Editors' ChoiceMicrobiology

The Microbial Origins of Obesity

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Science Translational Medicine  03 Sep 2014:
Vol. 6, Issue 252, pp. 252ec153
DOI: 10.1126/scitranslmed.3010265

The advent of advanced genomic sequencing and analytical tools has enabled the field of microbiome research to grow exponentially. One clinically relevant disease state with well-known microbiome associations is that of obesity and related metabolic disorders. In their new study, Cox et al. delve more deeply into this association with a series of mouse experiments that explore the underlying mechanisms.

The authors begin with the hypothesis that even transient perturbations in the gut microbiota at the time of initial acquisition will have lasting metabolic consequences. They achieved these perturbations by using low-dose penicillin, a practice frequently used to promote growth in livestock. Here, penicillin administration to pregnant mice was started shortly before birth and continued through weaning. This resulted in greater metabolic perturbations as compared with that of penicillin treatment started weeks after birth, at the time of weaning. Treated animals, particularly those treated before birth, led to obesity-related alterations in body mass, bone mineral content, adiposity, ileal atrophy, and concomitant host gene expression changes. Moreover, alterations in the gut microbiota preceded the metabolic changes, suggesting that they may be the mechanistic link. To better define causality, the gut microbiota from penicillin-treated animals was transferred to germ-free animals. These recipients, despite no actual penicillin exposure, experienced many of the same metabolic, histologic, and gene expression changes observed in penicillin-treated animals.

Another notable finding was that early antibiotic administration even of short duration led to lifelong metabolic changes despite a normalization in the gut microbiota. The authors also detailed the taxonomic composition of the microbiota, providing clues as to which among the bacterial species may play the key roles in these biological events.

Although the relevance of these findings should be tempered by the mouse model used, which has shown differences compared with other mammals, the implications are potentially far-reaching. They bear relevance to the livestock industry, which routinely uses low-dose antibiotics to enhance growth at the cost of rising antibiotic resistance. Perhaps antibiotic-free strategies can be identified that alter the gut microbiota and achieve the desired effect. These findings also introduce another element of caution in the use of antibiotics perinatally.

L. M. Cox et al., Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 158, 705–721 (2014). [Abstract]

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