An overview of the immunomodulatory effects exerted by probiotics and prebiotics in grouper fish

  • Jiun Yan LohEmail author
  • Hor Kuan Chan
  • Hok Chai Yam
  • Lionel Lian Aun In
  • Crystale Siew Ying Lim


While health benefits imparted by probiotics and prebiotics in various finfish have been extensively researched over the past few decades, little emphasis has been given to its role in immunomodulation in grouper fish health. From this billion-dollar aquaculture industry, the production of an estimated 100,000 tons per annum of grouper fish is required to fulfill the needs of the global market by 2020. Thus, this huge demand has resulted in a rapid rise of grouper fish farms, especially in the Asia-Pacific region. Unfortunately, grouper farming is often blighted by viral and bacterial diseases, which consequently devastate yields, resulting in economic losses. This review provides an overview of the functional role of probiotics and prebiotics, with specific emphasis on their immunomodulatory effects toward the advancement of grouper fish farming as one of the rising aquaculture commodities in the near future. Types of grouper-related diseases, probiotic strains, prebiotic types, dietary manipulations, immunological functions, and immunomodulatory mechanisms are reviewed and discussed in this article.


Dietary supplementation Grouper fish Immunomodulation Probiotics Prebiotics 



Alternative complement activity


Adenosine monophosphate


Cluster of differentiation


Colony-forming unit




Denaturing gradient gel electrophoresis


Food and Agriculture Organization


Fluorescent in situ hybridization


Gastrointestinal tract








Lactic acid bacteria




Next-generation sequencing


Microbe-associated molecular pattern


Mushroom beta-glucan mixture


Pathogen-associated molecular pattern


Peripheral blood leukocyte


Phagocytic index


Respiratory burst activity


Reactive oxygen species


Superoxide dismutase


Terminal restriction fragment length polymorphism


Transforming growth factor-beta


Tumor necrosis factor-alpha


viral nervous necrosis


World Health Organization


Author Contributions

J.Y.L. contributed to the introduction, disease, dietary supplementation, manuscript improvement, and conclusion sections. H.K.C. contributed to the probiotic section. H.C.Y. contributed to the prebiotic section. L.L.A.I. contributed to the immunomodulation section. C.S.Y.L. contributed to the editing and compilation of the manuscript


This work was partly supported by UCSI–CERVIE PSIF Grant (Proj-in-FAS-031). The authors would like to thank the reviewers have made valuable comments and suggestions that have improved the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with animals performed by any of the authors.


  1. Adedeji BO, Onianwa O, Okerentugba PO, Okonko IO (2012) Immune response of fish to viral infection. Nat Sci 10:70–76Google Scholar
  2. Anderson DP (1996) Environmental factors in fish health: immunological aspects. In: Iwama G, Nakanishi T (eds) The fish immune system, organism, pathogen, and environment. Academic Press, San Diego, CA, pp 289–310CrossRefGoogle Scholar
  3. Barton BA (2002) Stress in fishes: a diversity of responses with particular reference to changes in circulating corticosteroids. Integr Comp Biol 42:517–525PubMedCrossRefPubMedCentralGoogle Scholar
  4. Biller-Takahashi JD, Takahashi LS, Saita MV, Gimbo RY, Urbinati EC (2013) Leukocytes respiratory burst activity as indicator of innate immunity of pacu Piaractus mesopotamicus. Braz J Biol 73:425–429PubMedCrossRefPubMedCentralGoogle Scholar
  5. BorchK PIE, Hogmo RO (2015) The use of probiotics in fish feed for intensive aquaculture to promote healthy guts. Advances in Aquaculture and Fisheries Management 3:264–273Google Scholar
  6. Boshra H, Li J, Sunyer JO (2006) Recent advances on the complement system of teleost fish. Fish and Shellfish Immunology 20:239–262PubMedCrossRefPubMedCentralGoogle Scholar
  7. Castro R, Tafalla C (2015) Overview of fish immunity. In: Beck BH, Peatman E (eds) Mucosal health in aquaculture. Academic Press, San Diego, CA, pp 3–54CrossRefGoogle Scholar
  8. Chang CS, Huang SL, Chen S, Chen SN (2013) Innate immune responses and efficacy of using mushroom beta-glucan mixture (MBG) on orange-spotted grouper, Epinephelus coioides, aquaculture. Fish and Shellfish Immunology 35:115–125PubMedCrossRefPubMedCentralGoogle Scholar
  9. Chen YM, Kuo CE, Chen GR, Kao YT, Zou J, Secombes CJ, Chen TY (2014) Functional analysis of an orange-spotted grouper (Epinephelus coioides) interferon gene and characterisation of its expression in response to nodavirus infection. Dev Comp Immunol 46:117–128PubMedCrossRefPubMedCentralGoogle Scholar
  10. Cheng CA, John JAC, Wu MS, Lee CY, Lin CH, Lin CH, Chang CY (2006) Characterization of serum immunoglobulin M of grouper and cDNA cloning of its heavy chain. Vet Immunol Immunopathol 109:255–265PubMedCrossRefPubMedCentralGoogle Scholar
  11. Chiu ST, Tsai RT, Hsu JP, Liu CH, Cheng W (2008) Dietary sodium alginate administration to enhance the non-specific immune responses, and disease resistance of the juvenile grouper Epinephelus fuscoguttatus. Aquaculture 277:66–72CrossRefGoogle Scholar
  12. Chiu CH, Cheng CH, Gua WR, Guu YK, Cheng W (2010) Dietary administration of the probiotic, Saccharomyces cerevisiae P13, enhanced the growth, innate immune responses, and disease resistance of the grouper, Epinephelus coioides. Fish and Shellfish Immunology 29:1053–1059PubMedCrossRefPubMedCentralGoogle Scholar
  13. Das S, Mondal K, Haque S (2017) A review on application of probiotic, prebiotic and symbiotic for sustainable development of aquaculture. Growth 14:15Google Scholar
  14. Delgadom GTC, Tamashiro WMDSC, Junior MRM, Moreno YMF, Pastore GM (2011) The putative effects of prebiotics as immunomodulatory agents. Food Res Int 44:3167–3173CrossRefGoogle Scholar
  15. Dibner JJ, Richards JD (2005) Antibiotic growth promoters in agriculture: history and mode of action. Poult Sci 84:634–643PubMedCrossRefPubMedCentralGoogle Scholar
  16. FAO (2014) The state of world fisheries and aquaculture. pp.223. Rome.Google Scholar
  17. Fuglem B, Jirillo E, Bjerkås I, Kiyono H, Nochi T, Yuki Y, Raida M, Fischer U, Koppang EO (2010) Antigen-sampling cells in the salmonid intestinal epithelium. Dev Comp Immunol 34:768–774PubMedCrossRefPubMedCentralGoogle Scholar
  18. Fuhrman JA (1999) Marine viruses and their biogeochemical and ecological effects. Nature 399:541–548PubMedCrossRefPubMedCentralGoogle Scholar
  19. Galindo-Villegas J, Hosokawa H (2004) Immunostimulants: towards temporary prevention of diseases in marine fish. Advances en Nutricion Acuicola VII Memorias del VII Simposium Internationale de Nutricion Acuícola:16–19Google Scholar
  20. Gatesoupe J (2005) Probiotics and prebiotics for fish culture, at the parting of the ways. Aqua feeds: Formulation and beyond 2:3–5Google Scholar
  21. Gibson GR, Roberfroid MB (1995) Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 125:1401–1412CrossRefGoogle Scholar
  22. Granja AG, Leal E, Pignatelli J, Castro R, Abós B, Kato G, Fischer U, Tafalla C (2015) Identification of teleost skin CD8α+ dendritic-like cells, representing a potential common ancestor for mammalian cross-presenting dendritic cells. J Immunol 195:1825–1837PubMedCrossRefPubMedCentralGoogle Scholar
  23. Harikrishnan R, Balasundaram C, Heo MS (2010a) Lactobacillus sakei BK19 enriched diet enhances the immunity status and disease resistance to streptococcosis infection in kelp grouper, Epinephelus bruneus. Fish and Shellfish Immunology 29:1037–1043PubMedCrossRefPubMedCentralGoogle Scholar
  24. Harikrishnan R, Balasundaram C, Heo MS (2010b) Molecular studies, disease status and prophylactic measures in grouper aquaculture: economic importance, diseases and immunology. Aquaculture 309:1–14CrossRefGoogle Scholar
  25. Harikrishnan R, Kim JS, Kim MC, Balasundaram C, Heo MS (2011a) Lactuca indica extract as feed additive enhances immunological parameters and disease resistance in Epinephelus bruneus to Streptococcus iniae. Aquaculture 318:43–47CrossRefGoogle Scholar
  26. Harikrishnan R, Balasundaram C, Heo MS (2011b) Diet enriched with mushroom Phellinus linteus extract enhances the growth, innate immune response, and disease resistance of kelp grouper, Epinephelus bruneus against vibriosis. Fish and Shellfish Immunology 30:128–134PubMedCrossRefPubMedCentralGoogle Scholar
  27. Haugland GT, Jordal AEO, Wergeland HI (2012) Characterization of small, mononuclear blood cells from salmon having high phagocytic capacity and ability to differentiate into dendritic like cells. PLoS One 7:e49260PubMedPubMedCentralCrossRefGoogle Scholar
  28. He RP, Feng J, Tian XL, Dong SL, Wen B (2017) Effects of dietary supplementation of probiotics on the growth, activities of digestive and non-specific immune enzymes in hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀). Aquac Res 48:5782–5790CrossRefGoogle Scholar
  29. Heemstra PC, Randall JE (1993) FAO species catalogue, vol. 16 Groupers of the world (family Serranidae, subfamily Epinephelinae): an annotated and illustrated catalogue of the grouper, rockcod, hind, coral grouper, and lyretail species known to date. Food and Agriculture Organization of the United Nations.Google Scholar
  30. Hoseinifar SH, Esteban MÁ, Cuesta A, Sun YZ (2015) Prebiotics and fish immune response: a review of current knowledge and future perspectives. Rev Fish Sci Aquac 23:315–328CrossRefGoogle Scholar
  31. Hoseinifar SH, Ringø E, Shenavar Masouleh A, Esteban MÁ (2016) Probiotic, prebiotic and symbiotic supplements in sturgeon aquaculture: a review. Rev Aquac 8:89–102CrossRefGoogle Scholar
  32. Huang JB, Wu YC, Chi SC (2014) Dietary supplementation of Pediococcus pentosaceus enhances innate immunity, physiological health and resistance to Vibrio anguillarum in orange-spotted grouper (Epinephelus coioides). Fish and Shellfish Immunology 39:196–205PubMedCrossRefPubMedCentralGoogle Scholar
  33. Huang MY, Chang CI, Chang CC, Tseng LW, Pan CL (2015) Effects of dietary levan on growth performance, nonspecific immunity, pathogen resistance and body composition of orange-spotted grouper (Epinephelus coioides H.). Aquac Res 46:2752–2767CrossRefGoogle Scholar
  34. Johansson P, Corripio-Miyar Y, Wang T, Collet B, Secombes CJ, Zou J (2012) Characterization and expression analysis of the rainbow trout (Oncorhynchus mykiss) homologue of the human dendritic cell marker CD208/lysosomal associated membrane protein 3. Dev Comp Immunol 37:402–413PubMedCrossRefPubMedCentralGoogle Scholar
  35. Johnston B, Yeeting B (2006) Economics and marketing of the live reef fish trade in Asia-Pacific. ACIAR Working Paper No. 60. Australian Centre for International Agricultural Research: Canberra, 73.Google Scholar
  36. Kuo HP, Chung CL, Hung YF, Lai YS, Chiou PP, Lu MW, Kong ZL (2016) Comparison of the responses of different recombinant fish type I interferons against betanodavirus infection in grouper. Fish and Shellfish Immunology 49:143–153PubMedCrossRefPubMedCentralGoogle Scholar
  37. Lazado CC, Caipang CMA (2014) Mucosal immunity and probiotics in fish. Fish and Shellfish Immunology 39:78–89PubMedCrossRefPubMedCentralGoogle Scholar
  38. Lee PP, Lin YH, Chen MC, Cheng W (2017) Dietary administration of sodium alginate ameliorated stress and promoted immune resistance of grouper Epinephelus coioides under cold stress. Fish and Shellfish Immunology 65:127–135PubMedCrossRefPubMedCentralGoogle Scholar
  39. Lin YH, Wang H, Shiau SY (2009) Dietary nucleotide supplementation enhances growth and immune responses of grouper, Epinephelus malabaricus. Aquac Nutr 15:117–122CrossRefGoogle Scholar
  40. Liu CH, Chiu CH, Wang SW, Cheng W (2012) Dietary administration of the probiotic, Bacillus subtilis E20, enhances the growth, innate immune responses, and disease resistance of the grouper, Epinephelus coioides. Fish and Shellfish Immunology 33:699–706PubMedCrossRefPubMedCentralGoogle Scholar
  41. Loh JY, Ting ASY (2017) Bioprospecting gastrointestinal microflora of common fishes for disease control in aquaculture. In: Kalia V, Shouche Y, Purohit H, Rahi P (eds) Mining of Microbial Wealth and MetaGenomics. Springer, Singapore, pp 161–182CrossRefGoogle Scholar
  42. Loh JY, Lim YY, Harmin SA, Ting ASY (2014) In vitro assessment on intestinal microflora from commonly farmed fishes for control of the fish pathogen Edwardsiella tarda. Turk J Vet Anim Sci 38:257–263CrossRefGoogle Scholar
  43. Lugo-Villarino G, Balla KM, Stachura DL, Bañuelos K, Werneck MB, Traver D (2010) Identification of dendritic antigen-presenting cells in the zebrafish. Proc Natl Acad Sci 107:15850–15855PubMedCrossRefPubMedCentralGoogle Scholar
  44. Martin SA, Król E (2017) Nutrigenomics and immune function in fish: new insights from omics technologies. Dev Comp Immunol 75:86–98PubMedPubMedCentralCrossRefGoogle Scholar
  45. Martínez Cruz P, Ibáñez AL, Monroy Hermosillo OA, Ramírez Saad HC (2012) Use of probiotics in aquaculture. ISRN Microbiology.Google Scholar
  46. Mo ZQ, Li YW, Zhou L, Li AX, Luo XC, Dan XM (2015) Grouper (Epinephelus coioides) IL-34/MCSF2 and MCSFR1/MCSFR2 were involved in mononuclear phagocytes activation against Cryptocaryon irritans infection. Fish and Shellfish Immunology 43:142–149PubMedCrossRefPubMedCentralGoogle Scholar
  47. Mohanty BR, Sahoo PK (2007) Edwardsiellosis in fish: a brief review. J Biosci 32:1331–1344PubMedCrossRefPubMedCentralGoogle Scholar
  48. Moumita D, Mazlan AG, Yosni B, Zaidi CC, Simon KD (2016) Optimum temperature for the growth form of tiger grouper (Epinephelus fuscoguttatus ♀) × giant grouper (E. lanceolatus ♂) hybrid. Sains Malaysiana 45:541–549Google Scholar
  49. Nagasawa K, Cruz-Lacierda ER (2004) Diseases of cultured groupers. Southeast Asian Fisheries Development Center (SEAFDEC). Aquaculture Department, Iloilo, Philippines, p 81Google Scholar
  50. Nayak SK (2010) Probiotics and immunity: a fish perspective. Fish and Shellfish Immunology 29:2–14PubMedCrossRefPubMedCentralGoogle Scholar
  51. Oliva-Teles A, Guedes MJ, Vachot C, Kaushik SJ (2006) The effect of nucleic acids on growth, ureagenesis and nitrogen excretion of gilthead sea bream Sparus aurata juveniles. Aquaculture 253:608–617CrossRefGoogle Scholar
  52. Pedrajas-Mendoza SA, Torres JL, Amar E (2008) Enhancing nonspecific immune response of grouper, Epinephelus coioides using levamizole as immunostimulant. UPV J Nat Sci 13:1–10Google Scholar
  53. Perdigon G, Galdeano CM, Valdez JC, Medici M (2002) Interaction of lactic acid bacteria with the gut immune system. Eur J Clin Nutr 56:S21PubMedCrossRefPubMedCentralGoogle Scholar
  54. Piazzon MC, Savelkoul HF, Pietretti D, Wiegertjes GF, Forlenza M (2015) Carp IL10 has anti-inflammatory activities on phagocytes, promotes proliferation of memory T cells, and regulates B cell differentiation and antibody secretion. J Immunol 194:187–199PubMedCrossRefPubMedCentralGoogle Scholar
  55. Pomeroy RS (2002) The status of grouper culture in Southeast Asia. SPC Live Reef Fish Information Bulletin 10:22–26Google Scholar
  56. Qi Z, Zhang XH, Boon N, Bossier P (2009) Probiotics in aquaculture of China—current state, problems and prospect. Aquaculture 290:15–21CrossRefGoogle Scholar
  57. Raa J (1996) The use of immunostimulatory substances in fish and shellfish farming. Rev Fish Sci 4:229–288CrossRefGoogle Scholar
  58. Ramadan A, Atef M, Afifi NA (1991) Effect of the biogenic performance enhancer (Ascogen “S”) on growth rate of tilapia fish. Acta Veterinaria Scandinavica Supplementum (Denmark) 87:S304–S306Google Scholar
  59. Reyes-Becerril M, Tovar-Ramírez D, Ascencio-Valle F, Civera-Cerecedo R, Gracia-López V, Barbosa-Solomieu V, Esteban MÁ (2011) Effects of dietary supplementation with probiotic live yeast Debaryomyces hansenii on the immune and antioxidant systems of leopard grouper Mycteroperca rosacea infected with Aeromonas hydrophila. Aquac Res 42:1676–1686CrossRefGoogle Scholar
  60. Reyes-Becerril M, Ascencio-Valle F, Gracia-Lopez V, Macias ME, Roa MC, Esteban MÁ (2014) Single or combined effects of Lactobacillus sakei and inulin on growth, non-specific immunity and IgM expression in leopard grouper (Mycteroperca rosacea). Fish Physiol Biochem 40:1169–1180PubMedPubMedCentralGoogle Scholar
  61. Ringø E, Olsen RE, Vecino JLG, Wadsworth S, Song SK (2012) Use of immunostimulants and nucleotides in aquaculture: a review. Journal of Marine Science: Research and Development 2:104Google Scholar
  62. Sahoo PK, Mukherjee SC (2002) The effect of dietary immunomodulation upon Edwardsiella tarda vaccination in healthy and immunocompromised Indian major carp (Labeo rohita). Fish and Shellfish Immunology 12:1–16PubMedCrossRefPubMedCentralGoogle Scholar
  63. Sakai M (1999) Current research status of fish immunostimulants. Aquaculture 172:63–92CrossRefGoogle Scholar
  64. Sakai M, Taniguchi K, Mamoto K, Ogawa H, Tabata M (2001) Immunostimulant effects of nucleotide isolated from yeast RNA on carp, Cyprinus carpio L. J Fish Dis 24:433–438CrossRefGoogle Scholar
  65. SEAFDEC (2017) Report of the Forty-ninth Meeting of the Council of the Southeast Asian Fisheries Development Center, Brunei Darussalam pp 26.Google Scholar
  66. Somga JR, Somga SS, Reantaso MB (2002) Impacts of disease on small-scale grouper culture in the Philippines. FAO Fisheries Technical Paper 207-214.Google Scholar
  67. Son VM, Chang CC, Wu MC, Guu YK, Chiu CH, Cheng W (2009) Dietary administration of the probiotic, Lactobacillus plantarum, enhanced the growth, innate immune responses, and disease resistance of the grouper Epinephelus coioides. Fish and Shellfish Immunology 26:691–698PubMedCrossRefPubMedCentralGoogle Scholar
  68. Song SK, Beck BR, Kim D, Park J, Kim J, Kim HD, Ringø E (2014) Prebiotics as immunostimulants in aquaculture: a review. Fish and Shellfish Immunology 40:40–48PubMedCrossRefPubMedCentralGoogle Scholar
  69. Sun YZ, Yang HL, Ma RL, Lin WY (2010) Probiotic applications of two dominant gut Bacillus strains with antagonistic activity improved the growth performance and immune responses of grouper Epinephelus coioides. Fish and Shellfish Immunology 29:803–809PubMedCrossRefPubMedCentralGoogle Scholar
  70. Sun YZ, Yang HL, Ma RL, Song K, Lin WY (2011a) Molecular analysis of autochthonous microbiota along the digestive tract of juvenile grouper Epinephelus coioides following probiotic Bacillus pumilus administration. J Appl Microbiol 110:1093–1103PubMedCrossRefPubMedCentralGoogle Scholar
  71. Sun YZ, Yang HL, Ma RL, Zhang CX, Lin WY (2011b) Effect of dietary administration of Psychrobacter sp. on the growth, feed utilization, digestive enzymes and immune responses of grouper Epinephelus coioides. Aquac Nutr 17:733–740CrossRefGoogle Scholar
  72. Sun YZ, Yang HL, Ma RL, Song K, Li JS (2012) Effect of Lactococcus lactis and Enterococcus faecium on growth performance, digestive enzymes and immune response of grouper Epinephelus coioides. Aquac Nutr 18:281–289CrossRefGoogle Scholar
  73. Sun YZ, Yang HL, Huang KP, Ye JD, Zhang CX (2013) Application of autochthonous Bacillus bioencapsulated in copepod to grouper Epinephelus coioides larvae. Aquaculture 392:44–50CrossRefGoogle Scholar
  74. Tacchi L, Bickerdike R, Douglas A, Secombes CJ, Martin SA (2011) Transcriptomic responses to functional feeds in Atlantic salmon (Salmo salar). Fish and Shellfish Immunology 31:704–715PubMedCrossRefPubMedCentralGoogle Scholar
  75. Wang T, Cheng Y, Chen X, Liu Z, Long X (2017) Effects of small peptides, probiotics, prebiotics, and synbiotics on growth performance, digestive enzymes, and oxidative stress in orange-spotted grouper, Epinephelus coioides, juveniles reared in artificial seawater. Chin J Oceanol Limnol 35:89–97CrossRefGoogle Scholar
  76. Yang HL, Xia HQ, Ye YD, Zou WC, Sun YZ (2014) Probiotic Bacillus pumilus SE5 shapes the intestinal microbiota and mucosal immunity in grouper Epinephelus coioides. Dis Aquat Org 111:119–127PubMedCrossRefPubMedCentralGoogle Scholar
  77. Zou J, Secombes CJ (2016) The function of fish cytokines. Biology 5:23PubMedCentralCrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Functional Food Research Group (FFRG), Faculty of Applied SciencesUCSI UniversityKuala LumpurMalaysia

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