Register      Login
Animal Production Science Animal Production Science Society
Food, fibre and pharmaceuticals from animals
RESEARCH ARTICLE (Open Access)

Bitter compound quinine hydrochloride improved post-weaning pig performance in the absence of zinc oxide

Elisabet Garcia-Puig https://orcid.org/0000-0001-6281-3275 A , Fan Liu https://orcid.org/0000-0003-2644-2416 B , Rebecca Morrison B , Maximiliano Müller https://orcid.org/0000-0001-9598-1371 A , Allan Lisle A and Eugeni Roura https://orcid.org/0000-0002-9073-9946 A *
+ Author Affiliations
- Author Affiliations

A Centre for Animal Science and Centre for Nutrition and Food Sciences, Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, St Lucia, Qld 4072, Australia.

B Rivalea (Australia) Pty Ltd, JBS Australia Pork Division, Redlands Road, Corowa, NSW 2646, Australia.

* Correspondence to: e.roura@uq.edu.au

Handling Editor: Dana Campbell

Animal Production Science 64, AN24201 https://doi.org/10.1071/AN24201
Submitted: 20 June 2024  Accepted: 27 November 2024  Published: 19 December 2024

© 2024 The Author(s) (or their employer(s)). Published by CSIRO Publishing. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)

Abstract

Context

Dietary zinc oxide (ZnO) (a bitter antimicrobial chemical) in pigs is being gradually phased out due to pollution and antibiotic resistance. Bitter compounds like quinine hydrochloride (HCl) have shown potential to enhance growth and feed efficiency by slowing gastric emptying and intestinal passage rates in pigs.

Aims

This study aimed to evaluate quinine’s ability to improve performance in weanling pigs without ZnO.

Methods

Two experiments were conducted. Experiment 1: 120 Landrace (LD) × Large White (LW) weaned piglets (initial BW 6.8 ± 0.1 kg) were randomly assigned to one of four diets in a 2 × 2 factorial design: with/without ZnO and copper sulfate (CuSO4) (3000 and 250 ppm, respectively) and two quinine levels (0 and 500 ppm). Parameters measured included average daily feed intake (ADFI), average daily gain (ADG), gain to feed ratio (G:F), and faecal score. Experiment 2: 1440 LD × LW piglets (initial BW 7.4 ± 0.2 kg) were housed in groups of 18 per pen and assigned the same four dietary treatments as in Experiment 1.

Key results

Growth performance parameters were recorded and analysed, showing that ZnO/CuSO4 supplement improved growth and feed efficiency (P < 0.05) compared to the ZnO/CuSO4-free diet group. In Experiment 1, pigs supplemented with quinine in non-ZnO/CuSO4 diets showed similar (P > 0.05) performance levels to the ZnO/CuSO4 fed group. In addition, an interaction (P < 0.05) was found, indicating that adding quinine improved or worsened ADG and G:F depending on the absence or presence of ZnO/CuSO4 in the diet, respectively. In Experiment 2, quinine inclusions in non-ZnO diets improved (P < 0.05) ADG but did not affect (P > 0.05) ADFI and G:F.

Conclusion

Our findings suggest that the anticipated deleterious effects of phasing out the use of dietary ZnO can be partially compensated by includingquinine in the diet of post-weaning pigs. The negative effect of quinine when provided together with ZnO is compatible with a competitive exclusion mechanism linked to both stimulating bitterness, a mechanism that warrants further investigation.

Implications

Quinine shows potential as a partial replacement for ZnO in post-weaning pig diets, providing a promising alternative to maintain piglet health and growth while transitioning away from ZnO.

Keywords: antimicrobials, bitter compounds, diarrhoea, feed efficiency, growth, piglets, quinine, ZnO.

References

Andreozzi P, Sarnelli G, Pesce M, Zito FP, Alessandro AD, Verlezza V, Palumbo I, Turco F, Esposito K, Cuomo R (2015) The bitter taste receptor agonist quinine reduces calorie intake and increases the postprandial release of cholecystokinin in healthy subjects. Journal of Neurogastroenterology and Motility 21, 511-519.
| Crossref | Google Scholar | PubMed |

Bednorz C, Oelgeschläger K, Kinnemann B, Hartmann S, Neumann K, Pieper R, Bethe A, Semmler T, Tedin K, Schierack P, Wieler LH, Guenther S (2013) The broader context of antibiotic resistance: zinc feed supplementation of piglets increases the proportion of multi-resistant Escherichia coli in vivo. International Journal of Medical Microbiology 303, 396-403.
| Crossref | Google Scholar | PubMed |

Bonetti A, Tugnoli B, Piva A, Grilli E (2021) Towards zero zinc oxide: feeding strategies to manage post-weaning diarrhea in piglets. Animals 11, 642.
| Crossref | Google Scholar | PubMed |

Bugnacka D, Falkowski J (2001) The effect of dietary levels of yellow lupin seeds (Lupinus luteus L.) on feed preferences and growth performance of young pigs. Journal of Animal and Feed Sciences 10, 133-142.
| Crossref | Google Scholar |

Burch DG (1982) Tiamulin feed premix in the prevention and control of swine dysentery under farm conditions in the UK. Veterinary Record 110, 244-246.
| Crossref | Google Scholar | PubMed |

Cho JH, Upadhaya SD, Kim IH (2015) Effects of dietary supplementation of modified zinc oxide on growth performance, nutrient digestibility, blood profiles, fecal microbial shedding and fecal score in weanling pigs. Animal Science Journal 86, 617-623.
| Crossref | Google Scholar | PubMed |

Cromwell G (2001) Chapter 18. Antimicrobial and promicrobial agents. In ‘Swine nutrition’. (Ed. AJ Lewis, LL Southern) pp. 401–406. (CRC Press: Boca Raton, FL, USA) 10.1201/9781420041842

da Silva EC, de Jager N, Burgos-Paz W, Reverter A, Perez-Enciso M, Roura E (2014) Characterization of the porcine nutrient and taste receptor gene repertoire in domestic and wild populations across the globe. BMC Genomics 15, 1057.
| Crossref | Google Scholar | PubMed |

Dagan-Wiener A, Di Pizio A, Nissim I, Bahia MS, Dubovski N, Margulis E, Niv MY (2019) BitterDB: taste ligands and receptors database in 2019. Nucleic Acids Research 47, D1179-D1185.
| Crossref | Google Scholar | PubMed |

Danilova V, Roberts T, Hellekant G (1999) Responses of single taste fibers and whole chorda tympani and glossopharyngeal nerve in the domestic pig, Sus scrofa. Chemical Senses 24, 301-316.
| Crossref | Google Scholar | PubMed |

Feng Z, Zhu H, Deng Q, He Y, Li J, Yin J, Gao F, Huang R, Li T (2018) Environmental pollution induced by heavy metal(loid)s from pig farming. Environmental Earth Sciences 77, 103.
| Crossref | Google Scholar |

Fu M, Collins CL, Henman DJ, Roura E (2015) Some bitter compounds show potential for decreasing feed intake and fat deposition while others improve growth and feed conversion ratio in finishing pigs. Animal Production Science 55, 1543.
| Crossref | Google Scholar |

Fu M, Val-Laillet D, Guerin S, Roura E (2018) Dietary bitter compounds delayed gastric emptying and glucose uptake while increased plasma insulinotropic hormone GLP-1 in pigs. 14th International Symposium of Digestive Physiology of Pigs. Advances in Animal Biosciences 9(S2), S84.
| Google Scholar |

Garcia-Puig E, Liu F, Morrison RS, Lisle A, Roura E (2021) In-feed quinine improved performance to a similar level as ZnO and CuSO4 in post-weaning pigs. Animal - Science Proceedings 12, 195.
| Crossref | Google Scholar |

Garcia-Puig E, Liu F, Morrison RS, Lisle A, Roura E (2023) In-feed quinine hydrochloride supplementation improved piglet growth in the absence of zinc oxide under commercial conditions. Animal - Science Proceedings 14, 882-883.
| Crossref | Google Scholar |

Glendinning JI, Yiin YM, Ackroff K, Sclafani A (2008) Intragastric infusion of denatonium conditions flavor aversions and delays gastric emptying in rodents. Physiology & Behavior 93, 757-765.
| Crossref | Google Scholar | PubMed |

Heo JM, Kim JC, Hansen CF, Mullan BP, Hampson DJ, Pluske JR (2010) Effects of dietary protein level and zinc oxide supplementation on performance responses and gastrointestinal tract characteristics in weaner pigs challenged with an enterotoxigenic strain of Escherichia coli. Animal Production Science 50, 827-836.
| Crossref | Google Scholar |

Heo JM, Opapeju FO, Pluske JR, Kim JC, Hampson DJ, Nyachoti CM (2013) Gastrointestinal health and function in weaned pigs: a review of feeding strategies to control post-weaning diarrhoea without using in-feed antimicrobial compounds. Journal of Animal Physiology and Animal Nutrition 97, 207-237.
| Crossref | Google Scholar | PubMed |

Hill GM, Mahan DC, Carter SD, Cromwell GL, Ewan RC, Harrold RL, Lewis AJ, Miller PS, Shurson GC, Veum TL (2001) Effect of pharmacological concentrations of zinc oxide with or without the inclusion of an antibacterial agent on nursery pig performance. Journal of Animal Science 79, 934-941.
| Crossref | Google Scholar | PubMed |

Hu CH, Gu LY, Luan ZS, Song J, Zhu K (2012) Effects of montmorillonite–zinc oxide hybrid on performance, diarrhea, intestinal permeability and morphology of weanling pigs. Animal Feed Science and Technology 177, 108-115.
| Crossref | Google Scholar |

Jacela JY, DeRouchey JM, Tokach MD, Goodband RD, Nelssen JL, Renter DG, Dritz SS (2010) Feed additives for swine: fact sheets – high dietary levels of copper and zinc for young pigs, and phytase. Journal of Swine Health and Production 18, 87-91.
| Crossref | Google Scholar |

Lien TF, Horng YM, Wu CP (2007) Feasibility of replacing antibiotic feed promoters with the Chinese traditional herbal medicine Bazhen in weaned piglets. Livestock Science 107, 97-102.
| Crossref | Google Scholar |

Long L, Chen J, Zhang Y, Liang X, Ni H, Zhang B, Yin Y (2017) Comparison of porous and nano zinc oxide for replacing high-dose dietary regular zinc oxide in weaning piglets. PLoS ONE 12, e0182550.
| Crossref | Google Scholar | PubMed |

Mawson R, Heaney RK, Zduńczyk Z, Kozłowska H (1994) Rapeseed meal-glucosinolates and their antinutritional effects. Part 5. Animal reproduction. Nahrung 38, 588-598.
| Crossref | Google Scholar | PubMed |

Medardus JJ, Molla BZ, Nicol M, Morrow WM, Rajala-Schultz PJ, Kazwala R, Gebreyes WA (2014) In-feed use of heavy metal micronutrients in U.S. swine production systems and its role in persistence of multidrug-resistant salmonellae. Applied and Environmental Microbiology 80, 2317-2325.
| Crossref | Google Scholar | PubMed |

Meyerhof W, Batram C, Kuhn C, Brockhoff A, Chudoba E, Bufe B, Appendino G, Behrens M (2010) The molecular receptive ranges of human TAS2R bitter taste receptors. Chemical Senses 35, 157-170.
| Crossref | Google Scholar | PubMed |

Nelson SL, Sanregret JD (1997) Response of pigs to bitter-tasting compounds. Chemical Senses 22, 129-132.
| Crossref | Google Scholar | PubMed |

O’Shea CJ, O’Doherty JV, Callanan JJ, Doyle D, Thornton K, Sweeney T (2016) The effect of algal polysaccharides laminarin and fucoidan on colonic pathology, cytokine gene expression and Enterobacteriaceae in a dextran sodium sulfate-challenged porcine model. Journal of Nutritional Science 5, e15.
| Crossref | Google Scholar |

Paniagua M, Villagómez-Estrada S, Crespo FJ, Pérez JF, Arís A, Devant M, Solà-Oriol D (2023) Citrus flavonoids supplementation as an alternative to replace zinc oxide in weanling pigs’ diets minimizing the use of antibiotics. Animals 13, 967.
| Crossref | Google Scholar | PubMed |

Pieper R, Vahjen W, Neumann K, Van Kessel AG, Zentek J (2012) Dose-dependent effects of dietary zinc oxide on bacterial communities and metabolic profiles in the ileum of weaned pigs. Journal of Animal Physiology and Animal Nutrition 96, 825-833.
| Crossref | Google Scholar | PubMed |

Poulsen HD (1998) Zinc and copper as feed additives, growth factors or unwanted environmental factors. Journal of Animal and Feed Sciences 7, 135-142.
| Crossref | Google Scholar |

Rattigan R, Sweeney T, Vigors S, Rajauria G, O’Doherty JV (2020) Effects of reducing dietary crude protein concentration and supplementation with laminarin or zinc oxide on the faecal scores and colonic microbiota in newly weaned pigs. Journal of Animal Physiology and Animal Nutrition 104, 1471-1483.
| Crossref | Google Scholar | PubMed |

Ribani A, Bertolini F, Schiavo G, Scotti E, Utzeri VJ, Dall’Olio S, Trevisi P, Bosi P, Fontanesi L (2017) Next generation semiconductor based sequencing of bitter taste receptor genes in different pig populations and association analysis using a selective DNA pool-seq approach. Animal Genetics 48, 97-102.
| Crossref | Google Scholar | PubMed |

Rodgers S, Glen RC, Bender A (2006) Characterizing bitterness: identification of key structural features and development of a classification model. Journal of Chemical Information and Modeling 46, 569-576.
| Crossref | Google Scholar | PubMed |

Roura E, Fu M (2017) Taste, nutrient sensing and feed intake in pigs (130 years of research: then, now and future). Animal Feed Science and Technology 233, 3-12.
| Crossref | Google Scholar |

Roura E, Navarro M (2018) Physiological and metabolic control of diet selection. Animal Production Science 58, 613-626.
| Crossref | Google Scholar |

Roura E, Shrestha B, Larequie M, Zeng Y, Umana F (2012) Pigs show no preference for low concentrations of several cereal starches, potato starch and tapioca and a high preference for hydrolysed corn starch. In ‘XVI International Symposium on Olfaction and Taste’, Stockholm, Sweeden, p. 215.

Roura E, Depoortere I, Navarro M (2019) Review: Chemosensing of nutrients and non-nutrients in the human and porcine gastrointestinal tract. Animal 13, 2714-2726.
| Crossref | Google Scholar | PubMed |

Shen J, Chen Y, Wang Z, Zhou A, He M, Mao L, Zou H, Peng Q, Xue B, Wang L, Zhang X, Wu S, Lv Y (2014) Coated zinc oxide improves intestinal immunity function and regulates microbiota composition in weaned piglets. British Journal of Nutrition 111, 2123-2134.
| Crossref | Google Scholar | PubMed |

Smith JW, Tokach MD, Goodband RD, Nelssen JL, Richert BT (1997) Effects of the interrelationship between zinc oxide and copper sulfate on growth performance of early-weaned pigs. Journal of Animal Science 75, 1861-1866.
| Crossref | Google Scholar | PubMed |

Straub R, Gebert S, Wenk C, Wanner M (2005) Growth performance, energy, and nitrogen balance of weanling pigs fed a cereal-based diet supplemented with Chinese rhubarb. Livestock Production Science 92, 261-269.
| Crossref | Google Scholar |

Swain PS, Rao SBN, Rajendran D, Dominic G, Selvaraju S (2016) Nano zinc, an alternative to conventional zinc as animal feed supplement: a review. Animal Nutrition 2, 134-141.
| Crossref | Google Scholar | PubMed |

Vahjen W, Pietruszyńska D, Starke IC, Zentek J (2015) High dietary zinc supplementation increases the occurrence of tetracycline and sulfonamide resistance genes in the intestine of weaned pigs. Gut Pathogens 7, 23.
| Crossref | Google Scholar | PubMed |

Walk CL, Wilcock P, Magowan E (2015) Evaluation of the effects of pharmacological zinc oxide and phosphorus source on weaned piglet growth performance, plasma minerals and mineral digestibility. Animal 9, 1145-1152.
| Crossref | Google Scholar | PubMed |

Wang W, Van Noten N, Degroote J, Romeo A, Vermeir P, Michiels J (2019) Effect of zinc oxide sources and dosages on gut microbiota and integrity of weaned piglets. Journal of Animal Physiology and Animal Nutrition 103, 231-241.
| Crossref | Google Scholar |

Wang H, Kim KP, Kim IH (2021) Evaluation of the combined effects of different dose levels of zinc oxide with probiotics complex supplementation on the growth performance, nutrient digestibility, faecal microbiota, noxious gas emissions and faecal score of weaning pigs. Journal of Animal Physiology and Animal Nutrition 105, 286-293.
| Crossref | Google Scholar | PubMed |

Wicks D, Wright J, Rayment P, Spiller R (2005) Impact of bitter taste on gastric motility. European Journal of Gastroenterology & Hepatology 17, 961-965.
| Crossref | Google Scholar | PubMed |