Related Experiment Video
Updated: Jul 7, 2025
Analysis of Interactions between Endobiotics and Human Gut Microbiota Using In Vitro Bath Fermentation Systems
Published on: August 23, 2019
Early concentrate starter introduction induces rumen epithelial parakeratosis by blocking keratinocyte
Kai Zhang1, Yali Zhang1, Jing Qin1
1Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China; Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Introduction:
Rumen epithelial parakeratosis, a common disease in ruminants caused by abnormalities in the ruminal stratified squamous epithelial keratinization process, negatively impacts ruminant health and performance. However, we still lack a comprehensive perception of the underlying mechanisms and the predisposing factors for this disorder.
Objectives:
Here, we investigated rumen epithelial cell heterogeneity, differentiation trajectories, and cornification to clarify the rumen epithelial keratinization process and discern the key ruminal metabolites contributing to rumen epithelial parakeratosis.
Methods:
Twenty-four 14-day-old lambs were divided into three groups, including only milk feeding, milk plus alfalfa hay feeding, and milk plus corn-soybean concentrate starter feeding. At 42 days of age, the lambs were slaughtered, and rumen tissues were collected for single-cell RNA-sequencing (scRNA-seq), immunofluorescence, and quantitative real-time PCR (qRT-PCR) analyses. Ruminal fluid samples were collected for metabolomic analyses. Rumen epithelial organoid was used to verify the key ruminal metabolites contributing to parakeratosis.
Results:
As expected, we observed that concentrate starter introduction resulted in rumen epithelial parakeratosis. Moreover, scRNA-seq analysis revealed a developmental impediment in the transition from differentiated keratinocytes to terminally differentiated keratinocytes (TDK) in lambs with concentrate starter introduction. Immunofluorescence and qRT-PCR analyses further verified the location and expression of marker genes of TDK. Metabolomic analysis showed a robust positive correlation between ruminal butyrate levels and rumen epithelial keratinization. More importantly, we successfully established a rumen organoid model capable of facilitating the study of the keratinization process in the rumen epithelia and further confirmed that high dose butyrate indeed contributed to rumen epithelial parakeratosis.
Conclusion:
Collectively, concentrate starter introduction induces ruminal epithelial parakeratosis by blocking keratinocyte differentiation with excessive ruminal butyrate accumulation in a neonatal lamb model. These findings enhance our understanding of rumen epithelial keratinization and provide valuable insights for addressing rumen epithelial parakeratosis using early nutritional intervention strategies.
