Allergy and Asthma Risk in Children: A Gut Bacteria Metabolite Culprit Identified

Two weeks ago, I wrote  about a retrospective study out of Loyola University in which researchers looked at the relationship of the early introduction of antibiotics to the development of allergy and asthma. If you recall, they found, “Exposure to these medicines in their first year was significantly correlated with the development of asthma, but not with allergic rhinitis.  However, there was a significant association of lifetime antibiotics to the development of both diseases.”

I thought it would be a good follow-up to report to you the results of a 2nd study on the topic, this one out of the University of California at San Francisco.[i]  Apparently, a particular fat molecule (12,13-diHOME) has been found at high levels in the feces of babies at high risk for developing asthma and allergy in childhood.  Previous research found that this particular molecule actually lowers both activity and levels of regulatory T cells (Treg) – which, as you know, are the “off switch” to the proinflammatory system, producing various anti-inflammatory cytokines (chemical messengers). These scientistis found,  in animal studies, that delivering this fat molecule into the guts of mice causes a direct reduction of Treg in their lungs while also increasing lung inflammation.

The researchers tracked down the production of  12,13-diHOME to a few bacterial genes, and when bacteria with those genes were introduced to the microbiomes of mice, sure enough, Tregs in the lungs were adversely affected.  (The genes were found overexpressed in specific strains of E. coli (E. faecalis), and 2 species of B. bifidum.)

They then looked at fecal samples from 1 month old babies and found a distinct association between bacteria with those genes and the subsequent likelihood of the baby developing asthma – and allergy and eczema:  “…12,13-diHOME was present in all neonatal stool; however, significantly higher concentrations were detected in the stool of neonates who subsequently developed atopy [by 2 years of age] and/or asthma [by 4 years of age], even after adjusting for potential confounding factors.”  This finding was replicated in a second group of babies.

Interestingly, the stool samples came from cohorts of babies that were collected years ago for research purposes. They were from ethnically diverse babies, collected in different places in California and years apart.  The researchers did indeed take into account factors known to influence asthma and allergy risk, like maternal smoking or breast feeding in that first month of life.  Essentially though, they were able to conclude that these did not sway the results:  elevated levels of 12,13-di-HOME was the deciding factor. Unfortunately, there was no information that I spotted in the article about antibiotics in that first month of life. That would be darn interesting to know, wouldn’t it?

At this point, we have no information as to how to lower levels of this molecule.  Would probiotics help, for example?  The authors conclude that this one fat molecule, and these 3 genes, are undoubtedly not the only factors involved in the development of allergy and asthma in children.  (They also didn’t look at whether or not any other inflammatory chronic diseases developed in the children.)  We’ll just have to wait for more research.  Still – this is an awfully compelling bit of work, isn’t it?

[i] Levan, SR, et. al. Elevated faecal 12,13-diHOME concentration in neonates at high risk for asthma is produced by gut bacteria and impedes immune tolerance.  Nature Microbiology. 2019. doi: 10.1038/s41564-019-0498-2

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