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Neonatal antibiotic exposure impairs child growth during the first six years of life by perturbing intestinal microbial colonization.

ABSTRACT: Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development. Here, we investigate the long-term impact of antibiotic treatment in the neonatal period and early childhood on child growth in an unselected birth cohort of 12,422 children born at full term. We find significant attenuation of weight and height gain during the first 6 years of life after neonatal antibiotic exposure in boys, but not in girls, after adjusting for potential confounders. In contrast, antibiotic use after the neonatal period but during the first 6 years of life is associated with significantly higher body mass index throughout the study period in both boys and girls. Neonatal antibiotic exposure is associated with significant differences in the gut microbiome, particularly in decreased abundance and diversity of fecal Bifidobacteria until 2 years of age. Finally, we demonstrate that fecal microbiota transplant from antibiotic-exposed children to germ-free male, but not female, mice results in significant growth impairment. Thus, we conclude that neonatal antibiotic exposure is associated with a long-term gut microbiome perturbation and may result in reduced growth in boys during the first six years of life while antibiotic use later in childhood is associated with increased body mass index.

SUBMITTER: Uzan-Yulzari A

PROVIDER: S-EPMC7838415 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Neonatal antibiotic exposure impairs child growth during the first six years of life by perturbing intestinal microbial colonization.

Uzan-Yulzari Atara A Turta Olli O Belogolovski Anna A Ziv Oren O Kunz Christina C Perschbacher Sarah S Neuman Hadar H Pasolli Edoardo E Oz Aia A Ben-Amram Hila H Kumar Himanshu H Ollila Helena H Kaljonen Anne A Isolauri Erika E Salminen Seppo S Lagström Hanna H Segata Nicola N Sharon Itai I Louzoun Yoram Y Ensenauer Regina R Rautava Samuli S Koren Omry O

Nature communications 20210126 1

Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development. Here, we investigate the long-term impact of antibiotic treatment in the neonatal period and early childhood on child growth in an unselected birth cohort of 12,422 children born at full term. We find significant attenuation of weight and height gain during the first 6 years of life after neonatal antibiotic exposure in boys, but not in girls, after adjusting for potentia ...[more]

PMID: 33500411

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Project description:BackgroundConsumption of antibiotics, a major global threat to public health, is perhaps the key driver of antibiotic resistance. Monitoring antibiotic consumption is crucial to tackling antimicrobial resistance. This study assessed antibiotic consumption trends during the last six years in the Bahir Dar branch of the Ethiopian pharmaceutical supply agency (EPSA), Northwest Ethiopia, in 2022.MethodsRetrospective data were collected in August 2022 based on antibiotic distribution data from the Bahir Dar Brach of EPSA from July 2016 to June 2022. Data were analyzed according to the Anatomic Therapeutic Classification (ATC) developed by the World Health Organization (WHO). We measured antibiotic consumption using a defined daily dose per 1000 inhabitants per day (DIDs) based on the Agency's catchment population. Descriptive statistics and trend analyses were conducted.ResultsAbout 30.34 DIDs of antibiotics were consumed during the six years. The consumption of antibiotics decreased by 87.4%, from 6.9 DIDs in 2016/17 to 0.9 DIDs in 2021/22. Based on the WHO AWaRe classification, 23.39 DIDs (77.1%) of the consumed antibiotics were from the Access category. Consumption of Access category antibiotics was decreased by 72.7% (from 5 to 0.5 DIDs) but Watch antibiotics decreased by 54.3% (from 1.8 to 0.4 DIDs). Oral antibiotics accounted for 29.19 DIDs (96.2%) of all consumed systemic antibiotics. The average cost expenditure per DDD for all antibiotics was 54.1 birr/DDD (0.4-482.3 birr/DDD). Only seven antibiotics accounted for DU90% and the cost expenditure per DDD for the DU90% antibiotics ranged from 0.4/DDD for Doxycycline to 232.8 birr/DDD for Piperacillin/tazobactam. Overall, during the last six years, the most commonly used antibiotic was Amoxicillin (10.1 DIDs), followed by Doxycycline (5.3 DIDs) and Ciprofloxacin (3.4 DIDs).ConclusionIn this study, we found that antibiotic usage was low and continuously declining over time. Minimizing unnecessary antibiotic usage is one possible approach to reduced AMR. However, a shortage of access to important medicines can compromise the quality of treatment and patient outcomes. A prospective study is needed to evaluate the balance of patient outcomes and reduce AMR by optimizing the community consumption of systemic antibiotics.

Project description:Antibiotics are frequently administered orally to treat bacterial infections not necessarily related to the gastrointestinal system. This has adverse effects on the commensal gut microbial community, as it disrupts the intricate balance between specific bacterial groups within this ecosystem, potentially leading to dysbiosis. We hypothesized that modulation of community composition and function induced by antibiotics affects intestinal integrity depending on the antibiotic administered. To address this a total of 60 Wistar rats (housed in pairs with 6 cages per group) were dosed by oral gavage with either amoxicillin (AMX), cefotaxime (CTX), vancomycin (VAN), metronidazole (MTZ), or water (CON) daily for 10-11 days. Bacterial composition, alpha diversity and caecum short chain fatty acid levels were significantly affected by AMX, CTX and VAN, and varied among antibiotic treatments. A general decrease in diversity and an increase in the relative abundance of Proteobacteria was observed for all three antibiotics. Additionally, the relative abundance of Bifidobacteriaceae was increased in the CTX group and both Lactobacillaceae and Verrucomicrobiaceae were increased in the VAN group compared to the CON group. No changes in microbiota composition or function were observed following MTZ treatment. Intestinal permeability to 4 kDa FITC-dextran decreased after CTX and VAN treatment and increased following MTZ treatment. Plasma haptoglobin levels were increased by both AMX and CTX but no changes in expression of host tight junction genes were found in any treatment group. A strong correlation between the level of caecal succinate, the relative abundance of Clostridiaceae 1 family in the caecum, and the level of acute phase protein haptoglobin in blood plasma was observed. In conclusion, antibiotic-induced changes in microbiota may be linked to alterations in intestinal permeability, although the specific interactions remain to be elucidated as changes in permeability did not always result from major changes in microbiota and vice versa.

Project description:BackgroundThe human intestinal microbiome is a complex community that contributes to host health and disease. In addition to normal microbiota, pathogens like carbapenem-resistant Enterobacteriaceae may be asymptomatically present. When these bacteria are present at very low levels, they are often undetectable in hospital surveillance cultures, known as occult or subclinical colonization. Through the receipt of antibiotics, these subclinical pathogens can increase to sufficiently high levels to become detectable, in a process called outgrowth. However, little is known about the interaction between gut microbiota and Enterobacteriaceae during occult colonization and outgrowth.ResultsWe developed a clinically relevant mouse model for studying occult colonization. Conventional wild-type mice without antibiotic pre-treatment were exposed to Klebsiella pneumoniae but rapidly tested negative for colonization. This occult colonization was found to perturb the microbiome as detected by both 16S rRNA amplicon and shotgun metagenomic sequencing. Outgrowth of occult K. pneumoniae was induced either by a four-antibiotic cocktail or by individual receipt of ampicillin, vancomycin, or azithromycin, which all reduced overall microbial diversity. Notably, vancomycin was shown to trigger K. pneumoniae outgrowth in only a subset of exposed animals (outgrowth-susceptible). To identify factors that underlie outgrowth susceptibility, we analyzed microbiome-encoded gene functions and were able to classify outgrowth-susceptible microbiomes using pathways associated with mRNA stability. Lastly, an evolutionary approach illuminated the importance of xylose metabolism in K. pneumoniae colonization, supporting xylose abundance as a second susceptibility indicator. We showed that our model is generalizable to other pathogens, including carbapenem-resistant Escherichia coli and Enterobacter cloacae.ConclusionsOur modeling of occult colonization and outgrowth could help the development of strategies to mitigate the risk of subsequent infection and transmission in medical facilities and the wider community. This study suggests that microbiota mRNA and small-molecule metabolites may be used to predict outgrowth-susceptibility. Video Abstract.

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Neonatal antibiotic exposure impairs child growth during the first six years of life by perturbing intestinal microbial colonization.

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Neonatal antibiotic exposure impairs child growth during the first six years of life by perturbing intestinal microbial colonization.

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