Disruption of ruminal homeostasis by malnutrition involved in systemic ruminal microbiota-host interactions in a pregnant sheep model

Background: Undernutrition is a prevalent and spontaneous condition in animal production which always affects microbiota-host interaction in gastrointestinal tract. However, how undernutrition affects crosstalk homeostasis is largely unknown. Here, we discover how undernutrition affects microbial profiles and subsequently how microbial metabolism affects the signal transduction and tissue renewal in ruminal epithelium, clarifying the detrimental effect of undernutrition on ruminal homeostasis in a pregnant sheep model. Results: Sixteen pregnant ewes (115 days of gestation) were randomly and equally assigned to the control (CON) and severe feed restriction (SFR) groups. Ewes on SFR treatment were restricted to a 30% level of ad libitum feed intake while the controls were fed normally. After 15 days, all ewes were slaughtered to collect ruminal digesta for 16S rRNA gene and metagenomic sequencing and ruminal epithelium for transcriptome sequencing. Results showed that SFR diminished the levels of ruminal volatile fatty acids and microbial proteins and repressed the length, width, and surface area of ruminal papillae. The 16S rRNA gene analysis indicated that SFR altered the relative abundance of ruminal bacterial community, showing decreased bacteria about saccharide degradation (SaccharofermentansandRuminococcus) and propionate genesis (Succiniclasticum) but increased butyrate producers (PseudobutyrivibrioandPapillibacter).Metagenome analysis displayed that genes related to amino acid metabolism, acetate genesis, and succinate-pathway propionate production were downregulated upon SFR, while genes involved in butyrate and methane genesis and acrylate-pathway propionate production were upregulated. Transcriptome and real-time PCR analysis of ruminal epithelium showed that downregulated collagen synthesis upon SFR lowered extracellular matrix-receptor interaction, inactivated JAK3-STAT2 signaling pathway, and inhibited DNA replication and cell cycle. Conclusions: Generally, undernutrition altered rumen bacterial community and function profile to decrease ruminal energy retention, promoted epithelial glucose and fatty acid catabolism to elevate energy supply, and inhibited the proliferation of ruminal epithelial cells. These findings provide the first insight into the systemic microbiota-host interactions that are involved in disrupting the ruminal homeostasis under a malnutrition pattern.