Abstract
Even though salbutamol (SAL) had remarkable effects on the enhancement of growth rate and carcass composition in different livestock species such as cattle, pigs, sheep and poultry, it was banned as a growth promoter because of its adverse effects on health. However, the specific mechanism by which salbutamol enhances growth efficiency remains unknown. In this study, Bama pigs were randomly allocated to receive salbutamol (5 mg/kg) for 30 or 60 days and were compared with untreated pigs. Pigs treated with salbutamol demonstrated enhanced growth rates and carcass composition; however, they showed deterioration in blood biochemical indices and organ development. We hypothesized that salbutamol exerts its effects by modulating the composition of the gut microbiota population. The faecal microbiome of pigs was characterized via pyrosequencing of the bacterial 16S rRNA gene. The gut microbiota population analysis showed that salbutamol caused shifts in the microbial composition of less abundant species. Redundancy analysis indicated an increase in abundance of the phylum Bacteroidetes, class Betaproteobacteria, family Christensenellaceae and genus Lactobacillus, and a decreased ratio of the phylum Firmicutes, class Clostridia and genera Ruminococcus, Blautia and Subdoligranulum. In conclusion, our study provided circumstantial evidence that the various effects of salbutamol are caused by gut microbiota modulation, and several potential candidates were identified for SAL detection via the gut microbiota. Our findings provided new insights into the roles of the gut microbiota during salbutamol treatment, and these findings will aid in the screening of alternative strategies for animal health improvement and production enhancement.
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Arhoghro EM, Ekpo KE, Anosike EO, Ibeh GO (2009) Effect of aqueous extract of bitter leaf (Vernonia amygdalina Del) on carbon tetrachloride (CCl4) induced liver damage in albino Wistar rats. Eur J Sci Res 26:122–130
Berg RD (1996) The indigenous gastrointestinal microflora. Trends Microbiol 4:430–435
Bik EM (2009) Composition and function of the human-associated microbiota. Nutr Rev 67:S164–S171
Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Peña AG, Goodrich JK, Gordon JI (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7:335–336
Chiang SS, Pan TM (2012) Beneficial effects of Lactobacillus paracasei subsp. paracasei NTU 101 and its fermented products. Appl Microbiol Biotechnol 93:903–916
Edgar RC (2010) Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26:2460–2461
Fukuda S, Toh H, Hase K, Oshima K, Nakanishi Y, Yoshimura K, Tobe T, Clarke JM, Topping DL, Suzuki T (2011) Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469:543–547
Gilliland S, Speck M (1977) Deconjugation of bile acids by intestinal lactobacilli. Appl Environ Microbiol 33:15–18
Goodrich JK, Waters JL, Poole AC, Sutter JL, Koren O, Blekhman R, Beaumont M, Van Treuren W, Knight R, Bell JT, Spector TD, Clark AG, Ley RE (2014) Human genetics shape the gut microbiome. Cell 159:789–799
Hayashi H, Shibata K, Sakamoto M, Tomita S, Benno Y (2007) Prevotella copri sp. nov. and Prevotella stercorea sp. nov., isolated from human faeces. Int J Syst Evol Microbiol 57:941–946
Holmstrøm K, Collins MD, Møller T, Falsen E, Lawson PA (2004) Subdoligranulum variable gen. nov., sp. nov. from human feces. Anaerobe 10:197–203
Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, Terasawa K, Kashihara D, Hirano K, Tani T (2013) The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun 4:842–848
Lamendella R, Santo Domingo JW, Ghosh S, Martinson J, Oerther DB (2011) Comparative fecal metagenomics unveils unique functional capacity of the swine gut. BMC Microbiol 11:1–17
Larsen N, Vogensen FK, Fw VDB, Nielsen DS, Andreasen AS, Pedersen BK, Alsoud WA, Sørensen SJ, Hansen LH, Jakobsen M (2010) Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 5:9085–9094
Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A 102:11070–11075
Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2007) Microbial ecology: human gut microbes associated with obesity. Nature 444:1022–1023
Manninen V, Tenkanen L, Koskinen P, Huttunen JK, Heinonen OP, Frick MH (1992) Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Endocrinologist 85:37–45
Marchantforde JN, Jr LD, Marchantforde RM, Mcmunn KA, Richert BT (2012) The effects of R-salbutamol on growth, carcass measures, and health of finishing pigs. J Anim Sci 90:4081–4089
Marchant-Forde J, Lay D, Pajor E, Richert B, Schinckel A (2003) The effects of ractopamine on the behavior and physiology of finishing pigs. J Anim Sci 81:416–422
Martinez-Navarro J (1990) Food poisoning related to consumption of illicit β-agonist in liver. Lancet 336:1311
Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC, Rolph MS, Mackay F, Artis D (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461:1282–1286
Masood MI, Qadir MI, Shirazi JH, Khan IU (2011) Beneficial effects of lactic acid bacteria on human beings. Crit Rev Microbiol 37:91–98
Mcintyre A, Gibson PR, Young GP (1993) Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut 34:386–391
Moser R, Dalrymple R, Cornelius S, Pettigrew J, Allen C (1986) Effect of cimaterol (CL 263,780) as a repartitioning agent in the diet for finishing pigs. J Anim Sci 62:21–26
Ouwehand AC, Salminen S, Isolauri E (2002) Probiotics: an overview of beneficial effects. Antonie Van Leeuwenhoek 82:279–289
Pajarillo AB, Chae JP, Balolong MP, Bum KH, Kang DK (2014) Assessment of fecal bacterial diversity among healthy piglets during the weaning transition. J Gen Appl Microbiol 60:140–146
Park SK, Kim MS, Roh SW, Bae JW (2012) Blautia stercoris sp. nov., isolated from human faeces. Int J Syst Evol Microbiol 62:776–779
Pedersen R, Andersen AD, Molbak L, Stagsted J, Boye M (2013) Changes in the gut microbiota of cloned and non-cloned control pigs during development of obesity: gut microbiota during development of obesity in cloned pigs. BMC Microbiol 13:30–38
Peng L, Li ZR, Green RS, Holzman IR, Lin J (2009) Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr 139:1619–1625
Poletto R, Rostagno M, Richert B, Marchant-Forde J (2009) Effects of a “step-up” ractopamine feeding program, sex, and social rank on growth performance, hoof lesions, and Enterobacteriaceae shedding in finishing pigs. J Anim Sci 87:304–313
Poletto R, Meisel R, Richert B, Cheng HW, Marchant-Forde J (2010) Behavior and peripheral amine concentrations in relation to ractopamine feeding, sex, and social rank of finishing pigs. J Anim Sci 88:1184–1194
Price AH, Clissold SP (1989) Salbutamol in the 1980s. Drugs 38:77–122
Pulce C, Lamaison D, Keck G, Bostvironnois C, Nicolas J, Descotes J (1991) Collective human food poisonings by clenbuterol residues in veal liver. Vet Hum Toxicol 33:480–481
Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D (2012) A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490:55–60
Ramotar K, Conly J, Chubb H, Louie T (1984) Production of menaquinones by intestinal anaerobes. J Infect Dis 150:213–218
Riboulet-Bisson E, Sturme MH, Jeffery IB, O’Donnell MM, Neville BA, Forde BM, Claesson MJ, Harris H, Gardiner GE, Casey PG (2012) Effect of Lactobacillus salivarius bacteriocin Abp118 on the mouse and pig intestinal microbiota. PLoS One 7:e31113
Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, Lesniewski RA, Oakley BB, Parks DH, Robinson CJ (2009) Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol 75:7537–7541
Segain JP, Raingeard de la Blétière D, Bourreille A, Leray V, Gervois N, Rosales C, Ferrier L, Bonnet C, Blottière HM, Galmiche JP (2000) Butyrate inhibits inflammatory responses through NFkB inhibition: implications for Crohn’s disease. Gut 47:397–403
Shahneh AZ, Nejhad HAB, Rowghani E, Eilami B, Rowghani S (2012) Effects of salbutamol on growth performance and carcass characteristics of Japanese quail (Coturnix japonica). Iran J Vet Res 13:112–119
Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, Patsch W (2001) Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins AI and B, and HDL density subfractions. Circulation 104:1108–1113
Steenekamp S (2014) Growth performance and meat characteristics of feedlot cattle fed R-salbutamol or zilpatero lhydrochloride during the finishing period. South African Feedlot Bulls
Turnbaugh PJ, Bäckhed F, Fulton L, Gordon JI (2008) Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3:213–223
Ulicná O, Greksák M, Vancová O, Zlatos L, Galbavý S, Bozek P, Nakano M (2003) Hepatoprotective effect of rooibos tea (Aspalathus linearis) on CCl4-induced liver damage in rats. Physiol Res 52:461–466
Wang Q, Garrity GM, Tiedje JM, Cole JR (2007) Naïve Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol 73:5261–5267
Watkins L, Jones D, Mowrey D, Anderson D, Veenhuizen E (1990) The effect of various levels of ractopamine hydrochloride on the performance and carcass characteristics of finishing swine. J Anim Sci 68:3588–3595
Yolton DP, Savage DC (1976) Influence of certain indigenous gastrointestinal microorganisms on duodenal alkaline phosphatase in mice. Appl Environ Microbiol 31:880–888
Yu Z, Morrison M (2004) Improved extraction of PCR-quality community DNA from digesta and fecal samples. BioTechniques 36:808–812
Zhang X, Zhao Y, Zhang M, Pang X, Xu J, Kang C, Li M, Zhang C, Zhang Z, Zhang Y (2012) Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats. PLoS One 7:e42529
Acknowledgements
This work was supported by the Key Specialty of Ningbo City and by the K.C. Wong Magna Fund in Ningbo University. We thank the Nature Research Editing Service for English language editing.
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Procedures of the experimental and animal care were performed in accordance with the guideline prepared by the Ningbo University Laboratory Animal Center (affiliated with the Zhejiang Laboratory Animal Common Service Platform), and all of the protocols were approved by the Ningbo University Laboratory Animal Center under permit number no. SYXK (ZHE 2008-0110).
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Lu, C., Zhou, J., Li, Y. et al. Structural modulation of gut microbiota in Bama minipigs in response to treatment with a “growth-promoting agent”, salbutamol. Appl Microbiol Biotechnol 101, 5809–5818 (2017). https://doi.org/10.1007/s00253-017-8329-y
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DOI: https://doi.org/10.1007/s00253-017-8329-y