Metabolism of Oak Leaf Ellagitannins and Urolithin Production in Beef Cattle

Oak leaves have a high concentration of ellagitannins. These phytochemicals can be beneficial or poisonous to animals. Beef cattle are often intoxicated by oak leaf consumption, particularly after suffering feed restriction. The severity of the poisoning has recently been associated with the ruminal microbiota, as different bacterial populations were found in animals that tolerated oak leaves and in those that showed clinical and pathological signs of toxicity. Intoxication has previously been linked to the production of phenolic metabolites, particularly catechol, phloroglucinol, and resorcinol. This suggested that the microbial metabolism of ellagitannins could also be associated with its tolerance or intoxication in different animals. Therefore, it is essential to understand the metabolism of ellagitannins in cattle. Here we show that ellagitannins are metabolized in the cattle rumen to urolithins. Different urolithins were detected in ruminal fluid, feces, urine, and plasma. Oak leaf ellagitannins declined as they were converted to urolithins, mainly isourolithin A and urolithin B, by the ruminal and fecal microbiota. Urolithin aglycons were observed in rumen and feces, and glucuronide and sulfate derivatives were detected in plasma and urine. Sulfate derivatives were the main metabolites detected in plasma, while glucuronide derivatives were the main ones in urine. The main urolithins produced in cattle were isourolithin A and urolithin B. This is a relevant difference from the monogastric mammals studied previously in which urolithin A was the main metabolite produced. Low molecular weight phenolics of the benzoic, phenylacetic, and phenylpropionic groups and metabolites such as catechol, resorcinol, and related compounds were also detected. There was a large variability in the kinetics of production of these metabolites in individual animals, although they produced similar metabolites in all cases. This large variability could be associated with the large variability in the rumen and intestine microbiota that has previously been observed. Further studies are needed to demonstrate if the efficiency in the metabolism of ellagitannins by the microbiota could explain the differences observed in susceptibility to intoxication by the different animals

Table_6_Elucidating genes and gene networks linked to individual susceptibility to milk fat depression in dairy goats.xlsx

Dietary supplementation with marine lipids modulates ruminant milk composition toward a healthier fatty acid profile for consumers, but it also causes milk fat depression (MFD). Because the dairy goat industry is mainly oriented toward cheese manufacturing, MFD can elicit economic losses. There is large individual variation in animal susceptibility with goats more (RESPO+) or less (RESPO–) responsive to diet-induced MFD. Thus, we used RNA-Seq to examine gene expression profiles in mammary cells to elucidate mechanisms underlying MFD in goats and individual variation in the extent of diet-induced MFD. Differentially expression analyses (DEA) and weighted gene co-expression network analysis (WGCNA) of RNA-Seq data were used to study milk somatic cell transcriptome changes in goats consuming a diet supplemented with marine lipids. There were 45 differentially expressed genes (DEGs) between control (no-MFD, before diet-induced MFD) and MFD, and 18 between RESPO+ and RESPO–. Biological processes and pathways such as “RNA transcription” and “Chromatin modifying enzymes” were downregulated in MFD compared with controls. Regarding susceptibility to diet-induced MFD, we identified the “Triglyceride Biosynthesis” pathway upregulated in RESPO– goats. The WGCNA approach identified 9 significant functional modules related to milk fat production and one module to the fat yield decrease in diet-induced MFD. The onset of MFD in dairy goats is influenced by the downregulation of SREBF1, other transcription factors and chromatin-modifying enzymes. A list of DEGs between RESPO+ and RESPO– goats (e.g., DBI and GPD1), and a co-related gene network linked to the decrease in milk fat (ABCD3, FABP3, and PLIN2) was uncovered. Results suggest that alterations in fatty acid transport may play an important role in determining individual variation. These candidate genes should be further investigated.</p

Table_5_Elucidating genes and gene networks linked to individual susceptibility to milk fat depression in dairy goats.xlsx

Dietary supplementation with marine lipids modulates ruminant milk composition toward a healthier fatty acid profile for consumers, but it also causes milk fat depression (MFD). Because the dairy goat industry is mainly oriented toward cheese manufacturing, MFD can elicit economic losses. There is large individual variation in animal susceptibility with goats more (RESPO+) or less (RESPO–) responsive to diet-induced MFD. Thus, we used RNA-Seq to examine gene expression profiles in mammary cells to elucidate mechanisms underlying MFD in goats and individual variation in the extent of diet-induced MFD. Differentially expression analyses (DEA) and weighted gene co-expression network analysis (WGCNA) of RNA-Seq data were used to study milk somatic cell transcriptome changes in goats consuming a diet supplemented with marine lipids. There were 45 differentially expressed genes (DEGs) between control (no-MFD, before diet-induced MFD) and MFD, and 18 between RESPO+ and RESPO–. Biological processes and pathways such as “RNA transcription” and “Chromatin modifying enzymes” were downregulated in MFD compared with controls. Regarding susceptibility to diet-induced MFD, we identified the “Triglyceride Biosynthesis” pathway upregulated in RESPO– goats. The WGCNA approach identified 9 significant functional modules related to milk fat production and one module to the fat yield decrease in diet-induced MFD. The onset of MFD in dairy goats is influenced by the downregulation of SREBF1, other transcription factors and chromatin-modifying enzymes. A list of DEGs between RESPO+ and RESPO– goats (e.g., DBI and GPD1), and a co-related gene network linked to the decrease in milk fat (ABCD3, FABP3, and PLIN2) was uncovered. Results suggest that alterations in fatty acid transport may play an important role in determining individual variation. These candidate genes should be further investigated.</p

Table_2_Elucidating genes and gene networks linked to individual susceptibility to milk fat depression in dairy goats.xlsx

Dietary supplementation with marine lipids modulates ruminant milk composition toward a healthier fatty acid profile for consumers, but it also causes milk fat depression (MFD). Because the dairy goat industry is mainly oriented toward cheese manufacturing, MFD can elicit economic losses. There is large individual variation in animal susceptibility with goats more (RESPO+) or less (RESPO–) responsive to diet-induced MFD. Thus, we used RNA-Seq to examine gene expression profiles in mammary cells to elucidate mechanisms underlying MFD in goats and individual variation in the extent of diet-induced MFD. Differentially expression analyses (DEA) and weighted gene co-expression network analysis (WGCNA) of RNA-Seq data were used to study milk somatic cell transcriptome changes in goats consuming a diet supplemented with marine lipids. There were 45 differentially expressed genes (DEGs) between control (no-MFD, before diet-induced MFD) and MFD, and 18 between RESPO+ and RESPO–. Biological processes and pathways such as “RNA transcription” and “Chromatin modifying enzymes” were downregulated in MFD compared with controls. Regarding susceptibility to diet-induced MFD, we identified the “Triglyceride Biosynthesis” pathway upregulated in RESPO– goats. The WGCNA approach identified 9 significant functional modules related to milk fat production and one module to the fat yield decrease in diet-induced MFD. The onset of MFD in dairy goats is influenced by the downregulation of SREBF1, other transcription factors and chromatin-modifying enzymes. A list of DEGs between RESPO+ and RESPO– goats (e.g., DBI and GPD1), and a co-related gene network linked to the decrease in milk fat (ABCD3, FABP3, and PLIN2) was uncovered. Results suggest that alterations in fatty acid transport may play an important role in determining individual variation. These candidate genes should be further investigated.</p

Table_12_Elucidating genes and gene networks linked to individual susceptibility to milk fat depression in dairy goats.xlsx

Dietary supplementation with marine lipids modulates ruminant milk composition toward a healthier fatty acid profile for consumers, but it also causes milk fat depression (MFD). Because the dairy goat industry is mainly oriented toward cheese manufacturing, MFD can elicit economic losses. There is large individual variation in animal susceptibility with goats more (RESPO+) or less (RESPO–) responsive to diet-induced MFD. Thus, we used RNA-Seq to examine gene expression profiles in mammary cells to elucidate mechanisms underlying MFD in goats and individual variation in the extent of diet-induced MFD. Differentially expression analyses (DEA) and weighted gene co-expression network analysis (WGCNA) of RNA-Seq data were used to study milk somatic cell transcriptome changes in goats consuming a diet supplemented with marine lipids. There were 45 differentially expressed genes (DEGs) between control (no-MFD, before diet-induced MFD) and MFD, and 18 between RESPO+ and RESPO–. Biological processes and pathways such as “RNA transcription” and “Chromatin modifying enzymes” were downregulated in MFD compared with controls. Regarding susceptibility to diet-induced MFD, we identified the “Triglyceride Biosynthesis” pathway upregulated in RESPO– goats. The WGCNA approach identified 9 significant functional modules related to milk fat production and one module to the fat yield decrease in diet-induced MFD. The onset of MFD in dairy goats is influenced by the downregulation of SREBF1, other transcription factors and chromatin-modifying enzymes. A list of DEGs between RESPO+ and RESPO– goats (e.g., DBI and GPD1), and a co-related gene network linked to the decrease in milk fat (ABCD3, FABP3, and PLIN2) was uncovered. Results suggest that alterations in fatty acid transport may play an important role in determining individual variation. These candidate genes should be further investigated.</p

Image_1_Elucidating genes and gene networks linked to individual susceptibility to milk fat depression in dairy goats.png

Dietary supplementation with marine lipids modulates ruminant milk composition toward a healthier fatty acid profile for consumers, but it also causes milk fat depression (MFD). Because the dairy goat industry is mainly oriented toward cheese manufacturing, MFD can elicit economic losses. There is large individual variation in animal susceptibility with goats more (RESPO+) or less (RESPO–) responsive to diet-induced MFD. Thus, we used RNA-Seq to examine gene expression profiles in mammary cells to elucidate mechanisms underlying MFD in goats and individual variation in the extent of diet-induced MFD. Differentially expression analyses (DEA) and weighted gene co-expression network analysis (WGCNA) of RNA-Seq data were used to study milk somatic cell transcriptome changes in goats consuming a diet supplemented with marine lipids. There were 45 differentially expressed genes (DEGs) between control (no-MFD, before diet-induced MFD) and MFD, and 18 between RESPO+ and RESPO–. Biological processes and pathways such as “RNA transcription” and “Chromatin modifying enzymes” were downregulated in MFD compared with controls. Regarding susceptibility to diet-induced MFD, we identified the “Triglyceride Biosynthesis” pathway upregulated in RESPO– goats. The WGCNA approach identified 9 significant functional modules related to milk fat production and one module to the fat yield decrease in diet-induced MFD. The onset of MFD in dairy goats is influenced by the downregulation of SREBF1, other transcription factors and chromatin-modifying enzymes. A list of DEGs between RESPO+ and RESPO– goats (e.g., DBI and GPD1), and a co-related gene network linked to the decrease in milk fat (ABCD3, FABP3, and PLIN2) was uncovered. Results suggest that alterations in fatty acid transport may play an important role in determining individual variation. These candidate genes should be further investigated.</p

Table_1_Elucidating genes and gene networks linked to individual susceptibility to milk fat depression in dairy goats.xlsx

Dietary supplementation with marine lipids modulates ruminant milk composition toward a healthier fatty acid profile for consumers, but it also causes milk fat depression (MFD). Because the dairy goat industry is mainly oriented toward cheese manufacturing, MFD can elicit economic losses. There is large individual variation in animal susceptibility with goats more (RESPO+) or less (RESPO–) responsive to diet-induced MFD. Thus, we used RNA-Seq to examine gene expression profiles in mammary cells to elucidate mechanisms underlying MFD in goats and individual variation in the extent of diet-induced MFD. Differentially expression analyses (DEA) and weighted gene co-expression network analysis (WGCNA) of RNA-Seq data were used to study milk somatic cell transcriptome changes in goats consuming a diet supplemented with marine lipids. There were 45 differentially expressed genes (DEGs) between control (no-MFD, before diet-induced MFD) and MFD, and 18 between RESPO+ and RESPO–. Biological processes and pathways such as “RNA transcription” and “Chromatin modifying enzymes” were downregulated in MFD compared with controls. Regarding susceptibility to diet-induced MFD, we identified the “Triglyceride Biosynthesis” pathway upregulated in RESPO– goats. The WGCNA approach identified 9 significant functional modules related to milk fat production and one module to the fat yield decrease in diet-induced MFD. The onset of MFD in dairy goats is influenced by the downregulation of SREBF1, other transcription factors and chromatin-modifying enzymes. A list of DEGs between RESPO+ and RESPO– goats (e.g., DBI and GPD1), and a co-related gene network linked to the decrease in milk fat (ABCD3, FABP3, and PLIN2) was uncovered. Results suggest that alterations in fatty acid transport may play an important role in determining individual variation. These candidate genes should be further investigated.</p

Table_4_Elucidating genes and gene networks linked to individual susceptibility to milk fat depression in dairy goats.xlsx

Dietary supplementation with marine lipids modulates ruminant milk composition toward a healthier fatty acid profile for consumers, but it also causes milk fat depression (MFD). Because the dairy goat industry is mainly oriented toward cheese manufacturing, MFD can elicit economic losses. There is large individual variation in animal susceptibility with goats more (RESPO+) or less (RESPO–) responsive to diet-induced MFD. Thus, we used RNA-Seq to examine gene expression profiles in mammary cells to elucidate mechanisms underlying MFD in goats and individual variation in the extent of diet-induced MFD. Differentially expression analyses (DEA) and weighted gene co-expression network analysis (WGCNA) of RNA-Seq data were used to study milk somatic cell transcriptome changes in goats consuming a diet supplemented with marine lipids. There were 45 differentially expressed genes (DEGs) between control (no-MFD, before diet-induced MFD) and MFD, and 18 between RESPO+ and RESPO–. Biological processes and pathways such as “RNA transcription” and “Chromatin modifying enzymes” were downregulated in MFD compared with controls. Regarding susceptibility to diet-induced MFD, we identified the “Triglyceride Biosynthesis” pathway upregulated in RESPO– goats. The WGCNA approach identified 9 significant functional modules related to milk fat production and one module to the fat yield decrease in diet-induced MFD. The onset of MFD in dairy goats is influenced by the downregulation of SREBF1, other transcription factors and chromatin-modifying enzymes. A list of DEGs between RESPO+ and RESPO– goats (e.g., DBI and GPD1), and a co-related gene network linked to the decrease in milk fat (ABCD3, FABP3, and PLIN2) was uncovered. Results suggest that alterations in fatty acid transport may play an important role in determining individual variation. These candidate genes should be further investigated.</p

Table_3_Elucidating genes and gene networks linked to individual susceptibility to milk fat depression in dairy goats.xlsx

Dietary supplementation with marine lipids modulates ruminant milk composition toward a healthier fatty acid profile for consumers, but it also causes milk fat depression (MFD). Because the dairy goat industry is mainly oriented toward cheese manufacturing, MFD can elicit economic losses. There is large individual variation in animal susceptibility with goats more (RESPO+) or less (RESPO–) responsive to diet-induced MFD. Thus, we used RNA-Seq to examine gene expression profiles in mammary cells to elucidate mechanisms underlying MFD in goats and individual variation in the extent of diet-induced MFD. Differentially expression analyses (DEA) and weighted gene co-expression network analysis (WGCNA) of RNA-Seq data were used to study milk somatic cell transcriptome changes in goats consuming a diet supplemented with marine lipids. There were 45 differentially expressed genes (DEGs) between control (no-MFD, before diet-induced MFD) and MFD, and 18 between RESPO+ and RESPO–. Biological processes and pathways such as “RNA transcription” and “Chromatin modifying enzymes” were downregulated in MFD compared with controls. Regarding susceptibility to diet-induced MFD, we identified the “Triglyceride Biosynthesis” pathway upregulated in RESPO– goats. The WGCNA approach identified 9 significant functional modules related to milk fat production and one module to the fat yield decrease in diet-induced MFD. The onset of MFD in dairy goats is influenced by the downregulation of SREBF1, other transcription factors and chromatin-modifying enzymes. A list of DEGs between RESPO+ and RESPO– goats (e.g., DBI and GPD1), and a co-related gene network linked to the decrease in milk fat (ABCD3, FABP3, and PLIN2) was uncovered. Results suggest that alterations in fatty acid transport may play an important role in determining individual variation. These candidate genes should be further investigated.</p

Table_8_Elucidating genes and gene networks linked to individual susceptibility to milk fat depression in dairy goats.xlsx

Dietary supplementation with marine lipids modulates ruminant milk composition toward a healthier fatty acid profile for consumers, but it also causes milk fat depression (MFD). Because the dairy goat industry is mainly oriented toward cheese manufacturing, MFD can elicit economic losses. There is large individual variation in animal susceptibility with goats more (RESPO+) or less (RESPO–) responsive to diet-induced MFD. Thus, we used RNA-Seq to examine gene expression profiles in mammary cells to elucidate mechanisms underlying MFD in goats and individual variation in the extent of diet-induced MFD. Differentially expression analyses (DEA) and weighted gene co-expression network analysis (WGCNA) of RNA-Seq data were used to study milk somatic cell transcriptome changes in goats consuming a diet supplemented with marine lipids. There were 45 differentially expressed genes (DEGs) between control (no-MFD, before diet-induced MFD) and MFD, and 18 between RESPO+ and RESPO–. Biological processes and pathways such as “RNA transcription” and “Chromatin modifying enzymes” were downregulated in MFD compared with controls. Regarding susceptibility to diet-induced MFD, we identified the “Triglyceride Biosynthesis” pathway upregulated in RESPO– goats. The WGCNA approach identified 9 significant functional modules related to milk fat production and one module to the fat yield decrease in diet-induced MFD. The onset of MFD in dairy goats is influenced by the downregulation of SREBF1, other transcription factors and chromatin-modifying enzymes. A list of DEGs between RESPO+ and RESPO– goats (e.g., DBI and GPD1), and a co-related gene network linked to the decrease in milk fat (ABCD3, FABP3, and PLIN2) was uncovered. Results suggest that alterations in fatty acid transport may play an important role in determining individual variation. These candidate genes should be further investigated.</p