Global agriculture faces unprecedented challenges, including a projected population of 10 billion by 2050, declining arable land, and the urgent need to phase out antibiotic growth promoters (AGPs) to stem antimicrobial resistance (AMR). This review evaluates fermentation technology as a sustainable solution to the “food–feed–fuel” three competing land uses. We systematically compare solid-state fermentation (SSF) and submerged fermentation (SmF), highlighting their quantitative advantages: SSF offers 2–3× higher volumetric productivity and 70–90% lower water usage for solid wastes (e.g., soybean meal, wheat bran), while SmF provides superior process control for high-value products (e.g., single-cell protein). Key molecular mechanisms are discussed, including enzymatic degradation of anti-nutritional factors (up to 95% phytate and 98.8% tannin removal), mycotoxin detoxification (60–80% reduction), and biosynthesis of bioactive compounds (e.g., vitamin B12 enrichment up to 15-fold). Fermented feeds benefit many livestock species, particularly in organic and high-density farming systems, improving growth performance, gut health, and disease resistance while reducing environmental footprints. Advanced technologies such as AI-driven digital twins, CRISPR-based strain engineering, and precision fermentation are explored to overcome bottlenecks, including heat dissipation, strain stability, and process control. Despite challenges in scale-up, economics, and divergent global regulations (EU, USA, China, Southeast Asia, and Africa), fermentation is a critical biotechnological paradigm for circularity—the circular bioeconomy—and long-term food security. Future research should prioritize cost-effective large-scale implementation and the harmonization of regulatory frameworks.

To address the challenge of depleting traditional feed resources, this study aimed to biovalorize sweet potato waste (SPW), a major byproduct of the Japanese shochu industry, into a high-value functional animal feed. An innovative two-stage solid-state fermentation (SSF) was employed, featuring an initial aerobic stage with Aspergillus oryzae for substrate degradation, followed by an anaerobic stage with Lactobacillus plantarum for nutritional enhancement. To optimize this complex, multi-variable process, the predictive performance of Artificial Neural Network (ANN) and Random Forest (RF) machine learning models was compared based on an augmented experimental dataset (N = 80). To ensure statistical robustness and prevent data leakage, a repeated k-fold cross-validation strategy was implemented. The RF model demonstrated significantly superior accuracy and reliability than the ANN model, particularly in predicting the primary metric, crude protein (R² = 0.61 ± 0.04 vs. R² = 0.12 ± 0.15). Subsequently, the validated RF model was integrated with a Constrained Differential Evolution (CDE) algorithm for global parameter optimization. The optimized process was predicted to yield a final product with a crude protein content of 25.0%, alongside significant increases of 114.1% in total amino acids and 123.9% in essential amino acids. These projections were experimentally validated in vitro, confirming the model’s accuracy with a relative error of less than 5%. Furthermore, comprehensive biochemical assays demonstrated a massive degradation of anti-nutritional factors and significant enhancements in total phenolic content and antioxidant activity. This study provides a scientifically validated, data-driven framework for the valorization of SPW. It confirms the superior efficacy of ensemble learning methods for optimizing complex bioprocesses with limited data, offering a contribution to the development of a circular bioeconomy and sustainable feed resources.

Background/Objectives: Aeromonas veronii is a significant pathogen affecting aquatic animals and has the potential to infect humans. Vaccination remains the most effective strategy for preventing infections caused by this bacterial strain. Methods: This study aimed to validate the efficacy of bacterial ghosts as an oral vaccine by administering them to Cyprinus carpio and evaluating the resultant innate and acquired immune responses. Following immunization, the vaccinated Cyprinus carpio were exposed to a lethal dose of the wild-type bacterial strain to assess survival rates and relative protection efficiency. Results: Oral vaccination with bacterial ghosts led to the significant enhancement of lysozyme (LZM) and myeloperoxidase (MPO) activity in koi serum. It also resulted in the upregulation of cytokines, such as IL-2 and TNF-α, as well as an increase in both systemic (IgM) and mucosal (IgZs) antibody responses. The immunized group demonstrated reduced cumulative mortality following bacterial challenge. The relative percent survival in the vaccinated group reached as high as 87.50%. Conclusions: The oral immunization of Cyprinus carpio with A. veronii-derived bacterial ghosts confers substantial immune protection, providing a foundational basis for the development of novel vaccines against A. veronii.

Prophylactic antibiotic use in intensive aquaculture promotes antimicrobial resistance, necessitating the development of microbial-based interventions. This study evaluated the individual, complementary, and synergistic effects of Bacillus subtilis natto (BSN) and Lactobacillus plantarum (LP) on the physiological performance and intestinal microecology of juvenile Japanese flounder (Paralichthys olivaceus). Over a 60-day trial, juveniles (initial weight: 5.81 ± 0.03 g) received a basal diet (CON) or a diet supplemented with 10⁷ CFU/g of BSN, LP, or both (BSN + LP). The BSN + LP consortium elicited complementary improvements in final body weight (21.39 ± 0.75 g vs. 18.66 ± 0.44 g in CON) and feed conversion efficiency (p < 0.05). Transcriptomic analysis revealed synergistic upregulation of digestive proteases (trypsin, chymotrypsin). Notably, an in pro-inflammatory markers (IL-1β, TNF-α) was counterbalanced by substantial upregulation of anti-inflammatory cytokines (IL-10, 5.65-fold; TGF-β1, 4.48-fold), suggesting the induction of mucosal tolerance rather than pathological enteritis. High-throughput 16S rRNA sequencing showed that the control cohort had a potential baseline microbial, characterized by a high relative abundance of Proteobacteria. BSN + LP administration significantly altered this microbial community into a fermentative eubiosis enriched in Firmicutes and Bacteroidota. Correlation network analyses confirmed negative interaction dynamics: increased abundance of Lactobacillus, Bacteroides, and Muribaculaceae was negatively correlated with baseline pathobiont abundance. These findings indicate that co-administration of BSN and LP hypothetically enhances metabolic energy harvest via short-chain fatty acid-producing taxa, strengthens the gut–immune axis, and competitively mitigates opportunistic pathogens.

Background: Largemouth bass ranavirus (LMBV) triggers heavy mortality in farmed Largemouth bass (Micropterus salmoides). Oral subunit vaccines are suitable for mass fish immunization yet often yield unsatisfactory immunity. Intestinal microbiota strongly modulates mucosal immune competence. This study assessed whether PLGA/selenium nanoparticle (P/Se) pretreatment enhances protection afforded by a PLGA-based oral subunit vaccine (P/V) against LMBV. Methods: A 2 × 2 factorial design was applied. Fish received 28-day oral P/Se pretreatment followed by three oral doses of P/V. Material characterization, 16S rRNA high-throughput sequencing combined with microbial assembly analysis (diversity, NST, Sloan neutral model), qRT-PCR for immune related genes, serum specific antibody ELISA, LMBV immersion challenge and histopathological examination were conducted. Results: P/Se and P/V microspheres were successfully fabricated with acceptable particle size, and loading efficiency. P/Se pretreatment significantly elevated gut microbial α-diversity and enriched Actinobacteriota, in addition to increasing the relative contribution of stochastic processes to gut community assembly. The combined pretreatment–vaccine group markedly up-regulated intestinal mucosal immune genes (IL-1β, IL-8, IFN-γ, TNF-α, IgT) and systemic IgM. Consistently, higher serum-specific IgM antibody levels, improved survival rate, and alleviated virus-induced pathological injuries in trunk kidney and liver were observed in this combined group. Vaccination alone only conferred limited protection, and pretreatment alone produced no obvious antiviral protection. Conclusions: P/Se sequential intervention remodels intestinal microbiota and enhances the protective potency of oral subunit vaccine. This sequential feeding strategy offers a feasible way to optimize oral-vaccine performance for cultured largemouth bass.

Marine macroalgae and terrestrial halophytes represent a structurally distinct class of feed resources that can be produced without the arable land, fresh water, and synthetic fertilizer inputs required by conventional protein crops. Their direct incorporation into animal diets is, however, constrained by a convergent set of physical and toxicological barriers—viscous polysaccharides, lignocellulosic recalcitrance, anti-nutritional secondary metabolites, and accumulated heavy metals and halogens—that collectively impede practical use. Microbial fermentation can transform some of these barriers into functional resources through enzymatic deconstruction, catabolite conversion, and biosorption—a duality described here as the Barrier–Resource Duality. This critical narrative review synthesizes findings from publications across fermentation microbiology, animal nutrition, food safety, life cycle assessment, and regulatory science. The review analyzes cell-wall architectures of Chlorophyta, Rhodophyta, and Ochrophyta alongside the lignocellulosic matrix of terrestrial halophytes, maps the requisite carbohydrate-active enzyme families and polysaccharide-utilization loci, and evaluates the postbiotic mechanisms—TLR/NF-κB, histone deacetylase inhibition, and metabolite-mediated immunomodulation—by which fermentation-derived compounds may exert host benefit. The evidence base is assessed through a critical narrative synthesis that identifies knowledge gaps across five areas: (i) the absence of co-fermentation studies combining seaweeds and halophytes despite predicted substrate complementarity; (ii) the lack of pilot-scale fermentation data (no study exceeds 500 L); (iii) the single-study dependency of core in vivo efficacy claims; (iv) the absence of validated analytical methods for postbiotic quantification; and (v) the lack of a dedicated regulatory category for fermented marine biomass. It concludes that the field, while mechanistically rich, remains at Technology Readiness Level 2 (technology concept formulated), and that coordinated pilot-scale consortia, multi-institutional replication initiatives, and regulatory pathway design are prerequisites for commercial translation.