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.   

Yogurt may help combat colitis

Editor's note:  The following work comes out of Wendy Garrett's lab at Harvard.  Wendy will be an upcoming guest on the podcast.  If you have questions for her, feel free to email or call, and we will ask her on the show. 

A key signature of colitis is the build-up of reactive oxygen species (ROS) in the colon due to chronic inflammation.  One of major functions of ROS is actually to act as an antibiotic, and destroy any foreign bacteria that may exist at the site of inflammation.  However, ROS are known to be toxic to the host as well, and their high concentrations in colitis are likely a major contributor to the disease.  With this in mind, researchers at Harvard studied how probiotics from yogurt could ameliorate the disease by disposing the excess ROS.  They published their results last month in the Proceedings of the National Academy of Sciences.

The researchers had previously determined that a common yogurt that contained 5 strains of bacteria was helpful in decreasing symptoms in multiple mouse models of colitis.  In this study though, they identified Lactococcus lactis as being the most important of these strains in treating colitis symptoms.  They then compared the genome of L. lactis with the other strains in the yogurt and determined that a specific gene that codes for the enzyme, superoxide dismutase (SOD), which is capable of breaking down superoxide, an ROS, may be imparting L. lactis’ beneficial effects.  In order to support this hypothesis, the scientists showed that when this gene was removed from L. lactis the bacteria no longer reduced colitis.  They took this notion a step further and showed that superoxide levels were in fact decreased in vitro when combined with lysed L. lactis.  Finally, the scientists showed that the L. lactis must actually be lysed in the colons in order to release its SOD, destroy superoxide, and reduce colitis: when the scientists attempted to deliver SOD on its own to mice with colitis it was not as effective, and caused diarrhea.

This study is really interesting for two reasons.  The first is that it shows yogurt, like Activia, may be very helpful in dealing with colitis.  The second reason though, is that it shows a new system for deliverying SOD to a site of inflammation: via bacteria.  As they showed in the paper, simply using SOD was not effective, but using the bacteria as a vehicle for SOD, and then lysing it at the site was an effective means of drug delivery.  This has many important implications because ROS are important contributors to a variety of diseases.