Adaptive survival strategies of rumen microbiota with solid diet deficiency in early life cause epithelial mitochondrial dysfunction.

With extreme nutritional substrate deficiency, the adaptive responses of the gastrointestinal microbiota and host metabolism are largely unknown. Here, we successfully established a microbial substrate deficiency model in the rumen without solid diet introduction in neonatal lambs. In the absence of solid diet, we observed a reduction in the Simpson Index of rumen bacteria, along with a marked decline in the abundance of keystone microorganisms such as Prevotella, Selenomonas, Megasphaera, and Succiniclasticum, indicating a simplified microbial interaction network. Additionally, more urea and NH3-N production facilitated microbial efficient nitrogen utilization to prioritize ammonia as a nitrogen source for survival, reallocating energy to overcome nutritional limitations and sustain their viability. In addition, enriched archaea (Methanosarcina, Methanomicrobium, Methanobrevibacter, and Methanobacterium) promoted hydrogen removal and the growth of nitrogen-producing microorganisms (Pecoramyces, Piromyces, Caecomyces, and Orpinomyces). It also reinforced the glutamate-glutamine pathway, as evidenced by the higher expression of glnA, GLUL, gdhA, and ureAB, suggesting enhanced internal cycling of nitrogen for microbial survival. This selfish microbial survival strategy deprived the host of adequate volatile fatty acids for energy metabolism, resulting in the downregulation of rumen epithelial cell cycle proteins (CCNB1, CCNE), abnormal mitochondrial morphology, and reduced mitochondrial deoxyribonucleic acid copy number and adenosine triphosphate production. Overall, these findings revealed the adaptive survival strategies of rumen microbiota with solid diet deficiency in early life, which caused alterations in epithelial cell mitochondrial function.