Transcriptomic changes of the gut in dairy calves during pre-weaned period

  • Author / Creator
    Liang, Guanxiang
  • Maintenance of the gut health of calves is vital because enteric infections are associated with high mortality during the pre-weaned period. The small intestine is the primary site of many enteric infections and plays an important role in protecting the host from pathogenic infection through both barrier and mucosal immune functions. However, the molecular mechanisms regulating small intestine development in the pre-weaned calf have not been well characterized. Four studies (Chapters 2, 3, 4 and 5) were performed to investigate the expression profiles of protein-coding genes and microRNAs (miRNAs) in gut tissues of pre-weaned calves, identify their changes in response to gut microbial colonization and enteric infection, and elucidate potential mechanisms of the small intestinal development in the pre-weaned calves. The expression of miRNAs in the gastrointestinal tract had dynamic changes during the pre-weaned period, and their functions were related to the development of intestinal mucosal immune system Moreover, significant associations between miRNA expression and microbial populations in the small intestine provided evidences that miRNAs were involved in mediating host-microbial interactions. Further transcriptomic analysis revealed higher expression levels of genes involved in complement functional pathway, tight junction protein, and IgA complex in the jejunum than those in the ileum, suggesting the roles of the jejunum in the immune and barrier functions in pre-weaned calves. In addition, during the first week after birth, the temporal expression pattern of tight junction protein genes, antimicrobial peptide genes, NOD-like receptor genes, a regulatory T cell marker gene, and cytokine genes suggested that this is a critical developmental period for intestinal mucosal immune function. An ileal loop model was used to target Mycobacterium avium subspecies paratuberculosis (MAP) infection to the ileal region of the small intestine. Differentially expressed miRNAs and alternatively spliced genes in the infected versus uninfected ileal segment revealed significant changes in endothelial cell proliferation, macrophage maturation and lysosome function as possible mechanisms by which MAP escapes host immune responses. Finally, the same surgical model was used to analyze changes in miRNA expression when the intestinal microbiota was altered by treatment with a dose-dependent exposure to allicin, an antimicrobial compound present in garlic. The observed changes in miRNA expression and their predicted function in lymphocytes development following of the changes in gut bacterial population changes after antimicrobial treatment further supported the conclusion that miRNA expression was associated with microbial colonization and miRNA played a role in regulating the intestinal mucosal immune system of pre-weaned calves. In summary, the transcriptomic analysis revealed that the protein-coding genes and miRNAs are involved in regulating diverse aspects of small intestinal development that are age-dependent and vary among regions of the small intestine. Of particular importance were their functions in the immune system, which were associated with microbial colonization during early life.

  • Subjects / Keywords
  • Graduation date
    Spring 2016
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.