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.

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.

The nasal microbiome of infants may impact risk of developing asthma

Many lower respiratory illnesses have been shown to associate with specific lung, throat and nasal bacteria, but the role of the microbiome is still unclear, and mechanisms for the connection have yet to be proven.  Of particular interest is asthma, which affects around 7% of people in the US, and increases a person’s risk for many other conditions.  While it is normally diagnosed in toddlers, scientists believe that the groundwork for the disease is actually laid during infancy.  With that in mind, researchers in Australia performed the first longitudinal study of infants’ nasopharyngeal (nose and throat) during the first year of their lives, and tracked episodes of respiratory illness during that time.  They discovered a strong connection between the microbiome and respiratory illness, including asthma, and last month published their results in Cell Host and Microbe.

The researchers collected nasopharyngeal microbiome samples from 234 infants at different time points during their first year of life.  Most infants’ microbiomes were dominated by the following species: Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Alloiococcus otitidis.  Interestingly, this was true for infants regardless of birth delivery mode (i.e. cesarean or vaginal) as well as length of breast feeding.  In contrast, having a furry animal in the house tended to increase the abundance of Streptococcus, but having older siblings tended to decrease it.  In addition, there were strong seasonal effects on the microbiome, with Haemophilus being associated with the summer, and Moraxella the winter.  In children with respiratory illness, Haemophilus, Moraxella, and Streptococcus were most frequently measured, and Staphylococcus, Alloiococcus, and Corynebacterium least frequently measured.

When the scientists compared their results with the asthma outcomes of the children at 5 years old they noticed one significant trend.  Colonization by Streptococcus at around 2 months old, which was asymptomatic at the time and occurred in 14% of infants tested, was strongly connected to chronic wheezing (itself an indication of asthma) at 5 years old.  They suggest that the developing airways in infants may be especially vulnerable to Streptococcus.

This long term study does a really nice job of defining how the microbiome grows and develops in the airways of infants – something which previously hadn’t been performed at such a large scale.  While this study alone does not figure out exactly what the microbiome’s role is in childhood respiratory illnesses, it does provide a baseline for future studies to work off of.   

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.