Antibiotic perturbation of the murine gut microbiome enhances the adiposity, insulin resistance, and liver disease associated with high-fat dietReport as inadecuate




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Genome Medicine

, 8:48

Translating the microbiome: health and disease

Abstract

BackgroundObesity, type 2 diabetes, and non-alcoholic fatty liver disease NAFLD are serious health concerns, especially in Western populations. Antibiotic exposure and high-fat diet HFD are important and modifiable factors that may contribute to these diseases.

MethodsTo investigate the relationship of antibiotic exposure with microbiome perturbations in a murine model of growth promotion, C57BL-6 mice received lifelong sub-therapeutic antibiotic treatment STAT, or not control, and were fed HFD starting at 13 weeks. To characterize microbiota changes caused by STAT, the V4 region of the 16S rRNA gene was examined from collected fecal samples and analyzed.

ResultsIn this model, which included HFD, STAT mice developed increased weight and fat mass compared to controls. Although results in males and females were not identical, insulin resistance and NAFLD were more severe in the STAT mice. Fecal microbiota from STAT mice were distinct from controls. Compared with controls, STAT exposure led to early conserved diet-independent microbiota changes indicative of an immature microbial community. Key taxa were identified as STAT-specific and several were found to be predictive of disease. Inferred network models showed topological shifts concurrent with growth promotion and suggest the presence of keystone species.

ConclusionsThese studies form the basis for new models of type 2 diabetes and NAFLD that involve microbiome perturbation.

AbbreviationsclrCentered log-ratio

DEXADual energy X-ray absorptiometry

FnRFemale non-responders

HFDHigh-fat diet

HOMA-IRHomeostatic model assessment of insulin resistance

IPGTTIntraperitoneal IP glucose tolerance tests

IPITTIntraperitoneal insulin tolerance tests

ISOMDSIsometric multidimensional scaling

LEfSeLinear discriminant analysis effect size

MDSMultidimensional scaling

NAFLDNon-alcoholic fatty liver disease

pamPartitioning around mediods

PCoAPrincipal coordinates analysis

SPIEC-EASISparse Inverse Covariance estimation for Ecological ASsociation Inference

sPLSL1-penalized partial least squares regression

StARSStability approach to regularization selection

STATSub-therapeutic antibiotic treatment

T2DMType 2 diabetes

Electronic supplementary materialThe online version of this article doi:10.1186-s13073-016-0297-9 contains supplementary material, which is available to authorized users.

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