Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment
Yael R. Nobel1,*, Laura M. Cox1,2,*, Francis F. Kirigin1, Nicholas A. Bokulich1, , Shingo Yamanishi1, Isabel Teitler1, Jennifer Chung1, Jiho Sohn1, Cecily M. Barber1, David S. Goldfarb1,3, Kartik Raju1, Sahar Abubucker4,Yanjiao Zhou4,5,9, Victoria E. Ruiz1, Huilin Li6, Makedonka Mitreva4,7, Alexander V. Alekseyenko1,8,George M. Weinstock4,9, Erica Sodergren4,9 & Martin J. Blaser1,2,3
Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development.
Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.
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