Antibiotics affect the mouth and gut differently

When we discuss antibiotic resistance, it’s not always clear where the resistance is developing or how exactly the resistance develops. A study out of the UK and Sweden looked at two niches, the gut and the mouth, to understand the difference between how the different parts of the body react to antibiotics.

The scientists discovered that these two parts of the body reacted and recovered very differently after a one-week course of antibiotics. They took fecal and saliva samples prior to the antibiotic regime and then gave the study participants a weeklong course of clindamycin, ciprofloxacin, minocycline, amoxicillin, or a placebo and continued taking fecal and saliva samples for a year.

They found that the oral microbiome recovered much faster than the gut microbiome back to its normal state. It took much longer for the gut microbiome to recover and for participants taking ciprofloxacin, diversity was changed even after 12 months. They also found that while participants largely had genes associated with antibiotic resistance in their gut prior to the trial, the amount of antibiotic resistant genes increased after taking the antibiotic. Antibiotic resistant genes in the mouth remained largely stable before and after treatment.  It was also observed that butyrate production, a health associated short-chain fatty acid, was severely affected by ciprofloxacin and clindamycin.

This raises a number of questions like why does the oral microbiome recover so much faster than the gut microbiome? And why isn’t there a similar increase in antibiotic resistant genes in the mouth like we see in the gut? While this study raises many questions, it provides an opportunity to look at the mouth and better understand what is unique about that environment in comparison to the gut. 

The oral microbiome can predict childhood caries

Early childhood caries is an oral disease common in young children.  The infection leads to sustained demineralization of tooth enamel and dentin and can also spread to gums and surrounding areas.  Unfortunately, the damage from this disease is irreversible and can put a child at risk for tooth loss for the rest of his or her life.  In an effort to explore different ways to prevent childhood caries, researchers from China sought to investigate whether or not changes in the oral microbiomes of children could serve as a predictive measurement for development of caries.  

In a longitudinal cross sectional study conducted over 2 years, the researchers examined spatial and temporal variations in the microbiomes of 50 4-year old preschoolers.  The researchers took microbiota samples from saliva and plaque at four different time points.  Based on clinical monitoring among this cohort, the children were further segmented into 3 groups based on diagnosis: 1) healthy, which constituted 17 children, 2) caries onset, which constituted 21 children, or 3) caries progression, which represented 12 in the group. 

It was found that the caries onset group experienced delayed microbiota development, adjusted for age (which has shown to be a significant confounder as microbiota composition changes significantly during development).  Furthermore, changes in microbiota composition were more associated with ECC in onset children as opposed to progression, thus lending to the possibility of using the microbiome composition as a predictive tool.  In this light, the researchers developed a model termed Microbial Indicators of Caries (MiC) and successfully diagnosed ECC saliva/plaque samples from healthy samples with 70% accuracy, while predicting ECC onset in children with 80% accuracy.  The MiC model derived a readout based on an identified “intermediate” state of microbiota that represents a compositional shift. 

We’ve discussed in the past how microbiome composition and metabolites could be indicators of disease.  These findings point to another potential tool that can use features of the microbiome as a diagnostic method.  More research and further understanding of our microbiome can introduce a new field with the potential to provide immense health benefits.  

The oral microbiome of schizophrenics differs from controls

Self-portrait of Vincent van Gogh, who likely had schizophrenia

The gut-brain axis is a very intriguing field that offers a lot of promise in making progress in neurological diseases.  The science is still very new, though, so much work needs to be done in establishing any connections between the microbiome and these diseases.  The reason the gut is normally explored is because of the strong connection between the gut and the brain via the vagus nerve, which in initial studies has been shown to be an important pathway for afferent and efferent connections.  Other body microbiomes’ connections to the brain have not yet been studied.  A new study that came out last week makes a connection between the oral microbiome and schizophrenia, a disease which had previously been linked to the gut microbiome.  The results were published in the journal PeerJ.

The scientists performed whole genome sequencing on the oropharyngeal microbiomes of 16 people with schizophrenia and 16 healthy people.  Importantly, the scientists note that the people with schizophrenia were more likely to be smokers and to be overweight, two qualities that are already associated with alterations of the oral microbiome.  The results showed that the schizophrenics had lower overall diversity of their oral microbiomes compared to controls.  Specifically, lactic acid bacteria, and especially Lactobacillus gasseri, were more abundant in the mouths of those with schizophrenia, even after controlling for other variables such as age and smoking status.

While this paper does not attempt to explain why these differences occur, they are quite interesting nonetheless.  If somehow the disease state can be characterized by the oral microbiome this could be important for diagnostics.  The next step is to actually establish if any of the connections between the bacteria in the body (including the mouth) and the brain are partly responsible causing the disease.  If this is the case then not only would it help explain the environmental causes of schizophrenia, but it would also lend itself to possible microbiome treatments for the disease, such as pro- or pre-biotics.

Vaginal microbiome once again tied to preterm birth

Preterm birth is major global health challenge.  Today, around 11% of all babies are born prior to 37 weeks, and are considered preterm.  Many of the causes of these preterm births are still unknown, but it is thought that around 25% of them may be related to a bacterial infection that comes from somewhere in the mother’s own body, i.e. her microbiome.  Many studies are now linking specific vaginal bacteria to risk of preterm birth, and other studies have even shown a connection between other microbiome sites, such as the gut and oral microbiome.  Unfortunately, studies on the microbiome and preterm birth are extremely difficult to conduct, so there are just not enough to have any sort of scientific consensus on the topic.  Last week though, a very rigorous study out f Stanford University was published in the Proceedings of the National Academy of Sciences that monitored expectant mothers vagina, gut, and oral microbiome throughout the course of her pregnancy and then for one year after.  Among many interesting findings, which are discussed below, the most important one was yet another connection between bacterial vaginosis and preterm birth.

The researchers monitored the vaginal, distal gut, salivary, and tooth/gum microbiomes of 49 women, 15 of which ended up delivering preterm, over the course of their pregnancy and for one year after.  Interestingly, the non-vaginal sites’ microbiomes remained relatively stable over the duration of the pregnancy, and even for the one year after.  The vaginal microbiome, however, did show some differences during and after pregnancy.

As many of our readers already know, a healthy vaginal flora is dominated by Lactobacilli, but around 20% of American women are dominated by other species, such as Gardnerella vaginalis, and have an overall increased vaginal diversity.  These women have what is known as community state type four, or CST4, and these women could be diagnosed with bacterial vaginosis (BV), though the clinical diagnosis is not so specific.  The other community state types, CST1, 2, 3, and 5, are dominated by different strains of Lactobacilli, and are generally regarded as healthy.  This current research showed that many of the women’s vaginal microbiomes actually shifted between various CST’s during pregnancy, most often shifting to and from CST4.  These transitions had no association with preterm birth, though.  After giving birth the vaginal microbiome became more diverse, and had greater abundances in anaerobic bacteria, such as Peptoniphilus, Prevotella, and Anaerococcus.  In addition, this usually coincided with a decrease in Lactobacilli.  Surprisingly, these changes did not seem to relate to mode of delivery (C-section of vaginal).

CST4 has been linked to preterm birth before, and this was reinforced in this study.  The scientists found that the longer a women’s vaginal microbiome was within CST4, the greater risk she had for preterm birth.  In addition, the abundance of Gardnerella and Ureaplasma, specifically, were linked to preterm birth.

This study reinforces what many microbiome scientists already suspect, and that is the importance of the vaginal flora in preterm birth.  It is unclear at this point if manipulating the vaginal flora prior to, or during pregnancy would help prevent preterm birth, but it is certainly worthy of discussion and clinical testing.  If you are reading this and wondering what your vaginal microbiome is, then we recommend you participate in the citizen science project, YourPrivateBiome, to find out.  You can learn more about it by following this link on our site, or just click the link above.

Periodontitis and its possible contribution to preterm birth

Evidence is accumulating that gum disease can lead to chronic systemic inflammation throughout the entire body.  In fact, bacteria from the mouth may be entering the vasculature through the gums and can wind up in various places around the body, like in the plaques that cause heart attacks.  Another location that these mouth bacteria can end up is in the placenta of expecting mothers.  This is important because of the increasing association between the placental microbiome and preterm birth.  Researchers from Spain investigated this connection by determining the placental microbiomes of pregnant women with and without periodontitis.  The results of their study were published last week in the journal Oral Diseases.

The researchers measured the placental microbiomes of 57 pregnant women, as well as determined their periodontitis statuses.  They discovered that the abundance of placental bacteria was significantly higher in women with periodontitis.  In addition, they identified Fusobacterium nucleatum was significantly higher in the placentas of women with periodontitis.  Also, 90% of women who had either preterm birth or very low birth weight infants carried F. nucleatum, compared to 62% of full term pregnancies.

Interestingly, other studies have shown F. nucleatum in the mouths of folks with deep gum pockets, which strengthens this connection between the conditions.  It is strange to consider the relationship between the mouth and placenta, which have seemingly little in common.  However, the microbiome of both are connected by the vasculature, and they apparently share many of the same bugs.  Until further research can establish better connections between these pregnancy outcomes and the microbiome we recommend all expecting mothers to floss and brush their teeth every day.

Identifying probiotics using healthy individuals for preventing oral disease

The oral microbiome consists of many hundreds of species of bacteria, some harmful and some beneficial. The importance of a healthy microbiome should be stressed not only because having clean, white teeth looks good but because diseases like periodontitis increase risk of other issues such as respiratory infections and inflammatory diseases. Having unhealthy teeth can cause more systematic problems than you would think. Probiotics, different from antibiotics, are one way that microbiome science is combating the colonization of harmful bacteria in the body. Many researchers have investigated using probiotics to maintain a normal healthy oral microbiome, and in a new study published last week, scientists researched probiotics that may reduce the smell of “bad breath” that is caused by volatile sulfur compounds, and prevent cavities and periodontitis.

The study, performed by researchers at the Yakult Central Institute for Microbiological Research in Tokyo, Japan (a division of Yakult, the makers of yogurts and probiotics),  was aimed toward finding new potential probiotic candidates. Thirty-two volunteers were recruited and selected based on factors such as non-smoking habits, no large cavities or bleeding on probing, and no bad breath. Oral bacteria samples were taken from multiple specific locations in the mouth of the volunteers. The bacteria were cultured in a lab and tested for the characteristics that follow: lack of production of volatile sulfur compounds (causes bad breath) and water insoluble glucan (causes cavities), antibacterial activity against bacteria that cause periodontitis, ability to healthily adhere to teeth and cells in the mouth, and caused no infections in an artificial mouth system or in a rat model.

After culturing in a lab and testing the criteria on 896 oral samples from the 32 participants, the study found that Lactobacillus crispatus YIT 12319, L. fermentum  YIT 12320, L. gasseri YIT 12321, and Streptococcus mitis YIT 12322 are good candidates for probiotics.  The next step is to now test for these probiotics’ effects in the mouths of many people, and likely develop a product.  Interestingly, L. crispatus and L. gasseri are two of the major bacterial strains found in a healthy vaginal microbiome, and perhaps this suggests a route of access for these bacteria to access the vagina. In any case, the promise of new ways to help maintain a healthy oral microbiome is exciting, and it is encouraging to read papers from major companies that have the ability to actually manufacture products in this space.