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.   

Saliva may be able to predict severity of cirrhosis

Cirrhosis is a disease of the liver in which healthy liver tissue is replaced with scar tissue, preventing the liver from properly functioning. Scientists at Virginia Commonwealth University found that changes in the microbiome of saliva were found in cirrhosis patients in comparison to individuals without the disease.

The scientists analyzed the bacterial contents of both stool samples and salivary samples from patients with varying degrees of cirrhosis as well as healthy controls.  Previous studies had shown that cirrhosis patients had altered fecal microbiomes and in this study, they found that patients also had altered salivary microbiomes. 102 individuals with cirrhosis were studied including 43 of them who previously had hepatic encephalopathy (HE), a severe result of liver disease that results in confusion, coma, and can even lead to death.

Patients who previously had HE saw a decrease in bacteria in their saliva that were normally in the body and an increase in bacteria that were pathogenic, including Enterobacteriaceae and Enterococcaceae, Similar results were found in their stool samples. Of the 102 patients, 38 of them were hospitalized within 90 days of the study.  Those 38 individuals had greater salivary dysbiosis than those who were not hospitalized.

They also looked at an additional 43 individuals without cirrhosis and 43 with cirrhosis and looked at the inflammatory profile in the saliva. They found that the cirrhosis patients had immune deficiencies that were similar to that in the gut.

This study showed that the salivary microbiome was similar to the fecal microbiome in patients with cirrhosis. This provides evidence that you may be able to use saliva to predict the disease severity of patients with the disease as well as providing a tool for testing treatment options for patients with the disease. 

Saliva regulates our oral microbiome

We know that saliva is important during eating and digestion, but researchers from Harvard and MIT investigated how saliva may be influencing the microbiome.  In an article recently published in Applied and Environmental Microbiology the scientists describe results that show saliva also includes molecules that influence oral bacteria so as to prevent cavities.

Cavities are formed when bacterial biofilms form on teeth and produce acids that go on to dissolve tooth enamel.  Saliva, which flows through the mouth, works to wash away these bacteria and helps remineralize teeth.  Beyond this, it contains molecules called mucins, which are a component of body mucous that are known to influence the microbiome and which have been associated with many autoimmune disaeases.    Before now, it was unknown how salivary mucins impacted the oral microbiome.

Researchers combined the bacteria Streptococcus mutans, which is known to be one of the many bacterial culprits behind cavities, with salivary mucins in the presence of artificial teeth.  They discovered that while the mucins did not prevent the bacteria from growing and proliferating, they did in fact prevent the S. mutans from attaching to the artificial teeth.  In fact over 95% of biofilm formation (which can cause cavities) was decreased between control samples and samples with the mucins.  The scientists noted that in the samples with mucins the cells simply never formed biofilms, and stayed in the planktonic (i.e. free floating) form.  They speculate that the mucins either physically prevent binding or are somehow changing the genetics of S. mutans so as to prevent production of binding proteins.

Follow-up studies in human subjects that compare the presence of mucins with cavity abundance would be interesting to see.  We all know people who, despite brushing and flossing multiple times a day, still seem to get cavities (myself included!), and others who, despite not going to a dentist in years and never brushing, don’t get any cavities at all.  Perhaps the concentration of mucins is responsible, and perhaps we could add mucins to toothpaste and forget about cavities all together.  

'Kissing' your microbiome goodbye

Kissing is perhaps the most direct way in which we transfer our microbiomes to one another.  In fact, there is even speculation that kissing may have evolved as a way of probing a potential partner’s microbiome for compatibility!  An investigation into how this microbial swap occurs was recently published in the journal Microbiome.  In the article, researchers measured the oral microbiome of couples that engaged in intimate kissing.

The researchers collected salivary samples and tongue swabs from 21 partners in Amsterdam, Netherlands and asked them how often they kiss, and the time of the last kiss.  They discovered that partners that kiss have more similar tongue microbiomes than those that don’t, and this similarity loosely increases with the frequency of kissing.  In addition, they discovered that the salivary microbiome is quite transient, and after 2 hours there is little retention of any swapped bacteria.  Finally they used yogurt to answer the age-old question: how many bugs are swapped during the average kiss?  The answer: 80 million!

Remember that the next time you are kissing someone new you are actually involved in a genetic swap of 80 million bacteria.  If your partner’s breath smells bad or saliva tastes bad, remember that it’s just his or her microbiome, but he or she is probably not ‘the one’.