Abstract
   This study multidimensionally investigates the comprehensive effects of
   Lactobacillus plantarum (LP)-fermented feed on growth performance,
   intestinal health, and metabolic regulation in Pacific abalone
   (Haliotis discus hannai). The results demonstrate that LP fermentation
   significantly alters feed’s physical properties and nutritional
   profile, softening texture, increasing viscosity, and emitting an
   acidic aroma. Notably, it enhanced contents of cis-9-palmitoleic acid,
   α-linolenic acid (ALA), and functional amino acids (GABA, L-histidine,
   and L-asparagine), indicating that fermentation optimized ω-3 fatty
   acid accumulation and amino acid profiles through the modulation of
   fatty acid metabolic pathways, thereby improving feed biofunctionality
   and stress-resistant potential. Further analyses revealed that
   fermented feed markedly improved intestinal morphology in abalone,
   promoting villus integrity and upregulating tight junction proteins
   (ZO-1, Claudin) to reinforce intestinal barrier function. Concurrently,
   it downregulated inflammatory cytokines (TNF-α, NF-κB, IL-16) while
   upregulating anti-inflammatory factors (TLR4) and antioxidant-related
   genes (NRF2/KEAP1 pathway), synergistically mitigating intestinal
   inflammation and enhancing antioxidant capacity. Sequencing and
   untargeted metabolomics unveiled that fermented feed substantially
   remodeled gut microbiota structure, increasing Firmicutes abundance
   while reducing Bacteroidetes, with the notable enrichment of beneficial
   genera such as Mycoplasma. Metabolite profiling highlighted the
   significant activation of lipid metabolism, tryptophan pathway, and
   coenzyme A biosynthesis. A Spearman correlation analysis identified
   microbiota–metabolite interactions (such as Halomonas’ association with
   isethionic acid) potentially driving growth performance via metabolic
   microenvironment regulation. In conclusion, LP-fermented feed enhances
   abalone growth, immune response, and aquaculture efficiency through
   multi-dimensional synergistic mechanisms (nutritional optimization,
   intestinal homeostasis regulation, microbiota–metabolome crosstalk),
   providing critical theoretical foundations for aquafeed development and
   probiotic applications in aquaculture.
   Keywords: Haliotis discus hannai, Lactobacillus plantarum, fermented
   feed, growth, intestinal health
1. Introduction
   Haliotis discus hannai, a pivotal subspecies within the genus Haliotis
   (family Haliotidae) [[34]1], predominantly inhabits rocky substrates
   across tropical to temperate marine zones [[35]2]. Within these
   habitats, specific water temperature, transparency, and light intensity
   constitute critical ecological determinants, and wild populations
   establish stable ecological niches in algae- and kelp-rich environments
   [[36]3], exhibiting trophic specialization through macroalgal
   consumption. Despite these specific habitat requirements in the wild,
   H. discus hannai is recognized as the cornerstone species in China’s
   abalone aquaculture industry. H. discus hannai is the most extensively
   farmed abalone species in northern China, especially in the Shandong,
   Liaoning, and Fujian provinces. It constitutes > 70% of China’s farmed
   abalone output due to its rapid growth, superior flesh quality, and
   adaptability to controlled environments [[37]4]. However,
   industrial-scale farming faces dual challenges: escalating biosecurity
   risks from pathogenic infections, and systemic nutritional deficits.
   Vibriosis and pseudomonad-induced pathologies (such as pustule disease
   and abdominal rupture) have emerged as primary biosecurity threats
   [[38]5,[39]6,[40]7,[41]8], with elevated water temperatures during
   summer exacerbating pathogen proliferation, immunosuppression, and mass
   mortality events. Concurrently, high-density farming amplifies pathogen
   transmission via hydrodynamic vectors. Traditional algal-based feeds
   fail to meet protein–lipid requirements, while artificial formulations,
   despite storage stability advantages, suffer from suboptimal cellulose
   digestibility and imbalanced amino acid profiles, collectively
   impairing growth performance and elevating production costs [[42]9].
   These intertwined constraints necessitate innovative technological
   interventions.
   Probiotics, as bioactive microbial preparations, demonstrate
   multifaceted therapeutic potential through host–microbiome crosstalk
   modulation. Their tripartite mechanisms encompass the following: gut
   microbiota regulation via the competitive exclusion of pathogens
   (Vibrio harveyi) and short-chain fatty acid (SCFA)-mediated enteric
   homeostasis [[43]10]; nutrient metabolism enhancement through the
   enzymatic hydrolysis of recalcitrant feed components (cereal
   proteins/polysaccharides), achieving 8–34% weight gain improvement
   [[44]11,[45]12,[46]13]; and immunomodulation via microbial-associated
   molecular patterns (MAMPs) activating pattern recognition receptors
   (PRRs), thereby triggering TLR4/NRF2/KEAP1 signaling cascades to
   suppress pro-inflammatory cytokines (TNF-α, IL-16) [[47]14]. Notably,
   Shewanella-supplemented diets reduce V. harveyi mortality from 77% to
   27% [[48]15], while Bacillus strains enhance hemocyte vitality and
   apoptosis resistance [[49]16]. Furthermore, probiotics exhibit an
   environmental bioremediation capacity, degrading 99% of nitrites and
   ammonia nitrogen in aquaculture systems [[50]17]. Lactobacillus
   plantarum (LP) was selected as the focal probiotic agent in this study
   due to its (1) well-documented safety (GRAS/QPS status) and stability
   in feed matrices, (2) robust enzymatic repertoire (proteases,
   carbohydrases) that enables the efficient degradation of complex
   plant-derived antinutrients, (3) potent SCFA (particularly lactate)
   production capacity, which acidifies the gut lumen to inhibit Vibrio
   spp. colonization, and (4) proven immunostimulatory effects in aquatic
   species via the upregulation of antioxidant pathways and antimicrobial
   peptide expression [[51]17]. Its resilience to industrial processing
   (lyophilization, pelleting) further enhances its practical
   applicability in aquaculture feed production.
   The synergistic integration of probiotic engineering with feed
   biotechnology presents transformative potential. LP-fermented feeds
   degrade antinutritional factors, enrich γ-aminobutyric acid (GABA) and
   α-linolenic acid (ALA) profiles [[52]18], and activate the tryptophan
   metabolism. Probiotic formulations achieve mortality reduction [[53]19]
   and reshape gut microbiomes by elevating Firmicutes abundance,
   fostering nutrient assimilation and immune priming [[54]20]. The
   primary goal of this investigation is to rigorously evaluate the
   efficacy of a novel LP-fermented feed in (1) augmenting growth
   performance and feed utilization efficiency, (2) enhancing resistance
   against Vibrio harveyi challenges, and (3) modulating key
   immune-physiological and metabolic responses (e.g., microbiome
   structure, antioxidant status). This paradigm not only truncates
   traditional 3–4 year cultivation cycles, but enables precision health
   management through microbiome–metabolome axis elucidation
   (Halomonas–hydroxyethyl sulfonate metabolic coupling).
2. Materials and Methods
2.1. Preparation and Quality Analysis of Fermented Feed
2.1.1. Bacterial Culture Preparation and Fermentation Process
   The LP-NDMJ-4 bacterial suspension (viable count: 7 × 10^8 CFU/mL,
   isolated and preserved by our research center, Fuzhou, China) was mixed
   with soybean meal substrate (crude protein ≥ 45%, Shandong Sanwei
   Soybean Protein Co., Ltd., Linyi, China) at a 5% (v/v) inoculum ratio,
   and the moisture content was adjusted to 15%. The mixture was loaded
   into breathable membrane fermentation feed bags (specifications: 30 cm
   × 40 cm, air permeability: 5000 mL/(m^2·h); Qingdao Haida Biotechnology
   Group Co., Ltd., Qingdao, China) and fermented at 37 °C for 3 days in a
   constant temperature incubator (SPX-250B, Shanghai Yiheng Scientific
   Instruments Co., Ltd., Shanghai, China). Post-fermentation, samples
   were collected for quality assessment.
2.1.2. Feed Quality Assessment
Sensory Evaluation and pH Measurement
   The sensory attributes (aroma, color, and appearance) of fermented and
   unfermented feeds were comparatively scored. For pH measurement, 3 g of
   sample was mixed with 30 mL of ultrapure water (Milli-Q system, Merck
   Millipore, Darmstadt, Germany), incubated at 37 °C with shaking
   (THZ-98A thermostatic shaker, Shanghai Zhicheng Analytical Instruments
   Co., Ltd., Shanghai, China) for 30 min, and analyzed using a pH meter
   (FE28, Mettler Toledo, Greifensee, Switzerland).
Nutritional Profiling (Gas Chromatography–Mass Spectrometry, GC-MS Analysis)
   Samples were extracted with isopropanol (High Performance Liquid
   Chromatography HPLC grade, Sigma-Aldrich, St. Louis, MO, USA)-n-hexane
   (HPLC grade, Sinopharm Chemical Reagent Co., Ltd., Shanghai, China)
   (2:3 v/v, containing 0.2 mg/L internal standard), followed by liquid
   nitrogen grinding (JXFSTPRP-CL grinding instrument, Shanghai Jingxin
   Technology, Shanghai, China), ice-water bath ultrasonication (KQ-500DE,
   Kunshan Shumei Ultrasonic Instrument Co., Ltd., Kunshan, China) for 5
   min, and centrifugation at 12,000× g for 15 min at 4 °C (Centrifuge
   5424R, Eppendorf, Hamburg, Germany). The supernatant was dried under
   nitrogen gas (TurboVap LV, Biotage, Uppsala, Sweden), derivatized with
   methanol:trimethylsilyl diazomethane (1:2 v/v, Sigma-Aldrich),
   redissolved in n-hexane, and analyzed via GC-MS (7890B-5977B, Agilent
   Technologies, Santa Clara, CA, USA).
Amino Acid Analysis (UHPLC-MS/MS)
   Samples were extracted with acetonitrile (HPLC grade, Merck, Darmstadt,
   Germany)–methanol (HPLC grade, Sigma-Aldrich)–water (Milli-Q) (2:2:1
   v/v, containing isotope-labeled internal standards), subjected to
   liquid nitrogen grinding, ultrasonication, and centrifugation. The
   supernatant was analyzed using UltraHigh Performance Liquid
   Chromatography tandem mass spectrometry (UHPLC-MS/MS) (Vanquish
   Horizon-Q Exactive HF-X, Thermo Fisher Scientific, Waltham, MA, USA)
   for amino acid composition.
2.2. Experimental Animals and Husbandry
2.2.1. Experimental Design
   A total of 300 juvenile abalone (H. discus hannai) with similar body
   weights (19 ± 1.5 g) were obtained from Fujian Xiapu Rixing Aquaculture
   Cooperative (Ningde, China) and divided into three groups: the CK
   group, fed an unfermented basal diet (formulation: 15% fish meal, 40%
   kelp powder, 40% soybean meal, 5% spirulina; all ingredients purchased
   from Qingdao Haida Biotechnology Group); the HD group, fed on natural
   kelp feed (Fujian Xiapu Kelp Aquaculture Base, Ningde, China); and the
   LP group, fed L. plantarum NDMJ-4 fermented feed. Each group consisted
   of 100 individual abalone, with a 90-day rearing period. All animal
   experiments were conducted in accordance with the requirements of the
   Animal Ethics Committee of the Fujian Academy of Agricultural Sciences
   Institute of Animal Husbandry and Veterinary Medicine (MTLLSC
   2024-001-2).
2.2.2. Rearing Conditions
   Water temperature (22–28 °C) was monitored using a temperature logger
   (HOBO MX2201, Onset Computer, Bourne, MA, USA), pH (7.0–8.1) measured
   using a pH meter (FE28, Mettler Toledo), and dissolved oxygen (6.0–8.5
   mg/L) was calibrated using a portable dissolved oxygen meter (Pro20,
   YSI, Yellow Springs, OH, USA). Feed was administered every 5 days (500
   g per cage) using aquaculture cages (40 cm × 30 cm × 12 cm, Fujian
   Xiapu Fishing Gear Factory, Ningde, China).
2.2.3. Sample Collection
   At the end of the trial, 20 abalones per group were randomly selected.
   Body weight was measured using an electronic balance (ME104E, Mettler
   Toledo), and shell length/width were determined using a vernier caliper
   (500-196-30, Mitutoyo, Kawasaki, Japan). Intestinal tissues were
   divided into two portions: one portion from 10 abalones per group
   stored at −80 °C (DW-HL668 ultra-low temperature freezer, Zhongke
   Meiling, Hefei, China) for DNA extraction and subsequent microbiota
   analysis, and the other fixed in 4% paraformaldehyde (Servicebio,
   Wuhan, China) for HE staining.
2.3. Growth Performance Evaluation
   The following indices were calculated:
   Weight Gain Rate (WGR):
   [MATH: Final weight−Initial weightInitial weight×100% :MATH]
   Survival Rate (SR):
   [MATH: =Number of survivorsInitial number×100% :MATH]
   Specific Growth Rate (SGR)
   [MATH: =Final weight−Initial weightExperimental days×100% :MATH]
   Feed Conversion Ratio (FCR):
   [MATH: =Total feed intakeTotal weight gain×100% :MATH]
2.4. Intestinal Histomorphology and Barrier Function Analysis
2.4.1. Intestinal Tissue Fixation and HE Staining
   Abalone intestinal tissues were rinsed with physiological saline
   (Sinopharm Chemical Reagent Co., Ltd., Shanghai, China), and 1 cm
   segments were fixed in 4% paraformaldehyde (pH 7.4, Servicebio, Wuhan,
   China) at 4 °C for 24 h. Tissues were dehydrated in graded ethanol
   (70%, 80%, 90%, 100%; analytical grade, Sinopharm), cleared in xylene
   (analytical grade, Sinopharm), embedded in paraffin wax (Leica
   Biosystems, Wetzlar, Germany), and sectioned at 5 μm thickness.
   Sections were stained with hematoxylin (Harris method, Servicebio) for
   5 min, differentiated in 1% acid ethanol, blued in running water, and
   counterstained with eosin (Servicebio) for 1 min. Neutral resin
   (Servicebio) was used for mounting. Intestinal villus structure, goblet
   cell distribution, and inflammatory infiltration were observed under a
   Nikon ECLIPSE Ci microscope (Nikon, Tokyo, Japan), with images captured
   using the NIS-Elements D 5.11 system (Nikon).
2.4.2. Intestinal Barrier-Related Gene Expression Analysis
   Intestinal tissues (20 mg) were homogenized in liquid nitrogen, lysed
   with 1 mL NucleoZOL (Macherey-Nagel, Düren, Germany), and incubated for
   5 min. After adding 0.2 mL chloroform (HPLC grade, Sigma-Aldrich),
   samples were vortexed for 15 s and centrifuged at 12,000× g for 15 min
   at 4 °C (Eppendorf Centrifuge 5424R). The aqueous phase was mixed with
   isopropanol (Sigma-Aldrich) to precipitate RNA. RNA pellets were washed
   twice with 75% ethanol, dissolved in DEPC-treated water
   (Sigma-Aldrich), and quantified for purity (A260/A280 > 1.8, NanoDrop
   2000, Thermo Fisher Scientific) and concentration (Qubit 4.0
   Fluorometer, Thermo Fisher). Reverse transcription was performed using
   the Yeasen Hifair^® III 1st Strand cDNA Synthesis Kit (Yeasen,
   Shanghai, China) in a 20 μL reaction: 4 μL 5× gDNA Digester Mix, 4 μL
   5× Hifair^® Buffer, 1 μL Oligo(dT) primer, 1 μL Random Hexamers, and 1
   μL Enzyme Mix. The reaction conditions were 25 °C for 5 min, 55 °C for
   15 min, and 85 °C for 5 min. qRT-PCR was conducted in a 10 μL system
   containing 0.8 μL cDNA, 0.5 μM primers ([55]Table 1), and 5 μL 2× SYBR
   Green Master Mix (Yeasen) on a Roche LightCycler 96 qPCR system (Roche,
   Basel, Switzerland) with the following program: 94 °C for 30 s
   (pre-denaturation), 40 cycles of 94 °C for 5 s, 60 °C for 15 s, and 72
   °C for 10 s, followed by melt curve analysis (65–95 °C, 0.5 °C/s).
   Relative gene expression was calculated using the 2−ΔΔCt method with
   GAPDH as the reference, and three technical replicates were performed
   per group.
Table 1.
   Effects of LP-fermented soybean meal on sensory parameters.
   Group      Color              Odor         Texture Agglomeration  pH
    CK    Light yellow     Bean cake aroma     Firm   Loose granules 6.5
    LP   Brownish-yellow Sour alcoholic aroma  Soft    Agglomerated  6.7
   [56]Open in a new tab
   CK: control group; LP: LP-fermented group.
2.5. Gut Microbiota Diversity and Composition Analysis
2.5.1. Microbial Genomic DNA Extraction and Sequencing
   Total DNA was extracted from intestinal contents (50 mg) using the
   CTAB/SDS method. Samples were homogenized with 500 μL lysis buffer (100
   mM Tris-HCl, 40 mM EDTA, pH 8.0, Sigma-Aldrich) and 0.5 g glass beads
   (0.1 mm diameter, BioSpec Products, Bartlesville, USA), followed by
   incubation with 20 μL proteinase K (20 mg/mL, Qiagen, Hilden, Germany)
   at 65 °C for 1 h. After chloroform:isoamyl alcohol (24:1,
   Sigma-Aldrich) extraction and isopropanol precipitation, DNA pellets
   were washed with 75% ethanol and dissolved in TE buffer (10 mM
   Tris-HCl, 1 mM EDTA, pH 8.0, Sigma-Aldrich). DNA integrity was assessed
   via 1% agarose gel electrophoresis (Biowest, Barcelona, Spain),
   quantified using Qubit, and the V3-V4 region of 16S rDNA was amplified
   with primers 338F (ACTCCTACGGGAGGCAGCAG) and 806R
   (GGACTACHVGGGTWTCTAAT) (Sangon Biotech, Shanghai, China). PCR products
   were purified with AMPure XP beads (Beckman Coulter, Brea, CA, USA) and
   sequenced on the Illumina NovaSeq 6000 platform (Illumina, San Diego,
   CA, USA) in PE250 mode (≥50,000 reads per sample).
2.5.2. Bioinformatics Analysis
   Raw sequencing data were quality-controlled using Fastp v0.23.2 (BGI,
   Shenzhen, China) (Q20 ≥ 90%, removal of non-specific sequences). OTUs
   were clustered at 97% similarity using UPARSE v11 (Robert C. Edgar,
   Berkeley, CA, USA), chimeras were removed with UCHIME, and taxonomic
   annotation was performed using the SILVA v138 database
   ([57]https://www.arb-silva.de/). Alpha diversity indices (Shannon,
   Chao1, Simpson) were calculated via QIIME2 (Greg Caporaso, Flagstaff,
   AZ, USA). Beta diversity was analyzed using PCoA based on Unweighted
   Unifrac distances (phyloseq package in R, R Foundation R.4.3.8, Vienna,
   Austria). LefSe analysis (linear discriminant analysis (LDA) > 4,
   Kruskal–Wallis test p < 0.05) identified differential taxa, visualized
   using the R package ggplot2 (3.5.0).
2.6. Non-Targeted Metabolomic Analysis on Gastric and Intestinal Content
Samples
2.6.1. Metabolite Extraction and LC-MS Detection
   Liquid nitrogen-ground intestinal tissues (100 mg) were extracted with
   500 μL pre-cooled 80% methanol (containing 0.1% formic acid, HPLC
   grade, Sigma-Aldrich), vortexed for 1 min (Vortex-Genie 2, Scientific
   Industries, Bohemia, NY, USA), ultrasonicated in an ice bath (40 kHz,
   KQ-500DE, Kunshan Shumei, Kunshan, China) for 10 min, and centrifuged
   at 15,000× g for 20 min at 4 °C (Eppendorf). The supernatant (300 μL)
   was diluted with 120 μL ultrapure water (Milli-Q system, Merck
   Millipore) to 53% methanol, centrifuged again, and 200 μL was injected
   for analysis. Chromatographic separation was performed on a Thermo
   Scientific Hypersil Gold C18 column (2.1 mm × 100 mm, 1.9 μm, Thermo
   Fisher) with mobile phase A (0.1% formic acid in water) and B (0.1%
   formic acid in methanol). The gradient program was 0–1.5 min (2% B), 3
   min (85% B), and 10 min (100% B), followed by equilibration at 2% B.
   Metabolites were detected using a Thermo Q Exactive HF-X mass
   spectrometer (Thermo Fisher) with a HESI ion source (positive/negative
   modes), spray voltage 3.5 kV (+)/2.8 kV (−), full scan range m/z
   70–1050 (resolution: 120,000), and MS/MS in Top 10 mode.
2.6.2. Metabolite Identification and Pathway Analysis
   Raw data were converted to mzXML format using ProteoWizard
   (ProteoWizard Foundation, Cambridge, MA, USA). Peak extraction,
   alignment, and normalization were performed using XCMS (Scripps
   Research, San Diego, CA, USA; parameters: bw = 5, ppm = 10, minfrac =
   0.5). Metabolites were annotated via HMDB ([58]http://www.hmdb.ca/,
   accessed on 26 June 2025), KEGG ([59]https://www.kegg.jp//, accessed on
   26 June 2025), and METLIN (Scripps Research) databases (mass error < 5
   ppm, retention time deviation < 0.2 min, MS/MS similarity > 80%).
   Differential metabolites were subjected to KEGG pathway enrichment
   analysis (MetaboAnalyst 5.0, [60]https://www.metaboanalyst.ca//,
   accessed on 26 June 2025; p < 0.05, FDR-corrected), visualized as
   volcano plots, heatmaps, and pathway bubble charts using the R package
   ggplot2(3.5.0).
2.7. Correlation Analysis
   Correlation analysis among 19 gut microbial taxa, 19 differential
   metabolites, and key seawater indicators was performed as follows:
   Microbial taxa were identified via 16S rRNA sequencing of abalone
   gastrointestinal contents based on abundance variations. Metabolites
   were quantified via metabolomics, while seawater indicators were
   assessed using environmental monitoring tools (such as Lianchuan Cloud
   platform). Spearman’s rank correlation analysis evaluated monotonic
   relationships between variables, visualized via heatmaps to highlight
   interaction patterns.
2.8. Bioinformatics and Statistical Analysis
   Data were analyzed using GraphPad Prism 9.0 (GraphPad Software, San
   Diego, CA, USA). One-way ANOVA was applied, and the results are
   expressed as mean ± standard deviation. A p-value < 0.05 was considered
   statistically significant.
3. Results
3.1. Analysis of Feed Quality Before and After Fermentation
3.1.1. Sensory Evaluation of Fermented Feed
   As shown in [61]Table 1 and [62]Figure 1, the color of LP-fermented
   feed exhibited minimal variation compared to the control group, both
   presenting a brownish-yellow hue. Post-fermentation, the aroma of
   soybean meal transitioned from its original bean cake scent to a
   distinctive sour and alcoholic fragrance. The addition of fermentation
   broth increased feed moisture content, resulting in a softer texture
   with minor agglomeration, although no significant pH alteration was
   observed (pH 6.5 vs. 6.7).
Figure 1.
   [63]Figure 1
   [64]Open in a new tab
   Granular state of soybean meal before and after fermentation. (A)
   Pre-fermented soybean meal. (B) Fermented soybean meal.
3.1.2. Impact of Probiotic Fermentation on the Nutritional Profile of Soybean
Meal
   As indicated in [65]Table 2, LP fermentation notably enhanced specific
   fatty acid contents. The LP group demonstrated a two-fold increase in
   cis-9-palmitoleic acid (106.85 ± 21.37 mg/kg vs. 48.32 ± 9.18 mg/kg in
   CK) and a 14% elevation in α-linolenic acid (ALA) content (292.6 ±
   55.59 mg/kg vs. 256.6 ± 33.36 mg/kg). However, docosahexaenoic acid
   (DHA) levels decreased by 11.8% (66.47 ± 13.29 mg/kg vs. 75.33 ± 10.55
   mg/kg), warranting further investigation into fermentation-induced
   metabolic pathway alterations. A marginal increase was observed in
   cis-11,14,17-eicosatrienoic acid (2.47 ± 0.3 mg/kg vs. 1.97 ± 0.28
   mg/kg).
Table 2.
   Composition of unsaturated fatty acids in soybean meal (mg/kg).
   Free Fatty Acid CK LP p-Value
   Trans-9-myristoleic acid 0.2 ± 0.04 0.1 ± 0.02 0.063
   Trans-9-palmitoleic acid 1.1 ± 0.18 2.38 ± 0.33 0.082
   Cis-9-palmitoleic acid 48.32 ± 9.18 106.85 ± 21.37 0.023
   Trans-9-octadecenoic acid 3.08 ± 0.46 3.7 ± 0.7 0.079
   Cis-11-octadecenoic acid 122.78 ± 18.42 124.87 ± 24.97 0.057
   Cis-13-erucic acid 5.35 ± 0.75 5.42 ± 0.87 0.065
   Trans-13-docosenoic acid 3.49 ± 0.45 3.62 ± 0.36 0.073
   Cis-15-nervonic acid 3.11 ± 0.4 3.42 ± 0.55 0.056
   A-linolenic acid (ala) 256.6 ± 33.36 292.6 ± 55.59 0.017
   Cis-11,14,17-eicosatrienoic acid 1.97 ± 0.28 2.47 ± 0.3 0.045
   Cis-4,7,10,13,16,19-docosahexaenoic acid (dha) 75.33 ± 10.55 66.47 ±
   13.29 0.014
   Cis-9,12-linoleic acid (la) 23.58 ± 4.24 23.27 ± 3.72 0.061
   Γ-linolenic acid (gla) 2.57 ± 0.28 2.33 ± 0.33 0.078
   Cis-8,11,14-dihomo-γ-linolenic acid (dgla) 2.44 ± 0.49 2.47 ± 0.47
   0.089
   Arachidonic acid (aa) 23.56 ± 3.53 21.48 ± 2.79 0.051
   Cis-7,10,13,16-docosatetraenoic acid 4.53 ± 0.91 4.72 ± 0.52 0.091
   [66]Open in a new tab
   Data presented as mean ± standard deviation. CK: control group; LP:
   LP-fermented group.
   Concerning saturated fatty acids ([67]Table 3), caprylic acid (C8:0)
   content decreased by 20.53% in the LP group, while lauric acid (C12:0),
   tridecanoic acid (C13:0), and myristic acid (C14:0) exhibited dramatic
   increases of 357.14%, 163.64%, and 51.42%, respectively.
Table 3.
   Composition of saturated fatty acids in soybean meal (mg/kg).
        Free Fatty Acid              CK               LP        p-Value
      Caprylic acid (C8:0)      3.41 ± 0.55      2.71 ± 0.33     0.013
      Lauric acid (C12:0)       0.21 ± 0.03      0.96 ± 0.11     0.011
    Tridecanoic acid (C13:0)    0.11 ± 0.01      0.29 ± 0.04     0.032
     Myristic acid (C14:0)      30.34 ± 4.25     45.94 ± 9.19    0.017
   Pentadecanoic acid (C15:0)   9.31 ± 1.58      13.28 ± 2.66    0.025
     Palmitic acid (C16:0)    1520.93 ± 273.77 1685.45 ± 219.11  0.043
   Heptadecanoic acid (C17:0)   18.18 ± 3.45     21.92 ± 3.29    0.041
      Stearic acid (C18:0)     345.27 ± 65.6    350.38 ± 63.07   0.069
   [68]Open in a new tab
   Data presented as mean ± standard deviation. ND: not detected; CK:
   control group; LP: LP-fermented group.
3.1.3. Amino Acid Profile Modifications Induced by Probiotic Fermentation
   Fermentation significantly elevated amino acid levels in the LP group
   compared to CK([69]Table 4). The most pronounced increases were
   observed in L-histidine (+38.69%), L-asparagine (+36.10%),
   γ-aminobutyric acid (+32.88%), and L-Arginine (+29.51%).
Table 4.
   Effects of probiotic additives on amino acid content in feed before and
   after fermentation (g/kg).
           Amino Acid              CK           LP      p-Value
           β-Alanine          0.26 ± 0.01  0.32 ± 0.01   0.045
   γ-Aminobutyric acid (GABA) 14.72 ± 0.48 19.56 ± 0.41  0.021
           L-Proline          8.68 ± 0.08  9.35 ± 0.13   0.056
          L-Asparagine        73.43 ± 2.57 99.94 ± 6.77  0.023
          L-Glutamine         10.09 ± 0.35 12.79 ± 0.78  0.062
          L-Methionine        46.28 ± 0.86 51.73 ± 0.39  0.051
          L-Histidine         9.77 ± 0.09  13.55 ± 0.4   0.008
      3-Methyl-L-histidine    0.41 ± 0.01  0.49 ± 0.01   0.078
      1-Methyl-L-histidine    0.20 ± 0.01  0.23 ± 0.01   0.098
           L-Arginine         23.21 ± 0.13 30.28 ± 0.58  0.015
          L-Tryptophan        7.54 ± 0.24  7.81 ± 0.16   0.049
   [70]Open in a new tab
   Data presented as mean ± standard deviation. CK: control group; LP:
   LP-fermented group.
3.2. Production Performance
   Production performance refers to the comprehensive evaluation of
   abalone growth, survival rate, and feed utilization efficiency during
   aquaculture, serving as a critical indicator for assessing rearing
   conditions, feed quality, and management efficacy. As detailed in
   [71]Table 5, the growth performance of abalone varied significantly
   across feed treatment groups. The weight gain rate in the LP group
   (421%) was significantly higher than that in the CK (201%) and HD
   (263%) groups.
Table 5.
   Growth performance indexes of H. discus hannai.
              Group              HD      CK      LP    p-Value
   Total weight gain rate (%)   421%    201%    263%    0.017
        Survival rate (%)        69%   45.33%  61.66%   0.031
   Daily weight gain rate (%)    19%    9.5%   12.44%   0.018
   Feed conversion ratio (FCR) 2633.12 1586.37 1205.36  0.014
   [72]Open in a new tab
   Data presented as mean ± standard deviation. HD: natural feed group;
   CK: control group; LP: LP-fermented group.
   The feed conversion ratio (FCR), a key metric for evaluating feed
   utilization efficiency, was calculated as 2633.12 for the LP group,
   lower than both the CK (1586.37) and HD (1205.36) groups. In terms of
   survival rate, the LP group achieved 61.66%, outperforming the CK group
   (45.33%), but remaining lower than the HD group (69%). Notably, while
   the total weight gain rate of the LP group (263%) substantially
   exceeded that of the CK group (201%), it was markedly lower than the HD
   group’s 421%.
3.3. Determination of Abalone Quality
   The experiment compared changes in amino acid content in abalone muscle
   among the HD group (kelp-based feed), LP group (LP-fermented feed), and
   CK group (basal feed) ([73]Table 6). The results reveal that the LP
   group exhibited higher concentrations of most amino acids in abalone
   muscle compared to both the HD and CK groups. Specifically, histidine,
   phenylalanine, and cystine levels in the LP group were 0.21 g/kg, 0.41
   g/kg, and 0.11 g/kg, respectively. These values represented increases
   of 0.10 g/kg, 0.09 g/kg, and 0.10 g/kg compared to the CK group (0.11
   g/kg, 0.32 g/kg, and 0.09 g/kg), and increments of 0.03 g/kg, 0.04
   g/kg, and 0.10 g/kg relative to the HD group (0.18 g/kg, 0.37 g/kg, and
   0.01 g/kg). These findings indicate that fermented feed enhances the
   umami-related components in abalone muscle.
Table 6.
   Effects of different diets on amino acid content of abalone muscle
   quality.
   Amino Acid g/KG     HD          LP          CK      p-Value
    Aspartic acid  1.21 ± 0.12 1.26 ± 0.16 1.19 ± 0.12  0.058
      Threonine    0.53 ± 0.08 0.57 ± 0.14 0.56 ± 0.16  0.121
       Serine      0.62 ± 0.12 0.62 ± 0.15 0.54 ± 0.07  0.087
    Glutamic acid  2.04 ± 0.55 2.1 ± 0.55  2.03 ± 0.26  0.042
       Glycine     1.15 ± 0.12 1.02 ± 0.29 0.97 ± 0.16  0.036
       Alanine     0.77 ± 0.2  0.76 ± 0.15 0.72 ± 0.2   0.231
       Cystine      0.01 ± 0   0.11 ± 0.02 0.09 ± 0.01  0.011
     Lavandulin    0.51 ± 0.14 0.55 ± 0.1  0.46 ± 0.12  0.063
     Methionine    0.29 ± 0.07 0.3 ± 0.03  0.25 ± 0.04  0.079
     Isoleucine    0.47 ± 0.08 0.51 ± 0.13 0.47 ± 0.12  0.092
       Leucine     0.82 ± 0.19 0.89 ± 0.24 0.88 ± 0.17  0.152
      Tyrosine     0.36 ± 0.1  0.4 ± 0.09  0.34 ± 0.07  0.035
    Phenylalanine  0.37 ± 0.1  0.41 ± 0.09 0.32 ± 0.04  0.012
       Lysine      0.72 ± 0.07 0.82 ± 0.22 0.76 ± 0.21  0.055
      Histidine    0.18 ± 0.03 0.21 ± 0.06 0.11 ± 0.02  0.034
      Arginine     1.31 ± 0.3  1.29 ± 0.35 1.21 ± 0.3   0.048
       Proline     0.55 ± 0.09 0.5 ± 0.07  0.44 ± 0.04  0.053
   [74]Open in a new tab
   Data presented as mean ± standard deviation. HD: natural feed group;
   CK: control group; LP: LP-fermented group.
3.4. Effects of LP-Fermented Feed on Intestinal Morphology of Abalone
   A comparative analysis of intestinal tissue structure ([75]Figure 2)
   revealed significant morphological differences in abalone intestines
   across feed treatment groups. In the HD group, the intestinal
   architecture remained relatively intact, characterized by
   well-developed villi and a continuous mucosal layer. The abundant
   villous structure effectively expanded the nutrient absorption surface
   area, thereby enhancing dietary nutrient utilization and promoting
   growth. These findings suggest that kelp-based feed may exert
   protective effects on intestinal integrity, supporting barrier function
   and nutrient assimilation. In contrast, the CK group exhibited
   disorganized intestinal folds with shortened, sparse villi and
   localized structural damage, indicating the limited benefits of basal
   feed on intestinal health. Such compromised morphology likely reduced
   nutrient absorption efficiency, ultimately impairing growth
   performance.
Figure 2.
   [76]Figure 2
   [77]Open in a new tab
   Section of the intestinal tissue of Abalone discus humphead (HE
   staining, 40×). HD: natural feed group; CK: control group; LP:
   LP-fermented group.
   The LP group demonstrated markedly improved intestinal integrity
   compared to CK, with significantly elongated and denser villi and no
   observable structural defects. Although slightly inferior to the HD
   group, the LP group’s intestinal morphology surpassed that of CK,
   highlighting that LP NDHJ-4 fermentation enhanced digestive capacity
   and intestinal health in H. discus hannai through structural
   optimization.
3.5. Effects of LP-Fermented Feed on Intestinal Barrier Function, Cytokines,
and Antioxidant Factors in Abalone
   A comparative analysis of intestinal tight junction protein mRNA
   expression across feed treatment groups ([78]Figure 3) revealed
   distinct molecular responses. The LP group exhibited significantly
   elevated Claudin mRNA expression compared to both CK and HD groups (p <
   0.001), with no significant difference observed between CK and HD (ns).
   Similarly, ZO-1 mRNA expression was markedly higher in the LP group
   than in CK and HD (p < 0.01), indicating enhanced tight junction
   assembly and intestinal barrier integrity in the fermented feed group.
Figure 3.
   [79]Figure 3
   [80]Open in a new tab
   Effects of feeding different diets on the intestinal tissue and
   cytokine mRNA expression of H. discus hannai. **: p < 0.01; ***: p <
   0.001; ns = not significant (p ≥ 0.05).
   Inflammatory and immune-related cytokine profiling demonstrated the
   regulatory effects of LP treatment. While TLR4 mRNA expression showed
   no difference between CK and HD, it was significantly upregulated in LP
   (p < 0.01). Conversely, TNF-α mRNA expression in LP decreased sharply
   compared to CK and HD (p < 0.01), with no intergroup difference between
   CK and HD. Notably, NF-κB mRNA levels were lowest in LP, while HD
   displayed the highest expression (p < 0.001 vs. both groups), and CK
   levels exceeded LP (p < 0.01). Additionally, IL-16 mRNA expression in
   LP was reduced by 42% compared to CK and HD (p < 0.01), further
   suggesting that fermented feed mitigates inflammatory signaling.
   An antioxidant pathway analysis revealed that Keap1 mRNA expression
   peaked in CK, but was suppressed in LP and HD (p < 0.001). Although
   Nrf-2 mRNA levels showed no difference between CK and LP, HD exhibited
   significantly higher Nrf-2 expression than CK (p < 0.05), highlighting
   divergent antioxidant activation mechanisms.
3.6. Effects of Fermented Feed on the Intestinal Microbiota of Abalone
3.6.1. OTU Distribution and Diversity Analysis
   The Venn diagram ([81]Figure 4) illustrates the similarity of
   operational taxonomic unit (OTU) composition among three abalone
   intestinal microbiota groups. A total of 46,574 OTUs were identified
   across all groups, with 3063 OTUs shared among all three groups.
   Specifically, the CK group contained 13,159 OTUs (4879 unique), the HD
   group exhibited the highest richness with 17,963 OTUs (10,191 unique),
   and the LP group comprised 16,318 OTUs (9795 unique). This hierarchical
   distribution indicates that the HD group demonstrated the highest OTU
   richness, followed by the LP and CK groups.
Figure 4.
   [82]Figure 4
   [83]Open in a new tab
   Effects of fermented feed on gut microbiota composition in abalone.
   (A1) Venn diagram of OTU distribution. (A2) Analysis of Beta diversity.
   (A3) Analysis of LDA effect size of the different groups. (B1–B5)
   Changes in microbial flora at the portal level. (C1–C9) Changes in
   microbial flora at the genus level. * p < 0.05; **: p < 0.01; ***: p <
   0.001; ns = not significant (p ≥ 0.05).
   Alpha diversity indices were analyzed to evaluate microbial community
   characteristics ([84]Table 7). The HD group showed significantly higher
   Observed_species, Shannon, and Simpson indices compared to the CK and
   LP groups (p < 0.05), while no significant differences were observed
   between the CK and LP groups. Notably, the CK group exhibited the
   highest Chao1 and ACE indices, reflecting distinct patterns in species
   richness estimation. These results suggest that LP and HD feed
   modulates intestinal microbiota by enhancing microbial diversity
   (Shannon: 4.12 in CK vs. 4.27 in LP vs. 4.79 in HD) while maintaining
   comparable species richness to basal feed.
Table 7.
   Alpha diversity indices of intestinal microbiota in H. discus hannai.
    Group  Observed Species  Chao1    ACE   Shannon Simpson
     CK        2413.40      4580.73 5097.43  4.12    0.89
     LP        2358.60      2886.44 3168.66  4.27    0.89
     HD        2916.10      3905.55 4343.13  4.79    0.92
   p-value      0.047        0.015   0.027   0.032   0.159
   [85]Open in a new tab
   HD: natural feed group; CK: control group; LP: LP-fermented group.
   As illustrated in the PCoA plot (Unweighted Unifrac distance), each
   point represents an individual abalone sample, with the color
   corresponding to experimental groups (HD, LP, CK). The analysis
   revealed distinct clustering patterns: samples within the same group
   exhibited tight aggregation, while intergroup points were spatially
   separated without overlap. This clear segregation (PERMANOVA, * p <
   0.001) indicates that dietary interventions significantly restructured
   the intestinal microbial community composition of abalone.
3.6.2. Effects of Fermented Feed on Gut Microbiota Composition in Abalone
   Following species annotation processing, a comparative analysis of
   microbial communities was conducted based on relative abundance at both
   the phylum and genus levels. A total of 37 bacterial phyla and 1156
   bacterial genera were identified across all intestinal samples. Based
   on annotation results, the top 10 phyla accounting for over 99% of
   total annotated species in abalone gut microbiota from different marine
   areas were selected for analysis.
   [86]Figure 4 illustrates the phylum-level effects of fermented feed on
   abalone gut microbiota. The dominant phyla included Proteobacteria,
   Tenericutes, Bacteroidetes, Firmicutes, Actinobacteria, Planctomycetes,
   and Verrucomicrobia. Significant intergroup differences were observed
   in Acidobacteria, Spirochaetes, and Chloroflexi (p < 0.05).
   Notably, Proteobacteria showed no significant variation among the
   experimental groups. The LP group exhibited the significant
   upregulation of Tenericutes (p = 0.017) and downregulation of
   Bacteroidetes (p = 0.023) compared to controls. Although Firmicutes
   abundance showed no statistical difference from the CK group, it was
   significantly lower than the HD group (p = 0.035).
   At the genus level ([87]Figure 4C), the dominant genera comprised
   Curvibacter, Mycoplasma, Asinibacterium, Mycoplasmopsis, Ochrobactrum,
   Pandoraea, Hydrotalea, and Pelagibacterium. The LP group demonstrated
   3.08-fold and 14.42-fold increases in Mycoplasma and Ochrobactrum
   abundance, respectively, versus CK group, concomitant with 2.35-fold
   reduction in Pelagibacterium. Curvibacter, Asinibacterium, Pandoraea,
   and Hydrotalea showed no significant differences from the CK group, but
   were notably reduced compared to the HD group.
   Linear discriminant analysis (LDA > 4) revealed 31 differentially
   abundant species across groups ([88]Figure 4(A3)). The CK, HD, and LP
   groups contained seven, fourteen, and ten discriminant species,
   respectively, contributing to microbial structure variation. Notably,
   Lactobacillus plantarum-fermented feed enhanced differential microbiota
   diversity in H. discus hannai compared to the CK group. Although the LP
   group showed slightly lower diversity than the seaweed-fed HD group,
   its increased discriminant species count relative to the CK group
   indicates probiotic-fermented feed’s modulatory effect on intestinal
   microbial diversity.
3.7. Metabolite Identification and Quantification
   A total of 2478 compounds were identified through LC-MS-based
   metabolomic profiling combined with an in-house database. The annotated
   metabolites were classified into 14 major categories ([89]Figure 5):
   lipids and lipid-like molecules (877), organoheterocyclic compounds
   (391), organic oxides (167), organic acids and derivatives (460),
   organohalides (3), organosulfur compounds (11), organonitrogen
   compounds (52), 1,3-dipolar organic compounds (1), homogeneous
   non-metallic compounds (1), hydrocarbons and derivatives (7), alkaloids
   and derivatives (55), lignans/neolignans (8),
   nucleosides/nucleotides/analogs (52), benzenoids (243),
   phenylpropanoids/polyketides (120), and others (30).
Figure 5.
   [90]Figure 5
   [91]Open in a new tab
   Effects of fermented feed on metabolites composition in abalone gut.
   (A) Donut plot of metabolite classification and proportion. (B) Venn
   diagram of differential metabolites in each comparison group. (C) KEGG
   diagram of differential metabolic pathways in each comparison group.
   (D1–D6) OPLS-DA score diagram of different comparison groups. (E–G)
   Differential metabolite volcano plot.
3.7.1. OPLS-DA Modeling
   Untargeted LC-MS/MS metabolomics was performed on ten intestinal
   samples per group. Orthogonal Partial Least Squares Discriminant
   Analysis (OPLS-DA) with 1000 permutation tests (to mitigate overfitting
   risks) revealed distinct clustering patterns among the three groups
   ([92]Figure 4B). The clear spatial separation (R2Y > 0.98 for all
   pairwise comparisons) and absence of intergroup overlap confirmed
   significant metabolic profile differences. Model validity was further
   supported by high predictive capacity: CK vs. HD (R2Y = 0.99, Q2 =
   0.693), CK vs. LP (R2Y = 0.993, Q2 = 0.951), and HD vs. LP (R2Y =
   0.985, Q2 = 0.922). All Q2 values exceeded the 0.5 threshold,
   confirming robust model reliability ([93]Figure 4C).
3.7.2. Screening of Differential Metabolites
   Differential metabolites were identified using Variable Importance in
   Projection (VIP) scores from the first principal component of
   Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) models
   combined with independent t-test p-values. Among the 3254 detected
   metabolites, 959 showed significant intergroup variations (VIP > 1.0, p
   < 0.05), including 664 upregulated and 405 downregulated compounds in
   LP compared to CK ([94]Table 8). The key metabolic pathways impacted by
   fermented feed included lipid biosynthesis (23.1%), amino acid
   metabolism (18.7%), and secondary metabolite production (14.5%).
Table 8.
   Comparative analysis of differential metabolites across experimental
   groups.
   Comparison Group Total Differential Metabolites (Diff_All) Upregulated
   Metabolites (Diff_Up) Downregulated Metabolites (Diff_Down)
   CK vs. HD 494 286 208
   CK vs. LP 959 664 405
   HD vs. LP 963 460 503
   [95]Open in a new tab
   HD: natural feed group; CK: control group; LP: LP-fermented group.
3.7.3. Classification of Differential Metabolites
   In the CK vs. HD comparison, 494 differential metabolites were
   identified, including 167 lipids and lipid-like molecules, 96
   organoheterocyclic compounds, 35 organic oxides, 93 organic
   acids/derivatives, 1 organohalide, 2 organosulfur compounds, 11
   organonitrogen compounds, 2 hydrocarbons, 14 alkaloids/derivatives, 1
   lignan/neolignan, 12 nucleosides/nucleotides/analogs, 32 benzenoids, 24
   phenylpropanoids/polyketides, and 4 others, with 286 upregulated and
   208 downregulated metabolites.
   The CK vs. LP comparison revealed 959 differential metabolites: 346
   lipids/lipid-like molecules, 185 organoheterocyclic compounds, 68
   organic oxides, 153 organic acids/derivatives, 3 organohalides, 4
   organosulfur compounds, 14 organonitrogen compounds, 2 hydrocarbons, 18
   alkaloids/derivatives, 4 lignans/neolignans, 18
   nucleosides/nucleotides/analogs, 89 benzenoids, 46
   phenylpropanoids/polyketides, and 9 others, showing 664 upregulated and
   405 downregulated species.
   For HD vs. LP, 963 differential metabolites were detected: 355
   lipids/lipid-like molecules, 173 organoheterocyclic compounds, 65
   organic oxides, 155 organic acids/derivatives, 2 organohalides, 5
   organosulfur compounds, 13 organonitrogen compounds, 4 hydrocarbons, 15
   alkaloids/derivatives, 2 lignans/neolignans, 1 homogeneous non-metallic
   compound, 17 nucleosides/nucleotides/analogs, 99 benzenoids, 50
   phenylpropanoids/polyketides, and 7 others, with 460 upregulated and
   503 downregulated metabolites.
   Cross-group analysis identified lipids/lipid-like molecules,
   organoheterocyclic compounds, organic acids/derivatives, and benzenoids
   as the predominant differential metabolite categories. A core set of
   149 shared differential metabolites was observed across all comparisons
   ([96]Figure 5).
3.7.4. KEGG Pathway Enrichment Analysis
   KEGG pathway analysis (FDR-adjusted p < 0.05) revealed the significant
   enrichment of differential metabolites in ovarian steroidogenesis (p =
   0.018), tryptophan metabolism (p = 0.026), and pantothenate/CoA
   biosynthesis (p = 0.042) ([97]Figure 4). These pathways are
   hypothesized to regulate growth performance and immune responses in H.
   discus hannai.
3.7.5. Shared Differential Metabolites Across Groups
   Fourteen high-confidence differential metabolites (VIP > 1.0, p < 0.05)
   were identified between the CK and experimental groups (HD/LP) after
   filtering unnamed compounds ([98]Table 9). Three metabolites were
   downregulated in the LP/HD groups: cis-11,14,17-eicosatrienoic acid,
   thermozymocidin, and nabilone. Eleven metabolites exhibited upregulated
   trends, including the key intermediates of lipid remodeling
   (lysophosphatidylcholine 18:1) and amino acid derivatives
   (N-acetylglutamine).
Table 9.
   High-confidence differential metabolites.
   Metabolite Name log2 FC p-Value VIP Value Trend
   HD vs. CK LP vs. CK HD vs. CK LP vs. CK HD vs. CK LP vs. CK
   Artemether 0.98 2.98 <0.05 <0.01 1.29 1.90 ↑
   Pyropheophorbide A 2.00 6.93 <0.01 <0.01 1.97 1.90 ↑
   cis-11,14,17-Eicosatrienoic acid −1.12 −2.59 <0.05 <0.01 1.22 1.66 ↓
   Fumaroylcarnitine 0.81 2.81 <0.01 <0.01 1.69 1.86 ↑
   Formylfuranobenzopyrone 1.31 6.28 <0.03 <0.01 1.43 1.90 ↑
   Thermocidin −0.56 −3.26 <0.01 <0.01 2.09 1.93 ↓
   L-β-Homoserine 0.59 1.57 <0.01 <0.01 1.96 1.84 ↑
   Azithromide 0.91 4.37 <0.01 <0.01 1.98 1.81 ↑
   Hydroxyethylsulfonic acid 0.87 5.97 <0.01 <0.01 1.86 1.96 ↑
   D-Gulonic acid gamma-lactone 1.03 4.77 <0.01 <0.01 2.06 1.96 ↑
   2-Deoxy-beta-L-erythro-pentafuranose 1.15 4.35 <0.01 <0.01 2.32 1.95 ↑
   Nabilone −1.52 −3.90 <0.01 <0.01 2.36 1.88 ↓
   3-Phenethyl-2′-deoxyuridine 2.13 10.88 <0.01 <0.01 1.77 1.95 ↑
   4-Fluoro-3-phenoxybenzoic acid 3.70 5.81 <0.01 <0.01 2.53 1.91 ↑
   [99]Open in a new tab
   ↑ indicates upregulation, ↓ indicates downregulation HD vs. CK: High
   Dose vs. Control. LP vs. CK: Low Dose vs. Control; FC: Fold Change;
   VIP: Variable Importance in Projection. Note: Some metabolite names
   have been translated using standard IUPAC nomenclature and common
   biochemical naming conventions.
3.8. Correlation Analysis of Differential Microbial Genera, Metabolites, and
Production Performance in H. discus hannai
   To elucidate the potential mechanisms by which LP-fermented feed
   modulates abalone production performance through intestinal
   microbiota–metabolite crosstalk, a Spearman correlation analysis was
   conducted between the differential bacterial genera, metabolites,
   growth indices (total weight gain rate), and survival rate. The
   association heatmap ([100]Figure 6) reveals distinct interaction
   patterns, where the red and blue regions denote positive and negative
   correlations, respectively, reflecting the potential microbial
   regulation of metabolic pathways and host physiology.
Figure 6.
   [101]Figure 6
   [102]Open in a new tab
   Correlation analysis of differential bacterial genera with other
   indexes. * p < 0.05, ** p < 0.01.
4. Discussion
   This study multidimensionally evaluates the effects of soybean meal
   fermented with Lactobacillus plantarum (LP) on feed quality, growth
   performance, intestinal health, and metabolic regulation in abalone (H.
   discus hannai). The results demonstrate that LP fermentation
   significantly enhanced key fatty acids in soybean meal, including a
   two-fold increase in cis-9-palmitoleic acid and a 14% elevation in
   α-linolenic acid (ALA), alongside notable improvements in amino acids
   such as L-histidine and L-asparagine.
   Critically, these nutritional enhancements translated to significant
   biological outcomes. Feeding with LP-fermented feed markedly improved
   abalone growth rate (263% vs. 201% in the control group, CK) and
   survival rate (61.66% vs. 45.33% in CK). Beyond growth metrics,
   mechanistic investigations revealed profound effects on intestinal
   physiology: LP fermentation enhanced intestinal morphology (elongated
   villi and structural integrity), upregulated tight junction proteins
   (Claudin and ZO-1), suppressed inflammatory cytokines (TNF-α, IL-16),
   and activated antioxidant pathways (Keap1 downregulation), collectively
   optimizing intestinal health.
   Further elucidating the drivers of improved health and growth, LP-fed
   abalone exhibited increased gut microbiota diversity, elevated
   abundances of Mycoplasma and Ochrobactrum, and differential metabolites
   enriched in tryptophan metabolism and the pantothenate/CoA biosynthesis
   pathways, revealing a potential microbiota–metabolism axis driving
   growth promotion.
   Positioning these findings within existing knowledge, this study aligns
   with prior research on probiotic-fermented feeds in aquaculture, but
   also unveils novel insights. Regarding nutritional enhancement, earlier
   studies consistently reported that microbial fermentation degrades
   antinutritional factors in soybean meal and liberates free amino acids.
   For instance, N. Muhamad Nor [[103]21] observed significant increases
   in lysine and methionine content after lactic acid bacteria
   fermentation, consistent with the marked elevation of L-histidine and
   L-asparagine here. However, our work uniquely highlights the
   paradoxical enrichment of ω-3 fatty acids (ALA) alongside DHA
   reduction—a phenomenon seldom reported. This discrepancy may stem from
   LP’s metabolic specificity: earlier studies suggested that lactic acid
   bacteria preferentially degrade long-chain fatty acids via β-oxidation
   [[104]22], potentially accelerating DHA catabolism, while ALA
   accumulation could arise from bacterial biosynthesis or selective
   substrate utilization [[105]23]. These nuanced findings underscore the
   need for multi-omics approaches (e.g., lipidomics and transcriptomics)
   to dissect fatty acid metabolic networks.
   Transitioning to growth performance, while LP-fed abalone exhibited
   higher weight gain than CK, it underperformed compared to the
   seaweed-based HD group—a result partially congruent with [[106]24], who
   demonstrated that fermented soybean meal could replace 30% of fishmeal
   without compromising fish growth. The likely explanation for HD’s
   superiority resides in its polysaccharide-rich matrix and trace element
   content, unmatched by fermented feeds. Notably, a key advantage of the
   LP diet emerged in efficiency: the significantly lower feed conversion
   ratio (FCR) implies enhanced nutrient utilization, a mechanism
   plausibly linked to the observed intestinal remodeling and microbiota
   modulation. For example, villus elongation directly expands nutrient
   absorption surfaces [[107]25], while upregulated tight junction
   proteins fortify barrier integrity, mitigating leaky gut risks
   [[108]26]. These observations not only corroborate the “gut
   health–nutrient utilization” axis proposed in probiotic studies, but
   extend it by integrating structural, immunological, and microbial
   dimensions—a holistic perspective that was previously absent.
   The gut microbiota findings further reveal both consonance and
   divergence from the literature. The marked enrichment of Tenericutes
   and Mycoplasma in LP-fed abalone contrasts with Ifra Ghori et al.
   (2022) [[109]27], who reported the probiotic-driven suppression of
   conditional pathogens in fish. Significantly, the 14-fold surge in
   Ochrobactrum—a genus renowned for xenobiotic degradation
   [[110]28]—suggests its role in detoxifying feed-derived contaminants,
   indirectly bolstering host health. Nevertheless, comparative analysis
   highlights a challenge: the higher OTU diversity in the HD group
   underscores the ecological superiority of natural diets in maintaining
   microbial stability, urging the future exploration of hybrid feeding
   strategies.
   Metabolomic insights add another layer of understanding, delineating
   the multidimensional regulatory effects of LP fermentation.
   Differential metabolites enriched in the tryptophan metabolism
   (kynurenine pathway) align with suppressed TLR4/NF-κB signaling,
   implying that tryptophan derivatives mitigate intestinal inflammation—a
   mechanism known in mammals [[111]29], now extended to mollusks.
   Crucially, the upregulation of artemotil and isethionic acid,
   correlated with Wolinella abundance and growth metrics, provides direct
   evidence for a “microbiota–metabolite–host” axis. This multi-omics
   integration transcends conventional single-parameter analyses, offering
   unprecedented resolution into probiotic mechanisms—an advancement
   addressing critical gaps in earlier aquaculture research.
   Finally, this study identifies some key limitations that point to
   future directions: the metabolic mechanism driving DHA reduction
   remains unclear, potentially addressable by stable isotope tracing; the
   absence of long-term assessments on reproductive performance
   necessitates extended trials; and the lack of functional gut microbiota
   profiling (metagenomics) limits causal insights into
   microbiota–metabolite interactions, highlighting the need to integrate
   metagenomics with metabolic flux studies. And the potential for
   enhanced resistance against specific pathogens like Vibrio harveyi
   requires validation through dedicated challenge trials. Additionally,
   exploring yeast co-fermentation strategies may further optimize fatty
   acid composition and feed’s nutritional value.
5. Conclusions
   This study multidimensionally deciphers how LP-fermented soybean meal
   promotes abalone growth through three synergistic mechanisms: nutrient
   fortification, intestinal health optimization, and
   microbiota–metabolome network remodeling. These findings advance the
   theoretical framework for probiotic applications in aquaculture by
   establishing quantitative correlations between fermentation-induced
   nutritional shifts (ALA accumulation) and host physiological responses.
   Specifically, this study provides actionable insights for sustainable
   feed development, including optimizing fermentation parameters to
   enhance GABA production for improved stress resistance and modulating
   microbiota-metabolite crosstalk to promote growth efficiency.
Author Contributions
   Z.L.: conceptualization, methodology, software, investigation, formal
   analysis, writing—original draft, writing—review and editing; L.K. and
   C.H.: data curation, writing—original draft; S.P.: visualization and
   investigation; M.Z.: resources and supervision; F.L.:
   conceptualization, funding acquisition, resources, supervision. All
   authors have read and agreed to the published version of the
   manuscript.
Institutional Review Board Statement
   This study was conducted in accordance with the Declaration of Helsinki
   and was approved by the Ethical Committees of institute of
   Biotechnology, Fujian Academy of Agricultural Sciences
   (BI-AEC-20230307) on 7 March 2023.
Data Availability Statement
   The datasets presented in this study can be found in online
   repositories.
Conflicts of Interest
   The authors declare no conflicts of interest.
Funding Statement
   The authors declare that financial support was received for the
   research, authorship, and/or publication of this article. We are
   grateful for the financial support from Fujian Provincial Special Fund
   Project for Promoting the High-quality Development of Marine and
   Fishery Industry in 2023 (FJHYF-L-2023-7).
Footnotes
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References