Probiotics as Means of Diseases Control in Aquaculture, a Review of Current Knowledge and Future Perspectives

Along with the intensification of culture systems to meet the increasing global demands, there was an elevated risk for diseases outbreak and substantial loss for farmers. In view of several drawbacks caused by prophylactic administration of antibiotics, strict regulations have been established to ban or minimize their application in aquaculture. As an alternative to antibiotics, dietary administration of feed additives has received increasing attention during the past three decades. Probiotics, prebiotics, synbiotics and medicinal plants were among the most promising feed supplements for control or treatments of bacterial, viral and parasitic diseases of fish and shellfish. The present review summarizes and discusses the topic of potential application of probiotics as a means of disease control with comprehensive look at the available literature. The possible mode of action of probiotics (Strengthening immune response, competition for binding sites, production of antibacterial substances, and competition for nutrients) in providing protection against diseases is described. Besides, we have classified different pathogens and separately described the effects of probiotics as protective strategy. Furthermore, we have addressed the gaps of existing knowledge as well as the topics that merit further investigations. Overall, the present review paper revealed potential of different probiont to be used as protective agent against various pathogens.

Along with the intensification of culture systems to meet the increasing global demands, there was an elevated risk for diseases outbreak and substantial loss for farmers. In view of several drawbacks caused by prophylactic administration of antibiotics, strict regulations have been established to ban or minimize their application in aquaculture. As an alternative to antibiotics, dietary administration of feed additives has received increasing attention during the past three decades. Probiotics, prebiotics, synbiotics and medicinal plants were among the most promising feed supplements for control or treatments of bacterial, viral and parasitic diseases of fish and shellfish. The present review summarizes and discusses the topic of potential application of probiotics as a means of disease control with comprehensive look at the available literature. The possible mode of action of probiotics (Strengthening immune response, competition for binding sites, production of antibacterial substances, and competition for nutrients) in providing protection against diseases is described. Besides, we have classified different pathogens and separately described the effects of probiotics as protective strategy. Furthermore, we have addressed the gaps of existing knowledge as well as the topics that merit further investigations. Overall, the present review paper revealed potential of different probiont to be used as protective agent against various pathogens.

Probiotics: Definition and History
Nowadays, several types of beneficial feed additive such as probiotics, prebiotics, and synbiotics are being used in aquaculture to improve growth performance, immune responses and disease resistance as well as an alternative to antibiotics (Irianto and Austin, 2002;Hoseinifar et al., 2016Hoseinifar et al., , 2017bSayes et al., 2018). The term "probiotics" arose from the Greek words "pro" and "bios" meaning "for life"; generally referred to microbial feed additives which confer host organism through modulation of intestinal microbiota. Parker (1974) was the first who defined probiotics as organisms and substances that affect microbial in intestine. According to the Food and Agriculture Organization (FAO) and the World Health Organization (WHO), probiotics are live microorganisms which are used orally having some tangible health benefits to the host (Hotel and Córdoba, 2001). Considering the difference between environment in aquatic ecosystem and those terrestrial animals, a modified definition proposed for probiotics in aquaculture by Merrifield et al. (2010b) as, "a probiotic organism can be regarded as a live, dead or component of a microbial cell, which is administered via the feed or to the rearing water, benefiting the host by improving disease resistance, health status, growth performance, feed utilization, stress response or general vigor, which is achieved at least in part via improving the hosts microbial balance or the microbial balance of the ambient environment." The probiotics include different kinds of bacteria, bacteriophages, microalgae and yeast which have been widely used in aquaculture via water routine or feed supplement (Llewellyn et al., 2014) Currently, there are lots of commercially available probiotics in for of mono or multi-strains (Van Doan et al., 2017).

Modulation of Immune Parameters
The first defense line against infections is innate immune responses (or non-specific immune responses) which include different cells and mechanisms that protect host organism from infectious diseases. It has been reported that probiotics can affect the elements of non-specific immune system such as mono-nuclear phagocytes (monocytes, macrophages) and polymorphonuclear leukocytes (neutrophils), natural killer (NK) cells etc. Previous studies revealed increment of leucocytes (Korkea-aho et al., 2012), monocytes (Aly et al., 2008b), erythrocytes, granulocytes, macrophage, and lymphocytes in various fishes following treatment with probiotics (Kim and Austin, 2006a,b;Nayak et al., 2007;Kumar et al., 2008). For instance, rainbow trout fed Clostridium butyricum showed increased resistance against vibriosis through affecting phagocytic activity of leukocytes (Sakai et al., 1995). Furthermore, dietary Bacillus sp. S11 positively affected cellular and humoral immunity in tiger shrimp (Penaeus monodon) which resulted in protection against disease (Rengpipat et al., 2000). Also, combined administration of Bacillus and Vibrio sp. in young white shrimp showed beneficial effects on growth performance, survival as well as resistance against V. harveyi and white spot syndrome virus (Antony et al., 2011). The authors attributed the protection to elevation of phagocytosis and antibacterial activity; indeed immunomodulation. Beside these results on shrimps, dietary Lactobacillus rhamnosus (ATCC 53103) (10 5 CFU g −1 ) increased the respiratory burst in rainbow trout (Oncorhynchus mykiss) (Nikoskelainen et al., 2003). Therefore, probiotics are beneficial bacteria which not only capable of inhibiting pathogens, but also regulating the host immune system.Probiotics possess conserved microbe-associated molecular patterns (MAMPs), including peptidoglycan (PGN), lipoteichoic acids (LTA), S-layer protein A (SlpA), exopolysaccharides (EPS), flagellin and microbial nucleic acids which can be recognized by certain pattern recognition receptors (PRRs), and induces a signaling cascade that can result in the production of cytokines, chemokines, and other effector molecules thus activating the immune response in the host (Bron et al., 2012;Remus et al., 2012). During past years, there was increasing interests toward determination of mode of action of probiotics on intestinal immune system. In this regard, the researchers evaluated the possible relationship between TLR signaling-mediated recognition of probiotics and activation of the intestinal immunity. For example, it has been reported that TLR2 signaling pathway was involved in recognition of probiotic Psychrobacter sp. SE6 and inducing subsequently immune responses in grouper Epinephelus coioides .

Competition for Binding Sites
Competitive exclusion has been suggested as a mode of action of probiotic in prevention of pathogens (Mahdhi et al., 2012;Sorroza et al., 2012); achieved by colonization of probiotics in GI mucosal epithelium (Macey and Coyne, 2006;Merrifield et al., 2010a;Lazado et al., 2011;Korkeaaho et al., 2012). Different types of surface determinants suggested to be involved in probiotis interaction with intestinal epithelial cells and mucus which per se prevents pathogens colonization (so called competitive exclusion). The primary reason for this could be competitions for adhesion receptors (Montes and Pugh, 1993) which can antagonize pathogens (Luis-Villaseñor et al., 2011) and reduce their colonization (Chabrillón et al., 2005). This clearly shows the potential of probiotics administration as a substitute for antibiotics and other chemicals (Cheng et al., 2014). It has been reported that passive forces, electrostatic interactions, hydrophobic, steric forces, lipoteichoic acids were among the factors which affect adhesion of probiotics to attachment sites (Wilson et al., 2011). Westerdahl et al. (1991) stated that competition for attachment sites and nutrients following occupying mucosal surfaces could be possible mode of action for protective effects of probiotic against pathogens.

Production of Antibacterial Substances
In aquaculture, probiotics are used as an alternative to antibiotics and chemicals (Decamp et al., 2008;Van Hai et al., 2009;Heo et al., 2013). Though the mode of action through which probiotics exert antibacterial effects remained to be determined, many studies indicated that probiotics produced antibiotic compounds (Moriarty, 1998). Besides, reduce in pH following production of organic acids can inhibits growth of pathogenic bacteria . For example, Ramesh et al. (2015) reported antibacterial activity of Bacillus licheniformis and B. pumilus; which resist low pH and high bile concentrations. Another study with Bacillus licheniformis CPQB, revealed inhibition of Vibrio alginolyticus in whiteleg prawns (Ferreira et al., 2015). It has been demonstrated that Lactobacillus spp. (common probiotics) produce short chain fatty acids, diacetyl, hydro peroxide, and bactericidal proteins (Rengpipat et al., 1998;Verschuere et al., 2000;Faramarzi et al., 2011), which pre se improve immune responses as well as disease resistance (Raa, 1996;Gram et al., 1999). Consequently, probiotics can protect aquatic animals from challenge with pathogens by producing antibiotic compounds.

Competition for Nutrients
The competition of nutrients has been considered among the mechanisms through which probiotics inhibit pathogens . Previous study has reported that competition for iron is an essential element in marine bacteria (Verschuere et al., 2000). The majority of bacteria need Iron for their growth. However, there is limited available of iron in the tissues and body fluids of animals (Verschuere et al., 2000). The siderophores which are iron-binding agents, help bacteria to obtain the necessary amount of Iron for their growth. There is direct relation between production of siderophore and virulence of some pathogens (Gram et al., 1999).
The beneficial effects of Gram-positive genus Bacillus on water quality in culture environment has been reported in previous studies (Rafiee and Saad, 2005;El-Haroun et al., 2006;Hai, 2015;Dawood and Koshio, 2016). It seems that genus Bacillus is more effectual for converting organic matter to CO 2 as well as balancing phytoplankton production (Balcázar et al., 2006). It has been reported that supplemented F. vannamei feed with Bacillus sp., Saccharomyces cerevisiae, Nitrosomonas sp., and Nitrobacter sp. (a commercial product) could decrease the concent rations of inorganic nitrogen and phosphate from 3.74 to 1.79 mg/L and 0.1105 to 0.0364 mg/L, respectively (Li et al., 2006).

Lactic Acid Bacteria
Lactic acid bacteria (LAB) Gram positive, usually non-motile and non-sporing bacteria which mainly produce lactic acid during fermentation (Stanier et al., 1975). They were among the mostly studied probiotics . The extensive available literature revealed beneficial effects of LABs as probiotic on growth performance, immune responses and disease resistance shellfish (Ringø et al., 2010;. Another important feature of these probiont strains is disease protection which has been reviewed in this section.

Carnobacteria
Carnobacteria have been frequently isolated from fish intestine . It has shown antagonistic activity against different kinds of fish pathogens (Ringø et al., 2010). The C. inhibens K1 isolated from Atlantic salmon (Salmo salar L.) digestive tract inhibited fish pathogens under in vitro condition (Jöborn et al., 1997), and subsequently study showed that dietary administration of 5 × 10 7 cells g −1 C. inhibens K1 for 14 days reduced mortalities caused by A. salmonicida, Vibrio ordalii and Yersinia ruckeri in Atlantic salmon and rainbow trout (Robertson et al., 2000). The C. divergens strain 6251, isolated from Artic charr (Salvelinus alpinus L.) foregut, showed growth-inhibitory effects against both Aeromonas salmonicida and Vibrio anguillarum in vitro (Ringø et al., 2002;Ringø, 2008). Also, dietary administration of C. divergens for 3 weeks reduced vibriosis caused by V. anguillarum in Atlantic cod (G. morhua) fry (Gildberg et al., 1997). Kim and Austin (2006a) characterized two Carnobacteria isolates obtained from rainbow trout intestine (C. maltaromaticum B26 and C. divergens B33). Both strains stimulated non-specific immunity and demonstrated effectiveness against A. salmonicida and Y. ruckeri in vitro. Løvmo Martinsen et al. (2011) reported that C. maltaromaticum which was previously isolated from Atlantic cod hindgut chamber could, to a certain extent, outcompete V. anguillarum in an unidentified mechanism.
Lactococcus Balcázar et al. (2007) isolated Lc. lactis subsp. lactis (CLFP 100) and Lc. lactis subsp. cremoris (CLFP 102) from rainbow trout intestine. Subsequently, in a separate study, they administered Lc. Lactis in rainbow trout diet and observed increased immune parameters as well as protection against furunculosis (Balcázar et al., 2007). The same results observed with brown trout (Salmo trutta) challenged with Aeromonas salmonicida (Balcázar et al., 2009). Kim et al. (2013) reported that Lc. lactis BFE920 inhibits the growth of different pathogens including Streptococcus iniae, S. parauberis, Enterococcus viikkiensis as well as Lactococcus garviae under in vitro condition. The same authors supplemented olive flounder (Paralichthys olivaceus) diet with Lc. lactis BFE920 and after 2 weeks feeding observed activated the innate immune system which resulted in protection against S. iniae infection in both in experimental condition and large scale field condition. In accordance, Heo et al. (2013) reported that dietary Lc. lactis (10 8 CFU g −1 ) elevated serum immune parameters (e.g., lysozyme, antiprotease, serum peroxidase, and blood respiratory burst activities) as well as resistance against S. iniae in olive flounder. Recently, Beck et al. (2015), in an study with olive flounder, observed that dietary administration of mixed probiotic Lb. plantarum FGL0001 and Lc. lactis BFE920, or single Lc. lactis BFE920 for 30 days could improve the survival rates after challenged with S. iniae. An overview of different Lactococcus spp. revealed that the main focus was on Lc. Lactis and this species was capable of protecting different fish species against bacterial pathogens.
Leuconostoc Balcázar et al. (2007) reported that Lc. mesenteroides isolated from rainbow trout intestine inhibited the growth of various pathogens. The same research group supplemented rainbow trout and brown trout diets with Lc. mesenteroides (10 6 CFU g −1 ) and observed immunomodulation and increased resistance against furunculosis (Balcázar et al., 2007) and A. salmonicida infection (Balcázar et al., 2009). Dietary application of Lc. mesenteroides CLFP 196 to rainbow trout at 10 7 CFU g −1 of feed for 30 days dramatically reduced the mortalities following challenge with L. garvieae (Vendrell et al., 2008). However, Lc. mesenteroides subsp. Mesenteroides, obtained from rainbow trout intestine, failed to improve rainbow trout disease resistance to lactococcosis (Pérez-Sánchez et al., 2011). Although, there are limiting studies over Leuconostoc spp. potential to protect fish against diseases, but available results revealed beneficial effects of Luc. mesenteroides.

Pediococcus
Huang et al. (2014) isolated P. pentosaceus strain 4012 from cobia intestine and observed antagonistic effects on V. anguillarum under in vitro condition. Subsequently, dietary administration of P. pentosaceus 4012 significantly decreased the cumulative mortality of groupers after V. anguillarum infection . Dietary supplement with probiotic P. acidilactici increased resistance of rainbow trout fry against vertebral column compression syndrome (VCCS) . Also, combined administration of galactooligosaccharides and P. acidilactici for 8 weeks improved the immune parameters and resistance against S. iniae in rainbow trout fingerlings. An overview of literature revealed increasing attentions toward administration of P. acidilactici as probiotic in aquaculture, recently. It seems that this species is capable to be considered as disease protection agent in aquaculture.

Enterococcus
Chang and Liu (2002) administered a commercial product containing E. faecium SF 68 in European eel, Anguilla anguilla diet and observed lower edwardsiellosis in fish exposed to Edwardsiella tarda. E. gallinarum showed a strong inhibitory effect against V. anguillarum in vitro, and under in vivo condition protected sea bass against V. anguillarum infection (Sorroza et al., 2013). Recently, Safari et al. (2016) evaluated the benefits of dietary administration of host-derived candidate probiotics E. casseliflavus in juvenile rainbow trout, and results showed that E. casseliflavus could improve growth performance and enhance disease resistance when challenged with S. iniae.
Vagococcus Sorroza et al. (2012) supplemented sea bass diet with Vagococcus fluvialis (10 9 cfu g −1 ) for 20 days and observed that probiotic fed fish had higher relative percent of survival (42.3%) than control group following challenge with V. anguillarum. This study showed the potential of Vagococcus spp. and highlighted the needs to additional research in future.
Bacillus sp. as feed additives improves growth performance and immune response and disease resistance in fish has been extensively reviewed (Mingmongkolchai and Panbangred, 2018). Dietary administration of B. subtilis and B. licheniformis (BioPlus2B) improved trout resistance to infection with Y. ruckeri (Raida et al., 2003). Also, feeding Indian major carp, Labeo rohita with B. subtilis at 1.5 × 10 7 CFU g −1 increased resistance against A. hydrophila infection (Kumar et al., 2006). Newaj-Fyzul et al. (2007) administered different forms (viable, formalized or sonicated cells or cell-free supernatant) of B. subtilis AB1 in rainbow trout diet and observed higher resistance against Aeromonas (Newaj-Fyzul et al., 2007). Furthermore, B. subtilis (8 × 10 7 CFU g −1 ) reduced mortalities Ictalurus punctatus and striped catfish, Pangasianodon hypophthalmus following challenge with Edwardsiella ictaluri (Ran et al., 2012). Liu et al. (2012) proved that dietary B. subtilis (10 4 , 10 6 , and 10 8 CFU g −1 ) for 14 and 28 days was able to enhance the relative survival percentages of grouper, Epinephelus coioides challenged with Streptococcus sp. A diet supplemented with 0.1 or 0.3% B. subtilis enhanced prophylactic property of red hybrid tilapia, Oreochromis sp. against pathogenic Streptococcus agalactiae (Ng et al., 2014). Aly et al. (2008b) reported that feeding tilapia with 10 6 and 10 12 cells g −1 B. pumilus enhanced immune and health status and improve resistance against A. hydrophila. B. pumilus has also reported to dramatically improved survival of "Loco" Concholepas concholepas larvae (Leyton et al., 2012). Similarly, Sun et al. (2009) reported that B. pumilus SE5 and B. clausii DE5 obtained from orange-spotted grouper Epinephelus coioides, inhibited growth of pathogenic Staphylococcus aureus, V. harveyi and V. parahaemolyticus under in vitro condition. Also, feeding grouper E. coioides larvae with copepod (P. annandalei) enriched B. clausii DE5 and B. pumilus noticably larval survival (Sun et al., 2013). Bandyopadhyay and Das Mohapatra (2009) isolated Bacillus circulans PB7 from Catla catla intestine, and subsequently added to Catla catla fingerlings diet at rate of 2 × 10 4 , 2 × 10 5 , or 2 × 10 6 cells per 100 g. After 60 days feeding elevated immune parameters as well as resistance against A. hydrophila infection. Likewise, feeding Olive flounder (Paralichthys olivaceus) with (B. subtilis, B. pumilus, and B. licheniformis) at rate of 10 10 CFU g −1 elevated resistance against S. iniae (Cha et al., 2013). Han et al. (2015) stated that feeding with commercial B. licheniformis improved the disease resistance against Streptococcus iniae infection in tilapia. Similarly, Nile tilapia fed with 1 × 10 6 and 1 × 10 4 CFU g −1 of B. amyloliquefaciens for 30 days showed higher resistance against pathogenic Yersinia ruckeri or Clostridium perfringens type D (Selim and Reda, 2015). Interestingly, intraperitoneally administration of cellular components (cell wall proteins and whole cell proteins) of Bacillus licheniformis and B. pumilus have been reported to improve immune parameters which per se protected rohu Labeo rohita (Hamilton) against A. hydrophila infection (Ramesh et al., 2015). The overview of literature regarding Bacillus spp. as probiotic aimed at elevation of disease resistance revealed more information on B. subtilis. The extensive research on this species revealed high potential for immunomodulation and disease protection. Indeed, B. subtilis can be considered as beneficial agent for disease bio-control.

Other Gram-Positive Bacteria
Clostridium butyricum Sakai et al. (1995) demonstrated that dietary C. butyricum increased rainbow trout protection vibriosis. Pan et al. (2008a) stated that C. butyricum CB2 showed strong antagonistic activity to pathogenic A. hydrophila and V. anguillarum. Subsequently, oral administration of live or dead C. butyricum CB2 at dose of 10 8 CFU g −1 feed enhanced the phagocytic activity of leucocytes and resistance to vibriosis in Chinese drum, Miichthys miiuy (Basilewsky) (Pan et al., 2008b).

Micrococcus
Dietary application of probiotic Micrococcus luteus increased rainbow trout survival after A. salmonicida challenge (Irianto and Austin, 2002). Abd El-Rhman et al. (2009) reported that Nile tilapia fed M. luteus containing diets for 6-days per week for 90 days showed decreased mortality following A. hydrophila challenged.

Rhodococcus
It has reported that the cellular components (cell wall proteins and whole cell proteins) of Rhodococcus SM2 increased rainbow trout protection against V. anguillarum (Sharifuzzaman et al., 2011).

Gram-Negative Bacteria
Pseudomonas Rainbow trout exposed to P. fluorescens AH2 at rate of 10 5 CFU/ml for 5 days showed lower mortality after V. anguillarum challenge (Gram et al., 1999), while the probiotic did not confer protection of salmon against furunculosis (Gram et al., 2001). P. chlororaphis strain JF3835, obtained from perch (Perca fluviatilis L.) intestine, has ability to control Aeromonas sobria infection in perch (Gobeli et al., 2009). Pseudomonas M162 showed in vitro inhibition to Flavobacterium psychrophilum, and dietary application of M162 increased rainbow trout resistance against F. psychrophilum infection (Korkea-aho et al., 2012). The same research group evaluated protection caused by various strains of Pseudomonas M174 in rainbow trout and observed highest protection against F. psychrophilum caused by M174 strain (Korkea-aho et al., 2011). Giri et al. (2012) fed Labeo rohita with 10 7 and 10 9 CFU g −1 P. aeruginosa VSG-2 and evaluated fish resistance against A. hydrophila. The results revealed that probiotic fed fish had significantly higher resistance against A. hydrophila infection (Giri et al., 2012). Similarly, oral administration of P. aeruginosa PsDAHP1 inhibited biofilm formation and increased defense mechanisms which per se elevated zebrafish protection from V. parahaemolyticus DAHV2 infection (Vinoj et al., 2015).

Vibrio
Vibrio alginolyticus showed in vitro inhibition to V. ordalii, V. anguillarum, A. salmonicida and Y. ruckeri, and in vivo protection to Atlantic salmon challenged with A. salmonicida (Austin et al., 1995). Dietary administration of V. fluvialis resulted in higher survival in rainbow trout challenged with A. salmonicida (Irianto and Austin, 2002).
Flavobacterium Chi et al. (2014) supplemented carp diet with Flavobacterium sasangense BA-3 (1 × 10 8 cell g −1 ) isolated from the common carp intestine for 28 days. They observed enhanced immune parameters as well as resistance against A. hydrophila infection.

Yeast
The potential of yeast as probiotic to improve disease resistance has been demonstrated in several studies. Abdel-Tawwab et al. (2008) reported that diets supplemented with baker's yeast S. cerevisiae at dose of 0.25, 0.50, 1.0, 2.0, or 5.0 g yeast/kg reduced mortality in tilapia after intraperitoneal injection pathogenic A. hydrophila. Subsequently, the same group observed that Baker's yeast improves the resistance against the water-borne Cu toxicity in Galilee tilapia Sarotherodon galilaeus (L.) (Abdel-Tawwab et al., 2010). Quentel et al. (2005) reported that singular or combined administration of P. acidilactici and S. cerevisiae var. boulardii improved rainbow trout resistance against Y. ruckeri. Reyes-Becerril et al. (2011) supplemented Leopard grouper (Mycteroperca rosacea) diet with Debaryomyces hansenii CBS 8339 (10 6 CFU g −1 ) for 5 weeks. At the end of feeding trial, probiotic fed fish ad noticeably higher immunoglobulin M (IgM) level, catalase (CAT) and superoxide dismutase (SOD) activities following A. hydrophila AH-315 challenge. Generally, the majority of studies performed on yeasts revealed beneficial effects on immune system (Hai, 2015). Hence, it seems that they can be considered as beneficial means of disease control and control. (TABLE 2) Gram-Positive Bacteria Lactic Acid Bacteria Ajitha et al. (2004) supplemented Indian white shrimp (Penaeus indicus) diet with as single dose (5 × 10 6 CFU g −1 ) of different probiotics including Lb. acidophilus, S. cremoris, Lb. bulgaricus 56 or L. bulgaricus57 at doses of for 4 weeks and at the end of feeding trial shrimp exposed to experimental Vibrio alginolyticus infection. The results revealed substantially higher resistance (56-72%) compared control group (20%) (Ajitha et al., 2004). Also, dietary supplemented with 10 10 CFU kg −1 of Lb. plantarum upregulated proPO and PE genes, enhanced PO and SOD activities as well as resistance against V. alginolyticus in white shrimp (Chiu et al., 2007). Similarly, Vieira et al. (2010) reported that diet supplemented with probiotic Lb. plantarum modulated intestinal microbiota as well as resistance against V. harveyi. In addition, a Lactobacillus sp. has been reported to improve survival by 72% and performance of pearl oyster, P. mazatlanica (Aguilar-Macias et al., 2010). Furthermore, in a study with juvenile tiger shrimp (Penaeus monodon) Lb. acidophilus 04 (10 5 CFU g −1 ) was administered for 1 month and increased resistance (80% survival) was observed following exposure with pathogenic V. alginolyticus (Sivakumar et al., 2012). Interestingly, Dash et al. (2015) administered heat-killed form of Lb. plantarum at rate of 10 8 CFU g −1 in M. rosenbergii diet for 90 days. While no significant effects were observed on growth performance, feeding on probiotic supplemented diet noticeably enhanced immune responses and disease resistance. Swain et al. (2009) reported that feeding with E. faecium MC13 and Lactococcus garvieae B49 protected post larval shrimp, P. monodon, against challenge with V. harveyi and V. parahaemolyticus. Similarly, feeding blue shrimp (Litopenaeus stylirostris) with probiotic P. acidilactici enhanced protection against V. nigripulchritudo SFn1; the mortality in probiotic and control group were 25 and 41.7%, respectively (Castex et al., 2010). Dietary administration of Lb. pentosus HC-2 and E. faecium NRW-2 noticeably enhanced resistance against pathogenic V. parahaemolyticus ATCC 17802 in L. vannamei (Sha et al., 2016).

Bacillus
To study protective effects of Bacillus subtilis BT23, Vaseeharan and Ramasamy (2003) treated black tiger shrimp with 10 6 -10 8 CFU ml −1 probiotic for 6 days and then challenged with V. harveyi. The results revealed significantly lower mortality in treated groups (Vaseeharan and Ramasamy, 2003). Similarly, Balcázar et al. (2007) fed L. vannamei juvenile with B. subtilis for 28 days and then exposed to pathogenic V. harveyi for 24 h. The results revealed substantially lower mortality in treated group (18.25%) compared to those in control (51.75%) in the control group (Balcázar et al., 2007). Also, Zokaeifar et al. (2012) tested combined administration of two probiotic strains (B. subtilis L10 and G1) in juvenile white shrimp. Shrimps were fed with two levels of 10 5 and 10 8 CFU g −1 of selected probiotics for 8 weeks. At the end of feeding trial elevated growth performance, digestive enzyme activity, upregulated immune related genes as well as resistance against V. harveyi were observed (Zokaeifar et al., 2012). Liu et al. (2014) reported that dietary administration of B. subtilis strain S12 (isolated from L. vannamei digestive tract), beside in vitro antagonistic activity against aquatic animal pathogens, improved resistance against V. harveyi infection . Rengpipat et al. (1998) reported that supplementation of black tiger shrimp with different forms (i.e., of fresh cells, fresh cells in normal saline solution and a lyophilized form) of Bacillus S11 for 100 days resulted in significantly higher growth performance and survival. Also, the authorsperformed experimental challenge V. harveyi at the end of feeding trial and surprisingly observed no mortality in probiotic fed shrimps, while survival rate was just 26% in control group (Rengpipat et al., 1998). Subsequently, the same research group studied possible effects of Bacillus S11 and concluded limited improvement in resistance against V. harveyi (Rengpipat et al., 2003). In another routes of administration, Luis-Villaseñor  Scholz et al., 1999Scholz et al., et al. (2011 isolated four Bacillus strains from white shrimp digestive tract and added to white shrimp culture water at rate of 1 × 10 5 CFU mL −1 daily. Thereafter, the authors observed elevated overall survival of L. vannamei larvae (Luis-Villaseñor et al., 2011). In another study with post larvae, Ravi et al. (2007) claimed elevated resistance against V. harveyi following treatment of post larvae with Paenibacillus sp. EF012164 and Bacillus cereus DQ915582 (Ravi et al., 2007).
The same results were also reported in case of Bacillus sp. P11 which resulted in substantially higher survival in comparison with control group (0%) following experimental challenge with V. harveyi (Utiswannakul et al., 2011). The literature review denote that, perhaps, the most studied and effective probiont in shrimp culture is B. subtilis. This species showed positive effects on shrimp resistance to various pathogens. Hence, can be considered as a means of disease control and control in shrimp aquaculture.
Other Gram-Positive Bacteria Swain et al. (2009) demonstrated that feeding P. monodon post larvae with Streptococcus phocae P180 significantly improved growth performance as well as protection against V. harveyi. However, the probiotic failed to protect the animals against V. parahaemolyticus (Swain et al., 2009). The probiotic Arthrobacter XE-7 was administered orally at four different doses of 0, 10 6 , 10 8 , and 10 10 CFU g −1 feed for 63 days in Pacific white shrimp, L. vannamei. Li et al. (2008) supplemented shrimp diet with Arthrobacter XE-7 and observed beneficial effects on intestinal microbiota, immune response as well as resistance against V. parahaemolyticus (Li et al., 2008).

Gram-Negative Bacteria
Vibrio Thompson et al. (2010) demonstrate in vitro growth inhibition of shrimp pathogens by probiotic V. gazogenes NCIMB 2250. Also, the same author revealed that feeding white shrimp with dietary V. gazogenes NCIMB 2250 elevated performance and health status as well as decreased of Vibrio sp. count in intestinal microbiota (Thompson et al., 2010

Streptomyces
In 2016, Tan et al. (2016) have reviewed the use of the genus Streptomyces bacteria as a probiotic in controlling diseases and improving the health and quality of aquaculture production. Das et al. (2010) used Marine Streptomyces strains (CLS-28, CLS-39) in Artemia culture and concluded that this probiotic significantly increased resistance of Artemia nauplii and adult against V. harveyi and V. proteolyticus (Das et al., 2010). Thereafter, they supplemented black tiger shrimp post larvae diet with 1% Streptomyces for 15 days. The results revealed improved resistance against V. harveyi and growth performance in probiotic fed shrimps (Das et al., 2010).

Pseudomonas
Van Hai et al. (2009) supplemented western king prawns (Penaeus latisulcatus) diet with a single dose (20 × 10 5 CFU kg −1 ) of P. aeruginosa and P. synxantha for 84 days and reported higher survival rate in P.aeruginosa fed group. Also, combined administration of those probiotic was more effective than singular. Pai et al. (2010) ). Also, the same research group highlighted the potential of this probiotic to protect scallop and flat oyster from larvae against V. coralliilyticus, V. splendidus and V. pectenicida (Kesarcodi-Watson et al., 2010.

Pseudoalteromonas
Kesarcodi -Watson et al. (2012) reported that Pseudoalteromonas D41 as probiotic increased resistance of scallop larvae and Pacific oysters against V. splendidus and V. coralliilyticus, respectively.

Yeast
To the best of our knowledge there is limited information regarding application of yeasts as probiotic in shellfish aquaculture. In an early study Scholz et al. (1999) supplemented white shrimp with 1% Phaffia rhodozyma and S. cerevisiae and reported elevation of protection against vibriosis. Furthermore, feeding pearl oyster, P. mazatlanica with marine yeast (Yarrowia lipolytica) enriched microalgae resulted in enhanced growth and survival (Aguilar-Macias et al., 2010).

PROBIOTICS AND VIRAL DISEASES IN FISH
The occurrence of viral diseases causes mass mortality in aquaculture practice and considering still there is limited effective vaccine this could a bottleneck for aquaculture industry which resulted in substantial economic loss. In this regard, the potential of probiotics to be used as a means of controlling viral disease has been shown in few studies. For instance, Balcázar et al. (2007) in an in vitro study demonstrated antiviral activity of probiotic strains (including Vibrios spp., Pseudomonas spp., Aeromonas spp.) against infectious hematopoietic necrosis virus (IHNV). Likewise, Maeda et al. (1997) reported that Pseudoalteromonas undina, VKM-124 improved larval survival by giving the larvae a protection against Sima-aji Neuro Necrosis Virus (SJNNV) when added to Yellow Jack (Carangoides bartholomaei) larval tanks. Harikrishnan et al. (2010) studied antiviral activity of dietary two commercial probiotics (Lactobacil and/or Sporolac) in Olive flounder. The results revealed that both probiotics increased fish resistance against lymphocystis disease virus (LCDV) infection . The possible control of iridovirus in grouper (Epinephelus coioides) through dietary administration of probiotics (Lb. plantarum) was studied by Son et al. (2009). The results revealed higher survival in probiotic fed fish compared control group. In another study Liu et al. (2012) tested possible protection of grouper against iridovirus using dietary B. subtilis E20 and observed 50% higher survival than those in nonprobiotic group. Likewise, dietary S. cerevisiae at rate of 5.3 × 10 7 CFU kg −1 protected grouper against iridovirus (GIV) infection (Chiu et al., 2010). Indeed, while fish fed control diet had 16.7% survival, probiotic fed fish survival was 43.3%. Although there are extensive literature regarding immunomodulatory effects of probiotics, they are not enough to speculate potential antiviral effects of probiotics. Therefore, more studies should be conducted to illustrate the effect of probiotics on the viral diseases of fish and possible mechanisms.

PROBIOTICS AND VIRAL DISEASES IN SHELLFISH
Unlike fish, shrimp aquaculture suffers from substantial economical loses due to occurrence and spread of different viral diseases like white spot syndrome virus (WSSV), lymphocystis disease virus (LCDV), infectious hypodermal and hematopoietic necrosis virus (IHHNV) etc. Treatment of shrimp culture environment or feed with probiotics has been suggested as efficient means of prevention and controlling viral diseases (Lakshmi et al., 2013). For instance, Vibrio spp. obtained from tiger shrimp hatchery showed strong antagonistic activity against IHNV and Oncorhynchus masou virus (OMV) (Direkbusarakom et al., 1998). The majority of studies practiced dietary administration of probiotics and tested anti-viral effect in different shrimp species. Rodríguez et al. (2007) stated that treatment of L. vannamei with 10 5 CFU mL −1 probiotic V. alginolyticus significantly increased resistance against WSSV compared to non-treated shrimps. Moreover, dietary administration of 10 10 CFU g −1 B. megaterium has resulted in higher survival and increased protection against WSSV . Also, Leyva-Madrigal et al. (2011) reported that feeding white shrimp with either P. pentosaceus or Staphylococcus hemolyticus decrease WSSV infection. On the contrary, dietary supplemented with 10 5 CFU g −1 of a mixture lactic acid bacteria (BAL3, BAL7, BC1, and CIB1) had no significant effects on L. vannamei resistance against WSSV infections (Partida-Arangure et al., 2013). Recently, Chai et al. (2016) isolated Bacillus PC465 from Fenneropenaeus chinensis gut and evaluated its anti-viral effects via dietary administration. The results showed the application of Bacillus PC465 enhances the gut microbial structures, promotes the immune status of shrimp which per se protected against WSSV. Despite the needs for additional research to explain mechanisms, some researchers proposed immunomodulatory nature of probiotics as an important factor in observed protection against WSSV (Merrifield et al., 2010b).

PROBIOTICS AND PARASITIC DISEASES IN FISH AND SHELLFISH
In general, available information about the probiotic control parasite diseases in fish and shellfish was limited. Dietary administration of Aeromonas sobria GC2 BA211 for 14 days at rate of 10 8 and 10 10 cells g −1 , respectively, protected rainbow trout against Ichthyophthirius multifiliis parasite and reduced the mortalities from 98 to 0%. On the other hand, Brochothrix thermosphacta at dose of 10 10 cells g −1 of feed failed to protect rainbow trout against the skin parasite (Pieters et al., 2008). Atira et al. (2012) assessed the inhibition of the growth of the parasitic Saprolegnia parasitica A3 on catfish (Pangasius hypophthalamus) using Lactobacillus plantarum FNCC 226 under in vivo and in vitro conditions. They concluded the potential of L. plantarum for inhibiting S. parasitica and therefore suggested as an environment-friendly means of parasite control in catfish aquaculture.

CONCLUDING REMARKS AND FURTHER PERSPECTIVES
The review of available literature revealed the promising effects of probiotics on disease resistance of fish and shellfish. Therefore, it can be speculated that this environment friendly dietary supplement will receive increasing attention as an alternative for antibiotic in aquaculture. However, this fact should be kept mind that the results of previous researches revealed that the effects of probiotics are species specific. Therefore, optimum probiont, administration dose and dulactobacilli were among the most studied probiotics in shrimps. The studies reviewed here revealed the potential of lactobacilli to help in resolving the issue of diseases in shrimp culture. Given the primary nature of shrimp immune system as well as sensitivity to disease outbreak, development of such effective, environment-friendly means of disease bio-control is of high importance. The results of the mentioned above studies encourage further studies regarding bio-control of parasite in aquaculture using probiotics. However, the exact mode of actions remained to be clarified. Furthermore, despite promising effects obtained regarding probiotics as biocontrol against viral and parasitic disease in aquatic animals, there is very limited research available compared with other immunostimulants. Consequently, extensive research should be performed regarding determination of antiviral nature of known probiotics. The last but not the least, present understanding on modes of action of probiotics effects on immune system is very limited and merit further research, especially the molecular mechanisms of the interactions between the probiotic and host.

AUTHOR CONTRIBUTIONS
SH and ZZ drafted the manuscript. Y-ZS performed the literature collection. AW participated in this review. All authors performed the critical revision of the article and approved the final version for publication.