The widespread use of antibiotics in the poultry industry has led to the emergence of antibiotic-resistant bacteria, which pose a significant health risk to humans and animals. These public health concerns, which have led to legislation limiting antibiotic use in animals, drive the need to find alternative strategies for controlling and treating bacterial infections. Modulation of the avian innate immune system using immunostimulatory compounds provides a promising solution to enhance poultry immune responses to a broad range of bacterial infections without the risk of generating antibiotic resistance. An array of immunomodulatory compounds have been investigated for their impact on poultry performance and immune responses. However, further research is required to identify compounds capable of controlling bacterial infections without detrimentally affecting bird performance. It is also crucial to determine the safety and effectiveness of these compounds in conjunction with poultry vaccines. This review provides an overview of the various immune modulators known to enhance innate immunity against avian bacterial pathogens in chickens, and describes the mechanisms involved.
KEYWORDS immune modulators, chickens, avian bacterial pathogens, prebiotics and probiotics, pathogen associated molecular patterns (PAMPs), microbial metabolites and derivatives, vitamins.
1. WRI. Creating a sustainable food future: interim findings. In: World Resources Report. World Resources Institute Washington, DC (2013).
2. Kleyn FJ, Ciacciariello M. Future demands of the poultry industry: will we meet our commitments sustainably in developed and developing economies? World's Poultry Sci J (2021) 77(2):267–78. doi: 10.1080/00439339.2021.1904314
3. Godfray HCJ, Aveyard P, Garnett T, Hall Jim W, Key Timothy J, Lorimer J, et al. Meat consumption, health, and the environment. Science (2018) 361(6399):eaam5324. doi: 10.1126/science.aam5324
4. Hafez HM, Attia YA. Challenges to the poultry industry: current perspectives and strategic future after the COVID-19 outbreak. Front Veterinary Sci (2020) 7:516. doi: 10.3389/fvets.2020.00516
5. Bessei W. Impact of animal welfare on worldwide poultry production. World's Poultry Sci J (2018) 74(2):211–24. doi: 10.1017/s0043933918000028
6. Jones PJ, Niemi J, Christensen J-P, Tranter RB, Bennett RM. A review of the financial impact of production diseases in poultry production systems. Anim Production Sci (2019) 59(9):1585. doi: 10.1071/an18281
7. Meunier M, Guyard-Nicodème M, Dory D, Chemaly M. Control strategies against Campylobacter at the poultry production level: biosecurity measures, feed additives and vaccination. J Appl Microbiol (2016) 120(5):1139–73. doi: 10.1111/jam.12986
8. Stanaway JD, Atuhebwe PL, Luby SP, Crump JA. Assessing the feasibility of typhoid elimination. Clin Infect Dis (2020) 71(Supplement_2):S179–84. doi: 10.1093/ cid/ciaa585
9. Shane SM, Faust A. Evaluation of sanitizers for hatching eggs. J Appl Poultry Res (1996) 5(2):134–8. doi: 10.1093/japr/5.2.134
10. Coufal CD, Chavez C, Knape KD, Carey JB. Evaluation of a method of ultraviolet light sanitation of broiler hatching eggs. Poultry Sci (2003) 82(5):754–9. doi: 10.1093/ps/82.5.754
11. Ekperigin HE, McCapes RH, Redus R, Ritchie WL, Cameron WJ, Nagaraja KV, et al. Research note: microcidal effects of a new pelleting process. Poultry Sci (1990) 69 (9):1595–8. doi: 10.3382/ps.0691595
12. Dhillon AS, Jack OK. Two outbreaks of colibacillosis in commercial caged layers. Avian Dis (1996) 40(3):742–6. doi: 10.2307/1592290
13. Davis M, Morishita TY. Relative ammonia concentrations, dust concentrations, and presence of Salmonella species and Escherichia coli inside and outside commercial layer facilities. Avian Dis (2005) 49(1):30–5. doi: 10.1637/0005-2086(2005)49[30: RACDCA]2.0.CO;2
14. Roth N, Käsbohrer A, Mayrhofer S, Zitz U, Hofacre C, Domig KJ. The application of antibiotics in broiler production and the resulting antibiotic resistance in Escherichia coli: a global overview. Poult Sci (2019) 98(4):1791–804. doi: 10.3382/ps/ pey539
15. Mund MD, Khan UH, Tahir U, Mustafa B-E, Fayyaz A. Antimicrobial drug residues in poultry products and implications on public health: a review. Int J Food Properties (2017) 20(7):1433–46. doi: 10.1080/10942912.2016.1212874
16. Butaye P, Devriese LA, Haesebrouck F. Antimicrobial growth promoters used in animal feed: effects of less well known antibiotics on gram-positive bacteria. Clin Microbiol Rev (2003) 16(2):175–88. doi: 10.1128/cmr.16.2.175-188.2003
17. Castanon JIR. History of the use of antibiotic as growth promoters in European poultry feeds. Poultry Sci (2007) 86(11):2466–71. doi: 10.3382/ps.2007-00249
18. More SJ. European Perspectives on efforts to reduce antimicrobial usage in food animal production. Irish veterinary J (2020) 73:2–2. doi: 10.1186/s13620-019-0154-4
19. Scott HM, Acuff G, Bergeron G, Bourassa MW, Gill J, Graham DW, et al. Critically important antibiotics: criteria and approaches for measuring and reducing their use in food animal agriculture. Ann New York Acad Sci (2019) 1441(1):8–16. doi: 10.1111/nyas.14058
20. Founou LL, Founou RC, Essack SY. Antibiotic resistance in the food chain: a developing country-perspective. Front Microbiol (2016) 7. doi: 10.3389/ fmicb.2016.01881
21. Prestinaci F, Pezzotti P, Pantosti A. Antimicrobial resistance: a global multifaceted phenomenon. Pathog Global Health (2015) 109(7):309–18. doi: 10.1179/ 2047773215y.0000000030
22. Dadgostar P. Antimicrobial resistance: implications and costs. Infect Drug Resist (2019) 12:3903–10. doi: 10.2147/idr.s234610
23. O'Neill J. Tackling drug-resistant infections globally: final report and recommendations. London, UK: Wellcome Trust and HM Government. (2016).
24. Ravikumar R, Chan J, Prabakaran M. Vaccines against major poultry viral diseases: strategies to improve the breadth and protective efficacy. Viruses (2022) 14 (6):1195. doi: 10.3390/v14061195
25. Redweik GAJ, Jochum J, Mellata M. Live bacterial prophylactics in modern poultry. Front Veterinary Sci (2020) 7. doi: 10.3389/fvets.2020.592312
26. Grein K, Jungbäck C, Kubiak V. Autogenous vaccines: quality of production and movement in a common market. Biologicals (2022) 76:36–41. doi: 10.1016/ j.biologicals.2022.01.003
27. Rabie NS, Amin Girh ZMS. Bacterial vaccines in poultry. Bull Natl Res Centre (2020) 44(1):15. doi: 10.1186/s42269-019-0260-1
28. Dimitrov KM, Afonso CL, Yu Q, Miller PJ. Newcastle Disease vaccines-a solved problem or a continuous challenge? Vet Microbiol (2017) 206:126–36. doi: 10.1016/ j.vetmic.2016.12.019
29. Marangon S, Busani L. The use of vaccination in poultry production. Rev Sci Tech (2007) 26(1):265–74. doi: 10.20506/rst.26.1.1742
30. Ż bikowska K, M. Michalczuk and B. Dolka: the use of bacteriophages in the poultry industry. Animals (2020) 10(5):872. doi: 10.3390/ani10050872
31. Patterson JA, Burkholder KM. Application of prebiotics and probiotics in poultry production. Poult Sci (2003) 82(4):627–31. doi: 10.1093/ps/82.4.627
32. Al-Mnaser A, Dakheel M, Alkandari F, Woodward M. Polyphenolic phytochemicals as natural feed additives to control bacterial pathogens in the chicken gut. Arch Microbiol (2022) 204(5):253. doi: 10.1007/s00203-022-02862-5
33. Ricke SC. Perspectives on the use of organic acids and short chain fatty acids as antimicrobials. Poult Sci (2003) 82(4):632–9. doi: 10.1093/ps/82.4.632
34. Wigley P. Immunology of birds. In: eLS Chichester, UK:John Wiley and Sons, Ltd (Ed.). (2017). doi: 10.102/9780470015902.a0026259
35. Kaiser P. Advances in avian immunology–prospects for disease control: a review. Avian Pathol (2010) 39(5):309–24. doi: 10.1080/03079457.2010.508777
36. Qureshi M. Avian macrophage: effector functions in health and disease. Dev Comp Immunol (2000) 24(2-3):103–19. doi: 10.1016/s0145-305x(99)00067-1
37. Sabet T, Hsia W-C, Stanisz M, El-Domeiri A, Van Alten P. A simple method for obtaining peritoneal macrophages from chickens. J Immunol Methods (1977) 14 (2):103–10. doi: 10.1016/0022-1759(77)90001-1
38. Mutua MP, Muya S, Gicheru MM. Protective roles of free avian respiratory macrophages in captive birds. Biol Res (2016) 49(1):29. doi: 10.1186/s40659-016-0090-7
39. Toth TE, Siegel PB. Cellular defense of the avian respiratory system: doseresponse relationship and duration of response in intratracheal stimulation of avian respiratory phagocytes by a Pasteurella multocida bacterin. Avian Dis (1993) 37 (3):756–62. doi: 10.2307/1592025
40. Toth TE, Veit H, Gross WB, Siegel PB. Cellular defense of the avian respiratory system: protection against Escherichia coli airsacculitis by Pasteurella multocidaactivated respiratory phagocytes. Avian Dis (1988) 32(4):681–7. doi: 10.2307/1590985
41. Chaplin DD. Overview of the immune response. J Allergy Clin Immunol (2010) 125(2 Suppl 2):S3–S23. doi: 10.1016/j.jaci.2009.12.980
42. Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol (2014) 5:461. doi: 10.3389/fimmu.2014.00461
43. Temperley ND, Berlin S, Paton IR, Griffin DK, Burt DW. Evolution of the chicken toll-like receptor gene family: a story of gene gain and gene loss. BMC Genomics (2008) 9(1):62. doi: 10.1186/1471-2164-9-62
44. Rehman MS-U, Rehman S. U., Yousaf W, Hassan F-u, Ahmad W, Liu Q, et al. The potential of toll-like receptors to modulate avian immune system: exploring the effects of genetic variants and phytonutrients. Front Genet (2021) 12. doi: 10.3389/ fgene.2021.671235
45. Fellah JS, Jaffredo T, Nagy N, Dunon D. Chapter 3 - development of the avian immune system. In: Schat KA, Kaspers B, Kaiser P, editors. Avian immunology, 2nd ed. Boston: Academic Press (2014). doi: 10.1016/B978-0-12-396965-1.00003-0
46. Boodhoo N, Behboudi S. Marek’s disease virus-specific T cells proliferate, express antiviral cytokines but have impaired degranulation response. Front Immunol (2022) 13. doi: 10.3389/fimmu.2022.973762
47. Smith AL, Göbel TW. Chapter 5 - avian T cells: antigen recognition and lineages. In: Schat KA, Kaspers B, Kaiser P, editors. Avian immunology, 2nd ed. Boston: Academic Press (2014). doi: 10.1016/B978-0-12-396965-1.00005-4
48. Matsuyama-Kato A, Shojadoost B, Boodhoo N, Raj S, Alizadeh M, Fazel F, et al. Activated chicken gamma delta T cells are involved in protective immunity against marek’s disease. Viruses (2023) 15(2):285. doi: 10.3390/v15020285
49. Matsuyama-Kato A, Boodhoo N, Iseki H, Abdul-Careem MF, Plattner BL, Behboudi S, et al. Differential activation of chicken gamma delta T cells from different tissues by toll-like receptor 3 or 21 ligands. Dev Comp Immunol (2022) 131:104391. doi: 10.1016/j.dci.2022.104391
50. Matsuyama-Kato A, Iseki H, Boodhoo N, Bavananthasivam J, Alqazlan N, Abdul-Careem MF, et al. Phenotypic characterization of gamma delta (gd) T cells in chickens infected with or vaccinated against marek's disease virus. Virology (2022) 568:115–25. doi: 10.1016/j.virol.2022.01.012
51. Boodhoo N, Behboudi S. Differential virus-specific IFN-gamma producing T cell responses to marek’s disease virus in chickens with B19 and B21 MHC haplotypes. Front Immunol (2022) 12. doi: 10.3389/fimmu.2021.784359
52. Boodhoo N, Gurung A, Sharif S, Behboudi S. Marek’s disease in chickens: a review with focus on immunology. Veterinary Res (2016) 47(1):119. doi: 10.1186/ s13567-016-0404-3
53. Ratcliffe MJH, Härtle S. Chapter 4 - b cells, the bursa of fabricius and the generation of antibody repertoires. In: Schat KA, Kaspers B, Kaiser P, editors. Avian immunology, 2nd ed. Boston: Academic Press (2014). doi: 10.1016/B978-0-12-396965- 1.00004-2
54. McCormack WT, Tjoelker LW, Thompson CB. Avian b-cell development: generation of an immunoglobulin repertoire by gene conversion. Annu Rev Immunol (1991) 9(1):219–41. doi: 10.1146/annurev.iy.09.040191.001251
55. Sadeyen J-R, Wu Z, Davies H, van Diemen PM, Milicic A, La Ragione RM, et al. Immune responses associated with homologous protection conferred by commercial vaccines for control of avian pathogenic Escherichia coli in turkeys. Veterinary Res (2015) 46(1):5. doi: 10.1186/s13567-014-0132-5
56. Buchmann K. Evolution of innate immunity: clues from invertebrates via fish to mammals. Front Immunol (2014) 5:459. doi: 10.3389/fimmu.2014.00459
57. Flajnik MF, Kasahara M. Origin and evolution of the adaptive immune system: genetic events and selective pressures. Nat Rev Genet (2010) 11(1):47–59. doi: 10.1038/ nrg2703
58. Dubuffet A, Zanchi C, Boutet G, Moreau J, Teixeira M, Moret Y. Transgenerational immune priming protects the eggs only against gram-positive bacteria in the mealworm beetle. PloS Pathog (2015) 11(10):e1005178. doi: 10.1371/ journal.ppat.1005178
59. Kuć J. Induced immunity to plant disease. BioScience (1982) 32(11):854–60. doi: 10.2307/1309008
60. Loker ES, Adema CM, Zhang S-M, Kepler TB. Invertebrate immune systems– not homogeneous, not simple, not well understood. Immunol Rev (2004) 198:10–24. doi: 10.1111/j.0105-2896.2004.0117.x
61. Melillo D, Marino R, Italiani P, Boraschi D. Innate immune memory in invertebrate metazoans: a critical appraisal. Front Immunol (2018) 9. doi: 10.3389/ fimmu.2018.01915
62. Sánchez-Ramón S, Conejero L, Netea MG, Sancho D, Palomares Ó , Subiza JL. Trained immunity-based vaccines: a new paradigm for the development of broadspectrum anti-infectious formulations. Front Immunol (2018) 9:2936(2936). doi: 10.3389/fimmu.2018.02936
63. Netea MG, Domınguez-Andre ́ ́ s J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, et al. Defining trained immunity and its role in health and disease. Nat Rev Immunol (2020) 20(6):375–88. doi: 10.1038/s41577-020-0285-6
64. Verwoolde MB, van den Biggelaar RHGA, van Baal J, Jansen CA, Lammers A. Training of primary chicken monocytes results in enhanced pro-inflammatory responses. Veterinary Sci (2020) 7(3):115. doi: 10.3390/vetsci7030115
65. Goonewardene KB, Karu N, Ahmed KA, Popowich S, Chow-Lockerbie B, Ayalew LE, et al. CpG-ODN induced antimicrobial immunity in neonatal chicks involves a substantial shift in serum metabolic profiles. Sci Rep (2021) 11(1):9028. doi: 10.1038/s41598-021-88386-2
66. Divangahi M, Aaby P, Khader SA, Barreiro LB, Bekkering S, Chavakis T, et al. Trained immunity, tolerance, priming and differentiation: distinct immunological processes. Nat Immunol (2021) 22(1):2–6. doi: 10.1038/s41590-020-00845-6
67. Dominguez-Andres J, Netea MG. Long-term reprogramming of the innate immune system. J Leukocyte Biol (2019) 105(2):329–38. doi: 10.1002/jlb.mr0318-104r
68. Cheled-Shoval SL, Amit-Romach E, Barbakov M, Uni Z. The effect of in ovo administration of mannan oligosaccharide on small intestine development during the pre- and posthatch periods in chickens. Poultry Sci (2011) 90(10):2301–10. doi: 10.3382/ps.2011-01488
69. Pourabedin M, Xu Z, Baurhoo B, Chevaux E, Zhao X. Effects of mannan oligosaccharide and virginiamycin on the cecal microbial community and intestinal morphology of chickens raised under suboptimal conditions. Can J Microbiol (2014) 60 (5):255–66. doi: 10.1139/cjm-2013-0899
70. Chee SH, Iji PA, Choct M, Mikkelsen LL, Kocher A. Characterisation and response of intestinal microflora and mucins to manno-oligosaccharide and antibiotic supplementation in broiler chickens. Br Poultry Sci (2010) 51(3):368–80. doi: 10.1080/ 00071668.2010.503477
71. Yitbarek A, Echeverry H, Brady J, Hernandez-Doria J, Camelo-Jaimes G, Sharif S, et al. Innate immune response to yeast-derived carbohydrates in broiler chickens fed organic diets and challenged with clostridium perfringens. Poult Sci (2012) 91(5):1105– 12. doi: 10.3382/ps.2011-02109
72. Ibuki M, Kovacs-Nolan J, Fukui K, Kanatani H, Mine Y. Analysis of gut immune-modulating activity of b-1,4-mannobiose using microarray and real-time reverse transcription polymerase chain reaction. Poultry Sci (2010) 89(9):1894–904. doi: 10.3382/ps.2010-00791
73. Stefaniak T, Madej JP, Graczyk S, Siwek M, Łukaszewicz E, Kowalczyk A, et al. Selected prebiotics and synbiotics administered in ovo can modify innate immunity in chicken broilers. BMC Veterinary Res (2019) 15(1):105. doi: 10.1186/s12917-019-1850-8
74. Xie S, Zhao S, Jiang L, Lu L, Yang Q, Yu Q. Lactobacillus reuteri stimulates intestinal epithelial proliferation and induces differentiation into goblet cells in young chickens. J Agric Food Chem (2019) 67(49):13758–66. doi: 10.1021/acs.jafc.9b06256
75. Nii T, Jirapat J, Isobe N, Yoshimura Y. Effects of oral administration of Lactobacillus reuteri on mucosal barrier function in the digestive tract of broiler chicks. J Poultry Sci (2020) 57(1):67–76. doi: 10.2141/jpsa.0190035
76. Wu Y, Zhen W, Geng Y, Wang Z, Guo Y. Pretreatment with probiotic Enterococcus faecium NCIMB 11181 ameliorates necrotic enteritis-induced intestinal barrier injury in broiler chickens. Sci Rep (2019) 9(1):10256. doi: 10.1038/s41598-019- 46578-x
77. Wang B, Hussain A, Zhou Y, Zeng Z, Wang Q, Zou P, et al. Saccharomyces boulardii attenuates inflammatory response induced by clostridium perfringens via TLR4/TLR15-MyD8 pathway in HD11 avian macrophages. Poultry Sci (2020) 99 (11):5356–65. doi: 10.1016/j.psj.2020.07.045
78. Lee K-W, Kim DK, Lillehoj HS, Jang SI, Lee S-H. Immune modulation by Bacillus subtilis-based direct-fed microbials in commercial broiler chickens. Anim Feed Sci Technol (2015) 200:76–85. doi: 10.1016/j.anifeedsci.2014.12.006
79. Meijerink N, Kers JG, Velkers FC, van Haarlem DA, Lamot DM, de Oliveira JE, et al. Early life inoculation with adult-derived microbiota accelerates maturation of intestinal microbiota and enhances NK cell activation in broiler chickens. Front Veterinary Sci (2020) 7. doi: 10.3389/fvets.2020.584561
80. Zhang B, Guo Y, Wang Z. The modulating effect of b-1, 3/1, 6-glucan supplementation in the diet on performance and immunological responses of broiler chickens. Asian-Australas J Anim Sci (2008) 21(2):237–44. doi: 10.5713/ ajas.2008.70207
81. Huff GR, Huff WE, Jalukar S, Oppy J, Rath NC, Packialakshmi B. The effects of yeast feed supplementation on turkey performance and pathogen colonization in a transport stress/Escherichia coli challenge . Poultry Sci. (2013) 92(3):655–62. doi: 10.3382/ps.2012-02787
82. Shao Y, Guo Y, Wang Z. b-1,3/1,6-Glucan alleviated intestinal mucosal barrier impairment of broiler chickens challenged with Salmonella enterica serovar typhimurium. Poultry Sci (2013) 92(7):1764–73. doi: 10.3382/ps.2013-03029
83. Lowry VK, Farnell MB, Ferro PJ, Swaggerty CL, Bahl A, Kogut MH. Purified bglucan as an abiotic feed additive up-regulates the innate immune response in immature chickens against Salmonella enterica serovar enteritidis. Int J Food Microbiol (2005) 98(3):309–18. doi: 10.1016/j.ijfoodmicro.2004.06.008
84. Huff GR, Huff WE, Farnell MB, Rath NC, Solis de los Santos F, Donoghue AM. Bacterial clearance, heterophil function, and hematological parameters of transportstressed turkey poults supplemented with dietary yeast extract1. Poultry Sci (2010) 89 (3):447–56. doi: 10.3382/ps.2009-00328
85. Guo Y, Ali RA, Qureshi MA. The influence of beta-glucan on immune responses in broiler chicks. Immunopharmacol Immunotoxicol (2003) 25(3):461–72. doi: 10.1081/ iph-120024513
86. Zhuge X, Sun Y, Jiang M, Wang J, Tang F, Xue F, et al. Acetate metabolic requirement of avian pathogenic Escherichia coli promotes its intracellular proliferation within macrophage. Vet Res (2019) 50(31). doi: 10.1186/s13567-019-0650-2
87. Gomis S, Babiuk L, Godson DL, Allan B, Thrush T, Townsend H, et al. Protection of chickens against Escherichia coli infections by DNA containing CpG motifs. Infect Immun (2003) 71(2):857–63. doi: 10.1128/iai.71.2.857-863.2003
88. Gomis S, Babiuk L, Allan B, Willson P, Waters E, Ambrose N, et al. Protection of neonatal chicks against a lethal challenge of Escherichia coli using DNA containing cytosine-Phosphodiester-Guanine motifs. Avian Dis (2004) 48(4):813–22. doi: 10.1637/ 7194-041204R
89. Taghavi A, Allan B, Mutwiri G, Van Kessel A, Willson P, Babiuk L, et al. Protection of neonatal broiler chicks against Salmonella typhimurium septicemia by DNA containing CpG motifs. Avian Dis (2008) 52(3):398–406. doi: 10.1637/8196- 121907-Reg
90. He H, Genovese KJ, Swaggerty CL, Nisbet DJ, Kogut MH. In vivo priming heterophil innate immune functions and increasing resistance to Salmonella enteritidis infection in neonatal chickens by immune stimulatory CpG oligodeoxynucleotides. Veterinary Immunol Immunopathol (2007) 117(3):275–83. doi: 10.1016/ j.vetimm.2007.03.002
91. Kalhari Bandara G, Shelly P, Thushari G, Ashish G, Shanika K, Ruwani K, et al. Intrapulmonary delivery of CpG-ODN microdroplets provides protection against Escherichia coli septicemia in neonatal broiler chickens. Avian Dis (2017) 61(4):503– 11. doi: 10.1637/11684-060617-Reg.1
92. Gunawardana T, Foldvari M, Zachar T, Popowich S, Chow-Lockerbie B, Ivanova MV, et al. Protection of neonatal broiler chickens following in ovo delivery of oligodeoxynucleotides containing CpG motifs (CpG-ODN) formulated with carbon nanotubes or liposomes. Avian Dis (2015) 59(1):31–7. doi: 10.1637/10832-032814-Reg
93. Brenda A, Colette W, Wolfgang K, Mishal S, Andy P, Volker G, et al. In ovo administration of innate immune stimulants and protection from early chick mortalities due to yolk sac infection. Avian Dis (2018) 62(3):316–21. doi: 10.1637/ 11840-041218-Reg.1
94. Komori T, Saito K, Sawa N, Shibasaki Y, Kohchi C, Soma G, et al. Innate immunity activated by oral administration of LPSp is phylogenetically preserved and developed in broiler chickens. Anticancer Res (2015) 35(8):4461–6.
95. Hebishima T, Matsumoto Y, Watanabe GEN, Soma G-I, Kohchi C, Taya K, et al. Recovery from immunosuppression-related disorders in humans and animals by IPPA1, an edible lipopolysaccharide. Anticancer Res (2010) 30(8):3113.
96. Bansal M, Alenezi T, Fu Y, Almansour A, Wang H, Gupta A, et al. Specific secondary bile acids control chicken necrotic enteritis. Pathogens (2021) 10(8):1041. doi: 10.3390/pathogens10081041
97. Wang H, Latorre JD, Bansal M, Abraha M, Al-Rubaye B, Tellez-Isaias G, et al. Microbial metabolite deoxycholic acid controls clostridium perfringens-induced chicken necrotic enteritis through attenuating inflammatory cyclooxygenase signaling. Sci Rep (2019) 9(1):14541. doi: 10.1038/s41598-019-51104-0
98. Alrubaye B, Abraha M, Almansour A, Bansal M, Wang H, Kwon YM, et al. Microbial metabolite deoxycholic acid shapes microbiota against campylobacter jejuni chicken colonization. PloS One (2019) 14(7):e0214705. doi: 10.1371/ journal.pone.0214705
99. Sun X, Winglee K, Gharaibeh RZ, Gauthier J, He Z, Tripathi P, et al. Microbiotaderived metabolic factors reduce campylobacteriosis in mice. Gastroenterology (2018) 154(6):1751–1763.e2. doi: 10.1053/j.gastro.2018.01.042
100. Sunkara LT, Achanta M, Schreiber NB, Bommineni YR, Dai G, Jiang W, et al. Butyrate enhances disease resistance of chickens by inducing antimicrobial host defense peptide gene expression. PloS One (2011) 6(11):e27225. doi: 10.1371/ journal.pone.0027225
101. Gupta A, Bansal M, Wagle B, Sun X, Rath N, Donoghue A, et al. Sodium butyrate reduces Salmonella enteritidis infection of chicken enterocytes and expression of inflammatory host genes in vitro. Front Microbiol (2020) 11. doi: 10.3389/ fmicb.2020.553670
102. Bortoluzzi C, Rothrock MJ, Vieira BS, Mallo JJ, Puyalto M, Hofacre C, et al. Supplementation of protected sodium butyrate alone or in combination with essential oils modulated the cecal microbiota of broiler chickens challenged with coccidia and clostridium perfringens. Front Sustain Food Syst (2018) 2. doi: 10.3389/ fsufs.2018.00072
103. Sunkara LT, Jiang W, Zhang G. Modulation of antimicrobial host defense peptide gene expression by free fatty acids. PloS One (2012) 7(11):e49558. doi: 10.1371/ journal.pone.0049558
104. Geng Y, Ma Q, Wang Z, Guo Y. Dietary vitamin D3 supplementation protects laying hens against lipopolysaccharide-induced immunological stress. Nutr Metab (2018) 15:58. doi: 10.1186/s12986-018-0293-8
105. Morris A, Shanmugasundaram R, Lilburn MS, Selvaraj RK. 25- hydroxycholecalciferol supplementation improves growth performance and decreases inflammation during an experimental lipopolysaccharide injection. Poult Sci (2014) 93 (8):1951–6. doi: 10.3382/ps.2014-03939
106. Shojadoost B, Behboudi S, Villanueva AI, Brisbin JT, Ashkar AA, Sharif S. Vitamin D3 modulates the function of chicken macrophages. Res Veterinary Sci (2015) 100:45–51. doi: 10.1016/j.rvsc.2015.03.009
107. Boodhoo N, Sharif S, Behboudi S. 1a,25(OH)2 vitamin D3 modulates avian T lymphocyte functions without inducing CTL unresponsiveness. PloS One (2016) 11(2): e0150134. doi: 10.1371/journal.pone.0150134
108. Chou P-C, Lin P-C, Wu S-W, Wang C-K, Chung T-K, Walzem RL, et al. Differential modulation of 25-hydroxycholecalciferol on innate immunity of broiler breeder hens. Animals (Basel) (2021) 11(6):1742. doi: 10.3390/ani11061742
109. Fan X, Liu S, Liu G, Zhao J, Jiao H, Wang X, et al. Vitamin a deficiency impairs mucin expression and suppresses the mucosal immune function of the respiratory tract in chicks. PloS One (2015) 10(9):e0139131. doi: 10.1371/journal.pone.0139131
110. Uni Z, Zaiger G, Gal-Garber O, Pines M, Rozenboim I, Reifen R. Vitamin a deficiency interferes with proliferation and maturation of cells in the chicken small intestine. Br Poultry Sci (2000) 41(4):410–5. doi: 10.1080/713654958
111. Aye PP, Morishita TY, Saif YM, Latshaw JD, Harr BS, Cihla FB. Induction of vitamin a deficiency in turkeys. Avian Dis (2000) 44(4):809–17. doi: 10.2307/1593053
112. Raza A, Khan SA, Raza FK, Saeed MA, Bashir IN. Effects of vitamin-a on growth traits, immunoregulatory organs and immune response in broiler chicken. J Appl Anim Res (1997) 12(1):81–8. doi: 10.1080/09712119.1997.9706189
113. Alizadeh M, Astill J, Alqazlan N, Shojadoost B, Taha-Abdelaziz K, Bavananthasivam J, et al. In ovo co-administration of vitamins (A and d) and probiotic lactobacilli modulates immune responses in broiler chickens. Poultry Sci (2022) 101(4):101717. doi: 10.1016/j.psj.2022.101717
114. Shojadoost B, Alizadeh M, Taha-Abdelaziz K, Shoja Doost J, Astill J, Sharif S. In ovo inoculation of vitamin a modulates chicken embryo immune functions. J Interferon Cytokine Res (2021) 41(1):20–8. doi: 10.1089/jir.2020.0212
115. Kang BY, Chung SW, Kim SH, Kang SN, Choe YK, Kim TS. Retinoid-mediated inhibition of interleukin-12 production in mouse macrophages suppresses Th1 cytokine profile in CD4+T cells. Br J Pharmacol (2000) 130(3):581–6. doi: 10.1038/ sj.bjp.0703345
116. Konjufca VK, Bottje WG, Bersi TK, Erf GF. Influence of dietary vitamin e on phagocytic functions of macrophages in broilers. Poultry Sci (2004) 83(9):1530–4. doi: 10.1093/ps/83.9.1530
117. Huff GR, Huff WE, Balog JM, Rath NC, Izard RS. The effects of water supplementation with vitamin e and sodium salicylate (Uni-sol®) on the resistance of turkeys to Escherichia coli respiratory infection. Avian Dis (2004) 48(2):324–31. doi: 10.1637/7112
118. Liu YJ, Zhao LH, Mosenthin R, Zhang JY, Ji C, Ma QG. Protective effect of vitamin e on laying performance, antioxidant capacity, and immunity in laying hens challenged with Salmonella enteritidis. Poultry Sci (2019) 98(11):5847–54. doi: 10.3382/ps/pez227
119. Carr A, Maggini S. Vitamin c and immune function. Nutrients (2017) 9 (11):1211. doi: 10.3390/nu9111211
120. Andreasen CB, Frank DE. The effects of ascorbic acid on in vitro heterophil function. Avian Dis (1999) 43(4):656–63. doi: 10.2307/1592734
121. Gan L, Fan H, Mahmood T, Guo Y. Dietary supplementation with vitamin c ameliorates the adverse effects of Salmonella enteritidis-challenge in broilers by shaping intestinal microbiota. Poult Sci (2020) 99(7):3663–74. doi: 10.1016/j.psj.2020.03.062
122. Hernandez-Patlan D, Solis-Cruz B, Pontin KP, Latorre JD, Hernandez-Velasco X, Merino-Guzman R, et al. Evaluation of ascorbic acid or curcumin formulated in a solid dispersion on Salmonella enteritidis infection and intestinal integrity in broiler chickens. Pathogens (2019) 8(4):229. doi: 10.3390/pathogens8040229
123. Kim DK, Lillehoj HS, Lee SH, Jang SI, Bravo D. High-throughput gene expression analysis of intestinal intraepithelial lymphocytes after oral feeding of carvacrol, cinnamaldehyde, or capsicum oleoresin. Poult Sci (2010) 89(1):68–81. doi: 10.3382/ps.2009-00275
124. Placha I, Takacova J, Ryzner M, Cobanova K, Laukova A, Strompfova V, et al. Effect of thyme essential oil and selenium on intestine integrity and antioxidant status of broilers. Br Poultry Sci (2014) 55(1):105–14. doi: 10.1080/00071668.2013.873772
125. Islam MR, Oomah DB, Diarra MS. Potential immunomodulatory effects of non-dialyzable materials of cranberry extract in poultry production. Poultry Sci (2017) 96(2):341–50. doi: 10.3382/ps/pew302
126. Dorhoi A, Dobrean V, Zăhan M, Virag P. Modulatory effects of several herbal extracts on avian peripheral blood cell immune responses. Phytother Res (2006) 20 (5):352–8. doi: 10.1002/ptr.1859
127. Lee SH, Lillehoj HS, Hong YH, Jang SI, Lillehoj EP, Ionescu C, et al. In vitro effects of plant and mushroom extracts on immunological function of chicken lymphocytes and macrophages. Br Poultry Sci (2010) 51(2):213–21. doi: 10.1080/ 00071661003745844
128. Lee SH, Lillehoj HS, Jang SI, Lee KW, Park MS, Bravo D, et al. Cinnamaldehyde enhances in vitro parameters of immunity and reduces in vivo infection against avian coccidiosis. Br J Nutr (2011) 106(6):862–9. doi: 10.1017/s0007114511001073
129. Kamboh AA, Hang SQ, Khan MA, Zhu WY. In vivo immunomodulatory effects of plant flavonoids in lipopolysaccharide-challenged broilers. Animal (2016) 10 (10):1619–25. doi: 10.1017/S1751731116000562
130. Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr (1995) 125(6):1401–12. doi: 10.1093/jn/125.6.1401
131. Ricke SC. Impact of prebiotics on poultry production and food safety. Yale J Biol Med (2018) 91(2):151–9.
132. Takiishi T, Fenero CIM, Câmara NOS. Intestinal barrier and gut microbiota: shaping our immune responses throughout life. Tissue Barriers (2017) 5(4):e1373208. doi: 10.1080/21688370.2017.1373208
133. Gadde U, Kim WH, Oh ST, Lillehoj HS. Alternatives to antibiotics for maximizing growth performance and feed efficiency in poultry: a review. Anim Health Res Rev (2017) 18(1):26–45. doi: 10.1017/s1466252316000207
134. Yan F, Polk DB. Probiotics and immune health. Curr Opin Gastroenterol (2011) 27(6):496–501. doi: 10.1097/mog.0b013e32834baa4d
135. Kabir SML. The role of probiotics in the poultry industry. Int J Mol Sci (2009) 10(8):3531–46. doi: 10.3390/ijms10083531
136. Sakaridis I, Ellis RJ, Cawthraw SA, van Vliet AHM, Stekel DJ, Penell J, et al. Investigating the association between the caecal microbiomes of broilers and campylobacter burden. Front Microbiol (2018) 9. doi: 10.3389/fmicb.2018.00927
137. Dang AT, Marsland BJ. Microbes, metabolites, and the gut–lung axis. Mucosal Immunol (2019) 12(4):843–50. doi: 10.1038/s41385-019-0160-6
138. Synodinou KD, Nikolaki MD, Triantafyllou K, Kasti AN. Immunomodulatory effects of probiotics on COVID-19 infection by targeting the gut–lung axis microbial cross-talk. Microorganisms (2022) 10(9):1764. doi: 10.3390/microorganisms10091764
139. Harris V, Ali A, Fuentes S, Korpela K, Kazi M, Tate J, et al. Rotavirus vaccine response correlates with the infant gut microbiota composition in Pakistan. Gut Microbes (2018) 9(2):93–101. doi: 10.1080/19490976.2017.1376162
140. Jordan A, Carding SR, Hall LJ. The early-life gut microbiome and vaccine efficacy. Lancet Microbe (2022) 3(10):e787–94. doi: 10.1016/s2666-5247(22)00185-9
141. Yitbarek A, Astill J, Hodgins DC, Parkinson J, Nagy É , Sharif S. Commensal gut microbiota can modulate adaptive immune responses in chickens vaccinated with whole inactivated avian influenza virus subtype H9N2. Vaccine (2019) 37(44):6640–7. doi: 10.1016/j.vaccine.2019.09.046
142. Kim HS, Hong JT, Kim Y, Han SB. Stimulatory effect of b-glucans on immune cells. Immune Netw (2011) 11(4):191–5. doi: 10.4110/in.2011.11.4.191
143. Park J-H, Lee S-I, Kim I-H. Effect of dietary b-glucan supplementation on growth performance, nutrient digestibility, and characteristics of feces in weaned pigs. J Appl Anim Res (2018) 46(1):1193–7. doi: 10.1080/09712119.2018.1481855
144. Ma T, Tu Y, Zhang N-f, Guo J-p, Deng K-d, Zhou Y, et al. Effects of dietary yeast b-glucan on nutrient digestibility and serum profiles in pre-ruminant Holstein calves. J Integr Agric (2015) 14(4):749–57. doi: 10.1016/S2095-3119(14)60843-1
145. Dawood MAO, Koshio S, Ishikawa M, Yokoyama S, El Basuini MF, Hossain MS, et al. Dietary supplementation of b-glucan improves growth performance, the innate immune response and stress resistance of red sea bream, pagrus major. Aquaculture Nutr (2017) 23(1):148–59. doi: 10.1111/anu.12376
146. Ding B, Zheng J, Wang X, Zhang L, Sun D, Xing Q, et al. Effects of dietary yeast beta-1,3-1,6-glucan on growth performance, intestinal morphology and chosen immunity parameters changes in haidong chicks. Asian-Australas J Anim Sci (2019) 32(10):1558–64. doi: 10.5713/ajas.18.0962
147. Moon SH, Lee I, Feng X, Lee HY, Kim J, Ahn DU. Effect of dietary beta-glucan on the performance of broilers and the quality of broiler breast meat. Asian-Australas J Anim Sci (2016) 29(3):384–9. doi: 10.5713/ajas.15.0141
148. Chen L, Jiang T, Li X, Wang Q, Wang Y, Li Y. Immunomodulatory activity of beta-glucan and mannan-oligosaccharides from Saccharomyces cerevisiae on broiler chickens challenged with feed-borne aspergillus fumigatus. Pakistan Veterinary J (2016) 36:297–301.
149. Santin E, Maiorka A, Macari M, Grecco M, Sanchez JC, Okada TM, et al. Performance and intestinal mucosa development of broiler chickens fed diets containing saccharomyces cerevisiae cell wall. J Appl Poultry Res (2001) 10(3):236– 44. doi: 10.1093/japr/10.3.236
150. Gao J, Zhang HJ, Yu SH, Wu SG, Yoon I, Quigley J, et al. Effects of yeast culture in broiler diets on performance and immunomodulatory functions. Poultry Sci (2008) 87(7):1377–84. doi: 10.3382/ps.2007-00418
151. Vancamelbeke M, Vermeire S. The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol (2017) 11(9):821–34. doi: 10.1080/ 17474124.2017.1343143
152. Brown GD, Gordon S. A new receptor for b-glucans. Nature (2001) 413 (6851):36–7. doi: 10.1038/35092620
153. Rodrigues MV, Zanuzzo FS, Koch JFA, De Oliveira CAF, Sima P, Vetvicka V. Development of fish immunity and the role of b-glucan in immune responses. Molecules (2020) 25(22):5378. doi: 10.3390/molecules25225378
154. Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM. Collaborative induction of inflammatory responses by dectin-1 and toll-like receptor 2. J Exp Med (2003) 197(9):1107–17. doi: 10.1084/jem.20021787
155. Verwoolde MB, van den Biggelaar RHGA, de Vries Reilingh G, Arts JAJ, van Baal J, Lammers A, et al. Innate immune training and metabolic reprogramming in primary monocytes of broiler and laying hens. Dev Comp Immunol (2021) 114:103811. doi: 10.1016/j.dci.2020.103811
156. Santecchia I, Vernel-Pauillac F, Rasid O, Quintin J, Gomes-Solecki M, Boneca IG, et al. Innate immune memory through TLR2 and NOD2 contributes to the control of leptospira interrogans infection. PloS Pathog (2019) 15(5):e1007811–e1007811. doi: 10.1371/journal.ppat.1007811
157. Salem AK, Weiner GJ. CpG oligonucleotides as immunotherapeutic adjuvants: innovative applications and delivery strategies. Advanced Drug Delivery Rev (2009) 61 (3):193–4. doi: 10.1016/j.addr.2008.12.003
158. Sherbet GV. Chapter 26 - notable approaches to cancer immunotherapy. In: Sherbet GV, editor. Molecular approach to cancer management. Cambridge, Massachusetts, US: Academic Press (2017). doi: 10.1016/B978-0-12-812896-1.00026-X
159. Shirota H, Klinman DM. Chapter 9 - CpG oligodeoxynucleotides as adjuvants for clinical use. In: Schijns VEJC, O'Hagan DT, editors. Immunopotentiators in modern vaccines, 2nd ed. Cambridge, Massachusetts, US: Academic Press (2017). doi: 10.1016/ B978-0-12-804019-5.00009-8
160. Krieg AM. Chapter 53 - CpG oligodeoxynucleotides for mucosal vaccines. In: Mestecky J, Lamm ME, McGhee JR, Bienenstock J, Mayer L, Strober W, editors. Mucosal immunology, 3rd ed. Burlington: Academic Press (2005). doi: 10.1016/B978- 012491543-5/50057-7
161. Ferreira AV, Domigué z-André s J, Netea MG. The role of cell metabolism in innate immune memory. J Innate Immun (2022) 14(1):42–50. doi: 10.1159/000512280
162. Ribes S, Meister T, Ott M, Redlich S, Janova H, Hanisch UK, et al. Intraperitoneal prophylaxis with CpG oligodeoxynucleotides protects neutropenic mice against intracerebral Escherichia coli K1 infection. J Neuroinflamm (2014) 11:14. doi: 10.1186/1742-2094-11-14
163. Rosadini CV, Kagan JC. Early innate immune responses to bacterial LPS. Curr Opin Immunol (2017) 44:14–9. doi: 10.1016/j.coi.2016.10.005
164. Kohchi C, Inagawa H, Nishizawa T, Yamaguchi T, Nagai S, Soma G-I. Applications of lipopolysaccharide derived from pantoea agglomerans (IP-PA1) for health care based on macrophage network theory. J Bioscience Bioengineering (2006) 102(6):485–96. doi: 10.1263/jbb.102.485
165. Takahashi Y, Kondo M, Itami T, Honda T, Inagawa H, Nishizawa T, et al. Enhancement of disease resistance against penaeid acute viraemia and induction of virus-inactivating activity in haemolymph of kuruma shrimp, Penaeus japonicus, by oral administration of pantoea agglomerans lipopolysaccharide (LPS). Fish Shellfish Immunol (2000) 10(6):555–8. doi: 10.1006/fsim.2000.0268
166. Kadowaki T, Yasui Y, Nishimiya O, Takahashi Y, Kohchi C, Soma G, et al. Orally administered LPS enhances head kidney macrophage activation with downregulation of IL-6 in common carp (Cyprinus carpio). Fish Shellfish Immunol (2013) 34 (6):1569–75. doi: 10.1016/j.fsi.2013.03.372
167. Chow J, Lee SM, Shen Y, Khosravi A, Mazmanian SK. Chapter 8 - host– bacterial symbiosis in health and disease. In: Fagarasan S, Cerutti A, editors. Advances in immunology. Academic Press (2010). doi: 10.1016/B978-0-12-381300-8.00008-3
168. Rodrigues DR, Wilson KM, Bielke LR. Proper immune response depends on early exposure to gut microbiota in broiler chicks. Front Physiol (2021) 12. doi: 10.3389/ fphys.2021.758183
169. Levy M, Thaiss CA, Elinav E. Metabolites: messengers between the microbiota and the immune system. Genes Dev (2016) 30(14):1589–97. doi: 10.1101/ gad.284091.116
170. Yeşilyurt N, Yılmaz B, Ağ agündüz D, Capasso R. Involvement of probiotics and postbiotics in the immune system modulation. Biologics (2021) 1(2):89–110. doi: 10.3390/biologics1020006
171. Godlewska U, Bulanda E, Wypych TP. Bile acids in immunity: bidirectional mediators between the host and the microbiota. Front Immunol (2022) 13. doi: 10.3389/fimmu.2022.949033
172. Wu J, Wang K, Wang X, Pang Y, Jiang C. The role of the gut microbiome and its metabolites in metabolic diseases. Protein Cell (2021) 12(5):360–73. doi: 10.1007/ s13238-020-00814-7
173. Weichhart T, Hengstschläger M, Linke M. Regulation of innate immune cell function by mTOR. Nat Rev Immunol (2015) 15(10):599–614. doi: 10.1038/nri3901
174. Schulthess J, Pandey S, Capitani M, Rue-Albrecht KC, Arnold I, Franchini F, et al. The short chain fatty acid butyrate imprints an antimicrobial program in macrophages. Immunity (2019) 50(2):432–445.e7. doi: 10.1016/j.immuni.2018.12.018
175. Langfeld LQ, Du K, Bereswill S, Heimesaat MM. A review of the antimicrobial and immune-modulatory properties of the gut microbiota-derived short chain fatty acid propionate - what is new? Eur J Microbiol Immunol (Bp) (2021) 11(2):50–6. doi: 10.1556/1886.2021.00005
176. Li H, Zhao L, Liu S, Zhang Z, Wang X, Lin H. Propionate inhibits fat deposition via affecting feed intake and modulating gut microbiota in broilers. Poultry Sci (2021) 100(1):235–45. doi: 10.1016/j.psj.2020.10.009
177. Van Hoeck V, Sonawane M, Gonzalez Sanchez AL, Van Dosselaer I, Buyens C, Morisset D. Chromium propionate improves performance and carcass traits in broilers. Anim Nutr (2020) 6(4):480–7. doi: 10.1016/j.aninu.2020.03.005
178. Jacobson A, Lam L, Rajendram M, Tamburini F, Honeycutt J, Pham T, et al. A gut commensal-produced metabolite mediates colonization resistance to Salmonella infection. Cell Host Microbe (2018) 24(2):296–307.e7. doi: 10.1016/j.chom.2018.07.002
179. Park JW, Kim HY, Kim MG, Jeong S, Yun CH, Han SH. Short-chain fatty acids inhibit staphylococcal lipoprotein-induced nitric oxide production in murine macrophages. Immune Netw (2019) 19(2):e9. doi: 10.4110/in.2019.19.e9
180. Jeong S, Kim HY, Kim AR, Yun CH, Han SH. Propionate ameliorates staphylococcus aureus skin infection by attenuating bacterial growth. Front Microbiol (2019) 10:1363. doi: 10.3389/fmicb.2019.01363
181. Mora JR, Iwata M, Von Andrian UH. Vitamin effects on the immune system: vitamins a and d take centre stage. Nat Rev Immunol (2008) 8(9):685–98. doi: 10.1038/nri2378
182. Ismailova A, White JH, Vitamin D. Infections and immunity. Rev Endocrine Metab Disord (2022) 23(2):265–77. doi: 10.1007/s11154-021-09679-5
183. Chou PC, Chen YH, Chung TK, Walzem RL, Lai LS, Chen SE. Supplemental 25-hydroxycholecalciferol alleviates inflammation and cardiac fibrosis in hens. Int J Mol Sci (2020) 21(21):8379. doi: 10.3390/ijms21218379
184. Lin H-Y, Chung TK, Chen Y-H, Walzem RL, Chen S-E. Dietary supplementation of 25-hydroxycholecalciferol improves livability in broiler breeder hens. Poultry Sci (2019) 98(11):6108–16. doi: 10.3382/ps/pez330
185. Vazquez JR, Gómez GV, López CC, Cortés AC, Dıaz AC, Ferna ́ ́ndez SRT, et al. Effects of 25-hydroxycholecalciferol with two D3 vitamin levels on production and immunity parameters in broiler chickens. J Anim Physiol Anim Nutr (2018) 102(1): e493–7. doi: 10.1111/jpn.12715
186. Chou SH, Chung TK, Yu B. Effects of supplemental 25-hydroxycholecalciferol on growth performance, small intestinal morphology, and immune response of broiler chickens. Poultry Sci (2009) 88(11):2333–41. doi: 10.3382/ps.2009-00283
187. Broom LJ, Kogut MH. Inflammation: friend or foe for animal production? Poult Sci (2018) 97(2):510–4. doi: 10.3382/ps/pex314
188. Huang Z, Liu Y, Qi G, Brand D, Zheng SG. Role of vitamin a in the immune system. J Clin Med (2018) 7(9):258. doi: 10.3390/jcm7090258
189. Shojadoost B, Yitbarek A, Alizadeh M, Kulkarni RR, Astill J, Boodhoo N, et al. Centennial review: effects of vitamins a, d, e, and c on the chicken immune system. Poult Sci (2021) 100(4):100930. doi: 10.1016/j.psj.2020.12.027
190. Lessard M, Hutchings D, Cave NA. Cell-mediated and humoral immune responses in broiler chickens maintained on diets containing different levels of vitamin a. Poultry Sci (1997) 76(10):1368–78. doi: 10.1093/ps/76.10.1368
191. Savaris VDL, Broch J, de Souza C, Rohloff Junior N, de Avila AS, Polese C, et al. Effects of vitamin a on carcass and meat quality of broilers. Poult Sci (2021) 100 (12):101490. doi: 10.1016/j.psj.2021.101490
192. Stephensen CB, Vitamin A. Infection, and immune function. Annu Rev Nutr (2001) 21:167–92. doi: 10.1146/annurev.nutr.21.1.167
193. Sijtsma SR, Rombout JHWM, Dohmen MJW, West CE, van der Zijpp AJ. Effect of vitamin a deficiency on the activity of macrophages in Newcastle disease virusinfected chickens. Veterinary Immunol Immunopathol (1991) 28(1):17–27. doi: 10.1016/0165-2427(91)90039-F
194. Lewis ED, Meydani SN, Wu D. Regulatory role of vitamin e in the immune system and inflammation. IUBMB Life (2019) 71(4):487–94. doi: 10.1002/iub.1976
195. Khalifa OA, Al Wakeel RA, Hemeda SA, Abdel-Daim MM, Albadrani GM, El Askary A, et al. The impact of vitamin e and/or selenium dietary supplementation on growth parameters and expression levels of the growth-related genes in broilers. BMC Veterinary Res (2021) 17(1):251. doi: 10.1186/s12917-021-02963-1
196. Habibian M, Ghazi S, Moeini MM. Effects of dietary selenium and vitamin e on growth performance, meat yield, and selenium content and lipid oxidation of breast meat of broilers reared under heat stress. Biol Trace Element Res (2016) 169(1):142–52. doi: 10.1007/s12011-015-0404-6
197. Peč jak M, Leskovec J, Levart A, Salobir J, Rezar V, Dietary Vitamin E, et al. Selenium and their combination on carcass characteristics, oxidative stability and breast meat quality of broiler chickens exposed to cyclic heat stress. Animals (2022) 12 (14):1789. doi: 10.3390/ani12141789
198. Moriguchi S, Kobayashi N, Kishino Y. High dietary intakes of vitamin e and cellular immune functions in rats. J Nutr (1990) 120(9):1096–102. doi: 10.1093/jn/ 120.9.1096
199. Hieu TV, Guntoro B, Qui NH, Quyen NTK, Al Hafiz FA. The application of ascorbic acid as a therapeutic feed additive to boost immunity and antioxidant activity of poultry in heat stress environment. Vet World (2022) 15(3):685–93. doi: 10.14202/ vetworld.2022.685-693
200. Bozonet S, Carr A, Pullar J, Vissers M. Enhanced human neutrophil vitamin c status, chemotaxis and oxidant generation following dietary supplementation with vitamin c-rich SunGold kiwifruit. Nutrients (2015) 7(4):2574–88. doi: 10.3390/ nu7042574
201. Gierlikowska B, Stachura A, Gierlikowski W, Demkow U. Phagocytosis, degranulation and extracellular traps release by neutrophils-the current knowledge, pharmacological modulation and future prospects. Front Pharmacol (2021) 12:666732. doi: 10.3389/fphar.2021.666732
202. Yuandani M, Jantan I, Mohamad HF, K. Husain and AF. Abdul Razak: inhibitory effects of standardized extracts of Phyllanthus amarus and Phyllanthus urinaria and their marker compounds on phagocytic activity of human neutrophils. Evidence-Based Complementary Altern Med (2013) 2013:603634. doi: 10.1155/2013/ 603634
203. Harun NH, Septama AW, Jantan I. Immunomodulatory effects of selected Malaysian plants on the CD18/11a expression and phagocytosis activities of leukocytes. Asian Pacific J Trop Biomedicine (2015) 5(1):48–53. doi: 10.1016/S2221-1691(15) 30170-2
204. Yang HS, Haj FG, Lee M, Kang I, Zhang G, Lee Y. Laminaria japonica extract enhances intestinal barrier function by altering inflammatory response and tight junction-related protein in lipopolysaccharide-stimulated caco-2 cells. Nutrients (2019) 11(5):1001. doi: 10.3390/nu11051001
205. Chelakkot C, Ghim J, Ryu SH. Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp Mol Med (2018) 50(8):1–9. doi: 10.1038/s12276-018-0126-x
206. Swelum AA, Elbestawy AR, El-Saadony MT, Hussein EOS, Alhotan R, Suliman GM, et al. Ways to minimize bacterial infections, with special reference to Escherichia coli, to cope with the first-week mortality in chicks: an updated overview. Poult Sci (2021) 100(5):101039. doi: 10.1016/j.psj.2021.101039
207. Ciarlo E, Heinonen T, Thé roude C, Asgari F, Le Roy D, Netea MG, et al. Trained immunity confers broad-spectrum protection against bacterial infections. J Infect Dis (2020) 222(11):1869–81. doi: 10.1093/infdis/jiz692
208. Gray P, Jenner R, Norris J, Page S, Browning G. Antimicrobial prescribing guidelines for poultry. Aust Vet J (2021) 99(6):181–235. doi: 10.1111/avj.13034
209. Huang CM, Lee TT. Immunomodulatory effects of phytogenics in chickens and pigs [[/amp]]mdash; a review. Asian-Australasian J Anim Sci (2018) 31(5):617–27. doi: 10.5713/ajas.17.0657
210. Rehman A, Arif M, Sajjad N, Al-Ghadi MQ, Alagawany M, Abd El-Hack ME, et al. Dietary effect of probiotics and prebiotics on broiler performance, carcass, and immunity. Poultry Sci (2020) 99(12):6946–53. doi: 10.1016/j.psj.2020.09.043
211. Froebel LK, Jalukar S, Lavergne TA, Lee JT, Duong T. Administration of dietary prebiotics improves growth performance and reduces pathogen colonization in broiler chickens. Poultry Sci (2019) 98(12):6668–76. doi: 10.3382/ps/pez537
212. Kabir SML, Rahman MM, Rahman MB, Ahmed SU. The dynamics of probiotics on growth performance and immune response in broilers. Int J Poult. Sci (2004) 3(5):361–4. doi: 10.3923/ijps.2004.361.364
213. Guo FC, Kwakkel RP, Soede J, Williams BA, Verstegen MWA. Effect of a Chinese herb medicine formulation, as an alternative for antibiotics, on performance of broilers. Br Poultry Sci (2004) 45(6):793–7. doi: 10.1080/00071660400012741
214. Florou-Paneri P, Giannenas I, Christaki E, Botsoglou N. Performance of chickens and oxidative stability of the produced meat as affected by feed supplementation with oregano, vitamin c, vitamin e and their combinations. Archiv fur Geflugelkunde (2006) 70:232–40.
215. Atteh JO, Onagbesan OM, Tona K, Decuypere E, Geuns JMC, Buyse J. Evaluation of supplementary stevia (Stevia rebaudiana, bertoni) leaves and stevioside in broiler diets: effects on feed intake, nutrient metabolism, blood parameters and growth performance. J Anim Physiol Anim Nutr (2008) 92(6):640–9. doi: 10.1111/j.1439-0396.2007.00760.x
216. Zhu N, Wang J, Yu L, Zhang Q, Chen K, Liu B. Modulation of growth performance and intestinal microbiota in chickens fed plant extracts or virginiamycin. Front Microbiol (2019) 10. doi: 10.3389/fmicb.2019.01333
217. Pattison M, McMullin P, Bradbury JM, Alexander D. Poultry diseases. Elsevier Health Sci (2007) Hardback ISBN: 9780702028625. 6th Edition.
218. Legnardi M, Baranyay H, Simon C, Molnár J, Bijlsma T, Cecchinato M, et al. Infectious bronchitis hatchery vaccination: comparison between traditional spray administration and a newly developed gel delivery system in field conditions. Veterinary Sci (2021) 8(8):145. doi: 10.3390/vetsci8080145
219. Gautério GV, Silvé rio SIDC, Egea MB, Lemes AC. b-glucan from brewer’s spent yeast as a techno-functional food ingredient. Front Food Sci Technol 2(2022). doi: 10.3389/frfst.2022.1074505
220. Manyi-Loh C, Mamphweli S, Meyer E, Okoh A. Antibiotic use in agriculture and its consequential resistance in environmental sources: potential public health implications. Molecules (2018) 23(4):795. doi: 10.3390/molecules23040795
221. Coffman RL, Sher A, Seder RA. Vaccine adjuvants: putting innate immunity to work. Immunity (2010) 33(4):492–503. doi: 10.1016/j.immuni.2010.10.002
222. Lamb DJ, Eales LJ, Ferns GA. Immunization with bacillus calmette-guerin vaccine increases aortic atherosclerosis in the cholesterol-fed rabbit. Atherosclerosis (1999) 143(1):105–13. doi: 10.1016/s0021-9150(98)00284-6
223. Quintin J, Saeed S, Martens JHA, Giamarellos-Bourboulis EJ, Ifrim DC, Logie C, et al. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe (2012) 12(2):223–32. doi: 10.1016/ j.chom.2012.06.006
224. Arts RJW, Joosten LAB, Netea MG. The potential role of trained immunity in autoimmune and autoinflammatory disorders. Front Immunol (2018) 9:298. doi: 10.3389/fimmu.2018.00298