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.

Bacteria from infants’ microbiome metabolize breast milk differently.

Human milk oligosaccharides (HMOs) are a diverse group of carbohydrates found in breastmilk.  Because the HMOs can’t be used by the infant directly for energy, scientists believe their purpose is to stimulate the development of a healthy gut microbiome.  During the first year of life, an infant’s gut is dominated by Bifidobacteria, in particular B. infantis, and B. bifidum.  In a recent publication scientists measured the difference in HMO utilization between these bugs, and discovered they have very different and important strategies for HMO utilization. The results were published in Nature Scientific Reports.

The scientists first isolated multiple strains of each species, B. infantis and B. bifidum, from the feces of newborn infants.  They then attempted to culture each strain alone in a mixture of HMOs from breastmilk, as well as the individual HMOs alone.  They learned that the each B. infantum strain could grow on pooled HMOs, but interestingly some of the B. bifidum strains could not grow alone on HMOs.  When the bacteria were cultured with mucins (containing sialic acid or fucose, as previously discussed on this blog) none of the B. infantis could grow, whereas most of the B. bifidum could.  This implies that B. infantis alone cannot utilize fucose or sialic acid, but rather needs the help of other bugs to break these down to utilize them.  After, the scientists looked at the regulation of different genes during the culturing experiments.  From these results they determined that B. infantum transports the HMOs inside the cell before breaking them down for energy.  B. bifidum, on the other hand, breaks the oligosaccharides down extracellularly before taking up smaller, simpler sugars. 

All together we see that there is a complex assemblage of bugs in the guts of infants that all rely on one another for energy and metabolism.  The breastmilk cocktail of HMOs itself is so complicated that it almost necessitates the interdependent communities to grow.  Overall, this creates a robust and resilient microbiome that prevents pathogens from taking hold and protects the infant during his or her most vulnerable years.

Sialic acid may be key carbohydrate responsible for inflammation and dysbiosis in the gut

A surface mucous cell bordering on the stomach lumen secretes mucus (pink stain).

Our diet is full of various carbohydrates, composed of different monosaccharides and polysaccharides.  Many of these survive our own digestion and make it all the way to the colon where they modulate our microbiome.  Another source of saccharides for our gut bacteria is the mucous that we produce, which can be a rich source of fucose or sialic acid.  Sialic acid has been implicated in many inflammatory diseases, such as bacterial vaginosis.  Last week, researchers from Switzerland showed that sialic acid may play a critical role in colitis, at least in one colitis model commonly used in mice.  They published their results in Nature Communications.

One way to induce intestinal inflammation in mice is to feed them dextran sodium sulfate (DSS).  The reason this molecule causes colitis in this mice is unknown, but it is used in many models of the disease.  In order to understand the possible role of sialic acid in the colitis, scientists created mice that could not produce mucous with sialic acid.  They quickly realized that these mice were not as susceptible to the DSS-induced colitis as their normal counterparts.  After, they tested how various antibiotics affected colitis in the DSS—colitis mice and discovered that Escherichia coli abundance was directly associated with the severity of the disease. Putting these ideas together, they tested and discovered that E. coli used sialic acid as their main carbohydrate source in vitro.

Interestingly, the E. coli cannot actually access the sialic acid from mucins, but instead need other bacteria, such as Bacteroides vulgatus to cleave and release the sialic acid from the mucins in order to access it.  If sialic acid is indeed important to the human form of the disease there may be multiple approaches to combatting the disease.  First, by eliminating E. coli, and second by eliminating the free sialic acid.

The gut microbiome shift during pregnancy is related to the mother’s secretor status

Fucose chemical structure

An estimated 20% of women of European descent are not able to produce mucous that have fucose sugars attached to the ends of their mucin molecules.  These women are called ‘non-secretors’, as opposed to ‘secretors’ who can fucosylate their mucins.  This rather peculiar genetic anomaly is not appreciated until it is looked at under the lens of the microbiome.  Many of the microbiota in the gut feed off the host’s mucins for energy, and the lack of fucose is a major factor in dictating which communities can survive in their guts.  During pregnancy the mother’s gut microbiota undergoes a dramatic shift, although what variables are important in determining this shift remain unknown.  Last week though, researchers from Finland showed that secretor status was an important indicator in how a women’s gut microbiome shifts during pregnancy.  They published their results in PLoS ONE.

The researchers sampled the gut microbiome of 71 women throughout their pregnancy, and compared it to the secretor status, as determined by genetic testing.  In the first trimester of pregnancy each women, secretors and non-secretors alike, had similar diversities in their gut microbiota.  However, by the third trimester the non-secretor’s gut microbiomes were much lower than their secretor counterparts.  When the scientists measured specific phyla, they observed an increase in the abundance of Actinobacteria in the secreting women, and an increase In the abundance of Proteobacter in the non-secretors.

The changes in gut microbiota in these women may be very important to the microbiome of the infant that is born to them.  As an infant passes through the birth canal he or she is exposed to the mothers’ vaginal and gut microbiota, and these bacteria serve as the initial populations that seed the infants’ own guts.  In addition, some of these specific bacterial populations, such as Proteobacter, are implicated in diseases like IBD.  If these bacteria persist in the mother after birth they may explain the onset or increased risk of some of these diseases.

Breastmilk varies between mothers – affects microbiome of infant

Chemical structure of fucose molecule

We know that breastmilk is crucial to the development of a healthy infant’s microbiome.  It contains many oligosaccharides that cannot be digested by the infant, and whose primary purpose appears to be stimulating the growth of specific microbiome bugs.  There are, however, differences between new mothers’ milk.  For instance, some mothers cannot produce 2′-fucosylated oligosaccharides, which are oligosaccharides that have a fucose sugar on the end.  David Mills and his team at UC Davis recently investigated how the microbiomes of infants differed based on the presence or absence of fucosylated glycans in the milk that they drank.  They published their work in the journal Microbiome last week.

Forty four infants who were fed breast milk had their microbiomes measured throughout the first 120 days of their lives.  Thirty two of these infants were fed milk from woman with fucosylation ability (secretors), and twelve were from women without the fucosylation ability (non-secretors).  When the researchers investigated the contents of the milk they found that it varied in many ways, besides fucosylation.  For example, those women that did not fucosylate appeared instead to increase their monosaccharide sialylation, a sugar that has been linked to C. difficile infection.  When the scientists compared the infants’ microbiomes in the two groups they discovered that secretor-fed infants achieved higher levels of Bifidobacteria and Bacteroides, and achieved these levels more quickly than non-secretor-fed infants.  Instead, the non-secretor-fed infants had relatively higher levels of Enterobacteria, Clostridia, and Streptococci.

These differences may be important to the infants’ developments.  For example, Bifidobacteria in the gut is associated with lower gut permeability and less inflammation.  Also, Bifidobacteria and Bacteroides are large contributors to the production of short chain fatty acids and lactate, which have each been associated with gut health time and time again.  A full 20% of the U.S. population is non-secretors, and it would be interesting to see if any epidemiologically significant differences exist between the two groups into adulthood.  In either case, in the future it may be worth considering supplementing infant milk with fucosylated oligosaccharides if the lack of fucosylation does turn out to be detrimental to the baby.

What happens to our microbiome when we get sick?

Editors Note:  Yesterday a piece about the AMI was published by the website Gut Microbiota for Health.  Read about it here.

When people get sick, what happens to their gut bacteria? Does their microbiome become weaker like the rest of their body? A recent study led by a group at the University of Chicago and published in Nature found that in mice, the intestines begin producing a specific type of sugar, fucose, to keep the bacteria in their guts healthy when the rest of their body becomes ill. 

To observe this occurrence, the team of scientists exposed different sets of mice to a molecule that causes them to get sick, simulating infection. When the first set of mice was given this molecule, fucose was quickly and abundantly produced in their intestine. When the second set of mice, mice that were bred to lack a specific gene (Fut2) that allows them to produce fucose, was made to become sick, the mice recovered from the illness much slower than the mice able to produce fucose.

This study showed that these sugars keep the microbiome healthy when its host gets sicks and help the host recover faster. What does this mean for humans?  Do we too produce this sugar when we become sick?

Unfortunately, approximately 20% of humans lack this important gene for producing fucose and these same people have been associated with a higher incidence of Chrohn’s disease.  In this study, the gut microbes of the mice engineered to lack the gene for creating fucose had greater harmful bacteria in their gut than normal mice. It is likely that the production of fucose in our bodies not only helps feeds our healthy bacteria, but it also helps stave off potentially pathogenic bacteria from proliferating.

This important interaction may lead to new therapeutics that directly influence the microbiome.  So remember, always 'feed' your cold.