Multi‐omics reveals gastrointestinal metabolic disorder‐induced diarrhea in postpartum dairy cows

Abstract Nutritional diarrhea in ruminants is often regarded as a hindgut disorder, whereas the contribution of rumen dysfunction to downstream hindgut alterations remains insufficiently understood. We used a compartment‐resolved multi‐omics approach to investigate rumen‐hindgut microbial and metabolic features associated with diarrhea in postpartum dairy cows. Twenty‐four postpartum cows, including 12 diarrheic and 12 non‐diarrheic cows, underwent rumen and fecal metagenomic and metabolomic profiling, together with serum metabolomic analysis. Diarrheic cows showed altered ruminal microbial community structure and functional profiles, including enrichment of specific Prevotella ‐affiliated genomes and changes in carbohydrate‐ and purine‐related features. These ruminal changes coincided with greater fecal crude protein and reduced fermentable carbohydrate availability. In the hindgut, diarrheic cows showed lower Prevotella sp. 000436915 and higher Alistipes ‐affiliated metagenome‐assembled genomes, accompanied by lower short‐chain fatty acid production and enhanced nitrogen fermentation. Serum metabolomics further revealed changes in glucose and amino acid‐related metabolites. Multi‐omics factors linked fecal water content with coordinated rumen, hindgut, and serum variation. Together, these results define a cross‐compartment microbial‐functional‐metabolic signature of nutritional diarrhea and identify candidate markers for monitoring and targeted nutritional or microbiome‐based intervention.