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Simple Summary: Plant extracts have emerged as a viable alternative to antibiotics in livestock production, contributing to the sustainable development of modern animal husbandry. Among these extracts, tea polyphenols, derived from tea leaves as polyhydroxyphenolic compounds, exhibit diverse bioactive properties. This study aimed to assess the impact of tea polyphenols on serum parameters, rumen microbiota, rumen metabolism, and liver metabolism in Hu sheep. The results indicated that dietary supplementation with tea polyphenols did not significantly affect the serum physiological indices of the sheep but enhanced serum immunity and antioxidant levels. Moreover, Firmicutes dominated the network map of the top 80 abundant microorganisms at the genus level, identifying 13 biomarkers at the genus level. Furthermore, tea polyphenols have been found to modulate both rumen and liver metabolism, particularly in relation to energy and lipid metabolism. Furthermore, strong correlations were observed between liver and rumen metabolites, particularly between rumen succinic acid and liver alanyl−serine and methylmalonic acid. This establishes a theoretical basis for tea polyphenol applications and suggests directions for optimizing future additive dosages. This study investigated the impact of tea polyphenols on serum indices, rumen microorganisms, rumen metabolism, and liver metabolism in Hu sheep. Sixty healthy lambs, aged three months and with similar average weights, were chosen and randomly assigned to control (CON), TP400, TP800, and TP1200 groups, each consisting of fifteen lambs. The control group received a basal diet, while the experimental groups were provided with basal diet supplemented with 400 mg/kg, 800 mg/kg, and 1200 mg/kg of tea polyphenols, respectively. Compared with the CON group, the addition of tea polyphenols to the diet significantly increased serum IgA, GSH−Px, and TSOD. In addition, tea polyphenols were able to increase rumen pH but had no significant effect on the rumen NH3−N, VFA molar content, and the microbial top 10 phylum and genus levels. Moreover, Firmicutes predominated in the network map of the top 80 abundant microorganisms at the genus level, identifying 13 biomarkers at the genus level. In addition, strong correlations were observed between liver and rumen metabolites, particularly between rumen succinic acid and liver alanyl−serine and methylmalonic acid. Furthermore, tea polyphenol additions changed the enrichment of liver and rumen metabolites in the top five KEGG metabolic pathways, but 400−1200 mg/kg additions had no negative impact on the liver and rumen. In summary, TP significantly influences rumen and liver metabolites in Hu sheep, enhancing lamb immunity and antioxidant capacity, with 400 mg/kg being the most effective dosage. [ABSTRACT FROM AUTHOR]

Background: The microbiota and metabolites in the gastrointestinal tracts of female animals at different reproductive periods are very important to the growth, development, and health of themselves and their offspring. However, the changes in the gastrointestinal microbiota and metabolites throughout reproductive period of different sheep breeds and their effects on the growth and development of offspring lambs are still unclear. Hence, this study presents an assessment of the reproductive hormone levels, immune levels, rumen microbiota, and metabolites in Hu sheep and Suffolk ewes at different reproductive periods and their effects on the growth and development of offspring lambs. Results: Hu sheep and Suffolk during non-pregnancy, pregnancy, and lactation were used as the research objects to determine reproductive and immune indexes of ewes at different periods, analyze rumen microbiome and metabolome, and track the growth performance and development of offspring lambs. The results showed that the reproductive hormone and immune levels of Hu sheep and Suffolk underwent adaptive changes across different reproductive periods. Compared with non-pregnancy, the microbial energy metabolism and lipid metabolism function decreased during Hu sheep pregnancy, and energy metabolism function decreased during lactation. In Suffolk, energy metabolism, glycan biosynthesis, and metabolism function were enhanced during pregnancy, and the metabolism of cofactors and vitamins was enhanced during lactation. Prevotella increased in Suffolk during pregnancy and lactation (P < 0.05) and was positively correlated with the birth weight and body size of the lambs (P < 0.05). Moreover, the abundances of Butyrivibrio and Rikenellaceae_RC9_gut_group during pregnancy were positively correlated with the intestinal immunity of the offspring lambs (P < 0.05), thereby regulating the intestinal immunity level of the lambs. Metabolomic analysis revealed that the protein digestion, absorption, and amino acid metabolism of Hu sheep were enhanced during pregnancy, which provided amino acids for the growth and development of pregnant ewes and fetuses and was significantly correlated with the birth weight, body size, and intestinal immunity of lambs (P < 0.05). Simultaneously, there was an increase in acetate and propionate during the pregnancy and lactation period of both Hu sheep and Suffolk, providing energy for ewes during reproductive period. Moreover, the microbiota during the lactation period was significantly correlated with the milk quality and lambs daily gain (P < 0.05). Conclusions: This study revealed the characteristic succession changes in the rumen microbiota and its metabolites at different reproductive periods in sheep breeds and their regulation of reproductive hormone and immune levels and identified their potential effects on the growth and development of offspring lambs. The findings provide valuable insights into the health and feeding management of different sheep breeds during the reproductive stage. Cnu7uEJBESQuA-vs1kGzfa Video Abstract [ABSTRACT FROM AUTHOR]

Tibetan pigs are a unique swine strain adapted to the hypoxic environment of the plateau regions in China. The unique mechanisms underlying the adaption by Tibetan pigs, however, are still elusive. Only few studies have investigated hypoxia-associated molecular regulation in the lung tissues of animals living in the plateau region of China. Our previous study reported that ssc-miR-101-3p expression significantly differed in the lung tissues of Tibetan pigs at different altitudes, suggesting that ssc-miR-101-3p plays an important role in the adaptation of Tibetan pigs to high altitude. To understand the underlying molecular mechanism, in this study, the target genes of ssc-miR-101-3p and their functions were analyzed via various methods including qRT-PCR and GO and KEGG pathway enrichment analyses. The action of ssc-miR-101-3p was investigated by culturing alveolar type-II epithelial cells (ATII) of Tibetan pigs under hypoxic conditions and transfecting ATII cells with vectors overexpressing or inhibiting ssc-miR-101-3p. Overexpression of ssc-miR-101-3p significantly increased the proliferation of ATII cells and decreased the expression of inflammatory and apoptotic factors. The target genes of ssc-miR-101-3p were significantly enriched in FOXO and PI3K-AKT signaling pathways required to mitigate lung injury. Further, FOXO3 was identified as a direct target of ssc-miR-101-3p. Interestingly, ssc-miR-101-3p overexpression reversed the damaging effect of FOXO3 in the ATII cells. In conclusion, ssc-miR-101-3p targeting FOXO3 could inhibit hypoxia-induced apoptosis and inflammatory response in ATII cells of Tibetan pigs. These results provided new insights into the molecular mechanisms elucidating the response of lung tissues of Tibetan pigs to hypoxic stress. [ABSTRACT FROM AUTHOR]

Simple Summary: Rumen microorganisms and their hosts have co-evolved over a long period of time, adapting to their environment. This co-evolution not only impacts the host phenotype but also establishes a sophisticated regulatory network with the host to uphold organismal homeostasis. This study's findings indicated that the process of three-way hybridization had a notable impact on the taxonomic characteristics, functions, and metabolites of rumen microbes. Moreover, significant interactions were observed between rumen microbes and metabolites in sheep, with biomarkers playing a significant role in influencing the variation in rumen metabolites. Meanwhile, rumen microbial markers in Hu sheep exhibited a predominantly positive correlation with down-regulated metabolites and a negative correlation with up-regulated metabolites. In contrast, rumen microbial markers in CAH lambs showed an overall negative correlation with down-regulated metabolites and a positive correlation with up-regulated metabolites. The data obtained in this study provide a basis for understanding hybridization advantages from microbial metabolic pathways. The objective of this experiment was to explore the effects of three-way hybridization on rumen microbes and metabolites in sheep using rumen metagenomics and metabolomics. Healthy Hu and CAH (Charolais × Australian White × Hu) male lambs of similar birth weight and age were selected for short-term fattening after intensive weaning to collect rumen fluid for sequencing. Rumen metagenomics diversity showed that Hu and CAH sheep were significantly segregated at the species, KEGG-enzyme, and CAZy-family levels. Moreover, the CAH significantly increased the ACE and Chao1 indices. Further, correlation analysis of the abundance of the top 80 revealed that the microorganisms were interrelated at the species, KEGG-enzyme, and CAZy-family levels. Overall, the microbiome significantly affected metabolites of the top five pathways, with the strongest correlation found with succinic acid. Meanwhile, species-level microbial markers significantly affected rumen differential metabolites. In addition, rumen microbial markers in Hu sheep were overall positively correlated with down-regulated metabolites and negatively correlated with up-regulated metabolites. In contrast, rumen microbial markers in CAH lambs were overall negatively correlated with down-regulated metabolites and positively correlated with up-regulated metabolites. These results suggest that three-way crossbreeding significantly affects rumen microbial community and metabolite composition, and that significant interactions exist between rumen microbes and metabolites. [ABSTRACT FROM AUTHOR]

The Qinghai-Tibet Plateau is a valuable genetic resource pool, and the high-altitude adaptation of Tibetan pigs is a classic example of the adaptive evolution of domestic animals. Here, we report the presence of Darwinian positive selection signatures in Tibetan pigs (TBPs) using 348 genome-wide datasets (127 whole-genome sequence datasets (WGSs) and 221 whole-genome single-nucleotide polymorphism (SNP) chip datasets). We characterized a high-confidence list of genetic signatures related response to high-altitude adaptation in Tibetan pigs, including 4,598 candidate SNPs and 131 candidate genes. Functional annotation and enrichment analysis revealed that 131 candidate genes are related to multiple systems and organs in Tibetan pigs. Notably, eight of the top ten novel genes, RALB, NBEA, LIFR, CLEC17A, PRIM2, CDH7, GK5 and FAM83B, were highlighted and associated with improved adaptive heart functions in Tibetan pigs high-altitude adaptation. Moreover, genome-wide association analysis revealed that 29 SNPs were involved in 13 candidate genes associated with at least one adaptive trait. In particular, among the top ten candidate genes, CLEC17A is related to a reduction in hemoglobin (HGB) in Tibetan pigs. Overall, our study provides a robust SNP/gene list involving genetic adaptation for Tibetan pig high-altitude adaptation, and it will be a valuable resource for future Tibetan pig studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: The rumen is the most important digestive organ of ruminants, and its rich microbial co−evolved with the host to play a crucial role in immunomodulation, defense, digestive metabolism, animal productivity, and meat quality control. It also forms a complex regulatory network with host genes and phenotypes that are involved in maintaining organismal homeostasis. In this study, we compared the differences in rumen microorganisms between crossbred progeny of sheep and Hu sheep, identified key biomarkers, and analyzed their relationship with rumen function. The results showed that microbial diversity was significantly higher in crossbred progeny, which was able to alter the microbial community structure to regulate rumen fermentation, promote carbon homeostasis, and enhance amino acid metabolism. In addition, there were significant correlations between biomarkers and key traits. Therefore, we suggest that there is a link between sheep rumen microbes and differential traits in crossbred progeny, which provides new insights for sheep trait improvement. This experiment was conducted to investigate the effect of three–way hybrid sheep and Hu sheep on serum indicators, rumen fermentation, rumen enzyme activity, and microorganisms in sheep. Healthy and similar birth weights from three groups (Hu, n = 11; Charolais × Australian White × Hu, CAH, n = 11; Charolais × Dorper × Hu, CDH, n = 11) were selected to be fed by the ewes until 45 days of age. Subsequently, they were weaned intensively and underwent short–term fattening for 3 months along with selected male lambs fed intensively. During this period, they were fed and watered ad libitum. Blood and rumen fluid were collected and analyzed for serum indicators and rumen fluid microorganisms, enzyme activity, and VFA, respectively, at the end of the fattening period. Compared with Hu lamb, the offspring of the three–way hybrid lamb showed significant improvements in body weight, serum lactate dehydrogenase, and creatinine content. However, there was no significant effect on serum immunity and antioxidant indices. In addition, the rumen fluid volatile fatty acid (VFA) molar concentration and microcrystalline cellulose and lipase content were significantly lower in the three–way hybrid lamb compared to Hu lamb, but β–glucosidase, amylase, pepsin, and VFA molar ratio were not significantly affected. Subsequently, 16S rRNA sequencing diversity analysis revealed that three–way hybrid lamb significantly increased rumen microbial ACE and Chao1 indices compared to Hu lamb. Meanwhile, the abundance of Verrucomicrobiota and Synergistota significantly increased at the phylum level. Correlation analysis showed that Prevotella had the highest proportion, while Rikenellaceae_RC9_gut_group correlated most closely with others genus. The microbial communities isovaleric acid molar concentration and proportion were strongly correlated. In addition, there were significant differences in correlations between microbial communities and isobutyric acid, butyric acid and valeric acid content, and their molar proportion, but they were not significantly correlated with digestive enzymes. From the functional enrichment analysis, it was found that hybrid progeny were mainly enriched in the pyruvate metabolism, microbial metabolism in diverse environments, carbon metabolism, and quorum sensing pathways. In contrast, the Hu sheep were primarily enriched in the cysteine and methionine, amino sugar and nucleotide sugar, and biosynthesis of secondary metabolite pathways. These results suggest that hybridization can play a role in regulating organismal metabolism and improve animal production performance by influencing the structure and characteristics of microbial communities. [ABSTRACT FROM AUTHOR]

Rumen microbial urease inhibitors have been proposed for regulating nitrogen emission and improving nitrogen utilization efficiency in ruminant livestock industry. However, studies on plant-derived natural inhibitors of rumen microbial urease are limited. Urease accessory protein UreG, plays a crucial role in facilitating urease maturation, is a new target for design of urease inhibitor. The objective of this study was to select the potential effective inhibitor of rumen microbial urease from major protoberberine alkaloids in Rhizoma Coptidis by targeting UreG. Our results showed that berberine chloride and epiberberine exerted superior inhibition potential than other alkaloids based on GTPase activity study of UreG. Berberine chloride inhibition of UreG was mixed type, while inhibition kinetics type of epiberberine was uncompetitive. Furthermore, epiberberine was found to be more effective than berberine chloride in inhibiting the combination of nickel towards UreG and inducing changes in the second structure of UreG. Molecular modeling provided the rational structural basis for the higher inhibition potential of epiberberine, amino acid residues in G1 motif and G3 motif of UreG formed interactions with D ring of berberine chloride, while interacted with A ring and D ring of epiberberine. We further demonstrated the efficacy of epiberberine in the ruminal microbial fermentation with low ammonia release and urea degradation. In conclusion, our study clearly indicates that epiberberine is a promising candidate as a safe and effective inhibitor of rumen microbial urease and provides an optimal strategy and suitable feed additive for regulating nitrogen excretion in ruminants in the future. Key points: • Epiberberine is the most effective inhibitor of rumen urease from Rhizoma Coptidis. • Urease accessory protein UreG is an effective target for design of urease inhibitor. • Epiberberine may be used as natural feed additive to reducing NH3 release in ruminants. [ABSTRACT FROM AUTHOR]

Simple Summary: In the context of large-scale production, it is necessary to improve ewes health status and reproductive performance to promote newborns survival rate and later fattening performance. Previous studies have indicated that phenolic acids could change the host rumen microflora and inhibit pathogenic bacteria to ensure rumen health and host body health. However, there are few studies on isochlorogenic acid (ICGA) in ruminants. Therefore, based on regulating the rumen environment of breeding ewes during the whole physiological period, the experiment was conducted to study the effects of ICGA on rumen fermentation, microbial diversity and immunity of ewes at estrus, pregnancy and lactation stages. The experimental data obtained showed that adding ICGA could regulate ewes rumen fermentation mode, optimize microbial flora of different physiological stages by increasing Bacteroidota relative abundance while reducing Firmicutes relative abundance, maintain rumen microbial homeostasis at the pregnancy stage, and increase ewes blood immuneglobulin content, thereby improving ewes health. The effects of isochlorogenic acid (ICGA) on ewes rumen environment, microbial diversity, and immunity at different physiological stages (estrus, pregnancy and lactation) were studied in this experiment. Twenty healthy female Hu lambs of 1.5 months with similar body weight (17.82 ± 0.98 kg) and body condition were selected and randomly divided into two groups: the control group (CON) and the ICGA group (ICGA). The lambs of CON were fed a basal diet, while the lambs of ICGA were supplemented with 0.1% ICGA based on the basal diet. Lambs rumen fermentation characteristics, microbial diversity and immunity at estrus, pregnancy, and lactation stages were determined and analyzed, respectively. The results showed that the rumen pH in CON increased first and then decreased as lambs grew (p < 0.05). However, it showed the opposite change in ICGA. The content of ammonia nitrogen (NH3-N) showed the highest at estrus stage in both groups, but it was significantly higher in ICGA than that in CON (p < 0.05). The Acetic acid/propionic acid (A/P) ratio at estrus stage and the volatile fatty acids (VFAs) at pregnancy stage in ICGA were significantly higher than those of the CON (p < 0.05). The 16S rDNA sequencing analysis showed that the Shannon, Chao 1 and ACE indexes of the ICGA were significantly higher than those of the CON both at estrus and lactation stages (p < 0.05), while they showed higher at the pregnancy stage in CON (p > 0.05). Principal component analysis (PCA) showed that there were significant differences in rumen microorganism structure between CON and ICGA at all physiological stages (p < 0.01). At the phylum level, compared with the CON, Firmicutes relative abundance of three physiological stages decreased (p > 0.05) while Bacteroidota increased (p > 0.05). The relative abundance of Synergistota at estrus stage and Patescibacteria at the lactation stage increased significantly too (p < 0.05). At the genus level, compared with the CON, the relative abundance of Prevotella at three stages showed the highest (p > 0.05), while the relative abundance of Succiniclasticum, unclassified_Selenomonadaceae and Rikenellaceae_RC9_gut_group showed different abundances at different physiological stages in ICGA. Compared with the CON, the lambs of the ICGA showed higher blood IgG, IgM, and TNF- α contents at three physiological stages and higher IL-6 contents at pregnancy stage (p < 0.05). Conclusion: Adding ICGA could regulate ewes rumen fermentation mode at different physiological stages by increasing rumen NH3-N at estrus, VFAs at pregnancy, and the ratio of A/P at lactation. It optimizes rumen microbial flora of different physiological stages by increasing Bacteroidota relative abundance while reducing Firmicutes relative abundance, maintaining rumen microbial homeostasis at pregnant stage, increasing the number of beneficial bacteria in later lactating and ewes blood immunoglobulins content at three physiological stages. [ABSTRACT FROM AUTHOR]