Last week, I wrote about some research linking early childhood antibiotic use with obesity. One of the major limitations of those studies was that antibiotics were given at low doses, but over a long period of time, which does not really mimic how humans receive therapeutic doses.
But in a new study published today in Nature Communications (an open access journal - you can go read the paper yourself), that same lab followed up the earlier work exactly as you’d hope: they treated mice with therapeutic doses in short bursts, exactly as human children would experience treatment.
Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment
Before I get to the results, it’s worth considering a statistic mentioned in the introduction to this paper:
“In the United States, 262 million courses of antibiotics were prescribed to outpatients in 2011, a rate of 842 courses per 1,000 people annually. Use is highest in children under 10, who receive more than 40 million courses per year. Extrapolating from prescription data, the average US child receives three antibiotic courses in the first two years of life, and 10 courses by the age of 10”
This is extraordinary. Can it be true that American children get on average one life-threatening bacterial infection per year for their first 10 years of life? Somehow I think there might be another explanation. Interestingly, different regions of the US prescribe antibiotics at different rates. I mentioned in the last post that this corresponds with prevalence of obesity, but it’s also worth pointing out that areas with lower antibiotic use don’t seem to have more children dying from infections. But moving on to the present research…
As predicted, mice given early pulses of antibiotics gained more weight than their counterparts, though different antibiotics had different effects.
These differences are even particularly apparent when mice are fed a “high fat diet,” which more closely resembles Americans’ eating habits. It’s really not looking good for early childhood use of antibiotics. Sure, if you have a screaming infant and you don’t know what’s wrong, trying to treat them with something probably feels like the right call. But in many cases, antibiotics may be subscribed when they’re not warranted, and have unpredictable effects on the kid’s gut ecosystem.
Another interesting wrinkle - a couple of months ago I wrote about some work looking at the early childhood development of the microbiome, and how this might be altered or stunted by malnutrition. In this study, the authors used some fancy statistics to compute a “maturity score” - essentially looking at the presence of different microbial species that typically appear at different times during development and can give a rough “age” of the gut. They determined that the gut microbes of mice that received short pulses of antibiotics had lower maturity scores than those of untreated mice.
It’s unlikely these changes are the same changes that malnurished kids have, and it’s also unclear exactly what effect any of these alterations have. Probably, a lot of the species that serve as markers don’t actually have large effects on human health. Nobel et. al. did look at the gene expression of the altered microbiome and saw suggestive alterations, but I still don’t think it’s definitive.
One thing’s for sure though - if any other medical intervention caused such widespread disruption of any stage of human development, it would be applied a lot more judiciously. We have a long way to go before folks see our microbial passengers as the essential organ that they are, and a lot more work to understand all the ways it affects us. But work like this is necessary to move us on the way.