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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 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.

SUBMITTER: Nobel YR

PROVIDER: S-EPMC4491183 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment.

Nobel Yael R YR Cox Laura M LM Kirigin Francis F FF Bokulich Nicholas A NA Yamanishi Shingo S Teitler Isabel I Chung Jennifer J Sohn Jiho J Barber Cecily M CM Goldfarb David S DS Raju Kartik K Abubucker Sahar S Zhou Yanjiao Y Ruiz Victoria E VE Li Huilin H Mitreva Makedonka M Alekseyenko Alexander V AV Weinstock George M GM Sodergren Erica E Blaser Martin J MJ

Nature communications 20150630

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 ...[more]

PMID: 26123276

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Project description:The acquisition and development of infant gut microbiota can be influenced by numerous factors, of which early antibiotic treatment is an important one. However, studies on the effects of antibiotic treatment in early life on clinical outcomes and establishment and development of the gut microbiota of term infants are limited. Disturbed microbiota composition is hypothesized to be an underlying mechanism of an aberrant development of the immune system. This study aims to investigate the potential clinical and microbial consequences of empiric antibiotic use in early life.450 term born infants, of whom 150 are exposed to antibiotic treatment in early life and 300 are not (control group), are included in this observational cohort study with a one-year follow-up. Clinical outcomes, including coughing, wheezing, fever >38 °C, runny nose, glue ear, rash, diarrhea and >3 crying hours a day, are recorded daily by parents and examined by previously defined doctor's diagnosis. A blood sample is taken at closure to investigate the infant's vaccination response and sensitization for food and inhalant allergens. Fecal samples are obtained at eight time points during the first year of life. Potential differences in microbial profiles of infants treated with antibiotics versus healthy controls will be determined by use of 16S-23S rRNA gene analysis (IS-pro). Microbiota composition will be described by means of abundance, diversity and (dis)similarity. Diversity is calculated using the Shannon index. Dissimilarities between samples are calculated as the cosine distance between each pair of samples and analyzed with principal coordinate analysis. Clinical variables and possible associations are assessed by appropriate statistics.Both clinical quantitative and qualitative microbial effects of antibiotic treatment in early life may be demonstrated. These findings can be important, since there is evidence that manipulation of the infant microbiota by using pre- or probiotics can restore the ecological balance of the microbiota and may mitigate potential negative effects on the developing immune system, when use of antibiotics cannot be avoided.ClinicalTrials.gov NCT02536560. Registered 28 August 2015.

Project description:Background and objectivesThe impact of antibiotics use early in life on later-in-life morbidities has received substantial attention as explanations for atopic and metabolic disorders with a surge as modern lifestyle diseases. The objective of this study was to perform meta-analyses to determine if antibiotics administration during the first 2 years of infant life is associated with increased risks of atopic or metabolic disorders later in life.MethodologyWe screened more than 100 English-language prospective and retrospective studies published between January 2002 and March 2020 and assessed study quality using the Newcastle-Ottawa scale. We performed overall and subgroup meta-analyses on 31 high-quality comparable studies on atopic and 23 on metabolic disorders, involving more than 3.5 million children.ResultsAntibiotic exposure prenatally and during the first 2 years of life significantly impacts the risk of developing atopic and metabolic disorders. Exposure during the first 6 months of life appears most critical, consistent with this being the time when the microbiome is most susceptible to irreversible perturbations. The presence of dose-response associations and stronger impacts of broad- than narrow-spectrum antibiotics further point to effects being mediated by microbiota-induced changes.Conclusions and implicationsOur findings support that antibiotics use is a mismatch to modernity that can negatively affect the symbiotic associations we rely on for proper immune function and metabolism. Improving our understanding of these associations, the underlying proximate mechanisms and the impact of antibiotics use on future human-symbiont evolution will be important to improve human health.Lay summaryThe use of antibiotics in infancy has been suggested to increase the risks of atopic and metabolic disorders later in life. Through meta-analyses of more than 100 studies of >3.5 million children, we confirm these risks, and show that patterns are consistent with effects being due to microbiota-driven changes.

Dataset Information

Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment.

Publications

Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment.

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