Heat stress affects mammary metabolism by influencing the plasma flow to the glands.

BACKGROUND: Environmental heat stress (HS) can have detrimental effects on milk production by compromising the mammary function. Mammary plasma flow (MPF) plays a crucial role in nutrient supply and uptake in the mammary gland. In this experiment, we investigated the physiological and metabolic changes in high-yielding cows exposed to different degrees of HS: no HS with thermal-humidity index (THI) below 68 (No-HS), mild HS (Mild-HS, 68 ≤ THI ≤ 79), and moderate HS (Mod-HS, 79 < THI ≤ 88) in their natural environment. Our study focused on the changes in blood oxygen supply and mammary glucose uptake and utilization. RESULTS: Compared with No-HS, the MPF of dairy cows was greater (P < 0.01) under Mild-HS, but was lower (P < 0.01) in cows under Mod-HS. Oxygen supply and consumption exhibited similar changes to the MPF under different HS, with no difference in ratio of oxygen consumption to supply (P = 0.46). The mammary arterio-vein differences in glucose concentration were lower (P < 0.05) under Mild- and Mod-HS than under no HS. Glucose supply and flow were significantly increased (P < 0.01) under Mild-HS but significantly decreased (P < 0.01) under Mod-HS compared to No-HS. Glucose uptake (P < 0.01) and clearance rates (P < 0.01) were significantly reduced under Mod-HS compared to those under No-HS and Mild-HS. Under Mild-HS, there was a significant decrease (P < 0.01) in the ratio of lactose yield to mammary glucose supply compared to that under No-HS and Mod-HS, with no difference (P = 0.53) in the ratio of lactose yield to uptaken glucose among different HS situations. CONCLUSIONS: Degrees of HS exert different influences on mammary metabolism, mainly by altering MPF in dairy cows. The output from this study may help us to develop strategies to mitigate the impact of different degrees of HS on milk production.

Single-cell transcriptomics across 2,534 microbial species reveals functional heterogeneity in the rumen microbiome.

Deciphering the activity of individual microbes within complex communities and environments remains a challenge. Here we describe the development of microbiome single-cell transcriptomics using droplet-based single-cell RNA sequencing and pangenome-based computational analysis to characterize the functional heterogeneity of the rumen microbiome. We generated a microbial genome database (the Bovine Gastro Microbial Genome Map) as a functional reference map for the construction of a single-cell transcriptomic atlas of the rumen microbiome. The atlas includes 174,531 microbial cells and 2,534 species, of which 172 are core active species grouped into 12 functional clusters. We detected single-cell-level functional roles, including a key role for Basfia succiniciproducens in the carbohydrate metabolic niche of the rumen microbiome. Furthermore, we explored functional heterogeneity and reveal metabolic niche trajectories driven by biofilm formation pathway genes within B. succiniciproducens. Our results provide a resource for studying the rumen microbiome and illustrate the diverse functions of individual microbial cells that drive their ecological niche stability or adaptation within the ecosystem.

Novel mechanism of Clostridium butyricum alleviated coprophagy prevention-induced intestinal inflammation in rabbit.

As bacteria synthesize nutrients primarily in the cecum, coprophagy is indispensable for supplying rabbits with essential nutrients. Recent research has demonstrated its pivotal role in maintaining intestinal microbiota homeostasis and immune regulation in rabbits, although the specific mechanism remains unknown. Here, we used coprophagy prevention (CP) to investigate the effects of coprophagy on the cecum homeostasis and microbiota in New Zealand white rabbits. Furthermore, whether supplementation of Clostridium butyricum (C. butyricum) may alleviate the cecum inflammation and apoptosis caused by CP was also explored. Four groups were randomly assigned: control (Con), sham-coprophagy prevention (SCP), coprophagy prevention (CP), and CP and C. butyricum addition (CPCB). Compared to Con and SCP, CP augmented cecum inflammation and apoptosis, as well as bacterial adhesion to the cecal epithelial mucosa, while decreasing the expression of tight junction proteins (ZO-1, occluding, and claudin-1). The relative abundance of short-chain fatty acids (SCFAs)-producing bacteria was significantly decreased in the CP group. Inversely, there was an increase in the Firmicutes/Bacteroidetes ratio and the relative abundance of Christensenellaceae_R-7_group. Additionally, CP increased the levels of Flagellin, IFN-γ, TNF-a, and IL-1ß in cecum contents and promoted the expression of TLR5/MyD88/NF-κB pathway in cecum tissues. However, the CPCB group showed significant improvements in all parameters compared to the CP group. Dietary C. butyricum supplementation significantly increased the production of SCFAs, particularly butyric acid, triggering anti-inflammatory, tissue repairing, and barrier-protective responses. Notably, CPCB effectively mitigated CP-induced apoptosis and inflammation. In summary, CP disrupts the cecum epithelial barrier and induces inflammation in New Zealand white rabbits, but these effects can be alleviated by C. butyricum supplementation. This process appears to be largely associated with the TLR5/MyD88/NF-κB signaling pathway.

Genotype-associated heritable rumen bacteria can be a stable microbiota passed to the offspring.

Recent studies have reported that some rumen microbes are "heritable" (those have significant narrow sense heritability) and can significantly contribute to host phenotype variations. However, it is unknown if these heritable rumen bacteria can be passed to the next generation. In this study, the rumen bacteria from mother cows (sampled in 2016) and their offspring (sampled in 2019) were assessed to determine if vertical transmission occurred between the two generations. The analysis of relationship between host genotypes and heritable bacterial abundances showed that potential of five host genotypes can affect the relative abundances of two unclassified species level heritable bacteria (Pseudoscardovia and p-251-o5). The G allele of BTB-01532239 and A allele of ARS-BFGL-NGS-8960 were associated with a higher relative abundance of p-251-o5. The A allele of BTB-00740910 and BovineHD1300021786 and G allele of BovineHD1900005868 were associated with a higher relative abundance of Pseudoscardovia. The mother-offspring comparison revealed that the heritable rumen bacteria had higher compositional similarity than nonheritable bacteria between two generations, and the predicted heritable microbial functions had higher stability than those from nonheritable bacteria. These findings suggest that a high stability exists in heritable rumen bacteria, which could be passed to the next generation in dairy cows.

- Invited Review - Understanding the functionality of the rumen microbiota: searching for better opportunities for rumen microbial manipulation.

Rumen microbiota play a central role in the digestive process of ruminants. Their remarkable ability to break down complex plant fibers and proteins, converting them into essential organic compounds that provide animals with energy and nutrition. Research on rumen microbiota not only contributes to improving animal production performance and enhancing feed utilization efficiency but also holds the potential to reduce methane emissions and environmental impact. Nevertheless, studies on rumen microbiota face numerous challenges, including complexity, difficulties in cultivation, and obstacles in functional analysis. This review provides an overview of microbial species involved in the degradation of macromolecules, the fermentation processes, and methane production in the rumen, all based on cultivation methods. Additionally, the review introduces the applications, advantages, and limitations of emerging omics technologies such as metagenomics, metatranscriptomics, metaproteomics, and metabolomics, in investigating the functionality of rumen microbiota. Finally, the article offers a forward-looking perspective on the new horizons and technologies in the field of rumen microbiota functional research. These emerging technologies, with continuous refinement and mutual complementation, have deepened our understanding of rumen microbiota functionality, thereby enabling effective manipulation of the rumen microbial community.

Dynamic fecal microenvironment properties enable predictions and understanding of peripartum blood oxidative status and nonesterified fatty acids in dairy cows.

The transition period in dairy cows is a critical stage and peripartum oxidative status, negative energy balance (NEB), and inflammation are highly prevalent. Fecal microbial metabolism is closely associated with blood oxidative status and nonesterified fatty acids (NEFA) levels. Here, we investigated dynamic changes in total oxidative status markers and NEFA in blood, fecal microbiome, and metabolome of 30 dairy cows during transition (-21, -7, +7, +21 d relative to calving). Then the Bayesian network and 9 machine-learning algorithms were applied to dismantle their relationship. Our results show that the oxidative status indicator (OSI) of -21, -7, +7 d was higher than +21 d. The plasma concentration of NEFA peaked on +7 d. For fecal microenvironment, a decline in bacterial α diversity was observed at postpartum and in bacterial interactions at +7 d. Conversely, microbial metabolites involved in carbohydrate, lipid, and energy metabolism increased on +7 d. A correlation analysis revealed that 11 and 10 microbial metabolites contributed to OSI and NEFA variations, respectively (arc strength >0.5). The support vector machine (SVM) radial model showed the highest average predictive accuracy (100% and 88.9% in the test and external data sets) for OSI using 1 metabolite and 3 microbiota. The SVM radial model also showed the highest average diagnostic accuracy (100% and 91% in the test and external data sets) for NEFA with 2 metabolites and 3 microbiota. Our results reveal a relationship between variation in the fecal microenvironment and indicators of oxidative status, NEB, and inflammation, which provide a theoretical basis for the prevention and precise regulation of peripartum oxidative status and NEB.

Heat stress affects dairy cow health status through blood oxygen availability.

BACKGROUND: Rises in global warming and extreme weather occurrence make the risk of heat stress (HS) induced by high ambient temperatures more likely in high-yielding dairy cows, resulting in low milk quality and yield. In animals, oxygen is involved in many physiological and metabolic processes, but the effects of HS on oxygen metabolism remain unclear. Thus, the current study aimed to investigate how oxygen metabolism plays a role in health status of dairy cows by measuring the milk yield, milk composition, and blood biochemical variables of cows under different levels of HS: none (No-HS), mild (Mild-HS), and moderate HS (Mod-HS). RESULTS: The HS significantly increased rectal temperature (Ptreat < 0.01) and respiration rate (Ptreat < 0.01). Under Mod-HS, greater Na+ (P < 0.05) and lower total CO2, and pH (P < 0.05) were observed relative to those under No-HS and Mild-HS. Oxygen concentrations in both coccygeal artery and mammary vein (Ptreat < 0.01) were lower under Mod-HS than under No-HS. Coccygeal vein concentrations of heat shock protein 90 (HSP90) (P < 0.05) increased during Mod-HS compared with those in cows under No-HS. Malondialdehyde increased during Mod-HS, and glutathione peroxidase (P < 0.01) increased during Mild-HS. Coccygeal vein concentrations of vascular endothelial growth factor (P < 0.01), heme oxygenase-1 (P < 0.01), and hypoxia-inducible factor 1α (P < 0.01) were greater in cows under Mod-HS than those under No-HS. Red blood cell count (P < 0.01) and hemoglobin concentration (P < 0.01) were lower in the coccygeal vein of dairy cows under Mild- and Mod-HS than those of cows under No-HS. CONCLUSIONS: Exposure to HS negatively impacts the health status and lactation performance of dairy cows by limiting oxygen metabolism and transportation. However, the specific mechanism by which HS affects mammary function in cows remains unclear and requires further exploration.

Age- and Microbiota-Dependent Cell Stemness Plasticity Revealed by Cattle Cell Landscape.

Newborn ruminants are considered functionally monogastric animals. The poor understanding of cellular differences between newborn and mature ruminants prevents the improvement of health and performance of domestic ruminants. Here, we performed the single-cell RNA sequencing on the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, rectum, liver, salivary gland, and mammary gland from newborn and adult cattle. A comprehensive single-cell transcriptomic atlas covering 235,941 high-quality single cells and 78 cell types was deciphered. A Cattle Cell Landscape database (http://cattlecelllandscape.zju.edu.cn) was established to elaborately display the data and facilitate effective annotation of cattle cell types and subtypes for the broad research community. By measuring stemness states of epithelial cells in each tissue type, we revealed that the epithelial cells from newborn forestomach (rumen, reticulum, and omasum) were more transcriptionally indistinct and stochastic compared with the adult stage, which was in contrast to those of abomasum and intestinal tissues. The rapid forestomach development during the early life of calves was driven by epithelial progenitor-like cells with high DNA repair activities and methylation. Moreover, in the forestomach tissues of newborn calves, the Megasphaera genus was involved in regulating the transcriptional plasticity of the epithelial progenitor-like cells by DNA methylation regulation. A novel cell type, the STOML3+ cell, was found to be newborn-specific. It apparently plays a crucial role in stemness maintenance of its own and cholangiocytes in the hepatic microenvironment. Our results reveal that the age- and microbiota-dependent cell stemness plasticity drives the postnatal functional maturity of ruminants.

The hindgut microbiome contributes to host oxidative stress in postpartum dairy cows by affecting glutathione synthesis process.

BACKGROUND: Dairy cows are susceptible to postpartum systemic oxidative stress (OS), which leads to significant production loss and metabolic disorders. The gut microbiota has been linked to host health and stress levels. However, to what extent the gut microbiota is associated with postpartum OS remains unknown. In this study, the contribution of the fecal microbiota to postpartum systemic OS and its underlying mechanisms were investigated by integrating 16S rRNA gene sequencing, metagenomics, and metabolomics in postpartum dairy cattle and by transplanting fecal microbiota from cattle to mice. RESULTS: A strong link was found between fecal microbial composition and postpartum OS, with an explainability of 43.1%. A total of 17 significantly differential bacterial genera and 19 species were identified between cows with high (HOS) and low OS (LOS). Among them, 9 genera and 16 species showed significant negative correlations with OS, and Marasmitruncus and Ruminococcus_sp._CAG:724 had the strongest correlations. The microbial functional analysis showed that the fecal microbial metabolism of glutamine, glutamate, glycine, and cysteine involved in glutathione synthesis was lower in HOS cows. Moreover, 58 significantly different metabolites were identified between HOS and LOS cows, and of these metabolites, 19 were produced from microbiota or cometabolism of microbiota and host. Furthermore, these microbial metabolites were enriched in the metabolism of glutamine, glutamate, glycine, and cysteine. The mice gavaged with HOS fecal microbiota had significantly higher OS and lower plasma glutathione peroxidase and glutathione content than those orally administered saline or LOS fecal microbiota. CONCLUSIONS: Integrated results suggest that the fecal microbiota is responsible for OS and that lower glutathione production plays a causative role in HOS. These findings provide novel insights into the mechanisms of postpartum OS and potential regulatory strategies to alleviate OS in dairy cows. Video Abstract.

Gut microbiome is linked to functions of peripheral immune cells in transition cows during excessive lipolysis.

BACKGROUND: Postpartum dairy cows experiencing excessive lipolysis are prone to severe immunosuppression. Despite the extensive understanding of the gut microbial regulation of host immunity and metabolism, its role during excessive lipolysis in cows is largely unknown. Herein, we investigated the potential links between the gut microbiome and postpartum immunosuppression in periparturient dairy cows with excessive lipolysis using single immune cell transcriptome, 16S amplicon sequencing, metagenomics, and targeted metabolomics. RESULTS: The use of single-cell RNA sequencing identified 26 clusters that were annotated to 10 different immune cell types. Enrichment of functions of these clusters revealed a downregulation of functions in immune cells isolated from a cow with excessive lipolysis compared to a cow with low/normal lipolysis. The results of metagenomic sequencing and targeted metabolome analysis together revealed that secondary bile acid (SBA) biosynthesis was significantly activated in the cows with excessive lipolysis. Moreover, the relative abundance of gut Bacteroides sp. OF04 - 15BH, Paraprevotella clara, Paraprevotella xylaniphila, and Treponema sp. JC4 was mainly associated with SBA synthesis. The use of an integrated analysis showed that the reduction of plasma glycolithocholic acid and taurolithocholic acid could contribute to the immunosuppression of monocytes (CD14+MON) during excessive lipolysis by decreasing the expression of GPBAR1. CONCLUSIONS: Our results suggest that alterations in the gut microbiota and their functions related to SBA synthesis suppressed the functions of monocytes during excessive lipolysis in transition dairy cows. Therefore, we concluded that altered microbial SBA synthesis during excessive lipolysis could lead to postpartum immunosuppression in transition cows. Video Abstract.

Microbiota-host crosstalk in the newborn and adult rumen at single-cell resolution.

BACKGROUND: The rumen is the hallmark organ of ruminants, playing a vital role in their nutrition and providing products for humans. In newborn suckling ruminants milk bypasses the rumen, while in adults this first chamber of the forestomach has developed to become the principal site of microbial fermentation of plant fibers. With the advent of single-cell transcriptomics, it is now possible to study the underlying cell composition of rumen tissues and investigate how this relates the development of mutualistic symbiosis between the rumen and its epithelium-attached microbes. RESULTS: We constructed a comprehensive cell landscape of the rumen epithelium, based on single-cell RNA sequencing of 49,689 high-quality single cells from newborn and adult rumen tissues. Our single-cell analysis identified six immune cell subtypes and seventeen non-immune cell subtypes of the rumen. On performing cross-species analysis of orthologous genes expressed in epithelial cells of cattle rumen and the human stomach and skin, we observed that the species difference overrides any cross-species cell-type similarity. Comparing adult with newborn cattle samples, we found fewer epithelial cell subtypes and more abundant immune cells, dominated by T helper type 17 cells in the rumen tissue of adult cattle. In newborns, there were more fibroblasts and myofibroblasts, an IGFBP3+ epithelial cell subtype not seen in adults, while dendritic cells were the most prevalent immune cell subtype. Metabolism-related functions and the oxidation-reduction process were significantly upregulated in adult rumen epithelial cells. Using 16S rDNA sequencing, fluorescence in situ hybridization, and absolute quantitative real-time PCR, we found that epithelial Desulfovibrio was significantly enriched in the adult cattle. Integrating the microbiome and metabolome analysis of rumen tissues revealed a high co-occurrence probability of Desulfovibrio with pyridoxal in the adult cattle compared with newborn ones while the scRNA-seq data indicated a stronger ability of pyroxidal binding in the adult rumen epithelial cell subtypes. These findings indicate that Desulfovibrio and pyridoxal likely play important roles in maintaining redox balance in the adult rumen. CONCLUSIONS: Our integrated multi-omics analysis provides novel insights into rumen development and function and may facilitate the future precision improvement of rumen function and milk/meat production in cattle.

Blood neutrophil extracellular traps: a novel target for the assessment of mammary health in transition dairy cows.

BACKGROUND: Mammary health is important for transition dairy cows and has been well recognized to exert decisive effects on animal welfare. However, the factors influencing mammary health are still unclear. Differential somatic cell count (DSCC) could reflect the mastitis risk since it is the percentage of neutrophils plus lymphocytes in total somatic cells and could be reflective of mammary health of dairy cows. This work aimed to investigate the assessment and prognosis of the health of transition cows based on blood neutrophil extracellular traps (NETs). RESULTS: Eighty-four transition Holstein dairy cows were selected. The serum was sampled in all the animals at week 1 pre- and postpartum, and milk was sampled at week 1 postpartum. Based on the DSCC in milk at week 1, cows with lower (7.4% ± 4.07%, n = 15) and higher (83.3% ± 1.21%, n = 15) DSCCs were selected. High DSCC cows had higher levels of red blood cell counts (P < 0.05), hemoglobin (P = 0.07), and hematocrit (P = 0.05), higher concentrations of serum oxidative variables [(reactive oxygen species (P < 0.05), malondialdehyde (P < 0.05), protein carbonyl (P < 0.05), and 8-hydroxy-2-deoxyguanosine (P = 0.07)], higher levels of serum and milk NETs (P < 0.05) and blood-milk barrier indicators, including serum ß-casein (P = 0.05) and milk immunoglobulin G2 (P = 0.09), than those of low DSCC cows. In addition, lower concentrations of serum nutrient metabolites (cholesterol and albumin) (P < 0.05) and a lower level of serum deoxyribonuclease I (P = 0.09) were observed in high DSCC cows than in low DSCC cows. Among the assessments performed using levels of the three prepartum serum parameters (NETs, deoxyribonuclease I and ß-casein), the area under the curve (0.973) of NETs was the highest. In addition, the sensitivity (1.00) and specificity (0.93) were observed for the discrimination of these cows using NETs levels with a critical value of 32.2 ng/mL (P < 0.05). CONCLUSIONS: The formation of NETs in blood in transition dairy cows may damage the integrity of the blood-milk barrier and thereby increase the risk for mastitis in postpartum cows.

Heritable and Nonheritable Rumen Bacteria Are Associated with Different Characters of Lactation Performance of Dairy Cows.

Recent studies have reported that some rumen microbes are heritable. However, it is necessary to clarify the functions and specific contributions of the heritable rumen microbes to cattle phenotypes (microbiability) in comparison with those that are nonheritable. This study aimed to identify the distribution and predicted functions of heritable and nonheritable bacterial taxa at species level in the rumen of dairy cows and their respective contributions to energy-corrected milk yield, protein content and yield, and fat content and yield in milk. Thirty-two heritable and 674 nonheritable bacterial taxa were identified at species level, and the functional analysis revealed that predicted microbial functions for both groups were mainly enriched for energy, amino acid, and ribonucleotide metabolism. The mean microbiability (to reflect a single taxon's contribution) of heritable bacteria was found to range from 0.16% to 0.33% for the different milk traits, whereas the range for nonheritable bacteria was 0.03% to 0.06%. These findings suggest a strong contribution by host genetics in shaping the rumen microbiota, which contribute significantly to milk production traits. Therefore, there is an opportunity to further improve milk production traits through attention to host genetics and the interaction with the rumen microbiota. IMPORTANCE Rumen bacteria produce volatile fatty acids which exert a far-reaching influence on hepatic metabolism, mammary gland metabolism, and animal production. In the current study, 32 heritable and 674 nonheritable bacterial taxa at species level were identified, and shown to have different microbiability (overall community contribution) and mean microbiability (the average of a single taxon's contribution) for lactation performance. The predicted functions of heritable and nonheritable bacterial taxa also differed, suggesting that targeted nutritional and genetic breeding approaches could be used to manipulate them to improve dairy cow performance.

An Age Effect of Rumen Microbiome in Dairy Buffaloes Revealed by Metagenomics.

Age is an important factor in shaping the gut microbiome. However, the age effect on the rumen microbial community for dairy buffaloes remains less explored. Using metagenomics, we examined the microbial composition and functions of rumen microbiota in dairy Murrah buffaloes of different ages: Y (1 year old), M (3−5 years old), E (6−8 years old), and O (>9 years old). We found that Bacteroidetes and Firmicutes were the predominant phyla, with Prevotella accounting for the highest abundance at the genus level. The proportion of Bacteroides and Methanobrevibacter significantly increased with age, while the abundance of genus Lactobacillus significantly decreased with age (LDA > 3, p < 0.05). Most differed COG and KEGG pathways were enriched in Y with carbohydrate metabolism, while older buffaloes enriched more functions of protein metabolism and the processing of replication and repair (LDA > 2, p < 0.05). Additionally, the functional contribution analysis revealed that the genera Prevotella and Lactobacillus of Y with more functions of CAZymes encoded genes of glycoside hydrolases and carbohydrate esterases for their roles of capable of metabolizing starch and sucrose-associated oligosaccharide enzyme, hemicellulase, and cellulase activities than the other three groups (LDA > 2, p < 0.05), thus affecting the 1-year-old dairy buffalo rumen carbohydrate metabolism. This study provides comprehensive dairy buffalo rumen metagenome data and assists in manipulating the rumen microbiome for improved dairy buffalo production.

Formation of Blood Neutrophil Extracellular Traps Increases the Mastitis Risk of Dairy Cows During the Transition Period.

The current study was conducted to analyze the functions of blood neutrophils in transition cows and their association with postpartum mastitis risk as indicated by somatic cell counts (SCCs) in milk. Seventy-six healthy Holstein dairy cows were monitored from Week 4 prepartum to Week 4 postpartum. Five dairy cows with low SCCs (38 ± 6.0 × 103/mL) and five with high SCCs (3,753 ± 570.0 × 103/mL) were selected based on milk SCCs during the first three weeks of lactation. At Week 1 pre- and postpartum, serum samples were obtained from each cow to measure neutrophil extracellular trap (NET)-related variables, and blood neutrophils were collected for transcriptome analysis by RNA sequencing. The serum concentration of NETs was significantly higher (P < 0.05) in cows with high SCCs than in cows with low SCCs (36.5 ± 2.92 vs. 18.4 ± 1.73 ng/mL). The transcriptomic analysis revealed that the transcriptome differences in neutrophils between high- and low-SCC cows were mainly in cell cycle-related pathways (42.6%), including the cell cycle, DNA damage, and chromosomal conformation, at Week 1 prepartum. The hub genes of these pathways were mainly involved in both the cell cycle and NETosis. These results indicated that the formation of NETs in the blood of transition dairy cows was different between cows with low and high SCCs, which may be used as a potential indicator for the prognosis of postpartum mastitis risk and management strategies of perinatal dairy cows.

Constraints on the utilization of cereal straw in lactating dairy cows: A review from the perspective of systems biology.

Cereal straw, a human inedible crop byproduct, can be used as a roughage source in ruminants. However, the nutrition density and palatability are very low, limiting its efficient utilization in animal production. This review aims to systematically provide an overview of the limitations of cereal straws, which is crucial for developing new strategies to enhance the efficient use of cereal straws by lactating dairy cows. Evolutionary molecular biology makes it possible to comprehensively understand the limitations of using cereal straw as a roughage source in dairy cows by different techniques, e.g., multi-omics. Main constraints for utilization of cereal straw and stover in lactating dairy cows include low contents of easily fermented carbohydrates (pectin) and essential amino acids (Met, Phe, and branched-chain amino acids), high content of lignin and silica, and low nutrient digestibility. These cause insufficient supply of the precursors for milk synthesis and result in increased loss of nutrients in feces and urine. Several molecular mechanisms are revealed by multi-omics techniques, including changed amino acid and glucose metabolism, altered rumen microbial composition and function, and differential expression of miRNAs, mRNA, and protein in multi-organs that are associated with milk synthesis. These can be targets of approaches to improve the utilization of cereal straw by dairy cows. In addition, much attention should be given to the efficient countermeasures, including pretreatments by fibrolytic enzymes or steam explosion, dietary formulations such as supplement of pectin, methionine, and branched-chain amino acids, and feeding with other functional feedstuffs, which may improve the feeding and economic value of cereal straw for lactating dairy cows. The newly revealed functional genes (such as BAG3 in the rumen, PC in the liver, CSN1S2 in the mammary gland) and biomarkers (hippuric acid) as well as the integrative signaling and metabolic pathways (phenylalanine metabolism) related to the shortages of cereal straws could be used as nutritional or genetic regulatory targets to improve dairy cow production.

Feedomics provides bidirectional omics strategies between genetics and nutrition for improved production in cattle.

Increasing the efficiency and sustainability of cattle production is an effective way to produce valuable animal proteins for a growing human population. Genetics and nutrition are the 2 major research topics in selecting cattle with beneficial phenotypes and developing genetic potentials for improved performance. There is an inextricable link between genetics and nutrition, which urgently requires researchers to uncover the underlying molecular mechanisms to optimize cattle production. Feedomics integrates a range of omic techniques to reveal the mechanisms at different molecular levels related to animal production and health, which can provide novel insights into the relationships of genes and nutrition/nutrients. In this review, we summarized the applications of feedomics techniques to reveal the effect of genetic elements on the response to nutrition and investigate how nutrients affect the functional genome of cattle from the perspective of both nutrigenetics and nutrigenomics. We highlighted the roles of rumen microbiome in the interactions between host genes and nutrition. Herein, we discuss the importance of feedomics in cattle nutrition research, with a view to ensure that cattle exhibit the best production traits for human consumption from both genetic and nutritional aspects.

Cross-tissue single-cell transcriptomic landscape reveals the key cell subtypes and their potential roles in the nutrient absorption and metabolism in dairy cattle.

Introduction: Dairy cattle are a vitally important ruminant in meeting the demands for high-quality animal protein production worldwide. The complicated biological process of converting human indigestible biomass into highly digestible and nutritious milk is orchestrated by various tissues. However, poorly understanding of the cellular composition and function of the key metabolic tissues hinders the improvement of health and performance of domestic ruminants. Objectives: The cellular heterogeneity, metabolic features, interactions across ten tissue types of lactating dairy cattle were studied at single-cell resolution in the current study. Methods: Unbiased single-cell RNA-sequencing and analysis were performed on the rumen, reticulum, omasum, abomasum, ileum, rectum, liver, salivary gland, mammary gland, and peripheral blood of lactating dairy cattle. Immunofluorescences and fluorescence in situ hybridization were performed to verify cell identity. Results: In this study, we constructed a single-cell landscape covering 88,013 high-quality (500 < genes < 4,000, UMI < 50, 000, and mitochondrial gene ratio < 40% or 15%) single cells and identified 55 major cell types in lactating dairy cattle. Our systematic survey of the gene expression profiles and metabolic features of epithelial cells related to nutrient transport revealed cell subtypes that have preferential absorption of different nutrients. Importantly, we found that T helper type 17 (Th17) cells (highly expressing CD4 and IL17A) were specifically enriched in the forestomach tissues and predominantly interacted with the epithelial cell subtypes with high potential uptake capacities of short-chain fatty acids through IL-17 signaling. Furthermore, the comparison between IL17RAhighIL17RChigh cells (epithelial cells with IL17RA and IL17RC expression levels both greater than 0.25) and other cells explained the importance of Th17 cells in regulating the epithelial cellular transcriptional response to nutrient transport in the forestomach. Conclusion: The findings enhance our understanding of the cellular biology of ruminants and open new avenues for improved animal production of dairy cattle.

Metagenomics reveals differences in microbial composition and metabolic functions in the rumen of dairy cows with different residual feed intake.

BACKGROUND: Rumen microbial composition and functions have vital roles in feed digestion and fermentation and are linked to feed efficiency in cattle. This study selected Holstein cows, which are high in both milk protein content and milk yield, to analyse the relationship between the rumen microbiota and residual feed intake (RFI). Eighteen multiparous lactating cows were divided into low RFI (LRFI, high efficiency, n = 9) and high RFI (HRFI, low efficiency, n = 9) groups to investigate the differences in microbial composition and functions. RESULTS: The relative abundances of butyrate producers, including the Clostridium, Butyrivibrio, Eubacterium and Blautia genera, were higher in HRFI cows than in LRFI cows (P < 0.05). Four carbohydrate metabolic pathways (glycolysis/gluconeogenesis, pentose phosphate pathway, fructose and mannose metabolism, and butanoate metabolism) and one energy metabolism pathway (methane metabolism), were more abundant in HRFI animals (P < 0.05). Quorum sensing and DNA replication pathways were more abundant in HRFI cows. For CAZyme profiles, 14 out of 19 genes encoding carbohydrates-deconstructing enzymes were more abundant in HRFI cows (P < 0.05). Seven Lachnospiraceae species associated with carbohydrate metabolism and quorum sensing may contribute to the difference in feed efficiency. Moreover, the LRFI cows had lower abundances of Methanosphaera (P < 0.01), Methanobrevibacter ruminantium (P = 0.09) and methanogenesis functions (P = 0.04). CONCLUSIONS: The rumen microbiota of low-efficiency cows has stronger abilities to degrade carbohydrates and produce methane, and quorum sensing pathways could also be associated with differences in feed efficiency. This study provides a deeper understanding of the microbial ecology of dairy cows with different feed efficiencies and highlights the possibility of modulating the rumen microbiome or microbial functions to improve the feed efficiency of dairy cows.

Breed dependent regulatory mechanisms of beneficial and non-beneficial fatty acid profiles in subcutaneous adipose tissue in cattle with divergent feed efficiency.

The current study aimed to determine whether breed and feed efficiency affect the molecular mechanisms regulating beneficial and non-beneficial fatty acid profiles in subcutaneous adipose tissue of beef steers. Fatty acid profiling and RNA-Seq based transcriptome analysis were performed on subcutaneous adipose tissues collected from beef steers with three divergent breeds (Angus, ANG, n = 47; Charolais, CHAR, n = 48; Kinsella Composite, KC, n = 48) and different residual feed intake (RFI, a measure of feed efficiency). The comparison of fatty acid profiles showed that KC had higher beneficial FAs compared to the other two breeds. Distinct FA profiles between H-RFIfat and L-RFIfat steers was more obvious for KC steers, where H-RFIfat steers tended to have higher proportion of healthy FAs and lower proportion of the unhealthy FAs. A higher number of differentially expressed (DE) genes were observed for KC steers, whereas ANG and CHAR steers had a lower number of DE genes between H- and L-RFIfat steers. The association analyses of the gene expressions and FA profiles showed that 10 FA metabolism-associated genes together with the one upstream regulator (SREBF1) were associated with the proportion of C18:2n-6, total n-6, PUFA and PUFA/SFA for KC steers but not the other two breeds. Subcutaneous adipose tissue FA profiles and healthy FA index differed in cattle with divergent feed efficiency and such variation was unique for the three examined cattle breeds. Key FA metabolism-associated genes together with SREBF1 which is the upstream regulator of a set of genes involved in lipid metabolism may be of importance for genetic selection of meat with higher healthy FA index in beef cattle.