Alterations in the Microbiomes and Metabolic Profiles of the Ileal Between the Hu Sheep and East Friesian Sheep.

The East Friesian sheep is a dairy breed known for its high fertility and high milk production and is currently one of the best dairy sheep breeds in the world. This breed is known to have a poor disease-resistant phenotype compared to Hu sheep. Gut microbiota and metabolites play a role in host disease resistance. The intestinal bacterial microbiota is essential for maintaining the health of sheep and ensuring their productive potential, and it may also help explain disease-resistant phenotypic differences related to breeds. However, the ileum microbiota and metabolite profiles of Hu sheep and East Friesian sheep have remained poorly characterized. The ileal is a significant organ in the intestinal tract, and most nutrients and minerals in food are absorbed through the small intestine. It is necessary to understand the composition of both species' ileal microbiota and metabolites using the same feeding conditions. Therefore, studying the differences in the ileal microorganisms between breeds is essential to decipher the mechanisms behind these differences and identify microorganisms that influence the disease-resistant phenotype drive of ruminants. Due to the poor disease-resistant phenotype in sheep during the weaning period, with diarrhea and other diseases most likely to occur, we selected dairy sheep that were just two months old and had recently been weaned. This study comprehensively examined differences between the ileal microbiota in a large cohort of two breeds of sheep, including six Hu sheep and six East Friesian sheep. Using 16S rRNA and non-targeted metabolomics analysis, we determined that the Hu sheep had more microorganisms, including , , , and and more metabolites, including 2,7-Dihydroxy-5-methyl-1-naphthoic acid, Leu-Pro-Glu-Phe-Tyr, dodecanoic acid, Ala-Gln-Phe-Ile-Met, and Ala-Gln-Glu-Val-His, compared to the EF sheep group. Moreover, the Hu sheep were significantly enriched in amino acid biosynthesis, fatty acid metabolites, and bile secretion compared to the EF sheep groups, which may have been the main driver of the observed differences in disease-resistant phenotypes between the Hu sheep and East Friesian sheep. In addition, we hypothesized that there may be multiple beneficial microbes and metabolites that modulate the immune response and ultimately affect disease resistance. Therefore, these findings provide insights into the mechanisms underlying disease-resistant phenotype in sheep and may provide useful information for optimizing the composition of the ileal bacterial microbiota in sheep.