Weaning piglets are highly susceptible to enterotoxigenic Escherichia coli (ETEC) infections, which can cause intestinal barrier function dysfunction and death. However, there is still a lack of efficient, economical, and safe nutritional interventions. This study aimed to investigate the effects of combining butyrate with niacin on intestinal barrier function repair and resistance to ETEC infection in weaned piglets. In this study, two 14-d animal experiments were designed to observe the optimal butyrate-to-niacin ratio and assess their responses to the ETEC challenge.

Supplementation with butyrate and niacin at a ratio of 100:2 (2,000 mg/kg butyrate and 40 mg/kg niacin, BN2) increased the average daily gain (ADG) and reduced the diarrhea incidence. We also observed an increase in the levels of nicotinamide adenine dinucleotide (NAD) in the colon of weaned piglets. Notably, BN2 promoted amino acid anabolism in the colon and enhanced glycolysis and the tricarboxylic acid (TCA) cycle by increasing the acetylation of key enzymes in the TCA. Furthermore, BN2 enhanced the expression of indispensable genes for the colonic mucosal barrier, including antimicrobial peptides such as porcine β defensin 1 (pBD1), porcine β defensin 2 (pBD2), and proline-arginine rich 39-amino acid peptide (PR39), tight junction proteins, and improved colonic microbiome composition. Based on these findings, we found that BN2 alleviated growth restriction and diarrhea, and modulated the expression of antimicrobial peptides, tight junction proteins, and cytokines to reduce colonic barrier function dysfunction in weaned piglets challenged with ETEC. Mechanistically, we confirmed that BN2 elevated the protein expression of acetylation of histone 3 lysin 27 (H3K27ac) and enhanced the binding of acH3K27 to the promoter regions of pBD1 and PR39.

Supplementation with BN2 improved growth performance, supported colonic barrier function repair, and enhanced disease resistance in weaned piglets challenged with ETEC. This offers new insights into nutritional strategies for intestinal barrier function repair of piglets infected with ETEC.

Aquaculture has grown rapidly in recent decades, yet recurrent bacterial disease outbreaks continue to cause severe economic losses and fuel concerns over antibiotic resistance. With antibiotic use increasingly restricted, sustainable disease management strategies are urgently required. Probiotics and natural bioactive compounds, such as curcumin, have emerged as promising alternatives, but their combined application remains underexplored.

We evaluated the co-administration of encapsulated probiotics and curcumin in functional feeds on growth performance and disease resilience of Asian seabass (Lates calcarifer) fingerlings challenged with Streptococcus iniae and Vibrio parahaemolyticus. Among 11 probiotic strains screened, Lactiplantibacillus plantarum displayed the strongest inhibitory effect and highest viability following alginate-based encapsulation. Curcumin selectively inhibited pathogens without affecting probiotic growth, and synergistic antimicrobial effects were observed when combined with probiotics. Feeding trials showed that encapsulated probiotics increased body weight by 33% compared with controls. Diets supplemented with probiotics, curcumin, or their combination significantly improved feed conversion efficiency and survival. Notably, co-supplementation yielded the greatest benefits, achieving the highest survival rates under pathogen challenge and enhancing immune protection beyond individual treatments.

These findings demonstrate that probiotics combined with curcumin constitute a natural, antibiotic-free strategy to improve fish growth and disease resistance. This functional feed approach provides a scalable and sustainable platform for advancing responsible aquaculture and may inform broader applications in animal production systems.

Selective breeding has substantially improved productive and reproductive traits in pigs. Yet, these traits are biologically interconnected, and selection for one often affects others in unintended ways. While genomewide association studies (GWAS) have uncovered many loci linked to these traits, they provide limited insight into causal mechanisms. Mendelian randomization (MR) provides a robust framework for inferring causality and identifying shared genetic determinants. Here, we integrated MR, colocalization, and functional genomics to investigate the biological links between growth, carcass composition, and reproduction in pigs.

Using average daily gain (ADG) as the exposure, MR revealed potentially significant causal effects (P < 0.05) of ADG on carcass composition traits, including backfat thickness (BFT: ) and loin muscle depth (LMDEP: ), suggesting a potential causal contribution of increased ADG to both fat deposition and muscle development. Additionally, ADG showed a negative causal association with age at first farrowing (AFF: ), indicating that faster growth promotes earlier sexual maturity and reproductive onset. In addition to the statistical evidence, gene annotation of instrumental variants (IVs) identified overlapping candidate genes, which may help explain the causal associations observed across the four exposure-outcome analyses. Among these, MC4R and CDH20 were supported by colocalization analysis, indicating shared genetic signals potentially linking growth, carcass composition, and reproductive traits. Integrative analysis supported the tissue-specific roles of these genes in regulating growth, carcass composition, and reproduction.

Our findings suggest a shared genetic architecture and provide potential evidence of a causal influence of ADG on carcass composition and reproductive traits in pigs. This integrative framework supports the development of multi-trait breeding strategies that enhance productivity while managing inherent trade-offs in regulating complex traits.

Chronic exposure to low-dose lipopolysaccharide (LPS) in poultry farming environments induces persistent respiratory inflammation, resulting in lung injury and impaired growth performance in broilers. Bacillus velezensis (BV) is a probiotic with known antibacterial and immunomodulatory activities, yet its role in respiratory health remains poorly understood. This study aimed to assess the potential benefits of BV in alleviating chronic pneumonia triggered by LPS in broilers and to clarify its mechanistic pathways.

A chronic LPS intratracheal instillation model was established, comprising control, LPS, and BV + LPS groups. BV supplementation significantly ameliorated LPS-induced growth impairment (P < 0.05), inhibited the synthesis of key inflammatory mediators, and mitigated oxidative stress in serum and bronchoalveolar lavage fluid (P < 0.05). Integrated multi-omics analyses revealed that BV remodeled the pulmonary microbiota, enriching isoflavone-metabolizing taxa including Blautia and unclassified Lachnospiraceae (P < 0.05), which was associated with elevated pulmonary concentrations of daidzein, genistein, and glycitein (P < 0.05). Transcriptomic together with molecular analyses revealed that BV enhanced the activation of PPAR-γ while attenuating NF-κB pathway activity, thereby reducing the expression of genes associated with inflammation (P < 0.05). In vitro, experiments showed that daidzein and genistein inhibited cellular inflammatory responses through PPAR-γ signaling. BV culture supernatant directly suppressed NF-κB/NLRP3 inflammasome activation in chicken HD11 macrophages, reduced intracellular reactive oxygen species (ROS) generation, and shifted macrophage polarization toward an anti-inflammatory phenotype (P < 0.05).

These findings demonstrate that BV alleviates LPS-induced chronic pneumonia through two complementary pathways, as it remodels the pulmonary microbiota to enhance isoflavone metabolism and thereby suppress inflammation, while its own metabolites also directly inhibit inflammatory signaling. This study provides new insight into probiotic-based interventions for respiratory health in livestock.

The bovine liver is a key organ governing nutrient metabolism, immune regulation, and growth. However, the effects of birth season and growth potential on hepatic protein expression remain poorly understood.

This study investigated the liver proteome of steer calves born during the spring and fall 2023 calving seasons (n = 5-6 steer/growth trait/season). Using a comparative label-free quantitative proteomics approach, 2,133 proteins were identified and quantified following feedlot entry. Principal component and hierarchical clustering analyses revealed distinct segregation of protein expression profiles according to both birth season (spring vs. fall) and growth trait (high vs. moderate), with calving season exerting the stronger overall influence. Bioinformatic and pathway enrichment analyses identified significant growth- and season-independent proteins. Growth-associated proteins were primarily involved in immune signaling, including antigen processing and presentation, as well as glutathione-CYP detoxification pathways. In contrast, season-independent proteins were enriched in pathways related to circadian rhythm, hormonal regulation, and muscle contraction.

These results demonstrate that both growth trajectory and season of birth independently modulate the bovine liver proteome, with stronger seasonal effects, providing novel insight into the metabolic and immune mechanisms underlying variation in calf growth performance.

Mastitis, one of the most prevalent inflammatory diseases in female mammals, causes significant economic losses in livestock farming. Notably, the natural flavonoid compound baicalin exhibits potent anti-inflammatory activity. However, its efficacy in alleviating mastitis severity and the underlying molecular mechanisms remain unexplored. Therefore, this study aims to investigate the protective effects of baicalin in alleviating mastitis and its key molecular mechanisms.

This study demonstrated in vivo that baicalin effectively alleviates mastitis symptoms in dairy cows and mice, primarily manifested by reduced tissue pathological damage, decreased levels of pro-inflammatory cytokines, and maintain the integrity of the blood-milk barrier (BMB). Multi-omics sequencing analysis indicated that IL-17 and TNF signaling pathways play crucial roles in this process. Further studies demonstrated that IL-17RA^-/- mice exhibited a phenotype similar to that observed with baicalin treatment, confirming the importance of this pathway. Notably, network pharmacology screening combined with molecular dynamics simulations revealed stable binding of baicalin to IL-17RA, suggesting that baicalin exerts its protective effect to alleviate mastitis by targeting IL-17RA. Mechanistically, both baicalin treatment and IL-17RA deletion block activation of key downstream pathways of the IL-17 signaling pathway, including MAPK, ERK and NF-κB, thereby suppressing excessive activation of the TNF signaling pathway, preventing exacerbation of the inflammatory response and barrier damage.

In conclusion, this study demonstrates that baicalin inhibits excessive activation of the IL-17/TNF signaling pathway by targeting IL-17RA, thereby reducing inflammatory responses and BMB damage within the mammary gland and alleviating mastitis severity.

Scutellaria baicalensis, a traditional Chinese medicine (TCM), has demonstrated significant therapeutic efficacy in treating respiratory diseases caused by Mycoplasma gallisepticum (MG). However, the effective components of Scutellaria baicalensis are complex, and the material basis for its efficacy anti-MG infection remains unclear. This study aims to elucidate the molecular mechanism by which Scutellaria baicalensis exosome-like nanoparticles (SBELNs) and the key effector molecule, miR159a, regulate inflammation-induced injury caused by MG infection.

SBELNs were isolated from Scutellaria baicalensis root by ultracentrifugation. The in vivo and in vitro transport of SBELNs was investigated through live imaging and laser confocal microscopy after staining with DIR fluorescent dye. Key miRNAs were screened via RNA sequencing, and target genes were predicted using online databases. The interaction between miR159a and its target gene, cyclic nucleotide-gated channel alpha 1 (CNGA1), was validated using a dual-luciferase reporter assay. Furthermore, the regulatory network of the miR159a/CNGA1 axis was systematically analyzed.

SBELNs can specifically target lung tissue. Subsequently, SBELNs release bioactive components that alleviate the lung inflammatory damage caused by MG infection. This beneficial effect stems from two aspects. Firstly, the flavonoid metabolites encapsulated in SBELNs directly suppress the inflammatory damage caused by MG infection. Secondly, the microRNA in SBELNs regulates calcium ion homeostasis via the miR159a/CNGA1 axis. This relieves the intracellular calcium overload induced by MG and participates in the regulation of the immune system by modulating calcium ions. The microRNA in SBELNs regulates calcium ion homeostasis through the miR159a/CNGA1 axis, thereby alleviating MG-induced intracellular calcium overload, mitochondrial damage, excessive ROS, and overactivation of the NF-κB inflammatory pathway.

This article expounds that SBELNs alleviate lung injury caused by MG infection by regulating calcium homeostasis. This discovery demonstrates the anti-infective capability SBELNs, but also supports the development of natural drug delivery systems.

Under high-concentrate feeding conditions, ruminants often experience rumen microecological imbalance and dysfunction, which can impair growth performance and increase the risk of antibiotic resistance gene (ARG) dissemination.

To evaluate the ameliorative effects of Aspergillus niger (A. niger) cultures, fattening sheep were randomly allocated into the following five groups: a control group (CON), a control diet supplemented with 250, 500, or 1,000 mg/kg A. niger cultures (designated as LA, MA, and HA, respectively); and an antibiotic group supplemented with 5,000 mg/kg chlortetracycline premix (AN). Microbial community analysis indicated that several bacterial taxa, including Succinivibrio sp900317105, Prevotella sp002353485, Quinella sp017515635, Quinella sp015206805, and Prevotella sp900320255, were significantly enriched in the A. niger culture-supplemented groups (P < 0.05). ARG profiling showed that the abundance of tetracycline resistance genes was significantly lower in all A. niger groups compared with the CON and AN groups (P < 0.05), while β-lactam resistance genes were significantly reduced in the HA group (P < 0.05). Furthermore, the abundances of Rank I and Rank II ARGs were significantly higher in the AN group than in the other groups, whereas the abundances of Rank II and Rank IV ARGs were significantly lower in the A. niger culture groups than in the CON and AN groups. Metabolomic analysis further demonstrated that supplementation with A. niger cultures significantly decreased the concentration of N-decanoyl-L-homoserine lactone (P < 0.05) while increasing the levels of N-3-oxotetradec-7Z-enoyl-L-homoserine lactone, indole-3-methyl acetate, and indole-3-propionic acid (P < 0.05).

These findings suggest that A. niger cultures can reduce the abundance of ARGs and mitigate the risk of ARG dissemination by modulating the rumen microbial community and associated metabolites.

Colostrum is recognised as the "golden elixir of health" due to its optimal chemical, immunological and nutraceutical properties for newborns, but little is known about its nature in the pig. This study aims to provide a multi-omics characterisation of pig colostrum from different parities (gilts, n = 7, second, n = 7 and mature, n = 6 sows) to identify the most relevant bioactive compounds associated with piglet survival and average daily gain (ADG) and faecal microbiota till d 6 and d 24.

Nine hundred and fifty metabolites (108 chemically confirmed) and 71 fatty acids (FAs) were characterised in colostrum. Parity class was the main driver for piglet survivability (P < 0.001; highest in second parity), metabolomics (R² = 0.97; Q² = 0.52; > 200 discriminated metabolites) and lipidomic profile (22 discriminated FAs) and piglet faecal microbiota (beta diversity P < 0.05 at d 6 and d 24). Colostrum composition allowed clustering for piglet mortality from d 0 to d 6 (Q² > 0.50). Mortality classes at d 6 were discriminated by 177 metabolites and 2 FAs and 248 metabolites and 21 FAs at d 24. At both timepoints a higher abundance of C18∶2 8trans, 10cis discriminated for lower mortality (importance = 1 for d 6 and 0.34 for d 24). Pathway analysis at d 6 and d 24 indicated arginine biosynthesis and alphalinoleic acid metabolism as most enriched metabolism in swine colostrum related to higher survivability. The multiomics integration analysis revealed that a higher faecal abundance of Lachnospiraceae_FCS020, Holdemania, Roseburia, and a higher colostrum abundance of C18∶2 8trans, 10cis, and the C18∶1 5trans and salicylic acid as metabolites were the most associated with a lower mortality. The ADG classes d 0-24 were discriminated by 151 metabolites and 33 FAs. Higher ADG (240 g/d) was discriminated by colostrum vitamin E, histidine, and branched-chain amino acids (VIP score > 1), while L-kynurenine and gamma-aminobutyric acid were linked to lower growth, suggesting maternal stress.

This study confirms the importance of parity order in shaping colostrum composition and identifies several bioactive compounds, some parity-dependent and others parity-independent, that may be associated with improved piglet survival and gut microbiota maturation. The findings may also support the development of next-generation artificial colostrum supplements.

Follicular development is a prerequisite for vertebrate reproduction, and it is precisely regulated by complex genomic conformations and regulatory elements. However, the dynamic changes in the interaction between the three-dimensional genome and regulatory elements of granulosa cells (GCs) during avian follicular development are still unclear. Here, we integrated RNA sequencing, ATAC sequencing, CUT&Tag, and Hi-C of GCs in 7 stages of Pekin ducks (Anas platyrhynchos domestica) to construct a high-resolution three-dimensional cis-regulatory map of follicular development, revealing the chromatin dynamics basis of avian folliculogenesis.

Our integrative analysis reveals that H3K27ac dynamics, rather than chromatin accessibility alone, are strongly associated with the stage-specific transcriptional increase of follicle selection and maturation. We identified enhancers and super-enhancers (SEs) that are significantly correlated with the expression of key follicular genes. Regarding 3D genome organization, we observed that topologically associating domains (TADs) remained largely stable, serving as a structural scaffold. However, stage-specific boundary changes coincided with the transcriptional alterations of key regulator genes. Furthermore, we inferred putative gene regulatory networks (GRNs) comprising 46 core transcription factors (TFs) predicted to be closely linked to follicular development. Finally, comparative analysis highlighted both the conservation and species-specificity of these regulatory elements between birds and mammals.

Our study provides an integrative, multi-omics resource that offers novel insights into the epigenomic landscape of duck follicular development. The resulting dataset and regulatory map establish a valuable foundation for further mechanistic studies of folliculogenesis and for understanding regulatory divergence across species.