Changes in the host transcriptome and microbial metatranscriptome of the ileum of dairy calves subjected to artificial dosing of exogenous rumen contents

Authors: Li, Wenli; EDWARDS, ANDREA - University Of Wisconsin; MURPHY, BRIANNA - University Of Wisconsin; COX, MADISON - University Of Wisconsin; RAABIS, SARAH - University Of Wisconsin; SKARLUPKA, JOSEPH - University Of Wisconsin; STEINBERGER, ANDREW - University Of Wisconsin

Submitted to: Physiological Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/16/2020
Publication Date: 6/22/2020
Citation: Li, W., Edwards, A., Murphy, B., Cox, M., Raabis, S., Skarlupka, J., Steinberger, A. 2020. Changes in the host transcriptome and microbial metatranscriptome of the ileum of dairy calves subjected to artificial dosing of exogenous rumen contents. Physiological Genomics. 52:333-346. https://doi.org/10.1152/physiolgenomics.00005.2020.
DOI: https://doi.org/10.1152/physiolgenomics.00005.2020

Interpretive Summary: Numerous human and mouse studies indicated the significant impact of early colonization of the gut by microbial species on host health and development. However, little is known about the mechanisms how the microbial establishment can affect its host's physiology in ruminants, such as dairy cattle. Specifically, the immune system in the bovine small intestine is the host’s first line of defense against enteric infection and likely influences the colonization by commensal (nonharmful) microbes, though the molecular changes underlying such roles are largely unknown. This work performed artificial dosing of adult cow rumen content to new born calves. The main objective of this study was to examine the changes in the host ileum physiology using changes in gene expression as an indirect assessment. Knowledge gained through this study will shed light into the molecular changes in the ileum resulting from the artificial introduction of adult rumen microbial community into young calves. Further, this study provides a foundation for the development of probiotic treatments aimed at improving rumen development and host health.

Technical Abstract: The diverse range of microbial species in the gut of ruminants is critical for converting host non-digestible feed into usable nutrient sources to the host. Born without a functional rumen, ruminants were thought to acquire the functional ruminal microbes from the environment as the rumen develops. However, few attempts have been undertaken to understand the role of early rumen microbial colonization on gut development or host health in neonatal ruminants. Thus, the molecular changes associated with bacterial colonization remain largely unknown. In this study, we examined ileum transcriptome changes in response to dosing with exogenous rumen fluid in the early life of the calf, starting at birth, and repeated every other week. Six calves were included in this study, with three of them receiving artificial dosing and the rest of the three receiving autoclaved rumen fluid as control. At 8 weeks of age, calf ileum tissues were collected and subjected to host transcriptome and microbial meta-transcriptome analysis using RNA-sequencing. A total of 333 genes showed significantly differential expression (DE) between the dosed and control calves (fold-change>=1.5; adjusted P<0.1, mean read-count >=10). Gene ontology analysis indicated that these DE genes were predominantly enriched in immunity response (p-value <0.0001). The association analysis between the gene expression and the microbial species abundance identified 33 genes with significant correlation with the ileum microbial species (Pearson’r, p-value <0.0001). Among these, three genes showed the correlation with the most number of microbial species: LYZ2 (73 species), FABP5 (61) and FUT1 (49 species). Specifically, LYZ2 encodes an antibacterial lysozyme that acts efficiently against a wide range of bacteria. The more than 4-fold increase of expression of LYZ2 in treated calves suggested the activation of anti-bacterial activity and innate response from the host in response to the artificial dosing. This study’s findings shed light on the molecular processes in the ileum as a result of introducing an adult rumen microbial community into young calves. Further, this study provides a foundation for the development of probiotic treatments aimed at improving rumen development and host health.