1. Introduction

Aquaculture has grown rapidly over the past decades, playing a crucial role in global food security by meeting the rising demand for seafood [1]. However, this expansion has also led to significant challenges, particularly in disease management [2, 3]. Disease outbreaks in aquaculture can cause severe economic losses due to stock mortality, increased prevention and treatment costs, and, in extreme cases, the need to cull entire farms. For small-scale fish farmers, such outbreaks can be financially devastating [4, 5]. Beyond economic losses, disease outbreaks can have serious environmental consequences. Farmed fish diseases can spread to wild populations, threatening biodiversity and disrupting aquatic ecosystems [6, 7]. Additionally, managing diseases with antibiotics and other chemical treatments can lead to pollution and contribute to the growing problem of antimicrobial resistance (AMR) [8, 9]. Effective disease management is essential for ensuring the sustainability of aquaculture and maintaining consumer confidence in farmed seafood products [10, 11]. High stocking densities and recurring disease outbreaks can negatively impact public perception, leading to concerns about product safety and quality [12, 13]. To address these challenges, researchers and industry professionals have explored various solutions, including vaccines, improved farm management strategies, and genetic technologies to develop disease-resistant fish strains. These innovations not only enhance disease control but also improve the overall efficiency and sustainability of aquaculture operations [10, 14]. Among emerging strategies, probiotics have gained attention as a sustainable and effective alternative to conventional disease management methods [15, 16]. Probiotics are beneficial microorganisms that help maintain a balanced microbial environment in aquaculture systems, particularly in the gut of farmed fish and other aquatic organisms [16, 17]. They work by strengthening the immune system, suppressing harmful pathogens, and promoting overall fish health [18–20]. The use of probiotics reduces the dependence on antibiotics, thereby helping to curb AMR and minimize environmental pollution [21, 22]. Unlike chemical treatments, probiotics are biodegradable and do not leave harmful residues in the aquatic environment [15, 23]. As scientific understanding of probiotics continues to expand, their role in disease management in aquaculture is becoming increasingly prominent [24, 25]. This review explores the potential of probiotics in combating diseases caused by pathogens in Nile tilapia. By incorporating probiotics into disease management strategies, tilapia farming can adopt more sustainable and environmentally friendly practices, ultimately enhancing production efficiency, reducing AMR, and ensuring the long-term viability of this crucial aquaculture sector.

2. Review Methodology

A literature review was conducted on major bacterial diseases and antibiotics commonly used in Nile tilapia (Oreochromis niloticus) aquaculture, followed by a systematic review conducted to identify relevant studies on the use of probiotics for disease management in Nile tilapia. The review included original research articles retrieved from widely recognized databases such as Scopus, PubMed, Web of Science, and ScienceDirect, with keywords and search criteria presented in Table S1. The search was restricted to publications from the last 10 years (2015–2024) to ensure the inclusion of recent and relevant studies. The primary criterion for selecting articles in this review was the inclusion of in vivo challenge with bacterial pathogens. Studies that were limited solely to in vitro antimicrobial tests were excluded. To enhance the systematic review process, the online tool Rayyan QCRI (https://rayyan.qcri.org/) was employed for article screening. The review selection and screening process are summarized in Figure 1.

3. Major Bacterial Diseases in Nile Tilapia

Vibriosis is a systemic infection caused by various Vibrio species, including Vibrio vulnificus, Vibrio harveyi, Vibrio parahaemolyticus, and Vibrio alginolyticus. Infected tilapia exhibits dark coloration, external hemorrhages, exophthalmia, and skin ulcers. Internally, lesions include a pale liver with hemorrhagic spots, splenomegaly, and brain edema [7]. The disease spreads horizontally via water, with transmission favored by immersion or ingestion of contaminated material [26]. Streptococcosis, caused by Streptococcus agalactiae [27–29] and Streptococcus iniae [30–33], is a leading bacterial disease in tilapia, resulting in high mortality and economic losses [34, 35]. Outbreaks typically occur in warm water (≥ 27°C), and transmission can be horizontal or vertical [36].

Columnaris disease (Flavobacteriosis), caused by Flavobacterium columnare, recently reclassified as Flavobacterium oreochromis in tilapia, is characterized by gill necrosis, skin erosions, and “saddleback” lesions along the dorsal fin. Infection routes include horizontal transmission through water and possible vertical transmission via broodstock. Genetic selection for resistant tilapia strains offers a long-term solution [7]. Edwardsiellosis in tilapia is primarily caused by Edwardsiella ictaluri and Edwardsiella tarda [37]. E. ictaluri causes enteric septicemia, presenting as white nodules in the spleen and kidney, while E. tarda leads to systemic infections with corneal opacity, anal redness, and visceral granulomas. E. ictaluri is highly virulent, with LD50 values as low as 10² CFU/fish, and spreads horizontally via water. E. tarda is zoonotic, posing risks to humans through contaminated fish [38]. Motile Aeromonas septicemia (MAS), caused by motile Aeromonas species like Aeromonas hydrophila [39–41], Aeromonas veronii [42], and Aeromonas dhakensis, is a common opportunistic infection in tilapia [43, 44]. The symptoms include skin ulcers, hemorrhages, and lethargy [45]. Coinfections with Streptococcus or tilapia lake virus (TILV) increase mortality. Virulence factors include adhesins, toxins, and secretion systems (e.g., T3SS) [46, 47]. Francisellosis, caused by Francisella orientalis, is a systemic granulomatous disease in tilapia, marked by white nodules in the spleen, kidney, and liver [36]. The gram-negative, intracellular bacterium thrives at 23°C–26°C and transmits horizontally or vertically. Tilapia are also susceptible to lesser known bacterial pathogens. Lactococcosis, especially due to Lactococcus garvieae, causes septicemia with exophthalmia and hemorrhages [2]. Aerococcosis caused by Aerococcus viridans is rare but has been reported in Egypt and Indonesia, causing systemic infections. Pseudomoniasis due to Pseudomonas anguilliseptica leads to red spot disease and septicemia, often affecting stressed fish. Epitheliocystis due to Chlamydia species forms gill cysts in fish that impair respiration [7]. Mycobacteriosis caused by Mycobacterium marinum manifests as chronic “fish tuberculosis” with granulomas and is zoonotic, posing risks to handlers [48]. Nocardiosis due to some species of Nocardia causes chronic granulomas and has been linked to uncooked feed [49]. These diseases highlight the need for improved diagnostics, biosecurity, and sustainable therapies.

4. Overview of Antibiotics in Tilapia Aquaculture

Tilapia aquaculture in some countries like Thailand, Brazil, and India has become increasingly dependent on antibiotics to combat bacterial infections caused by pathogens like Streptococcus spp. and Aeromonas spp. [50, 51]. This reliance stems from intensive farming practices in open cage systems, where fish are exposed to fluctuating water quality and high stress levels. Several classes of antibiotics are frequently administered in tilapia aquaculture. Oxytetracycline (OTC) is commonly used against Aeromonas, Edwardsiella, and Streptococcus infections. Florfenicol is effective against Streptococcus spp. infections [52]. Sulfamethoxazole–trimethoprim (SMX-TMP) inhibits bacterial folate synthesis in Aeromonas and Edwardsiella [53]. Enrofloxacin is a fluoroquinolone antibiotic effective against gram-negative bacteria [50]. Used to treat Aeromonas and Streptococcus infections in tilapia, amoxicillin interferes with bacterial cell wall synthesis [54]. Erythromycin is mainly used to combat Streptococcus infections in tilapia aquaculture [54]. Antibiotics in tilapia aquaculture are administered through medicated feed, immersion, or injection, with feed-based application being the most common due to its practicality [8]. However, concerns have been raised regarding the misuse and overuse of antibiotics in aquaculture which pose risks to human health, the environment, ecology, and international trade [9]. The misuse and overuse of antibiotics in tilapia aquaculture contribute to the emergence of AMR, posing a serious threat to both aquaculture and public health [55].

5. Probiotics: A Sustainable Alternative

Probiotics are defined as “live microorganisms with a great capacity to improve host health, promoting a balance of intestinal microbiota” [15]. These beneficial microorganisms are typically introduced through feed additives or water treatments [25]. Their primary applications include enhancing disease resistance, improving growth performance, promoting gut health, and reducing reliance on antibiotics [17]. The selection of specific strains is guided by their ability to colonize the fish gut, produce antimicrobial compounds, modulate immune responses, or improve nutrient absorption [16]. In the context of Nile tilapia aquaculture, probiotics offer a practical and environmentally sustainable tool for disease prevention and performance enhancement under intensive farming conditions.

Fish microbiota is shaped by waterborne microbial exchange, differing from terrestrial hosts due to environmental variability (salinity and temperature) and diverse diets [56, 57]. The fish microbiota plays a crucial role in maintaining host health by supporting digestion, nutrient absorption, immune function, and disease resistance [56]. Probiotics can enhance fish microbiota by promoting microbial balance, inhibiting pathogens, and improving gut integrity [18, 58]. They can be bacteria, fungi, or yeast [59–61]. Supplementing fish diets with probiotics boosts growth performance, reduces infections, and minimizes antibiotic use, making them essential for sustainable aquaculture [43]. Figure 2 shows the diagram illustrating the mechanisms of action of probiotics against pathogens.

Table S2 details relevant information from the selected studies in this review, including microorganisms used as probiotics, method of administration of probiotics, origin of the probiotic strains, and mechanism of action in protecting the host from pathogens. Figure 3 shows the frequencies of major pathogen groups (Figure 3a), probiotic groups (Figure 3b), administration methods (Figure 3c), and mechanisms of action of probiotics (Figure 3d).

The research reveals critical patterns in pathogen prevalence, probiotic utilization, administration methods, and mechanistic actions that collectively support probiotics as a sustainable alternative to antibiotics in aquaculture practices. Pathogen distribution studies identified Streptococcus (48%) and Aeromonas (36%) as the dominant bacterial threats, collectively responsible for 84% of reported infections in farmed Nile tilapia. These findings underscore the need for targeted disease management strategies against these particularly virulent pathogens that frequently cause outbreaks in aquaculture systems.

The probiotic formulations examined in these studies showed a clear preference for specific microbial genera. Bacillus strains were the most frequently reported, accounting for 52% of all probiotic strains across the studies. This high frequency likely reflects their well-documented stability and efficacy in aquatic environments. Bacillus strains enhanced disease resistance in Nile tilapia primarily by stimulating innate and nonspecific immune responses [62–66], including increased phagocytic activity, leukocyte count [33, 63, 67], cytokine production [67, 68], and upregulation of immune-related genes [69, 70]. Additionally, they exert antimicrobial effects through the production of compounds like plantaricin and lipoteichoic acid, competitive exclusion of pathogens, and, in some cases, modulation of inflammation [71]. Lactobacillus species were the second most common, representing 24% of total probiotic occurrences based on the frequency of strain mentions. They act by boosting nonspecific immune responses [72, 73], enhancing immune parameters [74], increasing lysozyme activity, and modulating host immunity. They also inhibit pathogens through the production of antimicrobial compounds such as hydrogen peroxide, organic acids, and bacteriocins, while competing for space and nutrients in the gut [75]. The least used groups were yeast (4%) [30] and Lactococcus (4%) [76]. Other miscellaneous species (16%) include bacteria from groups like Paenibacillus, Pediococcus, and Pseudomonas [77–79]. This distribution reflects the aquaculture industry’s growing confidence in these particular microbial groups as effective probiotic candidates.

Administration methods were remarkably consistent across studies, with feed inclusion being the overwhelmingly preferred delivery mechanism (98%). This near-universal adoption of feed-based administration demonstrates its practical advantages in commercial aquaculture operations, including ease of application, consistent dosing, and direct delivery to the fish gastrointestinal tract where microbial interactions are most critical.

The mechanistic studies revealed a comprehensive profile of how probiotics exert their protective effects. Immune system improvement emerged as the most frequently documented mechanism, appearing in 57% of the reviewed papers. This predominant mode of action highlights probiotics’ ability to enhance the fish’s natural disease resistance through various immunostimulatory pathways. The production of antimicrobial compounds was the second most common mechanism (21%, 14 studies), demonstrating probiotics’ capacity for direct pathogen inhibition through bacteriocins and other antimicrobial substances. Competitive exclusion through nutrient and space competition accounted for 12% of the reported mechanisms (eight studies), illustrating how probiotics can outcompete pathogens for essential resources. A smaller but significant portion of studies (five studies, 7%) did not specify the exact mechanisms involved. Notably, anti-inflammatory action was the least explored mechanism (3%, two studies), suggesting an important area for future research given the potential benefits of inflammation control in disease management. Recent studies have begun to unravel the molecular underpinnings of probiotic action in Nile tilapia, revealing specific host signaling pathways and gene expression changes. For instance, dietary supplementation with Bacillus and Lactobacillus strains has been shown to upregulate key immune-related genes such as TNF-α, INF-γ, IL-1β [17, 59], and lysozyme C, enhancing both innate and adaptive immune responses. Some strains also modulate the NF-κB and MAPK [45] signaling pathways, crucial regulators of inflammation and cellular stress responses. The activation of these pathways leads to enhanced transcription of antimicrobial peptides, improved oxidative stress resistance, and elevated phagocytic activity. Moreover, pattern recognition receptors such as TLRs (toll-like receptors) are influenced by probiotic exposure, promoting immune priming without overstimulation [20]. This suggests that probiotic effects extend beyond phenotypic outcomes to targeted molecular reprogramming of immune responses in tilapia, underscoring their therapeutic potential in fine-tuning host defense.

These findings collectively validate the multifaceted role of probiotics in sustainable aquaculture. The strong emphasis on immune modulation (57%) coupled with direct antimicrobial action (21%) presents a compelling case for probiotics as a comprehensive alternative to antibiotics. The clear preference for Bacillus and Lactobacillus strains, particularly when administered through feed, provides practical guidance for aquaculture operators seeking to implement probiotic strategies. Despite the broad interest in probiotics’ immune stimulatory and antimicrobial effects, their role in modulating inflammation remains notably underexplored. Only 3% of the reviewed studies examined anti-inflammatory mechanisms, such as reduction in proinflammatory cytokines or oxidative stress markers. Yet chronic inflammation in fish is increasingly recognized as a hidden contributor to disease susceptibility, reduced growth, and compromised gut integrity—especially under stress-inducing conditions common in intensive aquaculture. Understanding how probiotics can downregulate inflammatory responses may offer a promising avenue for preventing subclinical infections and improving resilience to environmental stressors. This is particularly relevant for long-term health management, as controlling inflammation without suppressing immunity is a delicate but crucial balance. Expanding research in this area could enhance the precision of probiotic applications, tailoring strains not only to boost immunity but also to regulate the host’s inflammatory responses for optimal health outcomes.

6. Probiotics Over Antibiotics in the Disease Management

Probiotics offer a sustainable and environmentally safe strategy for managing fish health, primarily by enhancing the overall well-being and disease resistance of farmed populations. Through a range of biological functions, including the modulation of the host immune system, the competitive exclusion of pathogens, and the secretion of antimicrobial substances, probiotics help prevent disease without contributing to AMR or environmental degradation. In contrast, antibiotics, although highly effective in rapidly controlling infections, present significant risks such as AMR development, ecological disruption, and potential toxicity to aquatic organisms. Figure 4 provides a comparative overview of the mechanisms, benefits, and associated risks of antibiotics and probiotics in aquaculture disease management. It emphasizes that while antibiotics are suitable for acute, high-risk infections requiring immediate treatment, probiotics are better suited for long-term, preventive care due to their holistic and cumulative effects. The infographic underscores probiotics’ role in promoting sustainable aquaculture practices, particularly for species like Nile tilapia, where routine health management is essential. This visual comparison reinforces the need to adopt probiotic-based strategies as a primary approach, limiting antibiotic use to critical cases to safeguard environmental and public health.

One of the persistent limitations in probiotic application is strain specificity—the effectiveness of a probiotic strain can vary widely depending on the host species, pathogen strain, and environmental conditions such as temperature, salinity, and water quality [58]. Additionally, some probiotic strains may lose efficacy when moved from laboratory to farm conditions due to stress or poor colonization [47]. To overcome these challenges, several strategies are emerging. Genetically engineered probiotic strains offer the possibility of enhancing functional traits such as adhesion, antimicrobial peptide production, or environmental stress tolerance, though safety and regulatory issues remain hurdles [20]. Alternatively, synbiotic formulations, which combine probiotics with specific prebiotics (nondigestible fibers that selectively promote probiotic growth), can improve survival and colonization of probiotics in the gut [4, 64, 74]. Prebiotics like fructooligosaccharides (FOS) or inulin have been shown to synergize with Bacillus or Lactobacillus strains, enhancing immune modulation and gut health in Nile tilapia [74]. Additionally, microencapsulation techniques are being explored to protect probiotic cells during storage and passage through the acidic stomach environment, thereby increasing viability at the site of action [46]. Advancing these strategies could improve consistency, broaden application across diverse aquaculture systems, and ensure reproducible health benefits in real-world farming conditions.

7. Conclusion

Probiotics, particularly Bacillus and Lactobacillus species, show strong potential as sustainable alternatives to antibiotics in Nile tilapia aquaculture. They combat major pathogens such as Streptococcus and Aeromonas through immune enhancement, antimicrobial compound production, and competitive exclusion. Feed-based delivery emerges as the most practical administration method. While probiotics offer advantages in reducing AMR and environmental impact, challenges remain in terms of strain specificity, environmental variability, and regulatory frameworks. Future research should focus on field-level validation and uncovering lesser studied mechanisms like anti-inflammatory effects to fully harness the therapeutic potential of probiotics. Integrating these microbial tools into farm management can significantly enhance fish health and promote a resilient, eco-friendly aquaculture sector.

Conflicts of Interest

The authors declare no conflicts of interest.

Funding

No funding was received for this manuscript.