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Antibiotics in early life alter the murine colonic microbiome and adiposity
Open accessAbstract
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 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
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In the citing paper
“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”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [56]
In the citing paper
“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).”
From Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation (2015) · cites this paper as [31]
In the citing paper
“The use of antibiotics in early life is associated with obesity in both people and mice”
From Diet–microbiota interactions as moderators of human metabolism (2016) · cites this paper as [66]
In the citing paper
“Several lines of evidence support the role of gut microbiota in obesity.”
From Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook (2015) · cites this paper as [80]
In the citing paper
“Lean and obese individuals show marked differences in the gut microbiome.80”
From Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook (2015) · cites this paper as [80]
In the citing paper
“antibiotic administration increases bone density in young mice (11,12)”
From Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics (2016) · cites this paper as [11]
In the citing paper
“Subsequently, it was discovered that disruptions to the microbiome early in life can promote heightened adiposity5.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [5]
In the citing paper
“Exposure to antibiotics during weaning changed gut microbial communities with increasing metabolic capacity to produce acetate, propionate, and butyrate in C57BL/6J mice.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [5]
In the citing paper
“Influx of these SCFAs to the liver resulted in substantial changes in the regulation of hepatic lipid metabolism and obese phenotype5.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [5]
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McCabe, L. R., Britton, R. A., & Parameswaran, N. (2015) · Current Osteoporosis Reports · doi:10.1007/s11914-015-0292-x · Cited by 242
Effects of the gut microbiota on bone mass
Ohlsson, C., & Sjögren, K. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2014.11.004 · Cited by 242
Diet-driven microbiota dysbiosis is associated with vagal remodeling and obesity
Sen, T., Cawthon, C. R., Ihde, B. T., Hajnal, A., DiLorenzo, P. M., de La Serre, C. B., & Czaja, K. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.02.027 · Cited by 239
Emerging roles of the microbiome in cancer
Bultman, S. J. (2014) · Carcinogenesis · doi:10.1093/carcin/bgt392 · Cited by 239
The interplay between the gut microbiota and the immune system
Geuking, M. B., Köller, Y., Rupp, S., & McCoy, K. D. (2014) · Gut Microbes · doi:10.4161/gmic.29330 · Cited by 239
Microbiota-mediated inflammation and antimicrobial defense in the intestine
Caballero, S., & Pamer, E. G. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120238 · Cited by 238
The Microbiome in Psychology and Cognitive Neuroscience
Sarkar, A., Harty, S., Lehto, S. M., Moeller, A. H., Dinan, T. G., Dunbar, R., Cryan, J. F., & Burnet, P. W. J. (2018) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2018.04.006 · Cited by 238
Menni, C., Zierer, J., Pallister, T., Jackson, M. A., Long, T., Mohney, R. P., Steves, C. J., Spector, T. D., & Valdes, A. M. (2017) · Scientific Reports · doi:10.1038/s41598-017-10382-2 · Cited by 237
Nogacka, A. M., Salazar, N., Suárez, M., Milani, C., Arboleya, S., Sánchez, G. S., Fernández, N., Alaez, L., Hernández‐Barranco, A. M., Reyes‐Gavilán, C. G. D. L., et al. (2017) · Microbiome · doi:10.1186/s40168-017-0313-3 · Cited by 237
Morphogenesis and maturation of the embryonic and postnatal intestine
Chin, A. M., Hill, D. R., Aurora, M., & Spence, J. R. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.01.011 · Cited by 236
Review: Microbiome in Inflammatory Arthritis and Human Rheumatic Diseases
Scher, J. U., Littman, D. R., & Abramson, S. B. (2015) · Arthritis & Rheumatology · doi:10.1002/art.39259 · Cited by 234
Wang, T., Hu, X., Liang, S., Li, W., Wu, X., Wang, L., & Jin, F. (2015) · Beneficial Microbes · doi:10.3920/bm2014.0177 · Cited by 233
Pathogenesis of nonalcoholic steatohepatitis
Liu, W., Baker, R. D., Bhatia, T., Zhu, L., & Baker, S. S. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2161-x · Cited by 233
Early Development of the Gut Microbiota and Immune Health
Francino, M. P. (2014) · Pathogens · doi:10.3390/pathogens3030769 · Cited by 232
Xia, Y. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.04.003 · Cited by 239
Tulstrup, M. V.-L., Christensen, E. G., Carvalho, V., Linninge, C., Ahrné, S., Højberg, O., Licht, T. R., & Bahl, M. I. (2015) · PLoS ONE · doi:10.1371/journal.pone.0144854 · Cited by 232
Morton, E. R., Lynch, J., Froment, A., Lafosse, S., Heyer, E., Przeworski, M., Blekhman, R., & Ségurel, L. (2015) · PLOS Genetics · doi:10.1371/journal.pgen.1005658 · Cited by 231
Diet, genetics, and the gut microbiome drive dynamic changes in plasma metabolites
Fujisaka, S., Avila-Pacheco, J., Soto, M., Kostic, A., Dreyfuss, J. M., Pan, H., Ussar, S., Altindis, E., Li, N., Bry, L., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.060 · Cited by 231
“The nature of the microbial community and its changes in response to environmental factors such as dietary nutrients, fiber, and antibiotics is dependent on the genetic background of the host (Cho et al., 2012; Fujisaka et al., 2016; Parks et al., 2015; Tamburini et al., 2016; Ussar et al., 2016).”
BackgroundGarrido, D., Dallas, D. C., & Mills, D. A. (2013) · Microbiology · doi:10.1099/mic.0.064113-0 · Cited by 228
Gut Microbiota Composition Modifies Fecal Metabolic Profiles in Mice
Zhao, Y., Wu, J., Li, J. V., Zhou, N., Tang, H., & Wang, Y. (2013) · Journal of Proteome Research · doi:10.1021/pr400263n · Cited by 228
Regulation of energy balance by a gut–brain axis and involvement of the gut microbiota
Bauer, P. V., Hamr, S. C., & Duca, F. A. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2083-z · Cited by 231
Fecal and Mucosal Microbiota Profiling in Irritable Bowel Syndrome and Inflammatory Bowel Disease
Presti, A. L., Zorzi, F., CHIERICO, F. D., Altomare, A., Cocca, S., Avola, A., Biasio, F. D., Russo, A., Cella, E., Reddel, S., et al. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.01655 · Cited by 228
An exposome perspective: Early-life events and immune development in a changing world
Renz, H., Holt, P. G., Inouye, M., Logan, A. C., Prescott, S. L., & Sly, P. D. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.05.015 · Cited by 226
GPR43 Potentiates β-Cell Function in Obesity
McNelis, J., Lee, Y. S., Mayoral, R., van der Kant, R., Johnson, A. M. F., Wollam, J., & Olefsky, J. M. (2015) · Diabetes · doi:10.2337/db14-1938 · Cited by 226
Metadata
- 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.
- ORCID
- Venue
- Nature
- Published
- 2012-08
- Volume
- 488
- Issue
- 7413
- Pages
- 621-626
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3553221
- 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
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- 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 › Endocrinology, Diabetes and Metabolism › 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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