Mass antibiotic dosing alters children's gut microbiome, improves mortality
Mass administrations of azithromycin in Niger resulted in significant changes in the bacterial gut microbiome composition in children aged up to 5 years, according to study results published in Open Forum Infectious Diseases. However, changes in the microbiome stemming from antibiotic use did not suggest the presence of disease but were instead associated with improvements in childhood mortality, researchers said.
Although mass antibiotic dosing may increase the risk for the spread drug resistance, they been shown in previous research to reduce childhood mortality, particularly in sub-Saharan Africa.
In the MORDOR study — a large, double-masked, cluster-randomized controlled trial that took place between 2015 and 2017 in Niger, Malawi and Tanzania — researchers found “a significant 18% reduction in childhood mortality with mass azithromycin administrations in Niger.”
However, “the mechanism of mortality reduction is not clear, although the functional state of the gut microbiome has been linked in numerous ways to a child’s health and disease,” they said.
In a more recent analysis of the MORDOR trial, Thuy Doan, MD, PhD, of the Francis I. Proctor Foundation and the department of ophthalmology at the University of California, San Francisco, and colleagues studied children aged 1 to 60 months in 30 villages in the Dosa region of Niger who were randomly assigned to receive one oral administration of azithromycin or placebo every 6 months for 2 years. Rectal swabs were collected from 552 children in the placebo cohort and from 573 children in the azithromycin cohort 6 months after the second treatment. Using metagenomic deep sequencing, the researchers examined changes in the bacterial gut microbiome composition of the children.
They found significant changes in the bacterial gut microbiome composition in the children treated with azithromycin, with the stool bacterial communities treated with azithromycin significantly closer to each other or having a smaller Euclidean distance within groups compared with the placebo-treated children (P < .001). Researchers also found significantly less diversity of the gut microbiome in the azithromycin cohort compared with the placebo cohort when using inverse Simpson’s diversity index (P = .005).
“Generally, a reduction in the gut microbiome diversity at the individual level has been associated with a pathologic state, ranging from Clostridium difficile colitis to the development of obesity and diabetes,” the researches said. “This study illustrates that such an association does not hold at the community level.”
Rather, alterations in the gut microbiome was associated with improvements in mortality, they said.
“Two mass biannual azithromycin administrations in preschool children led to long-term alterations of the gut microbiome structure and community diversity,” the researchers concluded. “This same treatment resulted in a reduction in pediatric deaths. Determining the exact molecular mechanism(s) of azithromycin’s effect on mortality may help clarify possible large-scale implementation.” – by Bruce Thiel
Disclosures: The authors report no relevant financial disclosures.