nasal microbiome

Electron micrography of Staphylococcus aureus.

The nasal microbiome remains largely unstudied despite its potential importance to many diseases, such as rhinosinusitis, allergies, and staph infection (incuding MRSA).  Staphylococcus aureus is probably the most well-known nasal resident, but simple questions, such as which species of bacteria are most prevalent in the nose, are still not answered.  Understanding all the residents of the nasal microbiome, the influence of our genetics and the environment on defining their populations, and the influence each one has on others may be critically important to preventing diseases such as staph infection, and more research is needed.  Fortunately, a new study out of Johns Hopkins that investigated sets of twins shed light on many of these questions, and was published in Science Advances last week.

The scientists sequenced the nasal microbiomes of 46 identical and 43 fraternal pairs of twins.  First, thy learned that these people’s nasal microbiomes could be classified into 7 different phenotypes or community state types (CST) which broadly described their nasal microbiomes.  These 7 types are defined by their most abundant bacteria, and are as follows: CST1 – S. aureus, CST2 - Escherichia spp., Proteus spp., and Klebsiella spp., CST3 - Staphylococcus epidermidis, CST4 - Propionibacterium spp., CST5 - Corynebacterium spp., CST6 - Moraxella spp., and CST7 - Dolosigranulum spp.   The most common CTS was CTS4 with 29% of the sampled population having that CTS, whereas CTS4 was the least popular, coming in at 6% of the individuals tested.  The researchers noted that many of these bacteria, such as Proteus, were not considered to be important to the nasal microbiome at all, so their dominance in some noses was surprising.  The scientists learned that genetics plays nearly no role in the microbiome community composition, but does influence the overall microbiome population.  In addition, gender influenced the overall population, with women having about half as many total bacteria in their noses as men.

With regards to S. aureus, while it existed in 56% of the individuals studied, it was associated with other bacterial.   For example, the researchers discovered that Dolosigranulum, and Propionibacterium granulosum were negatively correlated to the existence of S. aureus, whereas S. epidermidis was positively correlated with S. aureus abundance.  This lends itself to the idea that specific bacteria can create colonization resistance against S. aureus, and thus could be used to prevent the disease.  The researchers suggest a probiotic should be tested for its therapeutic value in preventing S. aureus colonization, and hopefully they move forward with those trials.

A new drug from the microbiome may someday treat acne

Optical microscope image of Propionibacterium acnes, the bacteria that causes acne.

One of the most prevalent diseases caused by our microbiome is acne.  As many people know, those little red pimples are caused by an immune response to the otherwise normal skin bacterium, Propionibacterium acnes.  Many treatments for acne use broad spectrum oral antibiotics to eliminate the bacteria, which we at the AMI discourage for reasons we have blogged about before.  New research suggests that another common microbiome bacterium, Helicobacter pylori, may have utility in fighting P. acnes and preventing acne.

Research recently published by the British Journal of Dermatology investigated the effects of using a peptide made from the microbiome bacterium Helicobacter pylori to reduce levels of P. acnes and to decrease the immune response to these bacteria.  The researchers discovered that the peptide, known as HPA3NT3, was quite effective in destroying various strains of P. acnes.  Moreover, the treatment decreased the production of interleukin-8, which is responsible for inflammation.  Finally, the researchers showed the peptide did not destroy the skin of mice nor elicit an immune response on its own.

While the study did not use humans, which would have been ideal, it showed a potential new treatment for acne.  In addition, it is another example of using natural products from the microbiome to develop new drugs, and in this case treat a common microbiome disease.  Acne is among the top 10 most common diseases in the world, and while not usually medically dangerous it does have negative consequences, so we are glad that this microbiome disease is getting some attention.