Phytobiotics to improve health and production of broiler chickens: functions beyond the antioxidant activity

  • Kikusato, Motoi (Animal Nutrition, Life Sciences, Graduate School of Agricultural Science, Tohoku University)
  • Received : 2020.12.16
  • Accepted : 2021.02.02
  • Published : 2021.03.01


Phytobiotics, also known as phytochemicals or phytogenics, have a wide variety of biological activities and have recently emerged as alternatives to synthetic antibiotic growth promoters. Numerous studies have reported the growth-promoting effects of phytobiotics in chickens, but their precise mechanism of action is yet to be elucidated. Phytobiotics are traditionally known for their antioxidant activity. However, extensive investigations have shown that these compounds also have anti-inflammatory, antimicrobial, and transcription-modulating effects. Phytobiotics are non-nutritive constituents, and their bioavailability is low. Nonetheless, their beneficial effects have been observed in several tissues or organs. The health benefits of the ingestion of phytobiotics are attributed to their antioxidant activity. However, several studies have revealed that not all these benefits could be explained by the antioxidant effects alone. In this review, I focused on the bioavailability of phytobiotics and the possible mechanisms underlying their overall effects on intestinal barrier functions, inflammatory status, gut microbiota, systemic inflammation, and metabolism, rather than the specific effects of each compound. I also discuss the possible mechanisms by which phytobiotics contribute to growth promotion in chickens.


  1. Liu RH. Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr 2004;134:3479S-85S.
  2. Shimao R, Muroi H, Furukawa K, Toyomizu M, Kikusato M. Effects of low-dose oleuropein diet supplementation on the oxidative status of skeletal muscles and plasma hormonal concentration of growing broiler chickens. Br Poult Sci 2019; 60:784-9.
  3. Kikusato M, Xue G, Pastor A, Niewold TA, Toyomizu M. Effects of plant-derived isoquinoline alkaloids on growth performance and intestinal function of broiler chickens under heat stress. Poult Sci 2021;100:957-63.
  4. Kim DK, Lillehoj HS, Lee SH, Jang SI, Lillehoj EP, Bravo D. Dietary Curcuma longa enhances resistance against Eimeria maxima and Eimeria tenella infections in chickens. Poult Sci 2013;92:2635-43.
  5. Olson JB, Ward NE, Koutsos EA. Lycopene incorporation into egg yolk and effects on laying hen immune function. Poult Sci 2008;87:2573-80.
  6. Tsao R, Deng Z. Separation procedures for naturally occurring antioxidant phytochemicals. J Chromatogr B Analyt Technol Biomed Life Sci 2004;812:85-99.
  7. Lee MT, Lin WC, Yu B, Lee TT. Antioxidant capacity of phytochemicals and their potential effects on oxidative status in animals - a review. Asian-Australas J Anim Sci 2017;30:299-308.
  8. Perron NR, Brumaghim JL. A review of the antioxidant mechanisms of polyphenol compounds related to iron binding. Cell Biochem Biophys 2009;53:75-100.
  9. Halliwell B, Rafter J, Jenner A. Health promotion by flavonoids, tocopherols, tocotrienols, and other phenols: direct or indirect effects? Antioxidant or not? Am J Clin Nutr 2005; 81:268S-76S.
  10. Martel J, Ojcius DM, Ko YF, Young JD. Phytochemicals as prebiotics and biological stress inducers. Trends Biochem Sci 2020;45:462-71.
  11. Williamson G, Kay CD, Crozier A. The bioavailability, transport, and bioactivity of dietary flavonoids: a review from a historical perspective. Compr Rev Food Sci Food Saf 2018; 17:1054-112.
  12. Pandey AK, Kumar P, Saxena MJ. Feed additives in animal health. In: Gupta RC, Srivastava A, Lall R, editors. Nutraceuticals in veterinary medicine. London, UK: Springer, Cham; 2019. pp. 345-62.
  13. Qin S, Hou DX. The biofunctions of phytochemicals and their applications in farm animals: the Nrf2/Keap1 system as a target. Engineering 2017;3:738-52.
  14. AL-Sagan AA, Khalil S, Hussein EOS, Attia YA. Effects of fennel seed powder supplementation on growth performance, carcass characteristics, meat quality, and economic efficiency of broilers under thermoneutral and chronic heat stress conditions. Animals 2020;10:206.
  15. Starcevic K, Krstulovic L, Brozic D, et al. Production performance, meat composition and oxidative susceptibility in broiler chicken fed with different phenolic compounds. J Sci Food Agric 2015;95:1172-8.
  16. Cayan H, Erener G. Effect of olive leaf (Olea europaea) powder on laying hens performance, egg quality and egg yolk cholesterol levels. Asian-Australas J Anim Sci 2015;28:538-43.
  17. Attia YA, Bakhashwain AA, Bertu NK. Thyme oil (Thyme vulgaris L.) as a natural growth promoter for broiler chickens reared under hot climate. Ital J Anim Sci 2017;16:275-82.
  18. Liu ZY, Wang XL, Ou SQ, Hou DX, He JH. Sanguinarine modulate gut microbiome and intestinal morphology to enhance growth performance in broilers. PLoS One 2020;15:e0234920.
  19. Aljumaah MR, Suliman GM, Abdullatif AA, Abudabos AM. Effects of phytobiotic feed additives on growth traits, blood biochemistry, and meat characteristics of broiler chickens exposed to Salmonella typhimurium. Poult Sci 2020;99:5744-51.
  20. Lillehoj H, Liu Y, Calsamiglia S, et al. Phytochemicals as antibiotic alternatives to promote growth and enhance host health. Vet Res 2018;49:76.
  21. Valenzuela-Grijalva NV, Pinelli-Saavedra A, Muhlia-Almazan A, Dominguez-Diaz D, Gonzalez-Rios H. Dietary inclusion effects of phytochemicals as growth promoters in animal production. J Anim Sci Technol 2017;59:8.
  22. Manach C, Williamson G, Morand C, Scalbert A, Remesy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 2005;81: 230S-42S.
  23. Teng Z, Yuan C, Zhang F, et al. Intestinal absorption and first-pass metabolism of polyphenol compounds in rat and their transport dynamics in Caco-2 cells. PLoS One 2012;7:e29647.
  24. Gessner DK, Ringseis R, Eder K. Potential of plant polyphenols to combat oxidative stress and inflammatory processes in farm animals. J Anim Physiol Anim Nutr 2017;101:605-28.
  25. Murota K, Shimizu S, Miyamoto S, et al. Unique uptake and transport of isoflavone aglycones by human intestinal caco-2 cells: comparison of isoflavonoids and flavonoids. J Nutr 2002;132:1956-61.
  26. Manach C, Scalbert A, Morand C, Remesy C, Jimenez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004;79:727-47.
  27. Spencer JPE. Metabolism of tea flavonoids in the gastrointestinal tract. J Nutr 2003;133:3255S-61S.
  28. Scalbert A, Morand C, Manach C, Remesy C. Absorption and metabolism of polyphenols in the gut and impact on health. Biomed Pharmacother 2002;56:276-82.
  29. Holst B, Williamson G. Nutrients and phytochemicals: from bioavailability to bioefficacy beyond antioxidants. Curr Opin Biotechnol 2008;19:73-82.
  30. Liu EH, Qi LW, Li P. Structural relationship and binding mechanisms of five flavonoids with bovine serum albumin. Molecules 2010;15:9092-103.
  31. Dangles O, Dufour C, Manach C, Morand C, Remesy C. Binding of flavonoids to plasma proteins. Methods Enzymol 2001;335:319-33.
  32. Bieger J, Cermak R, Blank R, et al. Tissue distribution of quercetin in pigs after long-term dietary supplementation. J Nutr 2008;138:1417-20.
  33. Hu NX, Chen M, Liu YS, et al. Pharmacokinetics of sanguinarine, chelerythrine, and their metabolites in broiler chickens following oral and intravenous administration. J Vet Pharmacol Ther 2019;42:197-206.
  34. Rupasinghe HV, Ronalds CM, Rathgeber B, Robinson RA. Absorption and tissue distribution of dietary quercetin and quercetin glycosides of apple skin in broiler chickens. J Sci Food Agric 2010;90:1172-8.
  35. Wu XM, Tan RX. Interaction between gut microbiota and ethnomedicine constituents. Nat Prod Rep 2019;36:788-809.
  36. Suzuki T. Regulation of the intestinal barrier by nutrients: the role of tight junctions. Anim Sci J 2020;91:e13357.
  37. Quintana-Hayashi MP, Padra M, Padra JT, Benktander J, Linden SK. Mucus-pathogen interactions in the gastrointestinal tract of farmed animals. Microorganisms 2018;6:55.
  38. Capaldo CT, Powell DN, Kalman D. Layered defense: how mucus and tight junctions seal the intestinal barrier. J Mol Med 2017;95:927-34.
  39. Vicuna EA, Kuttappan VA, Galarza-Seeber R, et al. Effect of dexamethasone in feed on intestinal permeability, differential white blood cell counts, and immune organs in broiler chicks. Poult Sci 2015;94:2075-80.
  40. Nanto-Hara F, Kikusato M, Ohwada S, Toyomizu M. Heat stress directly affects intestinal integrity in broiler chickens. J Poult Sci 2020;57:284-90.
  41. Alhenaky A, Abdelqader A, Abuajamieh M, Al-Fataftah AR. The effect of heat stress on intestinal integrity and Salmonella invasion in broiler birds. J Therm Biol 2017;70:9-14.
  42. Kridtayopas C, Rakangtong C, Bunchasak C, Loongyai W. Effect of prebiotic and synbiotic supplementation in diet on growth performance, small intestinal morphology, stress, and bacterial population under high stocking density condition of broiler chickens. Poult Sci 2019;98:4595-605.
  43. Murakami Y, Tanabe S, Suzuki T. High-fat diet-induced intestinal hyperpermeability is associated with increased bile acids in the large intestine of mice. J Food Sci 2016;81:H216-22.
  44. Manco M, Putignani L, Bottazzo GF. Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk. Endocr Rev 2010;31:817-44.
  45. Mayangsari Y, Suzuki T. Resveratrol ameliorates intestinal barrier defects and inflammation in colitic mice and intestinal cells. J Agric Food Chem 2018;66:12666-74.
  46. Zhang C, Zhao XH, Yang L, et al. Resveratrol alleviates heat stress-induced impairment of intestinal morphology, microflora, and barrier integrity in broilers. Poult Sci 2017;96:4325-32.
  47. Liu L, Fu C, Yan M, et al. Resveratrol modulates intestinal morphology and HSP70/90, NF-κB and EGF expression in the jejunal mucosa of black-boned chickens on exposure to circular heat stress. Food Funct 2016;7:1329-38.
  48. Amasheh M, Schlichter S, Amasheh S, et al. Quercetin enhances epithelial barrier function and increases claudin-4 expression in Caco-2 cells. J Nutr 2008;138:1067-73.
  49. Suzuki T, Hara H. Quercetin enhances intestinal barrier function through the assembly of zonnula occludens-2, occludin, and claudin-1 and the expression of claudin-4 in Caco-2 cells. J Nutr 2009;139:965-74.
  50. Azuma T, Shigeshiro M, Kodama M, Tanabe S, Suzuki T. Supplemental naringenin prevents intestinal barrier defects and inflammation in colitic mice. J Nutr 2013;143:827-34.
  51. Singh R, Chandrashekharappa S, Bodduluri SR, et al. Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway. Nat Commun 2019;10:89.
  52. Viveros A, Chamorro S, Pizarro M, Arija I, Centeno C, Brenes A. Effects of dietary polyphenol-rich grape products on intestinal microflora and gut morphology in broiler chicks. Poult Sci 2011;90:566-78.
  53. Chamorro S, Romero C, Brenes A, et al. Impact of a sustained consumption of grape extract on digestion, gut microbial metabolism and intestinal barrier in broiler chickens. Food Funct 2019;10:1444-54.
  54. Iqbal Y, Cottrell JJ, Suleria HAR, Dunshea FR. Gut microbiota-polyphenol interactions in chicken: a review. Animals 2020;10:1391.
  55. Lee KW, Kim JS, Oh ST, Kang CW, An BK. Effects of dietary sanguinarine on growth performance, relative organ weight, cecal microflora, serum cholesterol level and meat quality in broiler chickens. J Poult Sci 2015;52:15-22.
  56. Abu Hafsa SH, Ibrahim SA. Effect of dietary polyphenol-rich grape seed on growth performance, antioxidant capacity and ileal microflora in broiler chicks. J Anim Physiol Anim Nutr 2018;102:268-75.
  57. Huang CM, Lee TT. Immunomodulatory effects of phytogenics in chickens and pigs - a review. Asian-Australas J Anim Sci 2018;31:617-27.
  58. Wang A, Al-Kuhlani M, Johnston SC, Ojcius DM, Chou J, Dean D. Transcription factor complex AP-1 mediates inflammation initiated by Chlamydia pneumoniae infection. Cell Microbiol 2013;15:779-94.
  59. Awad WA, Hess C, Hess M. Enteric pathogens and their toxin-induced disruption of the intestinal barrier through alteration of tight junctions in chickens. Toxins 2017;9:60.
  60. Shimizu M. Multifunctions of dietary polyphenols in the regulation of intestinal inflammation. J Food Drug Anal 2017;25:93-9.
  61. Huang S, Zhao L, Kim K, Lee DS, Hwang DH. Inhibition of Nod2 signaling and target gene expression by curcumin. Mol Pharmacol 2008;74:274-81.
  62. Shibata T, Nakashima F, Honda K, et al. Toll-like receptors as a target of food-derived anti-inflammatory compounds. J Biol Chem 2014;289:32757-72.
  63. Youn HS, Lee JY, Fitzgerald KA, Young HA, Akira S, Hwang DH. Specific inhibition of MyD88-independent signaling pathways of TLR3 and TLR4 by resveratrol: molecular targets are TBK1 and RIP1 in TRIF complex. J Immunol 2005;175: 3339-46.
  64. Frost RA, Lang CH. Regulation of muscle growth by pathogen-associated molecules. J Anim Sci 2008;86(Suppl 14): E84-93.
  65. Zheng YW, Zhang JY, Zhou HB, et al. Effects of dietary pyrroloquinoline quinone disodium supplementation on inflammatory responses, oxidative stress, and intestinal morphology in broiler chickens challenged with lipopolysaccharide. Poult Sci 2020;99:5389-98.
  66. Tachibana T, Kodama T, Yamane S, Makino R, Khan SI, Cline MA. Possible role of central interleukins on the anorexigenic effect of lipopolysaccharide in chicks. Br Poult Sci 2017;58: 305-11.
  67. Han H, Zhang J, Chen Y, et al. Dietary taurine supplementation attenuates lipopolysaccharide-induced inflammatory responses and oxidative stress of broiler chickens at an early age. J Anim Sci 2020;98:skaa311.
  68. Horvatic A, Guillemin N, Kaab H, et al. Integrated dataset on acute phase protein response in chicken challenged with Escherichia coli lipopolysaccharide endotoxin. Data Brief 2018;21:684-99.
  69. Roura E, Homedes J, Klasing KC. Prevention of immunologic stress contributes to the growth-permitting ability of dietary antibiotics in chicks. J Nutr 1992;122:2383-90.
  70. Zhou J, Liu B, Liang C, Li Y, Song YH. Cytokine signaling in skeletal muscle wasting. Trends Endocrinol Metab 2016;27: 335-47.
  71. Niewold TA. The nonantibiotic anti-inflammatory effect of antimicrobial growth promoters, the real mode of action? A hypothesis. Poult Sci 2007;86:605-9.
  72. Broom LJ, Kogut MH. Inflammation: friend or foe for animal production? Poult Sci 2018;97:510-4.
  73. Christensen LP, Christensen KB. The role of direct and indirect polyphenolic antioxidants in protection against oxidative stress. In: Watson RR, Preedy VR, Zibadi S, editors. Polyphenols in human health and disease. Cambridge, MA, USA: Academic Press; 2014. pp. 289-309.
  74. Kim J, Cha YN, Surh YJ. A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders. Mutat Res 2010;690:12-23.
  75. Qin S, Hou DX. Multiple regulations of Keap1/Nrf2 system by dietary phytochemicals. Mol Nutr Food Res 2016;60:1731-55.
  76. Sun L, Xu G, Dong Y, Li M, Yang L, Lu W. Quercetin protects against lipopolysaccharide-induced intestinal oxidative stress in broiler chickens through activation of Nrf2 pathway. Molecules 2020;25:1053.
  77. Geillinger KE, Kipp AP, Schink K, Roder PV, Spanier B, Daniel H. Nrf2 regulates the expression of the peptide transporter PEPT1 in the human colon carcinoma cell line Caco-2. Biochim Biophys Acta 2014;1840:1747-54.
  78. Kauppinen A, Suuronen T, Ojala J, Kaarniranta K, Salminen A. Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal 2013;25:1939-48.
  79. Chung S, Yao H, Caito S, Hwang J, Arunachalam G, Rahman I. Regulation of SIRT1 in cellular functions: role of polyphenols. Arch Biochem Biophys 2010;501:79-90.
  80. Baur JA, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006;444:337-42.
  81. Beher D, Wu J, Cumine S, et al. Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem Biol Drug Des 2009;74:619-24.
  82. Xie W, Tian Y. Xenobiotic receptor meets NF-κB, a collision in the small bowel. Cell Metab 2006;4:177-8.
  83. Moreau A, Vilarem MJ, Maurel P, Pascussi JM. Xenoreceptors CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response. Mol Pharm 2008;5:35-41.
  84. Satsu H, Hiura Y, Mochizuki K, Hamada M, Shimizu M. Activation of pregnane X receptor and induction of MDR1 by dietary phytochemicals. J Agric Food Chem 2008;56:5366-73.
  85. Hao H, Cheng G, Iqbal Z, et al. Benefits and risks of antimicrobial use in food-producing animals. Front Microbiol 2014;5:288.
  86. Misiak B, Loniewski I, Marlicz W, et al. The HPA axis dysregulation in severe mental illness: can we shift the blame to gut microbiota? Prog Neuropsychopharmacol Biol Psychiatry 2020;102:109951.