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.  

Antibiotic exposure during pregnancy may increase risk of obesity in children

We’ve talked a lot about the importance of a woman's microbiome during pregnancy.  Microbiota transfer from the mother to the fetus is critical toward development, having potential downstream health implications for the child.  Researchers in Denmark have recently pointed to the significance of the maternal microbiome with respective to risk of developing obesity during childhood.  Specifically, prenatal infection and neonatal antibiotic use are both associated with childhood obesity.  Researchers wanted to explore further and determine whether or not antibiotic administration prenatally is associated with childhood obesity.  

9,886 Danish children between the ages of 7 and 16 years old were analyzed over 10 years, and information was collected from routine school anthropometric evaluations.  To determine which of the children were exposed to antibiotics prenatally, prescription dispensations and infection-related hospital admissions information was collected from the mothers’ of the children.  Of all the children assessed, 3,280 – or 33% - were exposed to antibiotics prenatally. 

Among all 9,886 children, 768 (7.8%) were overweight as determined by body-mass index ratios.  Increase overweight incidence was correlated to antibiotic use during the second and third trimester.  309 (3.1%) children were considered obese.  Children with obesity were associated with increases in the number of antibiotic prescriptions for the mother.  Overall, antibiotic exposure prenatally was associated with a 26-29% increase in prevalence of both overweight and obesity in childhood. 

These findings point to an interesting relationship that deserves further exploration.  As mentioned, antibiotics have been shown to disrupt microbiome transfer from mother to fetus.  In addition, microbe-associated molecular patterns in development have been shown to be disrupted by antimicrobials.  These agents could also possibly disrupt endocrine and metabolic systems, leading to impaired energy homeostasis and metabolism, and consequently downstream weight issues. 

Obesity is becoming a major health concern for the global population.  Elucidating more information on the molecular underpinnings of the association between antibiotic use and prenatal development could help reveal more information, and perhaps create awareness of maternal antibiotic intake during pregnancy and/or encourage therapeutic intervention in children with obesity. 

Proton pump inhibitors increase risk of C. diff in children

Alka seltzer treats acid reflux without proton pump inhibitors

Acid reflux is a common problem among adults, and is often treated with acid suppression medication such as proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs). Acid suppression medication is also given to children over long periods of time. While there is a recognized connection between proton pump inhibition in adults and Clostridium difficile infection (CDI), a link between the drug intake by children and CDI has not been studied. As we’ve discussed on the blog before, infection by the bacteria C. difficile can cause serious harm to the intestinal tract and immune system. An article published by Clinical Infectious Diseases looks further into the relationship between acid suppression and CDI in children.

          Researchers at Columbia University Medical Center conducted a study using data from the Health Improvement Network, a medical records database. Data from 1995 to 2014 was used, and subjects were selected if they were aged 0-17 at the time of CDI diagnosis. The patients also needed the following requirements:  3 follow-up visits for patients younger than 1 year, and  1 follow-up visit for patients older than 1 year. Children with prior chronic conditions that may be linked to long-term acid suppression, such as neurological disorders and chronic gastrointestinal mucosal diseases, were excluded.

In the end, 650 cases were selected, with 68 of them being infants younger than 1 year. 3200 control cases were selected as well. After statistical analysis, it was found that there was no significant evidence of  age (1 year or 1-17 years) having an effect on the acid suppression-CDI relationship. It was found that the use of stronger proton pump inhibitors, rather than less-strong H2RAs, causes a significantly increased risk for CDI. Additionally, when the acid suppressant was used more recently (8-90 days) than distantly, the likely-hood of CDI was increased.

The researchers point out a potential error diagnosing CDI that could be causing the increase in children with the disease. In children, they say, symptoms of acid-related disorders may be very nonspecific, such as abdominal pain. Physicians then treat this with acid suppression medications, which, as discussed above, would then increase possibility of C. difficile colonization and growth.  However, the original abdominal pains may actually be symptoms of CDI. As a result, treating the CDI with acid suppressants is worsening the infection. With this new research, physicians might want to reconsider their options before treating what they think is an acid-related issue.