Background: Disease resistance phenotypes are associated with immune regulatory functions and immune tolerance and have implications for both the livestock industry and human health. Microbiota plays an essential role in regulating immunity and autoimmunity in the host organism, but the influence of host-microbiota interactions on disease resistance phenotypes remains unclear. Here, multiomics analysis was performed to identify potential regulatory mechanisms of disease resistance at both the microbiome and host levels in two pig breeds. Results: Acute colitis models were established in Min pigs and Yorkshire pigs, and control and diseased individuals were compared. Compared with Yorkshire pigs under the same nutritional and management conditions, Min pigs exhibited strong disease resistance, as indicated by a low disease activity index (DAI) and a low histological activity index (HAI). Microbiota sequencing analysis showed that potentially harmful microbes Desulfovibrio, Bacteroides and Streptococcus were enriched in diseased individuals of the two breeds. Notably, potentially beneficial microbes, such as Lactobacillus, Clostridia and Eubacterium, and several genera belonging to Ruminococcaceae and Christensenellaceae were enriched in diseased Min pigs and were found to be positively associated with the microbial metabolites related to intestinal barrier function. Specifically, the concentrations of indole derivatives and short-chain fatty acids were increased in diseased Min pigs, suggesting beneficial action in protecting intestinal barrier. In addition, lower concentrations of bile acid metabolites and short-chain fatty acids were observed in diseased Yorkshire pigs, which were associated with increased potentially harmful microbes, such as Bilophila and Alistipes. Concerning enrichment of the immune response, the increase in CD4⁺ T cells in the lamina propria improved supervision of the host immunity response in diseased Min pigs, contributing to the maintenance of Th2-type immune superiority and immune tolerance patterns and control of excessive inflammation with the help of potentially beneficial microbes. In diseased Yorkshire pigs, more terms belonging to biological processes of immunity were enriched, including Toll-like receptors signalling, NF-κB signalling and Th1 and Th17-type immune responses, along with the increases of potentially harmful microbes and damaged intestinal barrier. Conclusions: Cumulatively, the results for the two pig breeds highlight that host-microbiota crosstalk promotes a disease resistance phenotype in three ways: by maintaining partial PRR nonactivation, maintaining Th2-type immune superiority and immunological tolerance patterns and recovering gut barrier function to protect against colonic diseases.

Resveratrol, a plant phenol, affords protection against inflammation and oxidative stress. The objective of this study was to investigate the effects of dietary resveratrol supplementation during pregnancy and lactation on the antioxidant status of sows and piglets and on antioxidant gene expression and pathway in placenta. Forty sows were allotted to 2 dietary treatments 20 d after breeding. Sows were fed a control diet and a control diet with 300 mg/kg resveratrol. Oxidative stress biomarkers and antioxidant enzymes were measured in the placenta, milk, and plasma of sows and piglets. Antioxidant gene expression and protein expression of Kelch-like ECH-associated protein 1-Nuclear factor E2-related factor 2 (Keap1-Nrf2), nuclear factor kappa B-p65 (NFκB-p65) and sirtuin1 (Sirt1) were quantified in the placenta. Dietary resveratrol increased the litter and piglets weaning weights. Antioxidant status in the milk, placenta and plasma of sows and piglets was partially improved by dietary resveratrol. In placenta, Nrf2 protein expression was increased and Keap1 protein expression was decreased by dietary resveratrol. The mRNA expression of antioxidant genes including catalase (CAT), glutathione peroxidase 1 (GPX1), GPX4, superoxide dismutase 1 (SOD1) and heme oxygenase 1 (HO1), and phase 2 detoxification genes, including glutamate-cysteine ligase modifier (GCLM), microsomal glutathione S-transferase 1(MGST1) and UDP glucuronosyltransferase family 1 member A1 (UGT1A1), was increased by dietary resveratrol. Dietary resveratrol also increased Sirt1 and phosphorylated NFκB-p65 protein expression in the placenta. We failed to observe any influences of dietary resveratrol on pro-inflammatory cytokine levels, including those of interleukin 1β (IL-1β), IL-6, IL-8 and tumor necrosis factor α (TNF-α). However, we observed that the mRNA expression of IL-8 in placenta was reduced by maternal resveratrol. In addition, dietary resveratrol showed interactive effects with day of lactation on activities of SOD and CAT and levels of malonaldehyde (MDA) and hydrogen peroxide (H2O2) in milk. Dietary resveratrol supplementation during pregnancy and lactation improves the antioxidant status of sows and piglets, which is beneficial to the reproductive performance of sows. Dietary resveratrol regulates placental antioxidant gene expression by the Keap1-Nrf2 pathway and Sirt1 in placenta.

With the prohibition of antibiotics in feed, plant functional substances have been widely studied as feed additives. Resveratrol, a natural stilbene, and a non-flavonoid polyphenol found in plants, possesses antioxidant, anti-inflammatory, and metabolic regulatory features. Resveratrol generated intense scientific and public interest, primarily due to its widely reported ability to prevent cancer, delay aging and alleviate related metabolic diseases. Recently, resveratrol has been studied and applied as a feed additive in animal production. This review focuses on the outline of the absorption and metabolism and biological functions of resveratrol and summarizes the application of dietary resveratrol in animal production up to the present, including pigs, poultry, and ruminants. In pigs, dietary resveratrol improved intestinal health, mitochondrial function, meat quality, and more. In poultry, studies have shown that dietary resveratrol improves growth performance and meat and egg quality and alleviates heat stress induced adverse effects. There are few studies on dietary resveratrol in ruminants; however previous studies have indicated that dietary resveratrol increases nutrient digestibility and reduces methane emissions in sheep. It is hoped that this review could provide a specific theoretical basis and research ideas for the research and application of resveratrol.

Early weaning commonly results in gastrointestinal disorders, inflammation and diarrhea in infants and young animals. Resveratrol, a plant phenol, affords protection against inflammation and cancer. A porcine model was used to investigate the effects of maternal dietary resveratrol on diarrhea, intestinal inflammation and the intestinal morphology in offspring during weaning. The results showed that maternal dietary resveratrol alleviated weaning-associated intestinal inflammation and diarrhea and improved the intestinal morphology in offspring. In weaning piglets, maternal dietary resveratrol increased the proportion of butyrate-producing bacteria, such as Flavonifractor, Odoribacter and Oscillibacter, as determined by 16S rRNA sequencing. RNA-seq analysis identified 189 and 139 differentially expressed genes (DEGs) in weaning and post-weaning piglets, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DEGs were enriched for the T cell receptor, primary immunodeficiency, mitogen-activated protein kinase (MAPK) and Ras signaling pathways in weaning piglets and for the cytokine–cytokine receptor interaction pathway and metabolism-related pathways in post-weaning piglets.

Weaning transition usually impairs intestinal architecture and functions and results in gut-associated disorders in pigs. Understanding the changes in intestinal transcriptome and gut microbiota during weaning transition is important for elucidating the underlying mechanism of weaning stress. In the present study, we performed RNA-seq to determine the changes in intestinal transcriptome and 16S rRNA sequencing to measure the gut microbiota changes in the weaning transition. Transcriptome results indicated that weaning transition altered intestinal gene expression involved in nutrient transport and metabolism. Regarding fatty metabolism, fatty acid-binding protein 1 (FABP1), acyl-CoA dehydrogenase (ACADSB), and carnitine palmitoyltransferase 2 (CPT2) expression in the intestine was decreased by weaning. Genes related to bile acid metabolism were increased by weaning, including FABP6, farnesoid X receptor (FXR or NR1H4) and organic solute transporter-α (SLC51A). In addition, genes associated with oxidative stress were altered by weaning transition, including decreased catalase (CAT) and lactate dehydrogenase (LDHA) and increased glutathione peroxidase 2 (GPX2) and superoxide dismutase 3 (SOD3). Results of microbiota composition showed that the Firmicutes abundance and Firmicutes/Bacteroidetes ratio were increased and that the Proteobacteria abundance in the fecal microbiota was decreased by the weaning process; during the weaning transition, the Bacteroides and Fusobacterium abundances decreased markedly, and these bacteria nearly disappeared, while the Prevotella abundance showed a marked increase. Moreover, the levels of the microbial metabolites butyrate and acetate increased with changes in gut microbiota composition. In addition, predictive metagenome by PICRUSt analysis showed that the pathways related to D-glutamine and D-glutamate metabolism, citrate cycle (TCA cycle), peroxisome proliferators-activated receptor (PPAR) signaling, alpha-linolenic acid metabolism were decreased and the pathway related to retinol metabolism was increased in the gut microbiota of piglets during weaning transition. Our results showed that early weaning alters intestinal gene expression involved in nutrient metabolism, which may be due to the changes in microbiota composition.