Search Results (5,458)

Salinity stress represents a critical environmental constraint that significantly limits the development of tilapia aquaculture in brackish water environments. Its substantial impacts on fundamental physiological processes in fish, particularly osmotic balance, energy metabolism, and antioxidant defense mechanisms, have become a major scientific concern in aquaculture research. To systematically elucidate the molecular mechanisms underlying the response of genetically improved farmed tilapia (Oreochromis niloticus) to salinity stress and to test the hypothesis that it adapts through metabolic reprogramming for energy reallocation under such conditions, this study employed an integrated transcriptomic and metabolomic approach. Through a rigorously controlled experimental design with freshwater (0‰) as the control group and brackish water (24‰) as the experimental group, we conducted a comprehensive analysis of dynamic changes in gene expression profiles and metabolite spectra in the liver tissues of experimental fish. The study yielded the following key findings: First, salinity stress significantly suppressed growth performance indicators, including body weight and length, while simultaneously inducing extensive transcriptomic restructuring and profound metabolic remodeling in liver tissue. A total of 1529 differentially expressed genes (including 399 up-regulated and 1130 down-regulated genes) and 127 significantly differential metabolites were identified. Second, the organism achieved strategic reallocation of energy resources through coordinated suppression of multiple energy-consuming anabolic pathways, particularly steroid biosynthesis and fatty acid metabolism, with the remarkable down-regulation of Fasn, a key gene in the fatty acid synthesis pathway, being especially prominent. Energy-sensing and metabolic homeostasis regulatory networks played a central coordinating role in this process, guiding the organism through metabolic reprogramming by regulating downstream metabolic nodes. From a multi-omics integrative perspective, this study provides in-depth insights into the sophisticated metabolic remodeling and energy allocation strategies employed by GIFT to cope with salinity stress. These findings, particularly the suppression of fatty acid biosynthesis and the reprogramming of glycolysis/gluconeogenesis pathways, not only elucidate the molecular mechanisms by which teleosts achieve environmental adaptation through energy reallocation, but also provide actionable molecular targets for the selective breeding of salinity-resilient tilapia strains. Full article

Microcystin-LR (MC-LR), produced by Cyanobacteria, is being detected in many types of waters, posing a universal threat to aquatic animals. However, there have been few comprehensive endpoints assessed, including oxidative stress, transcriptome changes, intestinal microbiota, and histopathology, in anurans exposed to MC-LR. In this study, all these effects of MC-LR on Chinese brown frog (Rana chensinensis David, 1875) tadpoles were investigated by exposing the tadpoles to MC-LR at different concentrations (0, 0.1, 1.0, 5.0, and 10.0 μg/L) for 7 days. Our results revealed that treatment of tadpoles with the high MC-LR dosage (10.0 μg/L) induced a significant increase in malondialdehyde (MDA) content and decreases in superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity, and total antioxidant capacity (TAC). RNA-seq analysis of the liver showed that the number of differentially expressed genes (DEGs) was 2361 under lower MC-LR stress (1.0 μg/L), while the number of DEGs increased to 3185 under higher MC-LR stress (10.0 μg/L). Gene Ontology analysis showed that several biological processes and molecular functions related to digestion were enriched in both MC-LR treated groups, such as digestion, serine-type endopeptidase activity, and serine-type peptidase activity. KEGG enrichment analysis also indicated that the digestion for pancreatic secretion, protein digestion and absorption, and fat digestion and absorption pathways were significantly enriched in the treatment groups. Additionally, the bacterial richness was elevated by MC-LR exposure. At the phylum level, treatment with MC-LR changed the relative abundances of Desulfobacterota, Fusobacteriota, and Actinobacteriota. At the genus level, MC-LR caused significant alterations in the abundances of 23 genera. Furthermore, examination of sections obtained from the livers and intestines of tadpoles in the treatment groups showed damaged histological structure. The knowledge from this study will have potential value for understanding the mechanisms related to MC-LR toxicity in anurans. Full article

Early weaning in intensive lamb production improves reproductive efficiency but predisposes lambs to diarrhea, oxidative stress, and intestinal barrier dysfunction, highlighting the need for non-antibiotic strategies to protect gut health. This study evaluated whether a sheep-derived mixed probiotic could alleviate early weaning–induced intestinal injury and clarified its potential molecular mechanisms. Early weaning reduced body weight, average daily gain and feed efficiency, increased diarrhea, decreased plasma and colonic catalase (CAT), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) activities, increased malondialdehyde (MDA), elevated interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), reduced interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), increased plasma and mucosal immunoglobulin A, M, and G (IgA, IgM, IgG), and increased colonic lipopolysaccharide (LPS) with reduced diamine oxidase (DAO). Intestinally, EW induced villus atrophy, deeper crypts, lower villus height-to-crypt depth ratios, goblet cell loss, higher histopathological scores, and decreased colonic mucin 2, zonula occludens-1, claudin-1, and occludin. Probiotic supplementation partially reversed these alterations, restoring antioxidant enzyme activities, improving villus architecture and barrier protein expression, and rebalancing cytokine and immunoglobulin profiles. Transcriptomic and network analyses showed that early weaning activated Cytokine–cytokine receptor, NF-κB, TNF and Th17 pathways, whereas probiotics suppressed a weaning-responsive inflammatory gene module, downregulated key hub genes, and enhanced peroxisome proliferator-activated receptor (PPAR) signaling. These results show that supplementing early-weaned lambs with a mixed probiotic generated from sheep is an efficient nutritional strategy to reduce intestinal oxidative and inflammatory damage associated with weaning and to enhance their health and performance. Full article

Background/Objectives: Skin photoaging represents a predominant form of extrinsic aging, characterized by structural and functional impairment of the skin barrier. In severe cases, it may precipitate dermatological diseases and even tumors. Given the prevalence and detrimental effects of skin photoaging, strategies for its effective prevention and mitigation have garnered significant research interest. Chrysanthemum morifolium Ramat cv. ‘Hangju’ contains diverse bioactive compounds, including flavonoids, phenylpropanoids, phenolic acids, and polysaccharides, which have been proven to exhibit antioxidant and anti-inflammatory effects. Methods: This study employed a UVB-induced mouse model of skin photoaging to evaluate the potential of dietary supplementation with Chrysanthemum morifolium Ramat cv. ‘Hangju’ flower extract (CME) in vivo. Results: In the photoaged skin of female SKH-1 hairless mice, dietary supplementation with CME significantly increased skin moisture content, reduced wrinkle formation, suppressed epidermal hyperplasia, enhanced collagen density, and suppressed the senescence marker expression and DNA damage marker expression. Analysis of the skin transcriptome suggested that CME could alter gene expression patterns and potentially modulate critical signaling pathways involved in skin homeostasis. Moreover, 16S rRNA sequencing indicated that CME mitigated UVB-induced gut microbiota dysbiosis. Conclusions: These preclinical findings reveal the anti-photoaging property of dietary CME supplementation and point to its potential application as a functional dietary supplement for promoting skin health. Full article

Skin aging arises from extracellular matrix degradation, inflammation, and pigmentation dysregulation, yet most existing rejuvenation strategies target only a subset of these processes. This study investigated the multimodal rejuvenation potential of a dual hyaluronic acid compound (DHC), composed of low- and high-molecular-weight HA integrated within a minimally cross-linked hybrid complex. In vitro assays using dermal fibroblasts, melanoma cells, and macrophages demonstrated that DHC enhanced fibroblast viability, collagen I/III and elastin production, antioxidant enzyme activity, and wound-healing capacity while reducing senescence markers. DHC markedly suppressed melanogenesis by downregulating the gene expression of MITF, TYR, and TRP1, and exerted strong anti-inflammatory activity by decreasing nitric oxide (NO) production and key cytokines, including TNF-α, IL-1β, IL-6, and CCL1. In a UVB-induced photoaging rat model, DHC reduced wrinkle depth, epidermal thickening, and melanin accumulation while improving elasticity, collagen density, hydration, and barrier integrity. Across these outcomes, DHC demonstrated biological effects that were comparable to, and in selected endpoints greater than, those of commonly used biostimulators and HA fillers in preclinical models. Collectively, these laboratory findings suggest that DHC exhibits broad preclinical bioactivity through combined biostimulatory, antioxidant, anti-inflammatory, and pigmentation-modulating effects. Further mechanistic and clinical studies are required to determine its translational relevance. Full article

Significant differences in reproductive performance exist between meat-type ducks (e.g., Qiangying Duck, QD) and laying-type ducks (e.g., Shaoxing Duck, SD). The molecular mechanisms underlying these differences, particularly concerning ovarian development and function, remain incompletely understood. This study aimed to comprehensively characterize the ovarian transcriptomes of these two duck types, focusing on differential gene expression and post-transcriptional regulatory events. We performed an integrated full-length transcriptome analysis of ovarian tissues from these two breeds using PacBio SMRT and Illumina sequencing. Bioinformatic analyses, including functional annotation, differential expression analysis, and the identification of APA events, were used. We discovered substantial breed-specific differences in alternative polyadenylation (APA), with SD ducks exhibiting significant 3′UTR shortening in 3799 genes and 3′UTR lengthening in 1626 genes compared to QD. The integrated analysis of differential gene expression and APA events highlighted key genes related to steroid hormone synthesis (HMGCS1, DHCR24), lipid metabolism (SCD), signal transduction (HRAS), and antioxidant defense (SOD1). The functional enrichment implicated critical pathways such as mitochondrial energy metabolism, oxidative phosphorylation, and fatty acid degradation. Our study provides a comprehensive atlas of post-transcriptional regulation in the duck ovary and reveals APA as a crucial process of gene regulation. APA may contribute to the differential ovarian function and egg-laying capacity between meat and laying ducks, thus offering valuable targets for genetic selection. Full article

Background/Objectives: Testicular toxicity is one of the most important chemotherapeutic adverse effects of Cisplatin (Cisp), which restricts its use and effectiveness. This study investigated the preventive effects of Vitis vinifera L. extract on Cisp-induced testicular injury in rats. Methods: Forty adult albino male rats were allocated into four groups: control, Vitis vinifera L. extract, Cisp, and co-treated (Vitis vinifera L. extract + Cisp). Sperm motility and count, serum reproductive hormones, oxidative/antioxidant biomarkers, pro-inflammatory cytokines, ferroptosis biomarkers, and gene expression profiles were evaluated. Results: Cisp administration markedly impaired reproductive performance, as evidenced by significant declines in serum FSH, LH, testosterone, and sperm motility and count. Cisp also induced oxidative stress by elevating MDA, GSSG, GPx, and 8-OHdG, while reducing SOD, Catalase, NRF2, and Ho-1 along with total and reduced GSH levels. Moreover, it triggered strong inflammatory responses and ferroptosis activation, with notable up-regulation of NFκB, TNF-α, IL-1β, ferritin, and cathepsin. Gene expression analysis revealed down-regulation of ARNTL, PI3K, and miR-125b and up-regulation of ASCL4, GSK3B, and COX2 following Cisp exposure. Conversely, co-treatment with Vitis vinifera L. extract significantly ameliorated these alterations, restoring sperm quality, hormone balance, antioxidant defenses, and modulating inflammatory, ferroptosis, and genetic responses toward normalcy in addition to restoring testicular and epididymal histoarchitecture without any significant effect in NRF2 and ARNTL expression. Additionally, co-treated groups with Vitis vinifera L. extract showed a significant decline in NF-kB p65 and increased PCNA testicular immunoreactivity with a substantial down-regulation in NF-kB p65 and PCNA epididymal immunoreactivity. Vitis vinifera L. extract alone did not affect any studied parameters as compared to the control group. Conclusions: These findings suggested that Vitis vinifera L. extract has a significant protective effect against Cisp-related testicular injury through antioxidative, anti-inflammatory, and anti-ferroptotic mechanisms. Full article

Background/Objectives: Diabetes mellitus impairs skin wound healing by promoting a chronic inflammatory response and increased oxidative stress. This study aimed to investigate the healing potential of menthol in skin wounds of diabetic rats. Methods: A single dose of streptozotocin (50 mg/kg, i.p.) induced type 1 diabetes mellitus in male Wistar rats. After nine days, a skin wound was made on the rats’ back and treated with vehicle, insulin-based cream (0.5 U/g), or menthol-based cream (0.5%) for 14 days. After the euthanasia, the wound area was destined for assays of anti-inflammatory and antioxidant activity, protein expression levels by Western blotting, measurement of MPO activity, and quantitative mRNA expression. Nitrite levels were measured in blood plasma. Results: The group treated with menthol-based cream decreased the wound area by 94%. Also, menthol reduced the levels of TNF-α and IL-6 and increased IL-10 levels, besides stimulating the activity of antioxidant enzymes SOD, GPx, and GR, and enhancement in GSH and nitrite levels. Menthol downregulated the expression of Nfκb and upregulated the Il10 and Ki67 gene expression and the eNOS protein expression. Conclusions: Topically applied menthol accelerated the skin wound healing in diabetic rats through anti-inflammatory and antioxidant activities and increased cell proliferation, supporting its potential as a therapeutic strategy for diabetic wound management. Full article

Tomato (Solanum lycopersicum L.) is an important horticultural crop. Carotenoid cyclase dioxygenase (CCD) is an enzyme responsible for cleaving carotenoids, which is involved in regulating plant growth and response to abiotic stresses. However, the role of SlCCDs in tomato stress resistance remains unclear. This study used the tomato variety ‘Micro-Tom’ as the material to investigate the function of SlCCDs in stress responses. Through whole-genome analysis, a total of 12 SlCCDs members (SlCCD1–SlCCD12) were identified. Systematic evolutionary analysis classified them into four branches, and members within the same branch maintained a conserved structure. The promoter analysis revealed that SlCCDs contain multiple hormones and stress response elements. The qRT-PCR analysis revealed that SlCCD11 was the most highly expressed gene in the leaves. In addition, multiple SlCCDs showed significant responses to abscisic acid (ABA), methyl jasmonate (MeJA), light, and sodium chloride (NaCl) treatments. Among them, the expression of SlCCD11 significantly increased under salt stress. By silencing SlCCD11 using virus-induced gene silencing (VIGS) technology, it was found that the chlorophyll content, antioxidant enzyme activity, and ABA-related gene expression in the TRV:SlCCD11 plants under salt stress were all lower than the control samples, while the carotenoid content and ROS accumulation were higher. This indicates that SlCCD11 is a positive regulatory factor for salt stress. In conclusion, this study systematically analyzed the SlCCD gene family and revealed the positive role of SlCCD11 in tomato response to salt stress, providing a candidate gene for genetic improvement of crop stress resistance. Full article

Eugenia pyriformis Cambess., popularly known as uvaia, is a native Brazilian species belonging to the Myrtaceae family that has attracted pharmacological interest due to its richness in bioactive secondary metabolites. Previous studies have reported antimicrobial and antioxidant activities of the essential oil obtained from its leaves, reinforcing its therapeutic potential. In this context, the present study aimed to extract and characterize the essential oil from E. pyriformis leaves cultivated in the mountainous region of Rio de Janeiro, Brazil, and to evaluate its anti-inflammatory potential through in vitro and in vivo models. Gas chromatography mass spectrometry (GC–MS) analysis revealed a predominance of sesquiterpene hydrocarbons, mainly γ-muurolene, δ-cadinene, and β-caryophyllene. The oil exhibited significant anti-edematogenic activity in carrageenan-, prostaglandin E₂-, and bradykinin-induced paw edema models in adult female Swiss mice, suggesting modulation of inflammatory mediators, possibly through inhibition of the cyclooxygenase (COX) pathway. Conversely, no effect was observed in the compound 48/80-induced model, indicating the absence of activity on histamine- and serotonin-mediated processes. In vitro assays demonstrated that the oil reduced TNF-α and IL-1β gene expression in RAW 264.7 macrophages, confirming its ability to modulate pro-inflammatory cytokines. Taken together, these findings demonstrate that the essential oil of E. pyriformis exerts anti-inflammatory activity through multiple targets. Full article

Potato (Solanum tuberosum L.) is one of the most widely cultivated crops in the world; however, drought is a major constraint to its productivity. Arbuscular mycorrhizal fungi (AMF) have been shown to improve plant resistance under conditions of water stress. However, their effects on potato plants are poorly studied. The purpose of this study was to evaluate the potential of two AMF inocula (two different strains of the AMF species Rhizophagus irregularis with different origin: Southern Spain MI₁ and Tunisia MI₂) on potato tolerance to drought stress through the determination of growth parameters, photosynthetic parameters, and antioxidant systems, under well-watered (WW; field capacity) and drought stress (DS; 50% of field capacity) conditions. Therefore, the experiment consisted of two factors: AMF strain and watering regime. The results showed that under drought stress conditions, AMF inoculation considerably stimulated photosynthetic performance as compared with non-inoculated controls. Moreover, leaf superoxide dismutase (SOD) and catalase (CAT) activities of inoculated plants were higher in WW conditions, but unchanged in DS conditions. Inoculated plants had significantly higher ascorbate peroxidase (APX) and glutathione reductase (GR) activities than non-inoculated plants under DS conditions. Also, expression of some antioxidant enzyme genes were upregulated by inoculation. Lipid peroxidation content of inoculated plants was lower than that of non-inoculated. Furthermore, there was a high positive correlation between mycorrhizal root colonization (RC) and almost all the measured parameters. The results of this study indicated that AMF inoculation could enhance potato plant tolerance to water stress through the induction of antioxidant mechanisms implicated in scavenging oxygen-free radicals. Full article

Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, and disturbance of lysosomal degradation. Central to these processes is glutathione (GSH), a key antioxidant regulating redox balance and cellular homeostasis. This study aimed to evaluate the therapeutic potential of two dietary antioxidants—astaxanthin and Garcinia indica (kokum)—in modulating hepatic redox status, lysosomal function, and metabolic gene expression in a murine model of diet-induced NAFLD. A total of 120 male Swiss Webster mice were allocated into control and steatotic groups, followed by a 90-day supplementation period with astaxanthin, kokum, or their combination. Liver tissue was collected post-supplementation for biochemical, antioxidant, and qRT-PCR analyses. Outcomes included lysosomal enzymes activities, superoxide dismutase (SOD), GSH, vitamin C, total polyphenols, DPPH radical-scavenging activity, and total antioxidant capacity (TAC). NAFLD induced marked oxidative stress, lysosomal overactivation, and alteration of antioxidant-related gene expression. Combined supplementation restored GSH, enhanced TAC, reduced lysosomal stress markers, and significantly upregulated nuclear factor erythroid 2-related factor 2 (Nfe2l2) while downregulating fatty acid synthase (FASN) and partially rescuing lipoprotein lipase (LpL). Correlation analyses revealed strong associations between antioxidant capacity, lysosomal function, and transcriptional regulation, supporting the therapeutic relevance of combined antioxidant therapy for concurrent redox and lysosomal dysregulation in NAFLD. These findings underscore the therapeutic potential of targeting redox and cellular degradation pathways with antioxidant-based interventions to re-establish hepatic metabolic balance in NAFLD and related disorders. Full article

Macroalgae plays a significant role in the formulation of innovative and environmentally sustainable approaches to address food challenges. Specifically, green macroalgae serve as dietary supplements aimed at improving the health, growth, and feeding efficiency of various species of marine and freshwater fishes, as well as mollusks. The effects of Chaetomorpha linum extract (CLE) on growth performance, physiological responses, and disease resistance are studied in Bellamya bengalensis against Aeromonas hydrophila. In this experiment, adult B. bengalensis (4412 ± 165.25 mg) were randomly divided into 15 rectangular glass aquariums (35 snail/aquaria; 45 L capacity) and their basal diet was supplemented with different levels of CLE, including 0 (CLE0), 1 (CLE1), 2 (CLE2), 3 (CLE3), and 4 (CLE4) g/kg for 60 days. The growth performance in the CLE3 dietary group was significantly higher that of the CLE0 group, exhibiting both linear and quadratic trends in relation to dietary CLE levels (p < 0.05). The activities of pepsin, amylase, and lipase were found to be highest in CLE3 and lowest in CLE0. Both linear and quadratic responses to dietary CLE levels in digestive enzymes were observed (p < 0.05). The activities of superoxide dismutase and catalase in the hepatopancreas were found to be elevated in snails due to the synergistic effect of the supplemented CLE diet. Among different levels of diet given, CLE2-supplemented snails showed an increase in their enzyme activity (p < 0.05). Interestingly, all the CLE-treated snails expressed elevated levels of mucus lysozyme and mucus protein when compared to control (p < 0.05). Additionally, hepatopancreatic acid phosphatase and alkaline phosphatase activity were elevated in snails consuming CLE3 (p < 0.05). The transcription levels of immune-related genes, including mucin-5ac and cytochrome, were significantly elevated in snails that were fed a diet supplemented with 2–4 g of CLE/kg. Furthermore, the transcription level of the acid phosphatase-like 7 protein gene also increased in snails receiving CLE-supplemented diets. After a 14-day period of infection, snails that consumed a diet supplemented with 3–4 g/kg of CLE exhibited a notable increase in survival rates against virulent A. hydrophila. Based on the above findings, it is suggested that a diet supplemented with 3 g/kg of CLE may enhance growth, antioxidant and immune defense, and disease resistance in the freshwater snail B. bengalensis. Full article

Cannabinoids can bind to several cannabinoid receptors and modulate cellular signaling and gene expression relevant to inflammation and lipid homeostasis. Likewise, several vitamin E analogs can modulate inflammatory signaling and foam cell formation in macrophages by antioxidant and non-antioxidant mechanisms. We analyzed the regulatory effects on the expression of genes involved in cellular lipid homeostasis (e.g., CD36/FAT cluster of differentiation/fatty acid transporter and scavenger receptor SR-B1) and inflammation (e.g., inflammatory cytokines, TNFα, IL1β) by cannabinoids (cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC)) in human THP-1 macrophages with/without co-treatment with natural alpha-tocopherol (RRR-αT), natural RRR-αTA (αTAn), and synthetic racemic all-rac-αTA (αTAr). In general, αTAr inhibited both lipid accumulation and the inflammatory response (TNFα, IL6, IL1β) more efficiently compared to αTAn. Our results suggest that induction of CD36/FAT mRNA expression after treatment with THC can be prevented, albeit incompletely, by αTA (either αTAn or αTAr) or CBD. A similar response pattern was observed with genes involved in lipid efflux (ABCA1, less with SR-B1), suggesting an imbalance between uptake, metabolism, and efflux of lipids/αTA, increasing macrophage foam cell formation. THC increased reactive oxygen species (ROS), and co-treatment with αTAn or αTAr only partially prevented this. To study the mechanisms by which inflammatory and lipid-related genes are modulated, HEK293 cells overexpressing cannabinoid receptors (CB1 or TRPV-1) were transfected with luciferase reporter plasmids containing the human CD36 promoter or response elements for transcription factors involved in its regulation (e.g., LXR and NFκB). In cells overexpressing CB1, we observed activation of NFκB by THC that was inhibited by αTAr. Full article

This study aimed to investigate the effects of adding Red kojic rice (RKR) on the growth performance, digestive enzyme activity, non-specific immunity, antioxidant capacity, and intestinal health of Litopenaeus vannamei fed a diet with fishmeal replacement by soybean meal. Shrimps (initial mean weight = 1.88 ± 0.03 g) were fed six experimental diets for 8 weeks, including a normal fishmeal control group (FM), a soybean meal-replaced fishmeal group (H0), and four soybean meal-replaced fishmeal groups supplemented with 0.5%, 1%, 2%, and 4% RKR, respectively, which are designated as H1, H2, H3, and H4, respectively. Each group had three replicates, with 30 shrimp per replicate. The results showed that the final average weight (FWG), weight gain rate (WG), and specific growth rate (SGR) of H2 group were significantly higher than those of H0, H3, and H4 groups (p < 0.05). The feed conversion ratio (FCR) of H2 group was significantly lower than that of H0 and H4 groups (p < 0.05). In contrast to the H0 group, the blood ACP activity in the H2 group was significantly increased (p < 0.05). The blood lysozyme (LYZ) activity in H3 group was significantly higher than that in H1 group (p < 0.05), while the opposite was true for phenoloxidase (PO). The activities of trypsin and amylase in hepatopancreas of H3 group were significantly higher than those of H0 and H1 groups (p < 0.05). Compared with the FM group, the hepatopancreatic malondialdehyde (MDA) levels in H0, H3, and H4 groups were significantly increased (p < 0.05). Compared with the H0 group, the hepatopancreatic MDA levels in H1 and H2 groups were significantly decreased (p < 0.05). Analysis of gene expression levels in hepatopancreas revealed that antioxidant (gpx, sod, cat, gst, nrf2, trx, and ho-1), non-specific immune (tnf-α, il-1β, and ifn-γ), and digestive (trypsin and α-amylase) genes were suppressed in the H0 group but enhanced by RKR supplementation. Similar expression patterns of those genes were observed in the intestine. Microbial community analysis showed reduced diversity and altered composition in the H0 group, which were partially restored by RKR. Network analysis showed “small-world” property in microbial co-occurrence network. Metabolomic analysis revealed that among the differential metabolites, Bismurrayaquinone A and Harmol exhibit highly significant differences. Correlation analysis revealed that beneficial bacteria Rhodococcus_C and Oceanobacillus in H2 group exhibited higher richness and showed significant correlation. In conclusion, supplementation of 0.5–2% RKR promoted the growth performance, digestive enzyme activity, non-specific immunity, antioxidant capacity, and intestinal health of shrimp fed a diet with fishmeal replacement by soybean meal. The optimal RKR supplementing content is 1%. Full article