The intestinal lipid metabolism is a vital factor that affects energy homeostasis. However, the regulatory mechanisms of the intestinal lipid transport and absorption, which is the first step of intestinal lipid metabolism, remain unclear. In this study, we found that high-fat diet increased the expression of fatty acid transporter protein 4 (FATP4) and KDM4B in the small intestines of both male and female mice. In the enterocytes, fatty acids (palmitic acid and oleic acid) increased the expression of KDM4B and FATP4 dose- and time-dependently. Knockdown of KDM4B inhibited the fatty acids induced elevation of FATP4 and lipid absorption in the enterocytes. Meanwhile, our results showed that the HIF1α was increased by fatty acids in the small intestines and enterocytes, and the inhibition of HIF1α blocked the fatty acid-induced increase of KDM4B as well as FATP4 and lipid absorption. In summary, dietary fatty acids regulated FATP4 and lipid absorption in the small intestinal enterocytes via HIF1α and KDM4B. These findings provide insights into the regulatory mechanisms of intestinal lipid absorption and potential therapeutic targets to combat metabolic diseases such as obesity.
Drug-resistant bacteria pose an escalating threat to global public health, underscoring the urgent need for novel antibacterial agents. Natural green control strategies offer sustainable solutions against environmental pathogenic bacterial infections. Among them, natural antibacterial molecules derived from eukaryotic sources are undoubtedly the most compelling, owing to their safety, biocompatibility and resistance to drug resistance. The black soldier fly (Hermetia illucens, BSF) is recognized as a valuable reservoir of antibacterial factors due to its exceptional resistance to dense microbial environments. In this study, three previously uncharacterized antibacterial proteins were systematically identified from black soldier fly larvae (BSFL) using high-performance liquid chromatography-mass spectrometry (HPLC-MS). Hemoglobin (Hb) exhibited the strongest antibacterial activity in vitro, with low cytotoxicity, thermal stability, and acid resistance. Mechanistic analyses indicate that Hb compromises bacterial cell membrane integrity via biofilm disruption and direct membrane interaction, leading to nucleic acid and protein leakage, increased intracellular reactive oxygen species (ROS), and impairment of ATP-dependent energy metabolism. Furthermore, HiHb was structurally predicted to target intracellular components, including DNA topoisomerase and ribosomal proteins. Together, these multi-target effects accelerate bacterial cell death. Notably, ectopic expression of Hb markedly enhanced antibacterial ability in silkworms, suggesting that its antibacterial function is transferable across species. These findings highlight Hb derived from BSFL as a potent antibacterial protein, offering a promising resource for the development of novel therapeutics against bacterial infections and reduce the application of harmful bactericide.
Traditional selective breeding relies on observable phenotypic traits. Recent advances in omics technologies (e.g., genomics, transcriptomics, proteomics, and metabolomics) have revolutionized phenotyping in animal genetic breeding by providing deeper insights into complex traits and improving the efficiency of breeding programs. This review summarizes the applications of omics-based phenotyping technologies to improve the phenotypic traits, such as meat, egg, milk and wool quality, as well as yield, disease resistance and stress tolerance. Integrative multi-omics data enable the identification of key candidate genes, biomarkers and regulatory networks, thereby allowing earlier and more precise selection in breeding programs. The adoption of omics-driven strategies is accelerating the genetic enhancement of the economically important traits, offering a comprehensive framework to improve animal productivity and health. Nevertheless, significant challenges remain, including constructing species and traits-specific omics databases, establishing robust correlations between omics-derived phenotypes and traditional traits, and translating omics discoveries into practical breeding solutions.
Skin xenotransplantation offers a promising solution to the critical shortage of skin donors for extensive burns and complex wounds, yet its clinical translation remains hindered by fragmented research, non-standardized protocols, and regulatory hurdles. To address these challenges, we propose the establishment of the Research Consortium on Skin Xenotransplantation, a multidisciplinary platform integrating expertise in gene editing, burn medicine, biomaterials, and industrial translation. The Consortium focuses on five core missions: constructing standardized multi-gene-edited donor pigs, elucidating rejection mechanisms, developing GMP-compliant skin preservation and manufacturing technologies, conducting multicenter clinical trials, and training young investigators. By establishing collaborative mechanisms for resource sharing and joint research, the Consortium aims to streamline the translational pathway from bench to bedside, converting porcine skin xenotransplantation into a reliable, standardized clinical therapy worldwide.
Gut lactic acid bacteria are emerging as potential targets for modulating host purine metabolism and alleviating hyperuricemia-related disorders. This study aimed to isolate purine-degrading lactic acid bacterial strains from porcine intestine and systematically evaluate their probiotic potential through both in vitro and in vivo approaches. A strain designated Pedio6-1 was isolated and identified as Pediococcus acidilactici based on 16S rRNA sequencing. In vitro assays demonstrated that P. acidilactici Pedio6-1 exhibited nearly complete adenine clearance (approaching 100%) and a total purine clearance rate of 30.73%, along with strong tolerance to acidic conditions, bile salts, and gastrointestinal enzymes. To further assess its in vivo efficacy, a high-fat diet-induced obese mouse model was employed. After 8 weeks of intervention, Pedio6-1 supplementation significantly reduced the final body weight and liver index, and markedly decreased hepatic guanine levels (p < 0.05), with a trend toward lower total purine content compared to the obese control group. Mechanistically, Pedio6-1 treatment significantly downregulated the hepatic mRNA expression of pro-inflammatory cytokines IL-1β and TLR4 (p < 0.05). Serum untargeted metabolomics revealed that Pedio6-1 treatment shifted the metabolic profile toward that of normal diet-fed mice, with differential pathways predominantly enriched in porphyrin metabolism and amino acid biosynthesis and metabolism. Notably, key metabolites with antioxidant and metabolic regulatory functions, including bilirubin, biliverdin, glutathione, citrate, L-cystathionine, and 4-pyridoxic acid, were significantly elevated following treatment, while N-acetylornithine and methylmalonate ester were decreased, indicating coordinated remodeling of oxidative stress defense, vitamin B6 homeostasis, and energy metabolism. Collectively, these findings indicate that Pedio6-1 not only possesses direct purine-degrading activity in vitro, but also ameliorates purine metabolic disturbances, inflammation, and oxidative stress in obese mice, likely through the modulation of porphyrin and amino acid metabolic pathways, highlighting its promise as a functional probiotic candidate for managing obesity-associated purine metabolic disorders.
Weaning stress can severely damage the piglets' intestines. Microbial tryptophan catabolites play a vital role in maintaining the health of the intestinal mucosa. Indole-3-acetic acid (IAA), an indole derivative with known anti-inflammatory properties, has not yet been studied for its impact on piglets' intestinal health. Twenty-four weaned crossbred piglets (Duroc × Yorkshire × Landrace, weighing 6.58 ± 0.07 kg) were randomly allocated to receive diets containing 0, 120, or 240 mg/kg indole-3-acetate sodium (IAA-Na). Although dietary IAA-Na did not significantly impact growth performance or diarrhea incidence (P > 0.05), the 240 mg/kg IAA-Na elevated jejunal villus width (P < 0.05), tended to increase villus surface area (P < 0.10), and enhanced apparent nutrient digestibility alongside upregulating the mRNA expression of transporters (P < 0.05). Furthermore, dietary IAA-Na promoted intestinal epithelial cell proliferation and reduced secretory cell numbers (P < 0.05). Transcriptomic analysis of the jejunum of the 240 mg/kg group revealed significant modulation of pathways related to the "inflammatory response" and "immune system processes." Consistent with this, dietary supplementation with 240 mg/kg IAA-Na downregulated the content and expression of proinflammatory cytokines while upregulating the content and expression of anti-inflammatory cytokines in the jejunum. To further elucidate the effect of IAA on epithelial renewal, piglet jejunal organoids were employed as an in vitro model. Treatment with 0.5 and 2 μM IAA-Na significantly increased the organoids budding rate on d 3 (P < 0.01), indicating enhanced epithelial renewal capacity. In conclusion, although dietary IAA did not improve overall growth performance, 240 mg/kg IAA-Na promoted nutrient absorption in weaned piglets, potentially through enhancing anti-inflammatory responses and epithelial renewal.
Autophagy is a conserved cellular process that mediates degradation of damaged organelles, misfolded proteins, and invading pathogens, playing critical roles in intracellular homeostasis and immune regulation. Given that over 70% of infectious diseases and 60% of emerging infectious diseases are zoonotic, posing a major threat to global health, this review aims to summarize the cellular and molecular mechanisms underlying the crosstalk between autophagy and key zoonotic pathogens. We comprehensively retrieved relevant research literature from the PubMed, Web of Science, and Scopus databases (with the retrieval deadline set as December 2025), using core keywords including autophagy, zoonoses, and pathogen-host interactions. The inclusion criteria were original studies and high-quality reviews focusing on molecular mechanisms or clinical translational potential. Finally, a total of 216 core literatures were included for comprehensive analysis. This review is a narrative overview with comprehensive coverage, aiming to systematically summarize the research progress of autophagy in zoonoses, rather than a systematic meta-analysis strictly adhering to the PRISMA guidelines. Key findings include (1): Autophagy can restrict the replication of zoonotic pathogens such as influenza virus and Brucella by mediating their degradation; (2) Some pathogens have evolved strategies to hijack or inhibit autophagy for survival; (3) Several autophagy-related molecules (e.g., ATG5, Beclin-1) have been identified as potential targets for zoonoses prevention and treatment. This review highlights the dual role of autophagy in zoonotic infections and its potential as a therapeutic target. However, further studies are needed to clarify species-specific differences in autophagy regulation and develop targeted interventions. These insights may provide new avenues for the prevention and treatment of severe zoonotic diseases.
Intestinal inflammation, often driven by microbial dysbiosis and infections, remains a significant health challenge with limited effective treatments. Identifying probiotic strains with anti-inflammatory properties and elucidating their mechanisms is essential for developing novel therapeutic strategies. This study investigates the molecular mechanisms by which E. hirae—a lactic acid bacterium (LAB) isolated from Ningxiang piglets with low diarrhea incidence—alleviates E. coli-induced intestinal inflammation. In the present study, comparative analysis showed that Ningxiang piglets exhibited a significantly lower incidence of diarrhea and reduced E. coli abundance compared to Yorkshire piglets. Notably, E. hirae was more abundant in Ningxiang piglets and correlated with elevated secretory IgA levels. Additionally, in vitro antagonism assays found that E. hirae effectively inhibited E. coli growth. In vivo supplementation of E. hirae in E. coli-infected piglets restored intestinal microbial balance, increased levels of short-chain fatty acids (SCFAs) such as acetate and propionate, and mitigated E. coli colonization. Further analyses suggested that acetate and propionate downregulated the MyD88/NF-κB signaling pathway, thereby reducing pro-inflammatory cytokine expression. Molecular docking and MyD88 − / − experiments verified that MyD88 is involved in SCFA-mediated protection against E. coli-induced inflammation. Furthermore, analyses of public human datasets revealed that Crohn’s disease patients exhibited a similar reduction in SCFA levels and MyD88–NF-κB pathway activation, suggesting potential clinical relevance. Token together, our results reveal that Ningxiang pig-derived E. hirae alleviates E. coli-induced gut dysbiosis and inflammation potentially through the acetate/propionate–MyD88–NF-κB axis. This work provides mechanistic insights for further exploration of probiotic and postbiotic approaches against bacterial-induced intestinal inflammation.
This study aimed to evaluate the compensatory effects of amino acid (AA) supplementation on laying hens fed a low-protein diet, focusing on production performance, egg quality, blood immunity, total tract retention, and intestinal health. A total of 180 Hy-Line Brown laying hens (35 weeks old) were randomly allocated to three dietary treatments with 12 replicates (5 hens/replicate): (1) control diet (15.90% crude protein, CON), (2) reduced-protein diet (15.20% crude protein, NG), and (3) reduced-protein diet supplemented with 400 g/t methionine, 400 g/t lysine, and 300 g/t threonine (15.20% crude protein, LAA). Over the 12-week experimental period, production parameters were monitored weekly. The results showed that compared to the NG group, AA supplementation significantly increased laying rates during weeks 1-4 (p < 0.05) and reduced the feed-to-egg ratio during weeks 9-12 (p < 0.05), with a 3.10% decrease in feed conversion ratio (FCR). By week 12, the NG group exhibited lower Haugh unit values than both the CON and LAA groups (p < 0.05), indicating improved egg quality with AA supplementation. Serum analysis revealed elevated immunoglobulin Y levels and upregulated expression of the anti-inflammatory cytokine IL-10 in the LAA group (p < 0.05). Total tract retention of crude protein (CP) and phosphorus (P) was significantly enhanced in the LAA group compared to CON and NG groups (p < 0.05). However, in terms of cecal microbiota, no significant differences were observed among the experimental groups. These findings demonstrate that AA supplementation alleviates the adverse effects of low-protein diets by enhancing nutrient utilization and immune modulation, thereby improving productive performance, egg quality, and total tract retention in laying hens.
The intestinal microbiota and mucosal barrier are closely intertwined, with mucin O-glycans playing a key role in maintaining intestinal homeostasis. However, how nutrition regulates mucin O-glycans remains poorly understood. This study investigated the regulatory effects of mannooligosaccharides (MOS) on mucin secretion and O-glycan modification in a weaned piglet model. We evaluated the effects of MOS on intestinal morphology, gut microbiota, mucin secretion, and O-glycosylation profiles in weaned piglets. Transcriptome analysis revealed that MOS influenced key KEGG pathways, including mucin O-glycan biosynthesis, through the regulation of genes such as GALNT, GCNT3, and POFUT1. Furthermore, MOS increased the proportion of Core 2 structures in mucin and modulated the proportion of long-chain, sulfated and sialylated O-glycans, which may help protect the mucus layer from microbial degradation. Moreover, MOS improved colonic microbiota composition by promoting beneficial Lactobacillus species and suppressing potentially pathogenic Escherichia coli. This study highlights the molecular effects of MOS on mucin synthesis and modification, which may help preserve intestinal microbiota balance. These effects are important for maintaining intestinal barrier function in weaned piglets.
Intestinal health is critical for efficient swine production, yet effective intervention strategies remain limited. This study evaluated the impacts of dietary Brevibacillus laterosporus BL1 (live or heat-killed form) on finishing pigs, focusing on serum parameters, antioxidant capacity, intestinal barrier, cecal microbiota, and microbial metabolic profiles. Results demonstrated that relative to the control group (CON), B. laterosporus BL1 (both live and heat-killed forms) decreased serum pro-inflammatory cytokines, ameliorated serum lipids, and enhanced systemic antioxidant capacity. Moreover, the heat-killed form was comparable to the live bacteria in strengthening the intestinal barrier, as evidenced by improved intestinal morphology, upregulated barrier-related proteins (ZO-1, Muc-1, and Muc-2), decreased serum lipopolysaccharide levels, and raised intestinal anti-inflammatory cytokines (IL-10 and IL-22) and immunoglobulins (IgG and IgM). Further, metagenomic analysis of cecal digesta demonstrated that heat-killed B. laterosporus BL1 elevated the proportions of potentially beneficial genera Limosilactobacillus and Lactobacillus, while suppressed potential pathogens Clostridium and Terrisporobacter. Consistently, heat-killed B. laterosporus BL1 increased cecal levels of lactate, total short-chain fatty acids (SCFAs), acetic acid, and butyric acid, while decreasing the concentration of phenol, indole, skatole, and biogenic amines (total amines, methylamine, cadaverine, and putrescine). Thus, heat-killed B. laterosporus BL1 emerges as a promising agent for promoting overall physiological status and intestinal health in finishing pigs.
Diarrhea is a common condition in piglets. The intestinal mucosal barrier is the primary protective mechanism against external challenges. Iron-an essential trace element for the growth and metabolism of living organisms-is crucial for enhancing host defense functions. Newborn piglets and porcine colonic organoids were employed as experimental models to investigate the mechanisms underlying the regulation of the intestinal mucosal barrier by iron supplementation. A total of 24 seven-d-old piglets (body weight 1.75 ± 0.20 kg) were orally administered formula milk powder supplemented with different concentrations of iron (FeSO4) for 2 weeks. The treatment groups were low (without), middle (70 mg/kg), and high (700 mg/kg) iron (n = 8). Compared with the low group, iron supplementation significantly reduced fecal scores (P = 0.016), increased the number of colonic goblet cells (P = 0.009), and enhanced MUC2 production (P = 0.049). Additionally, fecal scores were negatively correlated with both the number of colonic goblet cells (P = 0.003, |r| = 0.772) and MUC2 production (P = 0.026, |r| = 0.636). To investigate the mechanism by which iron regulates goblet cells, a hypothesis was proposed that iron exerts its effects through both the gut microbiota and the host. Specific microbial taxa and metabolites were identified as potential regulators of goblet cell function. However, organoid-based in vitro experiments demonstrated that iron regulates goblet cells regardless of microbial metabolites. Additionally, porcine colonic organoids were treated with deferoxamine (DFO; 100 μmol/L), ammonium iron citrate (FAC; 100 or 200 μmol/L), or a mock treatment for 48 h, which was followed by gene expression profiling and transcriptome sequencing. Elevated iron concentrations increased MUC2 expression (P < 0.001). In the group with increased MUC2 expression, the MAPK and PI3K-Akt signaling pathways were downregulated (P = 0.001), whereas the mucin-type O-glycan biosynthesis pathway was upregulated (P = 0.002). Subsequent treatment of porcine colonic organoids with inhibitors specific to these pathways validated the crucial role of the PI3K-Akt signaling pathway in the iron-regulated goblet cell function. Therefore, dietary iron intake increased colonic goblet cell MUC2 production by inhibiting the PI3K-Akt signaling pathway, thereby alleviating diarrhea in piglets.
Deoxynivalenol (DON), a prevalent mycotoxin in crops, poses significant risks to public health. Single-component DON adsorbents exhibit poor polar affinity and limited binding sites. This study aims to develop a novel composite adsorbent capable of adsorption and toxicity mitigation against DON. Eggshell-based composite adsorbents (EC-1, EC-2, and EC-3) were developed by blending 500-CSAE (a novel adsorbent based on eggshell powder modification) with coconut shell biochar, yeast cell walls, and honeysuckle extract at ratios of 3:1:1:2, 2:2:1:2, and 1:3:1:2, respectively. The preferred EC-1 achieved adsorption of 99.7% and 99.5% for DON in simulated gastric and intestinal environments, respectively. EC-1 at 50, 100, and 200 μg/mL showed no cytotoxicity and counteracted DON-induced viability loss of IPEC-J2 cells. Dietary supplement with 0.2% EC-1 attenuated DON-compromised growth performance, liver function, immune function, antioxidant capacity, and intestinal morphology of piglets. In conclusion, EC-1 was developed and validated as a food additive for mitigating DON hazards.
The purpose of this study was to explore the effects of changing standardized ileal digestible (SID) Lys levels in the diet on growth performance, carcass traits, meat quality, blood biochemical indices, and colonic volatile fatty acid levels of Ningxiang pigs, in order to determine their optimal SID Lys requirement. A total of 164 castrated Ningxiang pigs (days of age 135 ± 5and initial body weight of 35.57 ± 0.56 kg) were randomly divided into 5 dietary treatments with SID Lys levels of 0.50%, 0.60%, 0.70%, 0.80%, and 0.90%, respectively. Each treatment had 5 replicates with 6 to 7 pigs per replicate, and a feeding trial lasted for 45 d. Results showed that reducing dietary SID Lys from 0.50% to 0.90% did not affect final body weight (FBW), average daily gain (ADG), the ratio of feed to gain (F:G), and carcass traits (P > 0.05). The 0.50% Lys group exhibited a significantly higher proportion of n-3 polyunsaturated fatty acids (PUFA) and a lower n-6/n-3 PUFA ratio in the longissimus dorsi (P < 0.05), the proportion of saturated fatty acids (SFA) in the soleus was also higher compared with the 0.90% group (P = 0.038). In the 0.70% group, the levels of essential, non-essential, umami, and total amino acids in the longissimus dorsi were significantly increased (P < 0.05) while essential amino acid levels in the soleus were significantly higher in the 0.50% group. Additionally, blood urea nitrogen level was significantly reduced (P = 0.026) and colonic butyrate and total volatile fatty acid contents were significantly increased in the 0.50% group compared with the 0.70% group (P < 0.05). In conclusion, dietary SID Lys levels significantly influenced meat quality, blood biochemical indices, and colonic volatile fatty acids in Ningxiang pigs; however, reducing dietary SID Lys to 0.50% did not adversely affect their growth performance or economic traits.
Microbial omics has progressed from isolated genomic analyses into a comprehensive, integrated multi-omics framework, profoundly advancing our understanding of microbial complexity and functionality. This mini-review systematically outlines the core technologies within microbial omics-including genomics, transcriptomics, proteomics, and metabolomics-by introducing their fundamental principles, common experimental workflows, and state-of-the-art bioinformatic strategies. We particularly highlight the emergence of single-cell microbial omics as a transformative methodology that resolves molecular and functional heterogeneity within communities, enabling the identification of rare taxa, strain-level microdiversity, and specialized functional roles that are obscured in bulk analyses. Furthermore, we discuss how artificial intelligence (AI)-driven tools are revolutionizing the interpretation of high-dimensional omics data, uncovering latent biological patterns, improving predictive modeling of microbial behavior, and facilitating the translation of microbiome insights into clinical and environmental applications. The review concludes by comparing the strengths, limitations, and optimal use cases of each omics layer and single-cell approach while also addressing ongoing technical challenges and future directions in the field.
Eucommia ulmoides leaf extract (ELE) boasts a high concentration of bioactive components including flavonoids, chlorogenic acid, and polysaccharides. It exhibits multiple biological functions, including antioxidant, anti-inflammatory, and gut microbiota-modulating properties, showing great potential in enhancing immunity, maintaining intestinal health, and delaying cellular senescence. This study investigated the protective effects and underlying mechanisms of ELE against D-galactose-induced senescence in chick embryo primary intestinal epithelial cells (IECs). Using an in vitro model (200 mmol/L D-galactose), we found that 100 µg/mL ELE pretreatment significantly preserved cell viability, mitigated apoptosis, and delayed cellular senescence, as evidenced by cytological and biochemical assays. Furthermore, RNA-seq transcriptomic analysis identified seven key differentially expressed genes (DEGs) mediating these anti-aging effects. Mechanistic investigations revealed that ELE modulates ATP6V0D2 and NCF2 to activate autophagy signaling pathways. This ELE-induced promotion of autophagy effectively suppresses inflammatory responses in IECs, thereby delaying senescence progression. These findings elucidate the molecular mechanisms by which ELE antagonizes intestinal cellular senescence, providing a solid theoretical foundation for its development as a functional anti-aging additive in the food industry.
Probiotics are crucial resources for improving pork quality, but it is not fully established how probiotics can modulate the muscle fiber type conversion, thereby improving pork quality. This investigation evaluated the effect of Lactobacillus reuteri isolated from Ningxiang pigs on meat quality, amino acid composition, fatty acid profile and muscle fiber type transition in finishing pigs. Sixteen healthy castrated finishing pigs (Duroc × Landrace × Yorkshire, DLY, 63.36 ± 1.28 kg) were randomly allocated to two experimental groups with 8 pigs in each group: one group was provided with a control diet (NC), and the other was provided the identical diet supplemented with 0.4 % (w/w) L. reuteri XY227 (1 × 1011 CFU/kg, LR) for 50 days. Supplementation with L. reuteri XY227 led to a significant elevation in Longissimus thoracis (LT) muscle area and lean weight (P < 0.05). Furthermore, L. reuteri XY227 supplementation increased meat redness and reduced meat lightness and shear force (P < 0.05). Additionally, supplementation with L. reuteri XY227 markedly elevated the concentrations of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and unsaturated fatty acids(UFA)compared to the NC group (P < 0.05). Compared with the control group, dietary supplementation with L. reuteri XY227 significantly increased the levels of free isoleucine, leucine, and glycine in the LT muscle. Moreover, dietary administration of L. reuteri XY227 exhibited upregulated transcript levels of FABP4, SLC1A5, and SLC7A5 in LT. Supplementation with L. reuteri XY227 significantly upregulated the gene expression of MyHCI and MyHCIIa (P < 0.05). In conclusion, L. reuteri XY227 enhances meat quality by modulating muscle fatty acid profiles and altering muscle fiber types in finishing pigs.
Methionine (Met) is known to enhance antioxidant defense and reproductive efficiency in sows, but its role under low-protein feeding conditions is unclear. This study evaluated the effects of Met supplementation on lactation performance, antioxidant status, and gut microbiota of sows and their piglets. Sixty-six multiparous sows with two parity and similar body weight (244.1 ± 1.73 kg) were assigned to a normal protein diet (18% crude protein [CP]) or low-protein diets (15% CP) containing graded standardized ileal digestible (SID) Met levels (0.23%, 0.30%, 0.37%, 0.44%, and 0.51%, respectively) from d 107 of gestation to d 21 of lactation, with 11 replicates in each group and 1 sow per replicate. The results showed that low-protein diets supplemented with 0.30% Met achieved milk yield and piglet growth comparable to the normal protein group (P > 0.05). In addition, 0.30% Met supplementation reduced serum urea nitrogen content, enhanced the concentrations of milk immunoglobulin M, glutathione, and taurine, and increased the activities of serum total superoxide dismutase in sows and glutathione peroxidase in piglets when compared with the normal protein diet (P < 0.05). Microbiome analysis indicated higher relative abundance of Christensenellaceae_R-7_group in piglets from the 0.30% Met group, positively correlated with growth traits. These findings suggest that a 0.30% Met level in a 15% CP diet supports sow performance and piglet development comparable to normal protein feeding through improved antioxidant capacity and beneficial microbial modulation.