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Title: Bacteria, phages, and pigs: the effects of in-feed antibiotics on the microbiome at different gut locations

item Looft, Torey
item Allen, Heather
item CANTAREL, BRANDI - Baylor University Medical Center
item Levine, Uri
item Bayles, Darrell
item Alt, David
item HENRISSAT, BERNARD - Aix-Marseille University
item Stanton, Thaddeus

Submitted to: Journal of the International Society for Microbial Ecology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/10/2014
Publication Date: 2/13/2014
Publication URL:
Citation: Looft, T.P., Allen, H.K., Cantarel, B., Levine, U.Y., Bayles, D.O., Alt, D.P., Henrissat, B., Stanton, T.B. 2014. Bacteria, phages, and pigs: the effects of in-feed antibiotics on the microbiome at different gut locations. Journal of the International Society for Microbial Ecology. 8(8):1566-1576. DOI: 10.1038/ismej.2014.12.

Interpretive Summary: Central to the debate surrounding the use of antibiotics that stop diseases or enhance growth of food-producing animals is the question, what are the broader and unknown effects of these antibiotics on gut bacteria? In our work we are defining the effects of one particular mixture of antibiotics that is administered to swine in the feed. Through metagenomic analyses (sequencing all of the microbial genes in intestinal samples), we found location-specific differences in gut bacteria that are important for determining antibiotic effects. We found that there are fewer types of bacteria in the small intestine than in the large intestine. Interestingly, there are more different bacteria associated with the mucosa (inner wall) of the small intestine than in the contents. This suggests that the mucosa is an important even if understudied habitat for gut bacteria. The data also show that the microbial activities are differentiated between small versus large intestine, suggesting that each microbial community is adapted to the local gut environment. Finally, we discovered that the antibiotic mixture changed the gut microbial community, both in terms of membership and function. Defining specific intestinal microbial communities and the effect of antibiotics on them will guide us in selecting effective alternatives to in-feed antibiotics and ultimately will help to improve food safety.

Technical Abstract: Disturbance of the beneficial gut microbial community is one collateral effect of antibiotics, which have many uses in animal agriculture (disease treatment or prevention and feed efficiency improvement). Antibiotic effects on bacterial communities at different intestinal locations are perhaps essential to realizing the full benefits and consequences of in-feed antibiotics. In this study, we defined the lumenal and mucosal bacterial communities from the small intestine (distal ileum) and large intestine (cecum and colon, plus feces) and characterized the effects of in-feed antibiotics (chlortetracycline, sulfamethazine, and penicillin [ASP250]) on these communities. 16S rRNA gene sequence and metagenomic analyses of bacterial membership and functions revealed dramatic differences between small and large intestinal locations, including enrichment of Firmicutes and phage-encoding genes in the ileum. The large intestinal microbiota encoded a large number of genes to degrade plant cell wall components, and these genes were lacking in the ileum microbiota. Surprisingly, the mucosa-associated ileal microbiota harbored greater bacterial diversity than the lumen but similar diversity to the mucosa of the large intestine, suggesting that most gut microbes can associate with the mucosa and might serve as an inoculum for the lumen. The microbiota of antibiotic-fed animals diverged from those of control animals, with notable changes being increases in E. coli populations in the ileum, Lachnobacterium spp. in all gut locations, and resistance genes to antibiotics not administered. The results demonstrate localized adaptations of swine gut bacterial communities. Characterizing the gut microbiome in health and in antibiotic-mediated disturbances will inform strategies to improve swine health and food safety.