AQUA-631033; No of Pages 7

Aquaculture xxx (2014) xxxxxx

Contents lists available at ScienceDirect

Aquaculture
journal homepage: www.elsevier.com/locate/aqua-online

Interrelationships between sh 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

a r t i c l e

i n f o

Article history:
Received 30 January 2014
Received in revised form 7 February 2014
Accepted 10 February 2014
Available online xxxx
Keywords:
Immunonutrition
Fish health
Feed additives
Immune responses

a b s t r a c t
An understanding of how to nurture and/or modulate the different components of the immune system is crucial
for the prevention and control of diseases in animal husbandry. It is well established that proper nutrition is essential for maintenance of normal growth and health of all animals including aquatic species. As such, nutritious
diets and appropriate feeding regimes play critical roles in intensive aquaculture. In recent years, heightened attention has been given to the development of nutritional strategies that positively inuence immunity and disease resistance of cultured organisms to reduce disease-related economic losses. The availability of specic
nutrients to immune cells plays a key role on how well those cells perform against a foreign invader. In this
sense, research with several sh species has established that not only immunocompetence can be compromised
by deciencies of various nutrients, but that dietary supplementation of some nutrients in excess of minimum
requirement levels for optimal growth has been shown to signicantly enhance immune responses and disease
resistance. For instance, ndings from recent studies indicate an important role of key amino acids and their derivatives, like arginine and glutamine, or vitamins, such as vitamin C and E, in modulating immune responses
such as increasing phagocytosis and pathogen killing capacity, as well as increasing antibody production and immunological memory. In addition, administration of non-nutritive compounds in the diet has become recognized
as a viable means of enhancing immunocompetence of various aquatic species, mainly by the provision of cellular
fractions such as -glucans, complex oligosaccharides (mannanoligosaccharides, fructooligosaccharides or
sulfated polysaccharides) or yeast and algae extracts. These compounds may act like Pathogen Associated Molecular Pattern (PAMP) molecules, interacting with the innate immune system through their Pattern Recognition
Receptors (PRRs) and increasing their capability for detecting and recognizing potential pathogens and readily
triggering immune responses. This article will review the broad range of dietary constituents which have been
shown to affect immunocompetence and health of aquatic species and how they may inuence components of
the immune system. Further advancements in nutritional modulation of the immune response hold promise as
an effective and relatively inexpensive alternative in combating diseases in aquaculture.
2014 Elsevier B.V. All rights reserved.

1. Introduction
Aquaculture has become a major source of animal protein for human
consumption and trends show it will be of even greater importance for
future generations, as sh farming has seen an annual growth higher
than other animal-production industries for the last several decades
(FAO, 2012). Although diseases are natural events in all animal groups,
the intensication of culture technologies has brought about an important increase in the emergence, dispersion and outbreak of infectious
diseases, which have placed them as one of the main growthconstricting factors in the industry (Costello, 2009; Pridgeon and
Klesius, 2013; Zagmutt et al., 2013). Therefore, the study of the defense
mechanisms of cultured animals and the understanding of how to

Corresponding author at: 216 Heep Laboratory Building, 2258 TAMUS, College Station,
TX 77843, USA. Tel.: +1 979 847 9333; fax: +1 979 845 4096.
E-mail address: d-gatlin@tamu.edu (D.M. Gatlin).

nurture and modulate the different components of the immune system

are crucial for the prevention, treatment and/or control of sh diseases,
hence for guaranteeing the sustainability and future of this important
endeavor.
Proper nutrition is critical not only to achieve optimal growth rates
but also to maintain the health of cultured sh (Sealey and Gatlin,
2001). For a number of years, the sh nutrition eld focused mainly
on establishing the minimum nutrient requirements for normal growth
of different sh species (NRC, 2011). However, nowadays, the role of
nutrition on health management through the modulation of immune
response and disease resistance has turned into a research area of top
priority with aims to lessen the dependence on chemotherapeutics
and 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 dened as the study of enhancing
immunological functions by means of using specic nutrients and/or
other dietary compounds which could be higher than those levels
needed for optimal growth.

http://dx.doi.org/10.1016/j.aquaculture.2014.02.008
0044-8486/ 2014 Elsevier B.V. All rights reserved.

Please cite this article as: Pohlenz, C., Gatlin, D.M., Interrelationships between sh nutrition and health, Aquaculture (2014), http://dx.doi.org/
10.1016/j.aquaculture.2014.02.008

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

The aim of the present review is to give a clearer picture of the interrelationships between sh nutrition and health. We do not intend to
cite all studies in which additives/supplements have been tested in
aquaculture, for this topic there are good broad or specic reviews published that the reader may consult (e.g. Dalmo and Bogwald, 2008;
Kiron, 2012; Meena et al., 2012; Oliva-Teles, 2012; Torrecillas et al., in
press). Rather, we intend to focus on nutrients or additive groups within
the context of the sh's immune response, and their potential to
enhance specic functions for better health and protection from
disease-causing organisms.

2. Fish immune system

Teleost sh possess an immune system very similar to the one found
in higher vertebrates, but evolutionarily less developed and even more
less understood (Magnadottir, 2006; Sunyer, 2013). The immune system constitutes a highly complex defense mechanism that utilizes a
broad range of individual components. It is composed of two major
branches, the innate and the adaptive immune systems. During an
immune response, both branches orchestrate an extremely close communication, fundamental for successful protection from and eradication
of pathogens (Tort et al., 2003).
The immune response is a process that involves multiple cellular and
humoral components of both immune branches (Table 1), including
dendritic cells, neutrophils, macrophages, lymphocytes, cytokines, immunoglobulins, the complement system, among others (Bassity and
Clark, 2012; Rauta et al., 2012; Secombes, 2008). However, an important
characteristic inherent to sh, is that because of its evolutionary development, the immune system tends to rely more on its innate response
for the clearance of an invading microorganism (Magnadottir, 2006),
and with this is mind, the macrophage could be considered the most important immune cell, as it not only produces key cytokines, but it is also
the chief cell in charge of phagocytosis and destruction of a pathogen
after initial recognition in nave or pre-exposed animals (Bayne and
Gerwick, 2001; Shoemaker et al., 2001; Zhu et al., 2013). Although recently, dendritic cells the most complete antigen presenting cell in
higher vertebrates (Banchereau and Steinman, 1998) has been described in sh. These cells' complete functional characterization during
a sh's immune response is yet to be elucidated (Bassity and Clark,
2012).
Noteworthy is that due to the great diversity of sh being cultured,
substantial differences might be found among some important components of the immune system. For instance, some species will express immunoglobulins (Ig)D, IgM and IgT/Z (Zhang et al., 2011) and others only
IgD and IgM (Bengtn et al., 2006); in addition the recombination of
these different immunoglobulin isotypes can vary among species
(Mashoof et al., 2014). Although these differences could have an impact
on specic interventions such as vaccine development, the overall
immune response is generally similar among sh species.

3. Immune responses and metabolism

There is a constant relation between a pathogen (true or opportunistic) trying to invade and a host limiting the invasion. An imbalance
among components of the hostpathogen-environment will create
ideal conditions for the onset of a disease (Bowden, 2008), triggering a
defense response (Fig. 1). The complexity and specicity of the response means that the limits or boundaries among participants are
poorly dened. For this review, the immune response may be divided into three stages: 1) Detection and recognition of the pathogen,
2) Phagocytosis, pathogen killing and antigen presentation, and
3) Immune expansion and creation of immunological memory. The
initial acute response against an infection (stages 1 and 2), characterized by a hypermetabolic stage (Lochmiller and Deerenberg,
2000; Wang et al., 2012), is probably the most important for the survival of an animal, because competence of the innate immune system,
mainly from phagocytes, is required to detect and activate a generalized
response against the invasion of a pathogen (Bayne and Gerwick, 2001;
Magnadottir, 2006).
The disruption of homeostasis and the establishment of a defense
state and/or disease is a costly metabolic process for the host. Infection promotes a complete shift in metabolic priorities towards nutrient needs associated with the immune system (Lochmiller and
Deerenberg, 2000). In quiescent immune cells, the utilization of nutrients happens at basal levels, merely for cellular maintenance. However,
during an immune challenge, the utilization of key nutrients dramatically increases, especially, there is an important demand for amino
acids (Kiron, 2012; Uribe et al., 2011). For instance, in vivo reports suggest important usage of glutamine in ill sh, represented by the rapid
decrease in plasma levels of this amino acid (Walker et al., 1996). On
the other hand, in vitro studies point out that an activated macrophage
consumes energy at a rate comparable to that used by a cardiac muscle
cell at maximum capacity (Newsholme and Newsholme, 1989); even
more, although the prole of the amino acids used will vary depending
on if there is phagocytic or lymphocytic response, arginine and glutamine will play a key role for the overall performance of these cells in
sh (Pohlenz et al., 2012a).
Besides the possible onset of an anorexic state after an initial infection, a diseased state will activate the mobilization of protein and energy
from reserves not only to support the initial acute phase of the immune
response, but also to sustain it until the resolution of the problem
(Sealey and Gatlin, 2001). Hence, a typical result during this period is
a negative nitrogen balance, which could vary depending on the severity of the infection (Lochmiller and Deerenberg, 2000; Lnnstrm et al.,
2001; Midtlyng and Lillehaug, 1998); such condition may be of great
importance in sh culture due to their natural history of requiring
high dietary levels of protein (NRC, 2011). Under this scenario, the adequate availability of specic nutrients plays a fundamental role in the
activation and performance of the immune system against an invading
pathogen.

Table 1
Main effector components of sh immune responses.
Immune system branch

Cellular components

Humoral components

Specicity

Innate

Physical barriers (mucosae)

Complement system
Lysozyme
Antimicrobial peptides
Pentraxins
Antiproteases
Natural Igsb
Ig M
Ig D
Ig Z/Tc

Pathogen associated molecular patterns (PAMPs)

Macrophages
Neutrophils
Dendritic cellsa
Adaptative

a
b
c

B lymphocytes
T lymphocytes

Antigen-specic epitopes

Role during an immune response is not totally elucidated in sh.

Igs, immunoglobulins.
Not found in all sh species.

Please cite this article as: Pohlenz, C., Gatlin, D.M., Interrelationships between sh nutrition and health, Aquaculture (2014), http://dx.doi.org/
10.1016/j.aquaculture.2014.02.008

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

Pathogen detection and

recognition
Fish:Pathogen encounter
PRRs:PAMPs*

Stage 1

Innate Response
Phagocytosis
Pathogen killing
Cytokine secretion

Success

Failure

Limitationof infection and

disease

Disease and death

Stage 2

Specific Response Initiation

and Instruction
Antigen presentation
Molecular co-stimulation
Cellular expansion

Humoral Response

Cellular Response

B lymphocyte activation
Synthesis of specific Igs**

T-helper lymphocytes
T-cytotoxic lymphocytes

Stage 3

Adaptive immunity
Immunological memory
Memory B and T lymphocytes
Protection vs. future infections
Survival

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

4. Interrelationships between nutrition and the immune system

4.1. Detection and recognition of the pathogen

Nutrition is a complex and multidimensional factor that will interrelate with the immune system, hence sh health, through a broad array
of direct or indirect mechanisms (Kiron, 2012; Oliva-Teles, 2012; Sealey
and Gatlin, 2001). Together with the formerly mentioned fact of a vast
range of sh species being cultured, the lack of a full understanding of
the teleost immune system represents a signicant limitation on studying the interrelationships between these two components and therefore
on entirely comprehending immunonutrition (Ponton et al., 2013).
Studies to date using a given nutrient as an immune system modulator
have shown different results among species and even within species
(Dalmo and Bogwald, 2008). For instance, contrary to the role of glutamine in mammalian leukocytes, which is consistent across species
(Crawford and Cohen, 1985), in sh, the role of glutamine in leukocyte
metabolism is complex and appears to be species specic. Conicting
reports document glutamine-dependent and -independent responses
of proliferating cultured lymphocytes (Ganassin et al., 1998; McBride
and Keast, 1997; Pohlenz et al., 2012a; Rosenberg-Wiser and Avtalion,
1982).
Exogenous sources of nutrients should supply minimum levels to
meet requirements for normal immune system performance and to
protect/restore tissues from collateral damage. However, in certain
situations, providing additional nutrients at levels above those required
for normal sh maintenance and growth, or even provision of some
compounds that are not required at all, may sustain and/or enhance
one or more functions of the immune system, hence increasing its efcacy and protection capacity against an invading pathogen (Kiron,
2012; Sealey and Gatlin, 2001). In this sense, there are various nutritional tools that may be implemented to accomplish this objective of enhancing the immune system. Following, we present results obtained
with some of the most promising feed additives/supplement groups
for functional aquafeeds targeted to the various components of the
sh immune system within the context of each response stage.

The immune system recognizes and responds to a broad variety of

pathogens, mainly through warning signals named pathogen associated
molecular patterns (PAMPs) detected by cellular or humoral pattern
recognition receptors/proteins (PRRs) (Abbas et al., 2012; Tort et al.,
2003). The encounter with PAMPs will trigger a cascade of cytokine
secretion (Roher et al., 2011) with aims to activate a general immune
response, including recruiting phagocytes and lymphocytes via chemotaxis, and the activation or secretion of cellular and humoral antimicrobial 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 specic additives to the diet (most of them nondigestible), such as mixed or puried extracts from microbial or vegetable structural components, can take advantage of these warning signals
because they may act as PAMPs or PAMP-like molecules and may increase non-specic protection (Fierro-Castro et al., 2012), which has
proven to efciently promote early functions of the immune response
of sh (Table 2). Mannanoligosaccharides, -glucans, sulfated polysaccharides and/or nucleotides are some of the most common additives
tested in aquafeeds and various reports indicate they may promote
the expression and/or secretion of important pro-inammatory and
chemotactic cytokines, such as Interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)- and -interferon (IFN), along with up-regulation
of important PRRs such as toll-like receptor (TLR)3, TLR5 and TLR9 in
different sh species.

4.2. Pathogen phagocytosis/killing and antigen presentation

Phagocytosis is the internalization of a pathogen with the purpose of
its destruction, and afterwards, under the correct conditions, to present
its antigens to lymphocytes. This process immediately follows the

Please cite this article as: Pohlenz, C., Gatlin, D.M., Interrelationships between sh nutrition and health, Aquaculture (2014), http://dx.doi.org/
10.1016/j.aquaculture.2014.02.008

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

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

Species

Alginic acid

Common carp, Cyprinus carpio

Rainbow trout, Oncorhynchus mykiss
Atlantic cod, Gadus morhua
Common carp
Pacic ounder, Paralichthys olivaceus
Rainbow trout

Effect

Reference

Increased leukocyte migratory capacity

Up-regulation of IL-1, IL-8, TNF- after vaccination
-Glucan
Up-regulation of IL-1 after bacterial challenge
Up-regulation of IL-1
Increased leukocyte migratory capacity
Primed the induction of TNF-2 expression,
Up-regulation of IL-1, IL-6 and C3 protein
Snakehead, Channa striata
Increased leukocyte count and total natural antibodies
Fructoligosaccharides
Caspian roach, Rutilus rutilus
Increased total natural antibodies
Stellate sturgeon, Acipenser stellatus
Increased leukocyte count
Triangular bream, Megalobrama terminalis Increased leukocyte count and total natural antibodies
Lipopolysaccharide
Rainbow trout
Up-regulation of IL-1, IL-8, TNF-2, TLR-5 and TLR-9
Mannanoligosaccharides
Atlantic cod
Up-regulation of IL-1, IL-8 after bacterial challenge
Common carp
Increased lymphocyte %
Giant sturgeon, Huso huso
Increased lymphocyte %
Labeo rohita
Increased leukocyte count
Rainbow trout
Increased natural antibody titers
Snakehead
Increased natural plasma antibodies and leukocyte count
after challenge with Aeromonas hydrophila
Marine algae extract
Gilthead seabream, Sparus aurata
Up-regulation of IL-1, IL8 and -defensin
Senegalese sole, Solea senegalensis
Increased leukocyte migratory capacity
Nucleotides
Turbot, Psetta maxima
Up-regulation of IL-1 in kidney
Rainbow trout
Increased plasma natural antibodies
Pathogen extract
Turbot
Increased leukocyte migratory capacity,
up-regulation of IL-1, TNF-
Peptidoglycans
Pacic ounder
Increased leukocyte migratory capacity
Polyinosinic polycytidylic acid Rainbow trout
Up-regulation of IL-1, IL-8, TNF- 1/2, Mx-1,
TLR-3, TLR-5 and TLR-9
Yeast extract
Labeo rohita
Increased leukocyte count
Rainbow trout
Increased total leukocyte, neutrophil and monocyte count
Snakehead
Increased leukocyte count and total natural antibodies

pathogen recognition by a macrophage or neutrophil, and possibly by a

dendritic cell (Shoemaker et al., 2001). Phagocytes respond with an important set of killing tools including superoxide anion, hydrogen peroxide, nitric oxide, lysozyme, and other lytic enzymes (Magnadottir, 2006;
Secombes and Fletcher, 1992; Tort et al., 2003; Uribe et al., 2011).
Supplementing diets with nutrients that could be metabolically used
by phagocytes has been an area of interest for enhancing this stage of
the immune response (Table 3). For instance, certain amino acids play
a crucial role in these immunological processes. Glutamine may provide
metabolic fuel to support reaction kinetics (Crawford and Cohen, 1985;
Newsholme and Newsholme, 1989). Similarly, arginine is the unique
precursor of nitric oxide in activated macrophages (Buentello and
Gatlin, 1999; Neumann et al., 1995; Wu and Morris, 1998), and the latter is a potent microbicidal compound and potent modulator of the eukaryotic cytoskeleton (Kasprowicz et al., 2009; Moffat et al., 1996). On
the other hand, another possible nutrition tool to enhance functions
during this response stage is using nutrients that might modify the
physical (uidity) nature of the plasma membrane and/or alter the expression of receptors involved in these cellular processes, which could
enhance the synthesis and secretion of antimicrobial compounds by
modulating the protein kinase C pathway (Balfry and Higgs, 2001;
Calder, 1998; Calder et al., 1990) or enhancing the synthesis of
molecules that could be closely related to antigen processing and
presentation 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 polyunsaturated
fatty acids n3 or n6, or antioxidant compounds such as vitamin C
and E has proven to be effective in this regard (Table 3). It is important
to state that even if the phagocytic activity is enhanced by a nutrient/
additive, that does not necessarily correlate to the killing capacity of the
cell. Therefore, it is crucial to evaluate both parameters in order to have
a better assessment of an immunomodulation effect (Pohlenz et al.,
2012a).

Fujiki and Yano (1997)

Gioacchini et al. (2008)
Lokesh et al. (2012)
Selvaraj et al. (2005)
Galindo-Villegas et al. (2006)
Iliev et al. (2005); Lovoll et al. (2007)
Talpur et al. (in press)
Soleimani et al. (2012)
Akrami et al. (2013)
Zhang et al. (2013)
Fierro-Castro et al. (2013); Iliev et al. (2005)
Lokesh et al. (2012)
Akrami et al. (2012)
Razeghi et al. (2012)
Andrews et al. (2009)
Staykov et al. (2007)
Talpur et al. (in press)
Reyes-Becerril et al. (2013)
Diaz-Rosales et al. (2005)
Low et al. (2003)
Tahmasebi-Kohyani et al. (2011)
Leiro et al. (2006)
Galindo-Villegas et al. (2006)
Fierro-Castro et al. (2013)
Andrews et al. (2009)
Tukmechi et al. (2011)
Talpur et al. (in press)

4.3. Immune expansion and memory creation

The ability to develop memory is a fundamental characteristic of the
immune system. The successful destruction and processing of an invading pathogen should result in the induction of a strong and lasting
response of memory lymphocytes. Because the rst contact with an
antigen usually induces relatively short-lived effector cells (Van
Muiswinkel and Nakao, 2014), the way by which clonal expansion of
T lymphocytes is induced and the dimension of the effector cell population generated is key for this process (Secombes, 2008). The capacity to
create immunological memory correlates with the expansion of nave
lymphocytes after antigen presentation, cytokine stimulation and molecular co-stimulation at the membrane level (Secombes, 2008; Uribe
et al., 2011). Although the synthesis of specic immunoglobulins is an
important component of the adaptive immune system, in sh, the correlates of protection are minimal unless there are high circulating titers
of these antibodies (Thune et al., 1997). As such, good activation and
expansion of B lymphocytes are required.
Similar to the previous stage, the supplementation of nutrients that
could be used as energy sources, precursors for or used for cellular proliferation or may inuence cellular membrane integrity are among the
top immunomodulating candidates (Table 4). As this stage requires
high proliferation of lymphocytes for appropriate immune expansion,
lymphoid tissue may have limited capacity for de novo synthesis of
important compounds, such as amino acids, nucleotides and their
derivatives, depending to a great extent on exogenous nutrient
supply (Navarro et al., 1996). Providing an external source of these nutrients may increase the expression of the recombinant activating gene
(RAG)-1 (Low et al., 2003), crucial for lymphocyte maturation (Hansen
and Kaattari, 1995), as well as the up-regulation of IgM expression in B
lymphocytes residing in the spleen (Low et al., 2003) or kidney (ReyesBecerril et al., 2011) which are essential for antibody secretion and
robust development of adaptive immunity.

Please cite this article as: Pohlenz, C., Gatlin, D.M., Interrelationships between sh nutrition and health, Aquaculture (2014), http://dx.doi.org/
10.1016/j.aquaculture.2014.02.008

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

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

Species

Effect

Reference

Arachidonic acid

Yellow croaker, Larimichthys

polyactis
Channel catsh, Ictalurus punctatus

Increased phagocytic activity and production of sPLA2 and PGE2

Li et al. (2012)

Increased phagocytic activity, phagocytic index, macrophage production of

nitric oxide, bactericidal capacity
Increased macrophage superoxide anion production

Buentello et al. (2007); Buentello and Gatlin

(1999); Pohlenz et al. (2012a)
Cheng et al. (2012)

Increased phagocytic index, macrophage superoxide anion production

Increased neutrophil respiratory burst and macrophage superoxide anion
production
Increased macrophage superoxide anion and nitric oxide production, upregulation of HIF-I, MIP1- and HAMP-1
Increased phagocytic index and capacity, macrophage superoxide anion
production
Increased neutrophil respiratory burst, macrophage bactericidal capacity

Galindo-Villegas et al. (2006)

Cheng et al. (2011)

Arginine

Hybrid striped bass, Morone

chrysops M. saxatilis
Pacic ounder
Red drum, Sciaenops ocellatus
Senegalese sole
Astaxanthin

Pacic ounder

-Hydroxy-methylbutyrate
Glutamine

Rainbow trout
Channel catsh
Hybrid striped bass
Red drum

Linoleic acid
n3 HUFA
Polyamines
Vitamin C

Vitamin E

Yellow croaker
Pacic ounder
Gilthead seabream
Atlantic salmon, Salmo salar
Gilthead seabream
Hybrid striped bass
Pacic ounder
Rainbow trout
Turbot
Yellow croaker
Gilthead seabream
Hybrid striped bass
Pacic ounder
Rainbow trout
Yellow croaker

Increased phagocytic index

Increased neutrophil respiratory burst and macrophage superoxide anion
production
Increased neutrophil respiratory burst and macrophage superoxide anion
production
Increased phagocytic activity, macrophage superoxide anion production
Increased macrophage superoxide anion production, complement activity
Increased phagocytic activity, up-regulation of MHC-I, CD8, Hep and C3
Increased leukocyte phagocytosis activity
Increased phagocytic index and activity, macrophage superoxide anion
production, complement activity
Increased macrophage superoxide anion production
Increased macrophage superoxide anion production
Increase natural cytotoxicity and leukocyte phagocytosis activity
Increased phagocytic index
Increased phagocytosis activity and superoxide anion production
Increased phagocytic index and activity, and complement activity
Increased macrophage superoxide anion production
Increased macrophage superoxide anion production
Increased bactericidal activity
Increased macrophage superoxide anion production, up-regulation of
MyD88

5. Conclusions
The aim of the present review was to give insights on how nutrition
interrelates with health within the context of the sh's immune responses, and to present a summary of data with promising compounds

Costas et al. (2011)

Galindo-Villegas et al. (2006)
Siwicki et al. (2003)
Pohlenz et al. (2012a)
Cheng et al. (2012)
Cheng et al. (2011)
Zuo et al. (2013)
Wang et al. (2006)
Reyes-Becerril et al. (2011)
Verlhac and Gabaudan (1994)
Ortuo et al. (2001); Ortuo et al. (1999)
Sealey and Gatlin (2002a)
Galindo-Villegas et al. (2006)
Verlhac and Gabaudan (1994)
Roberts et al. (1995)
Ai et al. (2006)
Ortuo et al. (2001); Ortuo et al. (2000)
Sealey and Gatlin (2002b)
Galindo-Villegas et al. (2006); Wang et al.
(2006)
Kiron et al. (1995)
Zuo et al. (2012)

that might be used for making functional aquafeeds to be used under

specic situations. Although it is important to state, that even if a specific compound will enhance early stages of the immune response, it does
not mean that it may have positive effects on the nal outcome of the
integrated immune response. Nutritional modulation of the immune

Table 4
Nutrients/additives of proven efcacy for the enhancement of expansion and creation of immunological memory (stage 3).
Nutrient/additive

Species

Effect

Reference

Arginine

Channel catsh

-carotene

Pohlenz et al. (2012b);

Pohlenz et al. (2012a)
Tachibana et al. (1997)

Increased non-specic proliferation of lymphocytes

Tachibana et al. (1997)

-Hydroxy--methylbutyrate

Japanese parrotsh,
Oplegnathus fasciatus
Spotted parrotsh,
Oplegnathus punctatus
Rainbow trout

Increased T and B lymphocyte proliferation, memory lymphocytes and antibody titer

against Edwardsiella ictaluri
Increased non-specic proliferation of T lymphocytes

Siwicki et al. (2003)

Glutamine

Channel catsh

n3 HUFA
Nucleotides

Rainbow trout
Atlantic salmon
Channel catsh
Hybrid tilapia, Oreochromis
niloticus O. aureus
Turbot
Gilthead seabream
Atlantic salmon
Milksh, Chanos chanos
Rainbow trout

Increased non-specic T and B lymphocyte proliferation and total plasma antibody titers
Increased non-specic T and B lymphocyte proliferation, tissue-residing B lymphocytes, memory specic lymphocytes and plasma antibody titer against E. ictaluri
Increased antibody titers against A. salmonicida
Increased plasma antibody titers against A. salmonicida
Increased antibody titers against E. ictaluri
Increased plasma antibody titers against A. hydrophila, non-specic lymphocyte proliferation
Up-regulation of IgM and RAG-1
Up-regulation of IgM
Increased proliferation of T lymphocytes, higher plasma antibody titers against Yersinia
ruckeri
Increased plasma antibody titers against Vibrio vulnicus, enhanced memory factor
Increased proliferation of T lymphocytes

Milksh

Increased plasma antibody titers against Vibrio vulnicus, enhanced memory factor

Polyamines
Vitamin C

Vitamin E

Pohlenz et al. (2012b);

Pohlenz et al. (2012a)
Kiron et al. (1995)
Burrells et al. (2001)
Welker et al. (2011)
Ramadan et al. (1994)
Low et al. (2003)
Reyes-Becerril et al. (2011)
Erdal et al. (1991); Verlhac
and Gabaudan (1994)
Azad et al. (2007)
Verlhac and Gabaudan
(1994)
Azad et al. (2007)

Please cite this article as: Pohlenz, C., Gatlin, D.M., Interrelationships between sh nutrition and health, Aquaculture (2014), http://dx.doi.org/
10.1016/j.aquaculture.2014.02.008

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

system continues to be a potentially powerful tool to improve the

health and growth of cultured sh, hence to improve production yield.
However, because of the great diversity of sh being cultured along
with a lack of full understanding regarding the sh's immune system,
immunonutrition is still not fully developed, but warrants a vast future
research in this eld. In particular, there is an immense need to netune dosing of various additives, feeding regimes, supplementation
times, etc. so that immunonutrition can become more effective and
used efciently to benet the industry.
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Please cite this article as: Pohlenz, C., Gatlin, D.M., Interrelationships between sh nutrition and health, Aquaculture (2014), http://dx.doi.org/
10.1016/j.aquaculture.2014.02.008