Tuesday, January 17, 2012

In-feed antibiotic effects on the swine intestinal microbiome

In-feed antibiotic effects on the swine intestinal microbiome

Torey Loofta,1, Timothy A. Johnsonb,c,1, Heather K. Allena,1, Darrell O. Baylesa, David P. Alta, Robert D. Stedtfeldb,d, Woo Jun Sulb,c, Tiffany M. Stedtfeldb, Benli Chaib, James R. Coleb, Syed A. Hashshamb,d, James M. Tiedjeb,c,2, and Thad B. Stantona,2 aAgricultural Research Service, National Animal Disease Center, US Department of Agriculture, Ames, IA 50010; and bCenter for Microbial Ecology, cDepartment of Crop and Soil Science, and dDepartment of Civil and Environmental Engineering, Michigan State University, East Lansing, MI 48823

Contributed by James M. Tiedje, December 19, 2011 (sent for review July 12, 2011)

Antibiotics have been administered to agricultural animals for disease treatment, disease prevention, and growth promotion for over 50 y. The impact of such antibiotic use on the treatment of human diseases is hotly debated. We raised pigs in a highly controlled environment, with one portion of the littermates receiving a diet containing performance-enhancing antibiotics [chlortetracycline, sulfamethazine, and penicillin (known as ASP250)] and the other portion receiving the same diet but without the antibiotics. We used phylogenetic, metagenomic, and quantitative PCR-based approaches to address the impact of antibiotics on the swine gut microbiota. Bacterial phylotypes shifted after 14 d of antibiotic treatment, with the medicated pigs showing an increase in Proteobacteria (1–11%) compared with nonmedicated pigs at the same time point. This shift was driven by an increase in Escherichia coli populations. Analysis of the metagenomes showed that microbial functional genes relating to energy production and conversion were increased in the antibiotic-fed pigs. The results also indicate that antibiotic resistance genes increased in abundance and diversity in the medicated swine microbiome despite a high background of resistance genes in nonmedicated swine. Some enriched genes, such as aminoglycoside O-phosphotransferases, confer resistance to antibiotics that were not administered in this study, demonstrating the potential for indirect selection of resistance to classes of antibiotics not fed. The collateral effects of feeding subtherapeutic doses of antibiotics to agricultural animals are apparent and must be considered in cost-benefit analyses.

intestinal microbiota | microbiome shifts | swine bacteria | BioTrove microarray | metagenomics



The results show that even a low, short-term dose of in-feed antibiotics increases the abundance and diversity of antibiotic resistance genes, including resistance to antibiotics not administered, and increases the abundance of E. coli, a potential human pathogen. Additionally, analysis of the metagenomes implicated functions potentially involved with improved feed efficiency. The study design featured environmental control in a single uniform inoculum source (the mother), control of the host genetics, no exposure of the sow or piglets to antibiotics except for the treatment, and identical diet except for the inclusion of ASP250 in one group. Future studies should include other in-feed antibiotics, multiple litters of swine with robust replication, and the identification of the antibiotic-induced mechanisms that lead to increased feed efficiency. Implications of antibiotic resistance on human and animal health need to be taken into account when discussing agricultural management policies and evaluating alternatives to traditional antibiotics. With the use of antibiotics in animal agriculture at a crossroads, studies like this and others that highlight the collateral effects of antibiotic use are needed.

Study provides new insights into antibiotics and pig feeds Contact: Layne Cameron, University Relations, Office: (517) 353-8819, Cell: (765) 748-4827, layne.cameron@ur.msu.edu; Thad Stanton, USDA-ARS National Animal Disease Center, Office: (515) 337-7244, thad.stanton@ars.usda.gov; James Tiedje, Crop and Soil Sciences, Office: (517) 355-0271, ext. 1287, tiedjej@msu.edu

Published: Jan. 16, 2012 E-mail Editor ShareThis

Jim Tiedje, University Distinguished professor of microbiology and molecular genetics, is the co-author of a comprehensive study on antibiotics use in pig feed. Photo by Kurt Stepnitz.

Antibiotics in pig feed are increasing antibiotic resistance genes in gastronintestinal microbes in pigs. Photo courtesy of MSU.

Click on an image to view a larger or high-resolution version.

Related Links PNAS paper (opens in new window) EAST LANSING, Mich. — Antibiotics in pig feed increased the number of antibiotic resistant genes in gastrointestinal microbes in pigs, according to a study conducted by Michigan State University and the U.S. Department of Agriculture’s Agricultural Research Service.

Published in the current edition of the Proceedings of the National Academy of Sciences, the comprehensive study focused on understanding the effects of conventional, in-feed antibiotics in U.S. farms.

For decades, many producers of pigs, chickens and other farm animals have used antibiotics not only to protect their livestock from disease, but also to boost growth rates and enhance feed efficiency, a measure of how well animals convert feed into weight gains.

Scientists don’t know precisely how antibiotics enhance growth rates and feed efficiency, but they are concerned that on-farm use of these medications may contribute to the development of strains of microbes resistant to conventional antibiotics, which are potentially harmful to humans and animals, said James Tiedje, MSU University Distinguished Professor of microbiology and molecular genetics and of crop and soil sciences.

“The growth of antibiotic resistance in pathogens is a huge challenge for society around the world,” said Tiedje, an MSU AgBioResearch scientist. “Studies to understand what contributes to the spread and what interventions can help control the problem are vital.”

Additional findings include:

Both diversity and abundance of antibiotic resistance genes increased in the intestinal microbial communities of the pigs treated with antibiotics. Longer term studies are needed. Some of the genes found in the treated pigs were unexpected and usually linked to antibiotics not used in the study. Microbial genes associated with production and use of energy by microbes increased in abundance in the antibiotic-fed pigs, which may shed light on how antibiotics increase livestock growth and feed efficiency. E. coli populations increased in the intestines of the treated pigs. Further study is needed to clarify this observation. “To our knowledge, this study is the first of its kind to look at the collateral impacts of in-feed antibiotic use in farm animals, using a comprehensive approach to detect shifts in the function and the makeup or membership of the microbial community in the model animal’s gastrointestinal tract,” said Torey Looft, USDA researcher.

Additional MSU researchers included Tim Johnson, doctoral student; Robert Stedtfeld, civil and environmental engineering research associate; Woo Jun Sul, doctoral student; Tiffany Stedtfeld, civil and environmental engineering technical aide; Benli Chai, information technologist, Center for Microbial Ecology; James Cole, assistant professor at the Center for Microbial Ecology; and Syed Hashsham, civil and environmental engineering professor.

Funding was provided by MSU’s Environmental Science and Policy Program initiative on Pharmaceuticals in the Environment, ARS and the National Institutes of Health and through the Alliance for the Prudent Use of Antibiotics program on Reservoirs of Antibiotic Resistance.


Michigan State University has been working to advance the common good in uncommon ways for more than 150 years. One of the top research universities in the world, MSU focuses its vast resources on creating solutions to some of the world’s most pressing challenges, while providing life-changing opportunities to a diverse and inclusive academic community through more than 200 programs of study in 17 degree-granting colleges.

As the USDA’s chief scientific research agency, ARS is leading America toward a better future through agricultural research and information. ARS conducts research to develop and transfer solutions to help answer agricultural questions that impact Americans every day.

Thursday, June 9, 2011

New Superbug Found in Cows and People

Wednesday, May 11, 2011

Methicillin-resistant Staphylococcus aureus in Retail Meat, Detroit, Michigan, USA

Monday, April 18, 2011

Multidrug-Resistant Staphylococcus aureus in US Meat and Poultry