Atopic dermatitis associated gut microbe identified

A moderate case of hand dermatitis

Atopic dermatitis, otherwise known as eczema, is an inflammatory autoimmune response of the skin.  Today in the United States it affects around 25% of children, and as many as 3% of adults, with its incidences increasing each year.  Like many other allergies, the microbiome is now being implicated in the cause of this disease.  A few months back evidence was published linking atopic dermatitis to the skin bacteria Staphylococcus aureus.  Other work, however, has shown that the gut microbiome may be critically important to this disease as well, especially because gut bacteria are more likely to control and elicit certain inflammatory responses seen in dermatitis, such as the release of specific cytokines.  A group of Korea recently compared the gut bacteria in atopic dermatitis patients and healthy controls and identified a specific organism that may be important to the disease.  They published their results last week in the Journal of Allergy and Clinical Immunology.

The researchers measured the gut microbiomes of 132 people, including 90 of which had atopic dermatitis and were seeking medical treatment.  They also measured gene expression by bacteria in the gut, and short chained fatty acids (SCFAs) in the guts of all the individuals.  They discovered that one particular bacterial species was much more abundant in dermatitis patients compared to controls, Faecalibacterium prausnitzii.  After, they measured SCFA production, and noted that a decrease in butyrate and propionate was directly linked with the presence of F. prausnitzii, suggesting an important link between this bug, SCFAs, and the disease state. In addition, they noted that the overall diversity of bacteria was similar in all microbiomes measured.  Finally, the scientists investigated the gene expression, and observed an increase in bacteria that are capable of breaking down gut mucins, or mucous, in the guts of atopic dermatitis individuals.  For example, these bugs were expressing proteins that break down fucose and N-acetylgalactosamine (GalNAc), two monosaccharides that are normally derived from mucins rather than food.

This study presents a number of differences in the gut microbiomes of individuals with an without atopic dermatitis.  The scientists suggest that an important species associated with this disease may be F. prausnitzii, and perhaps it may even be influencing the disease through a lack of SCFA production, and the breakdown of gut mucins.  Atopic dermatitis is a complex disease, and certainly cannot be explained by the presence of an individual bug.  However, this paper does support the notion that diseased individuals, who present rashes on their skin, may have disruptions to gut, and that changes in the gut microenvironment create a niche for specific bacteria to grow.  This, in turn, may inform new therapeutic strategies that target the gut microbiome, rather than topical treatments.

Probiotic shows effectiveness against skin allergy in mice

We’ve talked about atopic dermatitis on the blog before, because more and more evidence is linking this autoimmune disease with the microbiome.  In fact, a few weeks ago we wrote about a strong connection between Staphylococcus aureus and atopic dermatitis, which suggests this bug is the culprit behind the disease.  If atopic dermatitis does have a microbiome cause, then it makes sense that shifting the microbiome could help alleviate the disease.  This past week researchers investigated whether probiotics, specifically Lactobacillus casei, could help treat this disease in mice.  They published their results in the Journal of Applied Microbiology.

Scientists induced groups of mice to have atopic dermatitis by shaving their skin and challenging them with a molecule called trimellitic anhydride (TMA) on various days over the course of two weeks.  During that time, the scientists orally administered the probiotic to some of the groups of mice.  Over the course of the study the scientists measured various things like the changes in the microbiome and the amount of various immune-activated molecules, as well as dermatitis indicators, such as skin lesions and the amount of itching.  They discovered that the mice that took the probiotic had less severe symptoms than those that did not.  What’s more, is that this reduction of symptoms occurred in a probiotic dose-dependent manner, i.e. the more probiotic administered, the better the symptoms.  These symptoms included a reduction in the inflammatory response, as well as a desensitization of the TMA, as evidenced by less itching.  As for the microbiome, treatment with TMA decreased abundance of Bifidobacterium and Lactobacilli, and an increased abundance of Clostridia.  Probiotics on the other hand, increased the abundance of Lactobacilli and Bacteroides and decreased the abundance of Clostridia. 

This study is not the first to show in a health improvement through the administration of Lactobacillus, which we have written about before.  It seems this bug is almost always associated with health, except in the case of respiratory diseases.  Overall, it seems that you can’t get enough Lactobacilli, so the next time you are considering having a second serving of yogurt for breakfast, go right ahead.

A population based study of S. aureus colonization in infants for atopic eczema

Atopic eczema (AE) is a skin condition that is often measured by transepidermal water loss (TEWL), a mark of dry skin. The ailment is often associated with the colonization of Staphylococcus aureus and dysfunction of the skin barrier (a few months ago we had a long blog post about atopic eczema and S. aureus so if you're interested in this topic, take a look at that post as well).  A group of scientists in Oslo set out to find if whether S. aureus colonization in the nasal cavity or the back of the mouth, the fauces, led to increased TEWL in healthy infants and those with eczema. They also set out to identify if TEWL on the upper arm and forearm provide similar associations between TEWL and atopic excema.

In the study published in PLoS One, 240 infants were enrolled and 167 of them met the requirements.  Three study groups were included, those with no eczema, those with possible eczema, and those with eczema. Three samples were taken from the upper arm as well as three samples from the lower forearm.

They found that TEWL measurements from the upper arm and lower forearm were equally appropriate which is important because measurements are generally taken from the lower forearm. Taking measurements is often difficult in these young infants so the ability to take measurements from the upper arm would be seen as an advance as it is more readily accessible.  

The scientists also found that while 53% of the infants in the study had S. aureus colonization in the back of the nose and back of the mouth, this was not associated with higher levels of TEWL or atopic eczema. This lack of association differs from previous studies (such as the one I linked earlier) that have shown correlations between S. aureus colonization and atopic eczema. Other human studies have also shown associations with S. aureus on the forehead and cheek and increased TEWL.

The reason for these discrepancies may arise from several different factors including age and sampling site.  Adults generally have lower TEWL than infants and this study sampled the bacteria in the nose and mouth while other studies sampled on the eczematous or normal skin directly. While this study does not show a correlation between S. aureus colonization in the mouth and nose with atopic eczema, more work is needed to better understand differences between these studies and what the role of this bacteria is on the condition.

Episode 9 of The Microbiome Podcast: The skin microbiome and AOBiome with Dr. Larry Weiss

On the ninth episode of The Microbiome Podcast, we talked with Dr. Larry Weiss, Chief Medical Officer of AOBiome.  AOBiome is a leading company based in Cambridge, MA that is developing treatments for inflammatory skin conditions. They also have a cosmetic product on the market that consists of Ammonia Oxidizing Bacteria that the user applies to the skin twice a day. We discuss both the cosmetic product as well as AOBiome’s approach to treating skin conditions with Dr. Weiss. 

AOBiome is offering listeners of The Microbiome Podcast a 25% discount if you order their product before June 29th. The discount code is ami25. Click here to learn more about the product.

Also, as we discussed on last week’s podcast, the AMI is sponsoring a citizen science project where individuals can sequence their vaginal or penile microbiome. To be entered to win a free sampling, enter your information here. 

Remember to call in to ask any questions about the microbiome that you would like answered on future podcasts. The number is 518-945-8583. 

Listen to the podcast on our website, on iTunes, or on Stitcher. 

For more detailed shownotes, read below:

On this week’s podcast we discussed:

• (2:00) Ritter Pharmaceuticals, a microbiome pharmaceutical company that is working on an oral therapy for reducing lactose intolerance symptoms, filed for a $17 million IPO and is becoming a public company. Read more. 
• (2:30) Seres Health, a microbiome company working on a therapeutic for treating Clostridium difficile infection, also filed for an IPO for $100 million and received Breakthrough status from the FDA. Read more.
• (4:55) A study out of NYU found that wearing contact lenses altered the eye microbiome compared to non-contact wearers. Read the abstract. 
• (9:31) We talked a bit about AOBiome. Learn more about AOBiome. www.aobiome.com
• (11:17) Dr. Larry Weiss gave an overview of the skin microbiome and ammonia oxidizing bacteria.
• (13:22) An article out of NYU (led the same scientist who led the contact lens study) that studied a group of aboriginal Amerindians and found that they had perfect skin and still contained ammonia oxidizing bacteria on the skin. Read our blog post about the study. 
• (16:34) Dr. Weiss discussed the goals of AOBiome and how they are approaching the skin microbiome.
• (18:55) AOBiome’s cosmetic product that applies ammonia oxidizing bacteria to the skin. Learn more about the product. There is a discount code for our listeners for 25% off - ami25. 
• (26:00) Larry mentioned a Ted Talk about combatting smelly armpits. Watch the TED Talk. 
• (29:18) AOBiome’s therapeutic research areas and specifically acne.
• (32:25) Eczema and how the microbiome could be used to treat the condition.
• (39:15) Bacterial vaginosis and AOBiome’s approach to this infection.
• (42:51) Larry’s career going from a company called CleanWell, an antimicrobial company, to AOBiome, a company that administers bacteria to the body.
• (45:25) Hang hygiene and hand washing and Larry mentioned a study from the US Navy that found washing hands lowered the risk for getting a respiratory illness. Read the study.
• (50:16) On the aftershow, we discussed hand washing, whether we wear glasses or contacts, and Lebron James and the NBA finals.

New study suggests S. aureus and skin dysbioses cause eczema

Atopic dermatitis, also known as eczema, is a skin inflammation and rash that has an enigmatic cause.  There are many genetic and environmental risk factors involved, but to date the exact triggers and mechanisms that cause this autoimmune response are unknown.  Importantly, a growing percentage of infants and toddlers are developing this disease, which itself is a known risk factor for other autoimmune diseases like asthma and allergies.  Discovering the cause of atopic dermatitis is an important endeavor, because it may lead to a cure for a number of other diseases.

Staphylococcus aureus has long been associated with atopic dermatitis.  It appears to occur at relatively high abundances in the areas of skin that are affected.  Then again, S. aureus is a one of the most common skin microbiome bacteria (it is ubiquitous around the world), and it has yet to be definitively connected to the disease.  In addition, mouse models for many skin diseases, including this one, do not exist or are insufficient, so controllably studying the atopic dermatitis is difficult.  Recently though, a team of scientists from Japan and the NIH developed a mouse model for atopic dermatitis, and made a new discovery that showed S. aureus can indeed drive skin inflammation.  They published their results in Cell immunity.

The scientists were studying how a specific genetic mutation in mice affected bones and hair follicles when they serendipitously realized that it was causing eczema in the mice after around three weeks.  When they investigated the skin microbiomes of these mice, as well as normal mice, they realized that right around the time that the eczema was appearing in the mice, these mice’s skin microbiomes drastically shifted.  First, a bacterium called Corynebacterium mastitidis emerged, followed by S. aureus a few weeks later, which was coincident with the presentation of the worst symptoms.  Of note, species of Corynebacteria are associated with eczema in humans, much like S. aureus.

Next, the researchers then performed a series of experiments by providing mice with antibiotics in an effort to combat the dysbiosis.  When newborn mice with the genetic modification were treated with antibiotics they never developed eczema at all.  Moreover, genetically modified mice that were in the midst of the rash that were treated with antibiotics had their eczema subside soon after.  In addition, genetically modified mice that were taken off of antibiotics had eczema emerge shortly thereafter.  Strikingly, in all of the above situations changes in the skin microbiome corresponded with the disease state: a lack of S. aureus and high diversity were associated with healthy skin, and the emergence of S. aureus and a lack of diversity were associated with the disease.  Finally, when S. aureus was inoculated onto the skin of genetically modified mice, they developed eczema rapidly.

The researchers performed a number of other experiments to try and tease out the mechanism by which S. aureus causes atopic dermatitis.  Their results show that it appears a combination of genetic and environmental factors that affect the skin may be important in defining an individual’s risk for the disease.  Regardless, it appears that S. aureus is a major culprit in causing eczema, so future therapies that eradicate the bacteria, or at least decrease its abundance should be considered.

Hand washing dishes may decrease risk of allergies

A study published on Monday by the journal Pediatrics has gotten a lot of press this week because it shows a connection between allergies in children and the method by which parents wash their dishes. Parents, especially new parents, often consider good hygiene as one of the most important factors in raising their new child, but according to the hygiene hypothesis it may be true that too much cleanliness actually negatively affects a young child.  Asthma, eczema, and other autoimmune diseases are becoming more common conditions in children, and each has been linked to the hygiene hypothesis.  Researchers in Sweden reinforced this link when they discovered a possible connection between allergies in children and whether dishes were washed by hand (less clean) or by machine (more clean) in their homes.

 The researchers sent a questionnaire to parents of children aged 7-8 which was filled out by 717 families in Molndal, Sweden and 312 families in Kiruna, Sweden. The questionnaire asked many questions pertaining to the children, including previous symptoms of asthma or eczema, method of washing dishes, and if their food was farm grown or fermented.  When examining the results it is important to remember that all forms of bias cannot be eliminated when doing surveys, because, among other reasons, it is difficult to get a perfectly random sample.

Results of the study showed that there were lower instances of allergies in children whose families washed their dishes mainly by hand rather than by machine. In addition, this effect was amplified if the children ate food that was either fermented or purchased from a farm (both of which should introduce diverse bacteria to the children).  Of course, there were other variables that were not inquired in the questionnaire that are also known to decrease rates of allergies in children, and which may be related to washing dishes by hand, for example a lower socioeconomic status.  Then again, the authors suggest that hand washing dishes may reasonably be responsible for these lower rates of allergies in children of lower socioeconomic status.

So, you may be wondering how exactly this pertains to the microbiome. Hand washing dishes cleans less thoroughly than highly efficient machines, which sounds gross, but the exposure to more microbes when you are young may help develop the microbiome and immune system.  While this study is not perfect, it still shows us that exposure to bacteria is potentially a good thing for the new and developing microbiome.