Background: Aquaculture, a vital component of global food security, faces sustainability challenges due to intensive farming practices, including water pollution, disease outbreaks, and antibiotic overuse. Probiotics, prebiotics, and synbiotics have emerged as eco-friendly alternatives to antibiotics. However, research results remain heterogeneous across aquatic species and intervention strategies. Methods: Following PRISMA 2020, we searched two databases (up to January 2026) for in vivo trials. Two reviewers screened and extracted data, and 177 eligible studies were ultimately included, covering single-/multi-strain probiotics (SSP/MSP), live/inactivated microbial preparations, and diverse synbiotic formulations. Results: Among 177 studies, Bacillus spp. were the most widely reported and effective probiotic strains. MSP and synbiotics exhibited superior efficacy in boosting aquatic animal growth performance and disease resistance over SSP in 68% of the included trials. Probiotics act through the competitive exclusion of pathogens, immune modulation, and enhanced digestive enzyme activity; prebiotics selectively stimulate beneficial gut microbiota, improving nutrient absorption and immune function through metabolites such as short-chain fatty acids; synbiotics combine the advantages of both, exerting synergistic effects. Furthermore, as water additives or fermented feed ingredients, probiotics reduce nitrogenous waste and organic pollutants, contributing to bioremediation. Conclusions: All three additives are effective. Standardized application protocols and long-term trials are needed for sustainable aquaculture. This review provides a unified evidence-based foundation for the rational use of these additives in aquaculture.

Ergothioneine (EGT), a naturally occurring amino acid derivative with potent antioxidant and cytoprotective properties, is widely applied in the food, cosmetic, and medical industries. Traditional production methods are limited by high costs, low efficiency, and environmental concerns, so microbial fermentation serves as a sustainable alternative for EGT production. In this study, Escherichia coli BL21 (DE3) was employed as the chassis strain. First, a basic EGT-producing engineered strain was constructed by heterologously expressing the egtB gene from Methylobacterium pseudosasicola along with the egtD and egtE genes from Mycobacterium smegmatis. This initial strain achieved a yield of 84.84 ± 1.64 mg/L of EGT in shake-flask cultures. To enhance production, solubility-enhancing tags were introduced to improve the soluble expression of the key enzymes, and metabolic pathways were rationally engineered to strengthen the supply of essential precursor amino acids. These modifications led to the development of a high-yield EGT strain. After optimizing the fermentation process, the best results were achieved using a medium with glycerol as the carbon source, 0.5 g/L of histidine, 1.5 g/L of methionine, and 1.0 g/L of cysteine, along with induction at 25 °C using 0.2 mM IPTG for 120 h. Under these conditions, the final EGT yield reached 385.70 ± 4.86 mg/L. The engineered strain for EGT synthesis and optimized fermentation strategy developed in this study offer a useful basis for further process development.