Gut bacteria may help prevent asthma in children

The world has seen an explosive rise in asthma over the past three decades. Such a rise in prevalence cannot be only a result of genetic variation and leads us to believe that environmental factors play an important role in this change. There are several possible explanations for this including what we call the “hygiene hypothesis”, or the idea that we now live in an environment that is too clean and we are no longer exposed to the bacteria and germs that earlier generations were exposed to. Another possible explanation is as the world changes and becomes more modern, these environmental changes are affecting our microbiome and the “normal” microbiome is shifting to a new normal.

To better understand why some children are at high risk for becoming asthmatic, scientists in Canada studied the microbiome of 319 children in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. They sequenced fecal samples from the children and found that 4 groups of bacteria that were decreased in prevalence compared to the children without asthma. Bacteria from the genus Lachnospira, Veillonella, Faecalibacterium, and Rothia (FLVR) were at lower levels after 3 months for the children at high risk for asthma however over time, this leveled out and was similar to the children not at risk for asthma.

The study did not identify what exactly caused these differences as there could be several reasons for these differences including antibiotic use, the method in which the child was delivered either vaginally or by C-section, and if the child was breastfed or not. It is also possible and maybe even likely that some of the mother’s behaviors during the pregnancy such as diet could play an important role in the early development of the child’s microbiome.

The next obvious question is what can we do about this? Does this mean that we can now treat children that are deficient of these bacteria and they won’t get asthma? While it sounds simple, we don’t yet know too much about these bacteria and it will be important to better understand the impact his would have on the rest of development. Promising results from this study did show that when mice with low levels of FLVR were treated with probiotic samples of the bacteria, it protected them from getting asthma.

This is a very exciting study that may lead to new diagnostics for asthma and with more research and understanding, allow us to prevent the disease from developing. 

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 nasal microbiome of infants may impact risk of developing asthma

Many lower respiratory illnesses have been shown to associate with specific lung, throat and nasal bacteria, but the role of the microbiome is still unclear, and mechanisms for the connection have yet to be proven.  Of particular interest is asthma, which affects around 7% of people in the US, and increases a person’s risk for many other conditions.  While it is normally diagnosed in toddlers, scientists believe that the groundwork for the disease is actually laid during infancy.  With that in mind, researchers in Australia performed the first longitudinal study of infants’ nasopharyngeal (nose and throat) during the first year of their lives, and tracked episodes of respiratory illness during that time.  They discovered a strong connection between the microbiome and respiratory illness, including asthma, and last month published their results in Cell Host and Microbe.

The researchers collected nasopharyngeal microbiome samples from 234 infants at different time points during their first year of life.  Most infants’ microbiomes were dominated by the following species: Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Alloiococcus otitidis.  Interestingly, this was true for infants regardless of birth delivery mode (i.e. cesarean or vaginal) as well as length of breast feeding.  In contrast, having a furry animal in the house tended to increase the abundance of Streptococcus, but having older siblings tended to decrease it.  In addition, there were strong seasonal effects on the microbiome, with Haemophilus being associated with the summer, and Moraxella the winter.  In children with respiratory illness, Haemophilus, Moraxella, and Streptococcus were most frequently measured, and Staphylococcus, Alloiococcus, and Corynebacterium least frequently measured.

When the scientists compared their results with the asthma outcomes of the children at 5 years old they noticed one significant trend.  Colonization by Streptococcus at around 2 months old, which was asymptomatic at the time and occurred in 14% of infants tested, was strongly connected to chronic wheezing (itself an indication of asthma) at 5 years old.  They suggest that the developing airways in infants may be especially vulnerable to Streptococcus.

This long term study does a really nice job of defining how the microbiome grows and develops in the airways of infants – something which previously hadn’t been performed at such a large scale.  While this study alone does not figure out exactly what the microbiome’s role is in childhood respiratory illnesses, it does provide a baseline for future studies to work off of.   

Breastfeeding associated with intelligence later in life

Positive association between breastfeeding and intelligence, between three tiers of family income.  Five IQ points is 1/3 of a standard deviation. 

Editor’s note: I would like to tread very lightly on this topic because of the complexity of the relationships between all the factors discussed and the implications a study like this has.  I probably would not have written about it at all, had it not been published in such a prestigious medical journal, and had been as comprehensive as it was.

Breast milk is the ultimate pre- and probiotic.  It is essential in developing infants’ microbiomes by inoculating and enriching their guts in certain bacterial species.  There have been a number of studies showing alterations of the gut microbiomes of infants that are formula fed, and other studies showing that formula feeding results in a higher risk of asthma and allergies later in life.  The complicated relationship between breastfeeding, the microbiome, and phenotypes like autoimmune diseases are not understood at a mechanistic level.  Still though, it appears that formula feeding, rather than breastfeeding, may have long term consequences for the health of a child.

To that end, there had been a few small scale studies that demonstrated a general association between breastfeeding an IQ.  Just last week, a new study, much more comprehensive than any previous one, delved into this topic and found the same result: duration of breastfeeding was positively associated with IQ, educational level, and income.  The results of this study were published in The Lancet.

In 1982 researchers from Brazil began a longitudinal study using a cohort of over 500 newborn infants.  At that time, one of the things the scientists measured was the duration that each infant was breastfed.  Then, in 2012, the researchers followed up with 3000 of those people in the original study and surveyed them for their educational levels and incomes, as well as measured their IQs.  They discovered that each of these three variables was directly related with the length of breastfeeding, with the possibility that over 12 months of breastfeeding actually slightly decreased each.  Even after factoring in confounding variables such as maternal education, family income, and birthweight the relationship between breastfeeding and IQ, education, and income still held.  The researchers acknowledged the link was tenuous, and that there exists a whole host of other important variables that were not measured in 1982.  Nevertheless, the study suggests that breastfeeding improves intelligence upon adulthood.

Breastfeeding, if possible, is clearly preferred to formula feeding, and studies like this show that it may be in everyone’s interest to promote breastfeeding children.  It will be necessary to decipher the connection between breastfeeding, the microbiome, and these observations, but with more studies in the pipeline showing the value in breastfeeding everyone should be aware of its importance.