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Antibiotics in early life alter the murine colonic microbiome and adiposity.

ABSTRACT: Antibiotics administered in low doses have been widely used as growth promoters in the agricultural industry since the 1950s, yet the mechanisms for this effect are unclear. Because antimicrobial agents of different classes and varying activity are effective across several vertebrate species, we proposed that such subtherapeutic administration alters the population structure of the gut microbiome as well as its metabolic capabilities. We generated a model of adiposity by giving subtherapeutic antibiotic therapy to young mice and evaluated changes in the composition and capabilities of the gut microbiome. Administration of subtherapeutic antibiotic therapy increased adiposity in young mice and increased hormone levels related to metabolism. We observed substantial taxonomic changes in the microbiome, changes in copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids, increases in colonic short-chain fatty acid levels, and alterations in the regulation of hepatic metabolism of lipids and cholesterol. In this model, we demonstrate the alteration of early-life murine metabolic homeostasis through antibiotic manipulation.

SUBMITTER: Cho I

PROVIDER: S-EPMC3553221 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Antibiotics in early life alter the murine colonic microbiome and adiposity.

Cho Ilseung I Yamanishi Shingo S Cox Laura L Methé Barbara A BA Zavadil Jiri J Li Kelvin K Gao Zhan Z Mahana Douglas D Raju Kartik K Teitler Isabel I Li Huilin H Alekseyenko Alexander V AV Blaser Martin J MJ

Nature 20120801 7413

Antibiotics administered in low doses have been widely used as growth promoters in the agricultural industry since the 1950s, yet the mechanisms for this effect are unclear. Because antimicrobial agents of different classes and varying activity are effective across several vertebrate species, we proposed that such subtherapeutic administration alters the population structure of the gut microbiome as well as its metabolic capabilities. We generated a model of adiposity by giving subtherapeutic an ...[more]

PMID: 22914093

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Project description:Broad-spectrum antibiotics for suspected early-onset neonatal sepsis (sEONS) may have pronounced effects on gut microbiome development and selection of antimicrobial resistance when administered in the first week of life, during the assembly phase of the neonatal microbiome. Here, 147 infants born at ≥36 weeks of gestational age, requiring broad-spectrum antibiotics for treatment of sEONS in their first week of life were randomized 1:1:1 to receive three commonly prescribed intravenous antibiotic combinations, namely penicillin + gentamicin, co-amoxiclav + gentamicin or amoxicillin + cefotaxime (ZEBRA study, Trial Register NL4882). Average antibiotic treatment duration was 48 hours. A subset of 80 non-antibiotic treated infants from a healthy birth cohort served as controls (MUIS study, Trial Register NL3821). Rectal swabs and/or faeces were collected before and immediately after treatment, and at 1, 4 and 12 months of life. Microbiota were characterized by 16S rRNA-based sequencing and a panel of 31 antimicrobial resistance genes was tested using targeted qPCR. Confirmatory shotgun metagenomic sequencing was executed on a subset of samples. The overall gut microbial community composition and antimicrobial resistance gene profile majorly shift directly following treatment (R2 = 9.5%, adjusted p-value = 0.001 and R2 = 7.5%, adjusted p-value = 0.001, respectively) and normalize over 12 months (R2 = 1.1%, adjusted p-value = 0.03 and R2 = 0.6%, adjusted p-value = 0.23, respectively). We find a decreased abundance of Bifidobacterium spp. and increased abundance of Klebsiella and Enterococcus spp. in the antibiotic treated infants compared to controls. Amoxicillin + cefotaxime shows the largest effects on both microbial community composition and antimicrobial resistance gene profile, whereas penicillin + gentamicin exhibits the least effects. These data suggest that the choice of empirical antibiotics is relevant for adverse ecological side-effects.

Project description:BackgroundPrenatal antibiotic exposure has been associated with an altered infant gut microbiome composition and higher risk of childhood obesity, but no studies have examined if prenatal antibiotics simultaneously alter the gut microbiome and adiposity in infants.MethodIn this prospective study (Nurture: recruitment 2013-2015 in North Carolina, United States), we examined in 454 infants the association of prenatal antibiotic exposure (by any prenatal antibiotic exposure; by trimester of pregnancy; by number of courses; by type of antibiotics) with infant age- and sex-specific weight-for-length z score (WFL-z) and skinfold thicknesses (subscapular, triceps, abdominal) at 12 months of age. In a subsample, we also examined whether prenatal antibiotic exposure was associated with alterations in the infant gut microbiome at ages 3 and 12 months.ResultsCompared to infants not exposed to prenatal antibiotics, infants who were exposed to any prenatal antibiotics had 0.21 (95% confidence interval [CI] 0.02, 0.41) higher WFL-z at 12 months, and 0.28 (95% CI 0.02, 0.55) higher WFL-z if they were exposed to antibiotics in the second trimester, after adjustment for potential confounders, birth weight, and gestational age. We also observed a dose-dependent association (P-value for trend?=?0.006) with infants exposed to ??3 courses having 0.41 (95% CI 0.13, 0.68) higher WFL-z at 12 months. After further adjustment for delivery method, only second-trimester antibiotic exposure remained associated with higher infant WFL-z (0.27, 95% CI 0.003, 0.54) and subscapular skinfold thickness (0.49 mm, 95% CI 0.11, 0.88) at 12 months. Infants exposed to second-trimester antibiotics versus not had differential abundance of 13 bacterial amplicon sequence variants (ASVs) at age 3 months and 17 ASVs at 12 months (false discovery rate adjusted P-value <?0.05).ConclusionsPrenatal antibiotic exposure in the second trimester was associated with an altered infant gut microbiome composition at 3 and 12 months and with higher infant WFL-z and subscapular skinfold thickness at 12 months.

Dataset Information

Antibiotics in early life alter the murine colonic microbiome and adiposity.

Publications

Antibiotics in early life alter the murine colonic microbiome and adiposity.

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