Antibiotics in early life alter the murine colonic microbiome and adiposity.
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.
Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
Ilseung
I
Cho
Shingo
S
Yamanishi
Laura
L
Cox
Barbara A
BA
Methé
Jiri
J
Zavadil
Kelvin
K
Li
Zhan
Z
Gao
Douglas
D
Mahana
Kartik
K
Raju
Isabel
I
Teitler
Huilin
H
Li
Alexander V
AV
Alekseyenko
Martin J
MJ
Blaser
D050154:Adiposity / Q000187:drug effects* / Q000502:physiology; D000367:Age Factors; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D002432:Cecum / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000382:microbiology*; D005232:Fatty Acids, Volatile / Q000378:metabolism; D005243:Feces / Q000382:microbiology; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D054892:Metagenome / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D014886:Weaning
D000900:Anti-Bacterial Agents; D005232:Fatty Acids, Volatile; D005749:Gastric Inhibitory Polypeptide; D002784:Cholesterol