Cited by 1,613Gut microbiota and healthAnimal Nutrition and PhysiologyAdipokines, Inflammation, and Metabolic Diseases

Antibiotics in early life alter the murine colonic microbiome and adiposity

Open access
Cho, Ilseung, Yamanishi, Shingo, Cox, Laura, Methé, Barbara A., Zavadil, Jiri, Li, Kelvin, Gao, Zhan, Mahana, Douglas +5 more·2012·Nature

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.

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  • In humans, members belonging to the Lachnospiraceae family are protective against C. difficile and metabolic disorders.

    “In humans, members belonging to the Lachnospiraceae family have been shown to be protective against C. difficle (Petrof, 2013) and metabolic disorders (Cho et al., 2012).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Cho et al., 2012

    The Cho citation is attached to the claim about metabolic disorders, not the separate C. difficile claim. In ‘STAT alters the composition of intestinal microbiota’ (page unavailable), the paper reports a Lachnospiraceae bloom in antibiotic-exposed mice alongside increased adiposity. It does not show protection against metabolic disorders in humans; its reported association points in the opposite direction. (LLM, conf=0.79)

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  • Early antibiotic treatment changed intestinal microbiota significantly and altered short-chain fatty acid metabolism.

    “In addition, by investigating the effect of early antibiotics on intestinal microbiota, a study revealed that the composition of intestinal microbiota changed significantly and the metabolism of SCFAs was altered after treatment with subtherapeutic antibiotic therapy.56”
  • Difficulty in maintaining new (non-native) microbiota in recipient mice, whether germ-free or those in which gut microbiota suppression was initially performed with oral mixture of poorly absorbed antibiotics, has been reported in other studies.

    “Difficulty in maintaining new (non-native) microbiota in recipient mice, whether germ-free or those in which gut microbiota suppression was initially performed with oral mixture of poorly absorbed antibiotics, has been reported in other studies (30-32).”
  • Antibiotic exposure early in life correlates with obesity in people and in mice.

    “The use of antibiotics in early life is associated with obesity in both people and mice”
  • Multiple evidence streams indicate that gut microbes contribute to obesity.

    “Several lines of evidence support the role of gut microbiota in obesity.”

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Research works printed but not linked: 1

  1. [26]Ley RE Obesity alters gut microbial ecology Proc Natl Acad Sci USA 102 11070 11075 2005 16033867 PMC1176910

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Authors
Cho, I., Yamanishi, S., Cox, L., Methé, B. A., Zavadil, J., Li, K., Gao, Z., Mahana, D., Raju, K., Teitler, I., Li, H., Alekseyenko, A. V., & Blaser, M. J.
Affiliations
  • New York University (US)
  • J. Craig Venter Institute (US)
  • VA NY Harbor Healthcare System (US)
Corresponding author
Blaser, Martin J.
Venue
Nature
Published
2012-08
Volume
488
Issue
7413
Pages
621-626
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2003836872
Cited by
1,613
References
67
Citations by year
2026: 29 · 2025: 65 · 2024: 94 · 2023: 92 · 2022: 109 · 2021: 158 · 2020: 191 · 2019: 142 · 2018: 139 · 2017: 162 · 2016: 122 · 2015: 106 · 2014: 98 · 2013: 88 · 2012: 15
FWCI
39.50
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Rutgers University Community Repository (Rutgers University) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institutes of Health (UL1TR000038)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK090989, T-R01 DK090989)
  • National Center for Research Resources (UL1RR029893)
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
growth promoters, gut microbiota, colonic microbiota, adiposity, short-chain fatty acids, carbohydrate metabolism, lipid metabolism, cholesterol metabolism, metabolic homeostasis, livestock feed additives
MeSH terms
Age Factors, Animals, Anti-Bacterial Agents, Body Composition, Body Weight, Bone Development, Cecum, Cholesterol, Colon, Fatty Acids, Volatile, Feces, Female, Gastric Inhibitory Polypeptide, Liver, Male, Mice, Inbred C57BL, Weaning, Bone Density, Polymerase Chain Reaction, Adiposity, Lipid Metabolism, Mice, Metagenome

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