Interrelationships between fish nutrition and health

Aquaculture xxx (2014) xxx–xxx

AQUA-631033; No of Pages 7

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Interrelationships between fish nutrition and health

Camilo Pohlenz, Delbert M. Gatlin III ⁎Department of Wildlife and Fisheries Sciences and Intercollegiate Faculty of Nutrition, Texas A&M University, College Station, TX 77840, USA

⁎ Corresponding author at: 216Heep Laboratory BuildinTX 77843, USA. Tel.: +1 979 847 9333; fax: +1 979 845

E-mail address: [email protected] (D.M. Gatlin).

http://dx.doi.org/10.1016/j.aquaculture.2014.02.0080044-8486/© 2014 Elsevier B.V. All rights reserved.

Please cite this article as: Pohlenz, C., Gatlin10.1016/j.aquaculture.2014.02.008

a b s t r a c t
a r t i c l e i n f o
Article history:Received 30 January 2014Received in revised form 7 February 2014Accepted 10 February 2014Available online xxxx

Keywords:ImmunonutritionFish healthFeed additivesImmune responses

An understanding of how to nurture and/or modulate the different components of the immune system is crucialfor the prevention and control of diseases in animal husbandry. It is well established that proper nutrition is es-sential for maintenance of normal growth and health of all animals including aquatic species. As such, nutritiousdiets and appropriate feeding regimes play critical roles in intensive aquaculture. In recent years, heightened at-tention has been given to the development of nutritional strategies that positively influence immunity and dis-ease resistance of cultured organisms to reduce disease-related economic losses. The availability of specificnutrients to immune cells plays a key role on how well those cells perform against a foreign invader. In thissense, research with several fish species has established that not only immunocompetence can be compromisedby deficiencies of various nutrients, but that dietary supplementation of some nutrients in excess of minimumrequirement levels for optimal growth has been shown to significantly enhance immune responses and diseaseresistance. For instance, findings from recent studies indicate an important role of key amino acids and their de-rivatives, like arginine and glutamine, or vitamins, such as vitamin C and E, in modulating immune responsessuch as increasing phagocytosis and pathogen killing capacity, as well as increasing antibody production and im-munologicalmemory. In addition, administration of non-nutritive compounds in the diet has become recognizedas a viablemeans of enhancing immunocompetence of various aquatic species,mainly by the provision of cellularfractions such as β-glucans, complex oligosaccharides (mannanoligosaccharides, fructooligosaccharides orsulfated polysaccharides) or yeast and algae extracts. These compoundsmay act like Pathogen AssociatedMolec-ular Pattern (PAMP) molecules, interacting with the innate immune system through their Pattern RecognitionReceptors (PRRs) and increasing their capability for detecting and recognizing potential pathogens and readilytriggering immune responses. This article will review the broad range of dietary constituents which have beenshown to affect immunocompetence and health of aquatic species and how they may influence components ofthe immune system. Further advancements in nutritional modulation of the immune response hold promise asan effective and relatively inexpensive alternative in combating diseases in aquaculture.

© 2014 Elsevier B.V. All rights reserved.

1. Introduction

Aquaculture has become amajor source of animal protein for humanconsumption and trends show it will be of even greater importance forfuture generations, as fish farming has seen an annual growth higherthan other animal-production industries for the last several decades(FAO, 2012). Although diseases are natural events in all animal groups,the intensification of culture technologies has brought about an impor-tant increase in the emergence, dispersion and outbreak of infectiousdiseases, which have placed them as one of the main growth-constricting factors in the industry (Costello, 2009; Pridgeon andKlesius, 2013; Zagmutt et al., 2013). Therefore, the study of the defensemechanisms of cultured animals and the understanding of how to

g, 2258 TAMUS, College Station,4096.

, D.M., Interrelationships betw

nurture and modulate the different components of the immune systemare crucial for the prevention, treatment and/or control of fish diseases,hence for guaranteeing the sustainability and future of this importantendeavor.

Proper nutrition is critical not only to achieve optimal growth ratesbut also to maintain the health of cultured fish (Sealey and Gatlin,2001). For a number of years, the fish nutrition field focused mainlyon establishing theminimum nutrient requirements for normal growthof different fish species (NRC, 2011). However, nowadays, the role ofnutrition on health management through the modulation of immuneresponse and disease resistance has turned into a research area of toppriority with aims to lessen the dependence on chemotherapeuticsand reduce disease-related economic losses (Kiron, 2012; Oliva-Teles,2012). This has led to the emergence of the new discipline termed“immunonutrition”, which may be defined as the study of enhancingimmunological functions by means of using specific nutrients and/orother dietary compounds — which could be higher than those levelsneeded for optimal growth.

een fish nutrition and health, Aquaculture (2014), http://dx.doi.org/

http://dx.doi.org/10.1016/j.aquaculture.2014.02.008

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2 C. Pohlenz, D.M. Gatlin III / Aquaculture xxx (2014) xxx–xxx

The aim of the present review is to give a clearer picture of the inter-relationships between fish nutrition and health. We do not intend tocite all studies in which additives/supplements have been tested inaquaculture, for this topic there are good broad or specific reviews pub-lished that the reader may consult (e.g. Dalmo and Bogwald, 2008;Kiron, 2012; Meena et al., 2012; Oliva-Teles, 2012; Torrecillas et al., inpress). Rather, we intend to focus on nutrients or additive groupswithinthe context of the fish's immune response, and their potential toenhance specific functions for better health and protection fromdisease-causing organisms.

2. Fish immune system

Teleost fish possess an immune system very similar to the one foundin higher vertebrates, but evolutionarily less developed and even moreless understood (Magnadottir, 2006; Sunyer, 2013). The immune sys-tem constitutes a highly complex defense mechanism that utilizes abroad range of individual components. It is composed of two majorbranches, the innate and the adaptive immune systems. During animmune response, both branches orchestrate an extremely close com-munication, fundamental for successful protection from and eradicationof pathogens (Tort et al., 2003).

The immune response is a process that involvesmultiple cellular andhumoral components of both immune branches (Table 1), includingdendritic cells, neutrophils, macrophages, lymphocytes, cytokines, im-munoglobulins, the complement system, among others (Bassity andClark, 2012; Rauta et al., 2012; Secombes, 2008). However, an importantcharacteristic inherent to fish, is that because of its evolutionary devel-opment, the immune system tends to rely more on its innate responsefor the clearance of an invading microorganism (Magnadottir, 2006),andwith this ismind, themacrophage could be considered themost im-portant immune cell, as it not only produces key cytokines, but it is alsothe chief cell in charge of phagocytosis and destruction of a pathogenafter initial recognition in naïve or pre-exposed animals (Bayne andGerwick, 2001; Shoemaker et al., 2001; Zhu et al., 2013). Although re-cently, dendritic cells – the most complete antigen presenting cell inhigher vertebrates (Banchereau and Steinman, 1998) – has been de-scribed in fish. These cells' complete functional characterization duringa fish's immune response is yet to be elucidated (Bassity and Clark,2012).

Noteworthy is that due to the great diversity of fish being cultured,substantial differences might be found among some important compo-nents of the immune system. For instance, some specieswill express im-munoglobulins (Ig)D, IgM and IgT/Z (Zhang et al., 2011) and others onlyIgD and IgM (Bengtén et al., 2006); in addition the recombination ofthese different immunoglobulin isotypes can vary among species(Mashoof et al., 2014). Although these differences could have an impacton specific interventions such as vaccine development, the overallimmune response is generally similar among fish species.

Table 1Main effector components of fish immune responses.

Immune system branch Cellular components Hum

Innate Physical barriers (mucosae)

MacrophagesNeutrophilsDendritic cellsa

ComLysAntPenAntNat

Adaptative B lymphocytesT lymphocytes

Ig MIg DIg Z

a Role during an immune response is not totally elucidated in fish.b Igs, immunoglobulins.c Not found in all fish species.

Please cite this article as: Pohlenz, C., Gatlin, D.M., Interrelationships betw10.1016/j.aquaculture.2014.02.008

3. Immune responses and metabolism

There is a constant relation between a pathogen (true or opportunis-tic) trying to invade and a host limiting the invasion. An imbalanceamong components of the host–pathogen-environment will createideal conditions for the onset of a disease (Bowden, 2008), triggering adefense response (Fig. 1). The complexity and specificity of the re-sponse means that the limits or boundaries among participants arepoorly defined. For this review, the immune response may be divid-ed into three stages: 1) Detection and recognition of the pathogen,2) Phagocytosis, pathogen killing and antigen presentation, and3) Immune expansion and creation of immunological memory. Theinitial acute response against an infection (stages 1 and 2), charac-terized by a hypermetabolic stage (Lochmiller and Deerenberg,2000; Wang et al., 2012), is probably the most important for the sur-vival of an animal, because competence of the innate immune system,mainly fromphagocytes, is required to detect and activate a generalizedresponse against the invasion of a pathogen (Bayne and Gerwick, 2001;Magnadottir, 2006).

The disruption of homeostasis and the establishment of a defensestate and/or disease is a costly metabolic process for the host. Infec-tion promotes a complete shift in metabolic priorities towards nutri-ent needs associated with the immune system (Lochmiller andDeerenberg, 2000). In quiescent immune cells, the utilization of nutri-ents happens at basal levels, merely for cellular maintenance. However,during an immune challenge, the utilization of key nutrients dramati-cally increases, especially, there is an important demand for aminoacids (Kiron, 2012; Uribe et al., 2011). For instance, in vivo reports sug-gest important usage of glutamine in ill fish, represented by the rapiddecrease in plasma levels of this amino acid (Walker et al., 1996). Onthe other hand, in vitro studies point out that an activated macrophageconsumes energy at a rate comparable to that used by a cardiac musclecell at maximum capacity (Newsholme and Newsholme, 1989); evenmore, although the profile of the amino acids used will vary dependingon if there is phagocytic or lymphocytic response, arginine and gluta-mine will play a key role for the overall performance of these cells infish (Pohlenz et al., 2012a).

Besides the possible onset of an anorexic state after an initial infec-tion, a diseased statewill activate themobilization of protein and energyfrom reserves not only to support the initial acute phase of the immuneresponse, but also to sustain it until the resolution of the problem(Sealey and Gatlin, 2001). Hence, a typical result during this period isa negative nitrogen balance, which could vary depending on the sever-ity of the infection (Lochmiller and Deerenberg, 2000; Lönnström et al.,2001; Midtlyng and Lillehaug, 1998); such condition may be of greatimportance in fish culture due to their natural history of requiringhigh dietary levels of protein (NRC, 2011). Under this scenario, the ade-quate availability of specific nutrients plays a fundamental role in theactivation and performance of the immune system against an invadingpathogen.

oral components Specificity

plement systemozymeimicrobial peptidestraxinsiproteasesural Igsb

Pathogen associated molecular patterns (PAMPs)

/Tc

Antigen-specific epitopes




Pathogen detection and recognition

Fish:Pathogen encounterPRRs:PAMPs*

Innate ResponsePhagocytosis

Pathogen killingCytokine secretion

FailureDisease and death

SuccessLimitationof infection and

disease

Specific Response Initiation and Instruction

Antigen presentationMolecular co-stimulation

Cellular expansion

Humoral ResponseB lymphocyte activation

Synthesis of specific Igs**

Cellular ResponseT-helper lymphocytes

T-cytotoxic lymphocytes

Adaptive immunityImmunological memory

Memory B and T lymphocytesProtection vs. future infections

Survival

Stage 1

Stage 2

Stage 3

Fig. 1. General scheme of the three stages of a fish immune response. *PRRs: pathogen recognition receptors; PAMPs: pathogen associated molecular patterns. **Igs: immunoglobulins,secreted by plasma cells, which are derived from activated B-lymphocytes.Modified from Shoemaker et al. (2001).

3C. Pohlenz, D.M. Gatlin III / Aquaculture xxx (2014) xxx–xxx

4. Interrelationships between nutrition and the immune system

Nutrition is a complex andmultidimensional factor that will interre-late with the immune system, hence fish health, through a broad arrayof direct or indirectmechanisms (Kiron, 2012; Oliva-Teles, 2012; Sealeyand Gatlin, 2001). Together with the formerly mentioned fact of a vastrange of fish species being cultured, the lack of a full understanding ofthe teleost immune system represents a significant limitation on study-ing the interrelationships between these two components and thereforeon entirely comprehending immunonutrition (Ponton et al., 2013).Studies to date using a given nutrient as an immune system modulatorhave shown different results among species and even within species(Dalmo and Bogwald, 2008). For instance, contrary to the role of gluta-mine in mammalian leukocytes, which is consistent across species(Crawford and Cohen, 1985), in fish, the role of glutamine in leukocytemetabolism is complex and appears to be species specific. Conflictingreports document glutamine-dependent and -independent responsesof proliferating cultured lymphocytes (Ganassin et al., 1998; McBrideand Keast, 1997; Pohlenz et al., 2012a; Rosenberg-Wiser and Avtalion,1982).

Exogenous sources of nutrients should supply minimum levels tomeet requirements for normal immune system performance and toprotect/restore tissues from collateral damage. However, in certainsituations, providing additional nutrients at levels above those requiredfor normal fish maintenance and growth, or even provision of somecompounds that are not required at all, may sustain and/or enhanceone or more functions of the immune system, hence increasing its effi-cacy and protection capacity against an invading pathogen (Kiron,2012; Sealey andGatlin, 2001). In this sense, there are various nutrition-al tools that may be implemented to accomplish this objective of en-hancing the immune system. Following, we present results obtainedwith some of the most promising feed additives/supplement groupsfor functional aquafeeds targeted to the various components of thefish immune system within the context of each response stage.


4.1. Detection and recognition of the pathogen

The immune system recognizes and responds to a broad variety ofpathogens, mainly throughwarning signals named pathogen associatedmolecular patterns (PAMPs) detected by cellular or humoral patternrecognition receptors/proteins (PRRs) (Abbas et al., 2012; Tort et al.,2003). The encounter with PAMPs will trigger a cascade of cytokinesecretion (Roher et al., 2011) with aims to activate a general immuneresponse, including recruiting phagocytes and lymphocytes via chemo-taxis, and the activation or secretion of cellular and humoral antimicro-bial defense mechanisms, such as the complement system, lysozyme,antimicrobial peptides, etc. (Abbas et al., 2012; Bayne and Gerwick,2001; Reyes-Cerpa et al., 2012).

Providing specific additives to the diet (most of them non-digestible), such asmixed or purified extracts frommicrobial or vegeta-ble structural components, can take advantage of these warning signalsbecause they may act as PAMPs or PAMP-like molecules and may in-crease non-specific protection (Fierro-Castro et al., 2012), which hasproven to efficiently promote early functions of the immune responseof fish (Table 2). Mannanoligosaccharides, β-glucans, sulfated polysac-charides and/or nucleotides are some of the most common additivestested in aquafeeds and various reports indicate they may promotethe expression and/or secretion of important pro-inflammatory andchemotactic cytokines, such as Interleukin (IL)-1β, IL-6, IL-8, tumor ne-crosis factor (TNF)-α and γ-interferon (IFN), along with up-regulationof important PRRs such as toll-like receptor (TLR)3, TLR5 and TLR9 indifferent fish species.

4.2. Pathogen phagocytosis/killing and antigen presentation

Phagocytosis is the internalization of a pathogenwith the purpose ofits destruction, and afterwards, under the correct conditions, to presentits antigens to lymphocytes. This process immediately follows the




Table 2Nutrients/additives of proven efficacy for the enhancement of detection and recognition of the pathogen (stage 1).

Nutrient/additive Species Effect Reference

Alginic acid Common carp, Cyprinus carpio Increased leukocyte migratory capacity Fujiki and Yano (1997)Rainbow trout, Oncorhynchus mykiss Up-regulation of IL-1β, IL-8, TNF- α after vaccination Gioacchini et al. (2008)

β-Glucan Atlantic cod, Gadus morhua Up-regulation of IL-1β after bacterial challenge Lokesh et al. (2012)Common carp Up-regulation of IL-1β Selvaraj et al. (2005)Pacific flounder, Paralichthys olivaceus Increased leukocyte migratory capacity Galindo-Villegas et al. (2006)Rainbow trout Primed the induction of TNF-α2 expression,

Up-regulation of IL-1β, IL-6 and C3 proteinIliev et al. (2005); Lovoll et al. (2007)

Snakehead, Channa striata Increased leukocyte count and total natural antibodies Talpur et al. (in press)Fructoligosaccharides Caspian roach, Rutilus rutilus Increased total natural antibodies Soleimani et al. (2012)

Stellate sturgeon, Acipenser stellatus Increased leukocyte count Akrami et al. (2013)Triangular bream,Megalobrama terminalis Increased leukocyte count and total natural antibodies Zhang et al. (2013)

Lipopolysaccharide Rainbow trout Up-regulation of IL-1β, IL-8, TNF-α2, TLR-5 and TLR-9 Fierro-Castro et al. (2013); Iliev et al. (2005)Mannanoligosaccharides Atlantic cod Up-regulation of IL-1β, IL-8 after bacterial challenge Lokesh et al. (2012)

Common carp Increased lymphocyte % Akrami et al. (2012)Giant sturgeon, Huso huso Increased lymphocyte % Razeghi et al. (2012)Labeo rohita Increased leukocyte count Andrews et al. (2009)Rainbow trout Increased natural antibody titers Staykov et al. (2007)Snakehead Increased natural plasma antibodies and leukocyte count

after challenge with Aeromonas hydrophilaTalpur et al. (in press)

Marine algae extract Gilthead seabream, Sparus aurata Up-regulation of IL-1β, IL8 and β-defensin Reyes-Becerril et al. (2013)Senegalese sole, Solea senegalensis Increased leukocyte migratory capacity Diaz-Rosales et al. (2005)

Nucleotides Turbot, Psetta maxima Up-regulation of IL-1β in kidney Low et al. (2003)Rainbow trout Increased plasma natural antibodies Tahmasebi-Kohyani et al. (2011)

Pathogen extract Turbot Increased leukocyte migratory capacity,up-regulation of IL-1β, TNF-α

Leiro et al. (2006)

Peptidoglycans Pacific flounder Increased leukocyte migratory capacity Galindo-Villegas et al. (2006)Polyinosinic polycytidylic acid Rainbow trout Up-regulation of IL-1β, IL-8, TNF- α1/α2, Mx-1,

TLR-3, TLR-5 and TLR-9Fierro-Castro et al. (2013)

Yeast extract Labeo rohita Increased leukocyte count Andrews et al. (2009)Rainbow trout Increased total leukocyte, neutrophil andmonocyte count Tukmechi et al. (2011)Snakehead Increased leukocyte count and total natural antibodies Talpur et al. (in press)


pathogen recognition by a macrophage or neutrophil, and possibly by adendritic cell (Shoemaker et al., 2001). Phagocytes respondwith an im-portant set of killing tools including superoxide anion, hydrogen perox-ide, nitric oxide, lysozyme, and other lytic enzymes (Magnadottir, 2006;Secombes and Fletcher, 1992; Tort et al., 2003; Uribe et al., 2011).

Supplementing dietswith nutrients that could bemetabolically usedby phagocytes has been an area of interest for enhancing this stage ofthe immune response (Table 3). For instance, certain amino acids playa crucial role in these immunological processes. Glutaminemay providemetabolic fuel to support reaction kinetics (Crawford and Cohen, 1985;Newsholme and Newsholme, 1989). Similarly, arginine is the uniqueprecursor of nitric oxide in activated macrophages (Buentello andGatlin, 1999; Neumann et al., 1995; Wu and Morris, 1998), and the lat-ter is a potent microbicidal compound and potent modulator of the eu-karyotic cytoskeleton (Kasprowicz et al., 2009; Moffat et al., 1996). Onthe other hand, another possible nutrition tool to enhance functionsduring this response stage is using nutrients that might modify thephysical (fluidity) nature of the plasma membrane and/or alter the ex-pression of receptors involved in these cellular processes, which couldenhance the synthesis and secretion of antimicrobial compounds bymodulating the protein kinase C pathway (Balfry and Higgs, 2001;Calder, 1998; Calder et al., 1990) or enhancing the synthesis ofmolecules that could be closely related to antigen processing andpresentation such as phospholipase A2 (PA2), prostaglandin E2 (PE2)or myeloid differentiation factor (MyD) 88 (Horsnell et al., 2013;Paduraru et al., 2013; Yen et al., 2011). Supplementing polyunsaturatedfatty acids n−3 or n−6, or antioxidant compounds such as vitamin Cand E has proven to be effective in this regard (Table 3). It is importantto state that even if the phagocytic activity is enhanced by a nutrient/additive, that does not necessarily correlate to the killing capacity of thecell. Therefore, it is crucial to evaluate both parameters in order to havea better assessment of an immunomodulation effect (Pohlenz et al.,2012a).


4.3. Immune expansion and memory creation

The ability to developmemory is a fundamental characteristic of theimmune system. The successful destruction and processing of an invad-ing pathogen should result in the induction of a strong and lastingresponse of memory lymphocytes. Because the first contact with anantigen usually induces relatively short-lived effector cells (VanMuiswinkel and Nakao, 2014), the way by which clonal expansion ofT lymphocytes is induced and the dimension of the effector cell popula-tion generated is key for this process (Secombes, 2008). The capacity tocreate immunological memory correlates with the expansion of naïvelymphocytes after antigen presentation, cytokine stimulation and mo-lecular co-stimulation at the membrane level (Secombes, 2008; Uribeet al., 2011). Although the synthesis of specific immunoglobulins is animportant component of the adaptive immune system, in fish, the cor-relates of protection are minimal unless there are high circulating titersof these antibodies (Thune et al., 1997). As such, good activation andexpansion of B lymphocytes are required.

Similar to the previous stage, the supplementation of nutrients thatcould be used as energy sources, precursors for or used for cellular pro-liferation or may influence cellular membrane integrity are among thetop immunomodulating candidates (Table 4). As this stage requireshigh proliferation of lymphocytes for appropriate immune expansion,lymphoid tissue may have limited capacity for de novo synthesis ofimportant compounds, such as amino acids, nucleotides and theirderivatives, depending to a great extent on exogenous nutrientsupply (Navarro et al., 1996). Providing an external source of these nu-trients may increase the expression of the recombinant activating gene(RAG)-1 (Low et al., 2003), crucial for lymphocyte maturation (Hansenand Kaattari, 1995), as well as the up-regulation of IgM expression in Blymphocytes residing in the spleen (Low et al., 2003) or kidney (Reyes-Becerril et al., 2011) which are essential for antibody secretion androbust development of adaptive immunity.




Table 3Nutrients/additives of proven efficacy for the enhancement of pathogen phagocytosis and killing and antigen presentation (stage 2).

Nutrient/additive Species Effect Reference

Arachidonic acid Yellow croaker, Larimichthyspolyactis

Increased phagocytic activity and production of sPLA2 and PGE2 Li et al. (2012)

Arginine Channel catfish, Ictalurus punctatus Increased phagocytic activity, phagocytic index, macrophage production ofnitric oxide, bactericidal capacity

Buentello et al. (2007); Buentello and Gatlin(1999); Pohlenz et al. (2012a)

Hybrid striped bass,Moronechrysops × M. saxatilis

Increased macrophage superoxide anion production Cheng et al. (2012)

Pacific flounder Increased phagocytic index, macrophage superoxide anion production Galindo-Villegas et al. (2006)Red drum, Sciaenops ocellatus Increased neutrophil respiratory burst and macrophage superoxide anion

productionCheng et al. (2011)

Senegalese sole Increased macrophage superoxide anion and nitric oxide production, up-regulation of HIF-I, MIP1-α and HAMP-1

Costas et al. (2011)

Astaxanthin Pacific flounder Increased phagocytic index and capacity, macrophage superoxide anionproduction

Galindo-Villegas et al. (2006)

β-Hydroxy-β-methylbutyrate

Rainbow trout Increased neutrophil respiratory burst, macrophage bactericidal capacity Siwicki et al. (2003)

Glutamine Channel catfish Increased phagocytic index Pohlenz et al. (2012a)Hybrid striped bass Increased neutrophil respiratory burst and macrophage superoxide anion

productionCheng et al. (2012)

Red drum Increased neutrophil respiratory burst and macrophage superoxide anionproduction

Cheng et al. (2011)

Linoleic acid Yellow croaker Increased phagocytic activity, macrophage superoxide anion production Zuo et al. (2013)n−3 HUFA Pacific flounder Increased macrophage superoxide anion production, complement activity Wang et al. (2006)Polyamines Gilthead seabream Increased phagocytic activity, up-regulation of MHC-I, CD8, Hep and C3 Reyes-Becerril et al. (2011)Vitamin C Atlantic salmon, Salmo salar Increased leukocyte phagocytosis activity Verlhac and Gabaudan (1994)

Gilthead seabream Increased phagocytic index and activity, macrophage superoxide anionproduction, complement activity

Ortuño et al. (2001); Ortuño et al. (1999)

Hybrid striped bass Increased macrophage superoxide anion production Sealey and Gatlin (2002a)Pacific flounder Increased macrophage superoxide anion production Galindo-Villegas et al. (2006)Rainbow trout Increase natural cytotoxicity and leukocyte phagocytosis activity Verlhac and Gabaudan (1994)Turbot Increased phagocytic index Roberts et al. (1995)Yellow croaker Increased phagocytosis activity and superoxide anion production Ai et al. (2006)

Vitamin E Gilthead seabream Increased phagocytic index and activity, and complement activity Ortuño et al. (2001); Ortuño et al. (2000)Hybrid striped bass Increased macrophage superoxide anion production Sealey and Gatlin (2002b)Pacific flounder Increased macrophage superoxide anion production Galindo-Villegas et al. (2006); Wang et al.

(2006)Rainbow trout Increased bactericidal activity Kiron et al. (1995)Yellow croaker Increased macrophage superoxide anion production, up-regulation of

MyD88Zuo et al. (2012)


5. Conclusions

The aim of the present review was to give insights on how nutritioninterrelates with health within the context of the fish's immune re-sponses, and to present a summary of data with promising compounds

Table 4Nutrients/additives of proven efficacy for the enhancement of expansion and creation of immu

Nutrient/additive Species Effect

Arginine Channel catfish Increased T and B lymphocyteagainst Edwardsiella ictaluri

β-carotene Japanese parrotfish,Oplegnathus fasciatus

Increased non-specific prolife

Spotted parrotfish,Oplegnathus punctatus

Increased non-specific prolife

β-Hydroxy-β-methylbutyrate Rainbow trout Increased non-specific T andters

Glutamine Channel catfish Increased non-specific T andcytes, memory specific lymph

n−3 HUFA Rainbow trout Increased antibody titers agaiNucleotides Atlantic salmon Increased plasma antibody tit

Channel catfish Increased antibody titers agaiHybrid tilapia, Oreochromisniloticus × O. aureus

Increased plasma antibody titliferation

Turbot Up-regulation of IgM and RAGPolyamines Gilthead seabream Up-regulation of IgMVitamin C Atlantic salmon Increased proliferation of T lym

ruckeriMilkfish, Chanos chanos Increased plasma antibody titRainbow trout Increased proliferation of T ly

Vitamin E Milkfish Increased plasma antibody tit


that might be used for making functional aquafeeds to be used underspecific situations. Although it is important to state, that even if a specif-ic compound will enhance early stages of the immune response, it doesnot mean that it may have positive effects on the final outcome of theintegrated immune response. Nutritional modulation of the immune

nological memory (stage 3).

Reference

proliferation, memory lymphocytes and antibody titer Pohlenz et al. (2012b);Pohlenz et al. (2012a)

ration of T lymphocytes Tachibana et al. (1997)

ration of lymphocytes Tachibana et al. (1997)

B lymphocyte proliferation and total plasma antibody ti- Siwicki et al. (2003)

B lymphocyte proliferation, tissue-residing B lympho-ocytes and plasma antibody titer against E. ictaluri

Pohlenz et al. (2012b);Pohlenz et al. (2012a)

nst A. salmonicida Kiron et al. (1995)ers against A. salmonicida Burrells et al. (2001)nst E. ictaluri Welker et al. (2011)ers against A. hydrophila, non-specific lymphocyte pro- Ramadan et al. (1994)

-1 Low et al. (2003)Reyes-Becerril et al. (2011)

phocytes, higher plasma antibody titers against Yersinia Erdal et al. (1991); Verlhacand Gabaudan (1994)

ers against Vibrio vulnificus, enhanced memory factor Azad et al. (2007)mphocytes Verlhac and Gabaudan

(1994)ers against Vibrio vulnificus, enhanced memory factor Azad et al. (2007)





system continues to be a potentially powerful tool to improve thehealth and growth of cultured fish, hence to improve production yield.However, because of the great diversity of fish being cultured alongwith a lack of full understanding regarding the fish's immune system,immunonutrition is still not fully developed, but warrants a vast futureresearch in this field. In particular, there is an immense need to fine-tune dosing of various additives, feeding regimes, supplementationtimes, etc. so that immunonutrition can become more effective andused efficiently to benefit the industry.

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Interrelationships between fish nutrition and health