Antibiotics in early life alter the murine colonic microbiome and adiposity

Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
Nature (Impact Factor: 41.46). 08/2012; 488(7413):621-6. DOI: 10.1038/nature11400
Source: PubMed


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.

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    • "Plots of a PCoA are commonly used in microbial ecology studies to explore relationships between samples/subjects and can be based on any dissimilarity between samples. Examples include UniFrac [42] [37] [67], DPCoA [12] [9] [47], Jenson-Shannon [13] [34] and Bray-Curtis [48] [11]. To describe our kernel regression framework, we first describe these common exploratory analyses in the general framework of " constrained ordination " . "
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    ABSTRACT: The analysis of human microbiome data is often based on dimension-reduced graphical displays and clustering derived from vectors of microbial abundances in each sample. Common to these ordination methods is the use of biologically motivated definitions of similarity. Principal coordinate analysis, in particular, is often performed using ecologically defined distances, allowing analyses to incorporate context-dependent, non-Euclidean structure. Here we describe how to take a step beyond ordination plots and incorporate this structure into high-dimensional penalized regression models. Within this framework, the estimate of a regression coefficient vector is obtained via the joint eigen properties of multiple similarity matrices, or kernels. This allows for multivariate regression models to incorporate both a matrix of microbial abundances and, for instance, a matrix of phylogenetically-informed similarities between the abundance profiles. Further, we show how this regression framework can be used to address the compositional nature of multivariate predictors comprised of relative abundances; that is, vectors whose entries sum to a constant. We illustrate this regression framework with several simulations using data from two recent studies on the gut and vaginal microbiome. We conclude with an application to our own data, where we also incorporate a significance test for the estimated coefficients that represent associations between microbial abundance and a response.
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    • "Gut contains an extremely complex and dense microbial community , and the encoding gene capacity exceeds that of the human genome by at least 100 fold (Gill et al. 2006). Gut microbiota are involved in the regulation of multiple host metabolic pathways, including signaling and immune-inflammatory axes (Kau et al. 2011) that physiologically connect the functions of gut, liver, muscle and brain (Nicholson et al. 2005; Tremaroli and Backhed 2012), which play important roles in host health (Guarner and Malagelada 2003). "
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    ABSTRACT: Antibiotics have been widely used for disease prevention and treatment of the human and animals, and for growth promotion in animal husbandry. Antibiotics can disturb the intestinal microbial community, which play a fundamental role in animals' health. Misuse or overuse of antibiotics can result in increase and spread of microbial antibiotic resistance, threatening human health and ecological safety. In this study, we used Illumina Hiseq sequencing, (1)H nuclear magnetic resonance spectroscopy and metagenomics approaches to investigate intestinal microbial community shift and antibiotic resistance alteration of the mice drinking the water containing tetracycline hydrochloride (TET). Two-week TET administration caused reduction of gut microbial diversity (from 194 to 89 genera), increase in Firmicutes abundance (from 24.9 to 39.8 %) and decrease in Bacteroidetes abundance (from 69.8 to 51.2 %). Metagenomic analysis showed that TET treatment affected the intestinal microbial functions of carbohydrate, ribosomal, cell wall/membrane/envelope and signal transduction, which is evidenced by the alteration in the metabolites of mouse serum. Meanwhile, in the mouse intestinal microbiota, TET treatment enhanced the abundance of antibiotic resistance genes (ARGs) (from 307.3 to 1492.7 ppm), plasmids (from 425.4 to 3235.1 ppm) and integrons (from 0.8 to 179.6 ppm) in mouse gut. Our results indicated that TET administration can disturb gut microbial community and physiological metabolism of mice, and increase the opportunity of ARGs and mobile genetic elements entering into the environment with feces discharge.
    Ecotoxicology 10/2015; DOI:10.1007/s10646-015-1540-7 · 2.71 Impact Factor
    • "The composition of gut microbiota is constantly affected by antibiotics, which are routinely administered to treat various infections (Cho et al., 2010; Jernberg et al., 2010; Pérez-Cobas et al., 2012). Clinical research has shown that antibiotics induce diarrhoea (Alam and Mushtaq, 2009) in children and older patients, and could even cause IBD. "
    T Wang · X Hu · S Liang · W Li · X Wu · L Wang · F Jin ·
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    ABSTRACT: Gut microbiota play a vital role in maintaining the health of the host. Many factors affect gut microbiota; application of broad range antibiotics disturb microbiota, while probiotic application protects the microbiota. To investigate how probiotics alter the physiological and psychological changes induced by antibiotics, we tested the performance of ampicillin-treated rats in the presence or absence of Lactobacillus fermentum strain NS9, in elevated plus maze and Morris water maze. The results showed that NS9 normalised the composition of gut microbiota and alleviated the ampicillin-induced inflammation in the colon. The levels of the mineralocorticoid and N-methyl-D-aspartate receptors were also elevated in the hippocampus of the ampillicin+NS9 treated group. NS9 administration also reduced the anxiety-like behaviour and alleviated the ampicillin-induced impairment in memory retention. These findings suggest that NS9 is beneficial to the host, because it restores the physiological and psychological abnormalities induced by ampicillin. Our results highlight how gut contents regulate the brain, and shed light on the clinical applications of probiotics to treat the side effect of antibiotics and mental disorders.
    Beneficial Microbes 04/2015; 6(5):1-11. DOI:10.3920/BM2014.0177 · 2.61 Impact Factor
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