Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment

Abstract

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 pediatric 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.

Increasing dietary nitrate has no effect on cancellous bone loss or fecal microbiome in ovariectomized rats

“…Estrogen metabolites are directly exposed to the gut microbiome through enterohepatic circulation, but very little is known about the direct interactions between estrogens and the gut microbiome. Future investigations are required to determine whether there is a causal role of the gut microbiome in bone loss in OVX 30, 74, 79 and to explore specific mechanisms by which the gut microbiome may effect bone metabolism in sex‐steroid deficiency.…”

Antibiotic perturbation of the preterm infant gut microbiome and resistome

“…Humanized gnotobiotic models in particular have benefited the field greatly. 10,16,51 Development of a humanized infant mouse model for preterm antibiotic therapy would allow for testing of clinical antibiotic protocols in a controlled environment in order to discern their relative impacts on the developing gut microbiota. Such analyses would build on the foundation laid by Gibson et al to provide an evidence-base supporting a personalized medicine approach to antibiotic treatment, wherein antibiotic use in preterm infant populations will be tailored to limit collateral microbiota disruptions and selection for resistance.…”

“…[9][10][11][12][13][14] One of the most common perturbations during this period, antibiotic therapy, 13,15 can substantially alter the gut microbiota and infant physiology. 10,[16][17][18][19][20][21] Because preterm infants are at high risk for infection, antibiotics are the most commonly prescribed medications in neonatal intensive care units (NICUs) in the United States ( Fig. 1) 15,22,23 accounting for 3 of the top 6 medications with the greatest relative increase in use in NICUs in the United States between 2005 and 2010.…”

The Changing Face of Inflammatory Bowel Disease: Etiology, Physiopathology, Epidemiology

“…As anticipated above, we further found that the risk may be specifically linked to the use of macrolide molecules, which, favoring gut colonization by yeasts (4), might loosen tight junctions and abnormally increase gut permeability. This clinical evidence is being corroborated by cutting-edge data from experimental animal work, showing that macrolide treatment of murine gut strongly impacts microbiome, jeopardizing resiliency following a significant diet change, with such an effect lasting several months (23). Based on this laboratory and clinical evidence, it has now become our policy to recommend family physicians to carefully reconsider their macrolide prescriptions.…”