Time-course responses of ileal and fecal microbiota and metabolite profiles to antibiotics in cannulated pigs
We investigated the time-course effects of therapeutic antibiotics on intestinal microbial composition and metabolism in an ileal-cannulated pig model. Sixteen ileal-cannulated piglets (12 ± 0.5 kg) were assigned to two groups (n = 8) and fed standard diets with or without antibiotics. At 4 days before, and at days 2, 7, and 13 after antibiotic administration, ileal and fecal samples were collected for analysis of microbiota composition via 16S rRNA MiSeq sequencing and metabolites (short-chain fatty acids, biogenic amines, and indole). It was found that Lactobacillus and Bifidobacterium had decreased by an average 2.68-fold and 508-fold in ileum on days 2–13, and by an average 45.08-fold and 71.50-fold in feces on days 7–13 (P < 0.05). Escherichia/Shigella had increased by an average 265-fold in ileum on days 2–13, and by an average 36.70-fold in feces on days 7–13 (P < 0.05). Acetate concentration had decreased in ileum by an average 2.88-fold on days 2–13, and by 1.83-fold in feces on day 7 (P < 0.05). Cadaverine concentration had increased by an average 7.03-fold in ileum on days 2–13, and by an average 9.96-fold in feces on days 7–13 (P < 0.05), and fecal indole concentration had increased by an average 2.51-fold on days 7–13 (P < 0.05). Correlation analysis between significant microbes and metabolites indicated that the antibiotic-induced microbiota shift appeared to result in the changes of intestinal metabolism. In conclusion, antibiotic administration led to dynamic changes in microbial communities and metabolism in ileum and feces, with ileal microbiota being more prone to shift than fecal microbiota.
KeywordsAntibiotics Dynamic impact of antibiotics Temporal change of gut microbiota Microbial metabolites
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
- Amato KR, Yeoman CJ, Kent A, Righini N, Carbonero F, Estrada A, Gaskins HR, Stumpf RM, Yildirim S, Torralba M, Gillis M, Wilson BA, Nelson KE, White BA, Leigh SR (2013) Habitat degradation impacts black howler monkey (Alouatta pigra) gastrointestinal microbiomes. Isme J 7(7):1344–1353. https://doi.org/10.1038/ismej.2013.16 CrossRefPubMedPubMedCentralGoogle Scholar
- Birck MM, Nguyen DN, Cilieborg MS, Kamal SS, Nielsen DS, Damborg P, Olsen JE, Lauridsen C, Sangild PT, Thymann T (2016) Enteral but not parenteral antibiotics enhance gut function and prevent necrotizing enterocolitis in formula-fed newborn preterm pigs. Am J Physiol-Gastr Liver 310(5):G323–G333. https://doi.org/10.1152/ajpgi.00392.2015 CrossRefGoogle Scholar
- de Lange CF, Sauer WC, Souffrant WB, Lien KA (1992) 15N-leucine and 15N-isoleucine isotope dilution techniques versus the 15N-isotope dilution technique for determining the recovery of endogenous protein and amino acids in digesta collected from the distal ileum in pigs. J Anim Sci 70(6):1848–1856. https://doi.org/10.2527/1992.7061848x CrossRefPubMedGoogle Scholar
- Duncan SH, Barcenilla A, Stewart CS, Pryde SE, Flint HJ (2002) Acetate utilization and butyryl coenzyme A (CoA): acetate-CoA transferase in butyrate-producing bacteria from the human large intestine. Appl Environ Microbiol 68(10):5186–5190. https://doi.org/10.1128/Aem.68.10.5186-5190.2002 CrossRefPubMedPubMedCentralGoogle Scholar
- Jensen ML, Thymann T, Cilieborg MS, Lykke M, Molbak L, Jensen BB, Schmidt M, Kelly D, Mulder I, Burrin DG, Sangild PT (2014) Antibiotics modulate intestinal immunity and prevent necrotizing enterocolitis in preterm neonatal piglets. Am J Physiol Gastrointest Liver Physiol 306(1):G59–G71. https://doi.org/10.1152/ajpgi.00213.2013 CrossRefPubMedGoogle Scholar
- Li S, Sauer WC, Fan MZ (1993) The effect of dietary crude protein level on ileal and fecal amino-acid digestibility in early-weaned pigs. J Anim Physiol Anim Nutr 70(1-5):117–128. https://doi.org/10.1111/j.1439-0396.1993.tb00314.x CrossRefGoogle Scholar
- Looft T, Allen HK, Cantarel BL, Levine UY, Bayles DO, Alt DP, Henrissat B, Stanton TB (2014) Bacteria, phages and pigs: the effects of in-feed antibiotics on the microbiome at different gut locations. ISME J 8(8):1566–1576. https://doi.org/10.1038/ismej.2014.12 CrossRefPubMedPubMedCentralGoogle Scholar
- Makras L, Triantafyllou V, Fayol-Messaoudi D, Adriany T, Zoumpopoulou G, Tsakalidou E, Servin A, De Vuyst L (2006) Kinetic analysis of the antibacterial activity of probiotic lactobacilli towards Salmonella enterica serovar Typhimurium reveals a role for lactic acid and other inhibitory compounds. Res Microbiol 157(3):241–247. https://doi.org/10.1016/j.resmic.2005.09.002 CrossRefPubMedGoogle Scholar
- Mu CL, Yang YX, Su Y, Zoetendal EG, Zhu WY (2017) Differences in microbiota membership along the gastrointestinal tract of piglets and their differential alterations following an early-life antibiotic intervention. Front Microbiol 8:797. https://doi.org/10.3389/Fmicb.2017.00797 CrossRefPubMedPubMedCentralGoogle Scholar
- Perez-Cobas AE, Gosalbes MJ, Friedrichs A, Knecht H, Artacho A, Eismann K, Otto W, Rojo D, Bargiela R, von Bergen M, Neulinger SC, Daumer C, Heinsen FA, Latorre A, Barbas C, Seifert J, dos Santos VM, Ott SJ, Ferrer M, Moya A (2013) Gut microbiota disturbance during antibiotic therapy: a multi-omic approach. Gut 62(11):1591–1601. https://doi.org/10.1136/gutjnl-2012-303184 CrossRefPubMedGoogle Scholar
- Sangild PT, Siggers RH, Schmidt M, Elnif J, Bjornvad CR, Thymann T, Grondahl ML, Hansen AK, Jensen SK, Boye M, Moelbak L, Buddington RK, Westrom BR, Holst JJ, Burrin DG (2006) Diet- and colonization-dependent intestinal dysfunction predisposes to necrotizing enterocolitis in preterm pigs. Gastroenterology 130(6):1776–1792. https://doi.org/10.1053/j.gastro.2006.02.026 CrossRefPubMedGoogle Scholar
- Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, Lesniewski RA, Oakley BB, Parks DH, Robinson CJ, Sahl JW, Stres B, Thallinger GG, Van Horn DJ, Weber CF (2009) Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol 75(23):7537–7541. https://doi.org/10.1128/AEM.01541-09 CrossRefPubMedPubMedCentralGoogle Scholar