Infants’ saliva may react with breast milk to modulate their microbiomes

Breastmilk is critically important to developing a healthy infant gut microbiome.  The combination of oligosaccharides found in breastmilk are not found in any other individual food, and are intended to cultivate healthy bacteria in the gut.  Besides breast milk, really the only other fluid an infant consumes is his or her own saliva, but thus far not much is known about the role this saliva plays in culturing the proper microbiota.  A team of researchers from Australia recently studied how a mother’s breastmilk directly interacts with her infant’s saliva.  They discovered that when combined, saliva and breast milk produce specific molecules that inhibit the growth of some bacteria, but support the growth of others. They published their results in the journal PLoS ONE.

The researchers measured the molecular components of saliva in 77 adults and 60 infants.  They noticed some stark differences between the two types of saliva, including markedly higher levels of salivary hypoxanthine and xanthine.  Hypoxanthine and xanthine are both substrates for a protein called xanthine oxidase (XO), which reacts with them to form hydrogen peroxide (H2O2).  One of the places XO is predominantly found is in human breast milk, which led the researchers to hypothesize that xanthine and hypoxanthine in infant saliva reacts with XO in breastmilk to form H2O2.  Hydrogen peroxide is a reactive oxygen species (ROS) that can kill bacteria.  The scientists believe that infant saliva reacts with breast milk to form hydrogen peroxide at high enough levels to kill opportunistic pathogens, but allow others to grow.  In order to test their hypothesis, the researchers combined breast milk and infant saliva and attempted to culture the pathogen Staphylococcus aureus, along with gut commensal bacteria Lactobacillus plantarum, and Escherichia coli.  They found that the mixture created concentrations of hydrogen peroxide that killed the S. aureus but allowed the commensals to grow.

Overall this paper showed that infant saliva can combine with breast milk to form physiologically relevant concentrations of hydrogen peroxide.  The hydrogen peroxide may in fact select for the growth of specific bacteria in the mouth and gut, and lead to the development of a healthy microbiome.  Interestingly, pasteurized cow’s milk and infant formula did not contain XO, the enzyme necessary to create the hydrogen peroxide, adding another reason why there is no true substitute for breast milk.   

Fecal microbiota transplant as a treatment for MRSA enterocolitis

Fecal microbiota transplants (FMTs) are most commonly used for treating Clostridium difficile infection, an often lethal bacterial infection of the gut. However, there have been many hypotheses that FMTs could be used to treat other conditions that result in a dysbiosis of the microbiota. A new study published in BMC Infectious Diseases suggests that FMTs could be used to treat enterocolitis, infection of the gut, that is a result of Methicillin-resistant Staphylococcus aureus (MRSA).

The most common treatment for this to date has been antibiotic treatment, specifically vanomycin, but the results of how this impacted the microbiota were not measured. In this new study, 5 patients with enterocolitis as a result of MRSA were given FMTs, the infusion of fecal preparation into the GI tract of the patient from a healthy donor. After administration of the FMT, all 5 patients were cured of the MRSA enterocolitis showing no symptoms. MRSA in the feces was also eliminated after FMT.

They also measured the microbiome of patients undergoing the treatment. They found that prior to treatment, patients with MRSA enterocolitis had decreased numbers of species in the gut and S. aureus reached almost half of all intestinal flora.  After the FMT, the microbiome of the recipient trended closer to the microbiome of the donor and alleviated symptoms. 

While there remain concerns with the use of FMTs, there are certain instances where there are few options for treatment and the administration of a new microbiome from a donor fecal sample remain the most promising. While this was only a study of 5 patients at one hospital in Singapore, the investigators suggest FMT as a first-line measure treatment for enterocolitis resulting from MRSA. 

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.

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.