Using Pre-Probiotics and Immunomodulators to Prevent Diseases and Minimize Antimicrobial Use
World Small Animal Veterinary Association Congress Proceedings, 2017
Prof. Dušan Palić, DVM, MVSc, PhD, CertAqV, DECAAH
Faculty of Veterinary Medicine, Ludwig-Maximilians ­ University Munich, Munich, Germany

Intensive aquaculture systems create a highly stressful environment for fish. Crowding, handling, and manipulation suppress the immune response, and the suppression may be further augmented due to exposure to poor environmental conditions and pollutants. Fish kept under immunosuppressive conditions become highly susceptible to disease. Traditional use of synthetic chemicals and antibiotics to prevent or treat fish diseases has achieved partial success. The emergence of antibiotic-resistant microbes and rising concerns about the effects of chemotherapeutics on the surrounding ecosystems present today’s industry with challenges to find alternative approaches to prevent diseases. The use of vaccines in aquatic animal disease prevention and control has advanced in recent years, but with limited success. An alternative practical approach to increase disease resistance and vaccination success with reduced use of chemotherapeutics is necessary for continuous growth of the aquaculture industry globally. These alternative approaches, such as use of pre-probiotics (synbiotics) and immunomodulators, can be used to complement and potentially improve chemotherapeutics treatments, vaccination success, disease resistance, and well-being of fish in intensive aquaculture operations, but also in ornamental fish trade, retail and home aquariums. This presentation reviews major advances in dietary application of pre/probiotics and immunomodulating compounds to food and ornamental finfish.

Prebiotic is defined as selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-being and health”. Other dietary fibers also may fit the definition of prebiotics, such as resistant starch, pectin, beta-glucans, and xylooligosaccharides. Prebiotics can also be defined as: “food ingredients that help support growth of probiotic bacteria” or “nondigestible substances that act as food for the gut microbiota. Essentially, prebiotics stimulate growth or activity of certain healthy bacteria living in the body of an animal (in this case fish). It is however to note that the European Food Safety Authority (EFSA) differentiates between “prebiotic” and “dietary fiber” with maintaining the opinion that “a cause and effect relationship has not been established between the consumption of the food constituents which are the subject of the health claims and a beneficial physiological effect related to increasing numbers of gastrointestinal microbiota”. Therefore, under EFSA rules individual ingredients cannot carry a “probiotic” label, but can only be listed as dietary fiber and with no implication of health benefits.

Table 1. Different prebiotic substances used in aqua tic animal production (adapted from Song et al.)

Prebiotic substances


Aquatic organisms


Fructooligosaccharides (FOS)
Mannan Oligosaccharide (MOS)
Galactooligosaccharide (GOS)

Salmo salar L.
Megalobrama terminalis
Paralichthys olivaceus
Acipenser stellatus
Oreochromis niloticus
Dicentrarchus labrax
Panulirus ornatus
Sciaenops ocellatus
Atlantic Salmon
Siberian sturgeon

Poly Oligosaccharide


Nile tilapia
Huso huso
Pseudoplatystoma sp.


Probiotics are defined as live microorganisms that are believed to provide health benefits when consumed, and the term is currently used to name ingested microorganisms associated with benefits for humans and animals. Although there are numerous claimed benefits of using commercial probiotics, such as reducing gastrointestinal discomfort, improving immune health, relieving constipation, or avoiding the common cold, such claims are not backed by scientific evidence and are prevented as deceptive advertisements in the United States by the Federal Trade Commission. Probiotics are considered to be generally safe, but they may cause bacteria-host interactions and unwanted side effects in rare cases. Live probiotic cultures are available in fermented dairy products and probiotic fortified foods. However, tablets, capsules, powders, and sachets containing the bacteria in freeze-dried form are also available, and have been frequently added to commercially available pet foods, including ornamental fish food but also recently as part of some major aquaculture feed products. It is notable that many probiotics taken orally can be destroyed by the acidic conditions of the stomach and various approaches including microencapsulation are being developed to address this problem. In addition to this use in terrestrial animals, in aquaculture, the use of probiotics has also been investigated as water quality treatment, and essentially, improvement of biofiltration abilities of the various bacterial strains has been reported (table 2).

However, there is only preliminary evidence for most probiotic health claims. Even for the most studied strains, few have been sufficiently developed in basic and clinical research to warrant approval for health claim status by a regulatory agency such as the Food and Drug Administration or European Food Safety Authority and no such claims had been approved by those two agencies.

Table 2. Uses of probiotics in an aquaculture system (adapted from Cruz et al.)

Uses of probiotic

Probiotic species

Gram positive/negative bacteria

Target aquatic species

Water quality

Bacillus sp.
Vibrio sp. NE 17
Lactobacillus acidophilus


Penaeus monodon
Macrobrachium rosenbergii

Clarias gariepinus

Control of diseases

Enterococcus faecium SF 68
Pseudomonas fluorescens
Lactococcus lactis

Pseudomonas sp.
Bacillus sp.
Vibrio alginolyticus


Anguilla anguilla
Oncorhynchus mykiss
Epinephelus coioides

Oncorhynchus mykiss

Growth promoter

Lactobacillus lactis AR 2l
Bacillus sp.
Streptococcus thermophiles
Bacillus coagulans
Bacillus NL 110


Brachionus plicatilis
Scophthalmus maximus
Cyprinus carpio koi
M. rosenbergii


Lactobacillus acidophilus
Vibrio NE 17
Lactobacillus helveticus


Clarias gariepinus
M. rosenbergii

Scophthalmus maximus

Improvement of immune response

Clostridium butyricum
L. casei
L. acidophilus


Rainbow Trout
Poeciliopsis gracilis
Paralichthys olivaceus

Table 3. Application of synbiotic (pre/probiotic) combinations in different aquatic organisms (adapted from Cerezeula et al.)

Synbiotic (probiotic/prebiotic)

Aquatic organisms

Enterococcus faecalis/MOS. PHB

Oncorhynchus mykiss

Bacillus clausii/MOS. FOS

Paralichthys olivaceus

Bacillus subtilis/Chitosan

Rachycentron canadum

Bacillus subtilis/FOS



Immunomodulators are a diverse array of recombinant, synthetic, and natural preparations. Essentially, any compound that can modulate the immune system responses in a way significant enough to be used for immunotherapy, is considered to be an immunomodulator. However, dietary application of immunomodulators is rather restrictive in that only a small subset of possible treatments (varying from cytokines to corticosteroids) has been subjected to scrutiny of scientific investigation. One major subgroup of natural immunomodulating substances are structural polysaccharide elements of the plant and yeast cell walls, namely glucan molecules. Stimulatory effects of yeast cell wall components on neutrophils, as well as other components of the immune system, have long been recognized, and potent activation of neutrophil function, including an increase in phagocytosis and killing has been described in vitro. Differences in technology used to extract β-glucans can lead to marked differences in the immunostimulatory activity. New technologies for extraction enable inexpensive, high volume production of one of the most active β-glucans, originating from baker’s yeast cell wall. Several companies are now producing readily accessible and reasonably priced yeast products that can be used as food additives and Diamond V is one of them. The stimulatory effect of dietary β-glucan from yeast on neutrophil function, and increased disease resistance against several bacteria has been recently demonstrated in different fish and crustacean species. The emerging issue related to use of β-glucan from yeast as a food additive is the determination of the duration and dose necessary to provide the best protection.


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2.  Carnevali O, Maradonna F, Gioacchini G. Integrated control of fish metabolism wellbeing and reproduction: The role of probiotic. In: Aquaculture. Volume 472. Elsivier; 2017:144–155.

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4.  Cruz PM, Ibáñez AL, Hermosillo OAM, Saad HCR. Use of probiotic in aquaculture. ISRN Microbiol. 2012;1–13. doi:10.5402/2012/916845.

5.  Song SK, Beck BR, Kim D, Park J, Kim J, Kim HD, et al. Prebiotics as immunostimulants in aquaculture: A review. Fish Shellfish Immunol. 2014;40:40–48.


Speaker Information
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Dusan Palic
Fish Diseases and Fisheries Biology
Faculty of Veterinary Medicine
Munchen, Germany

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