Multi-omics comparisons emphasize alterations in tryptophan metabolism in yaks with retained placenta: perspectives on feces, serum, placenta and colostrum homeostasis

Retained placenta (RT) is a multifactorial postpartum disorder that reflects systemic immune and metabolic dysregulation. However, its integrative molecular mechanisms and impacts on milk bioactive components remain unclear in high-altitude yaks. In this study, a comprehensive multi-omics analysis integrating fecal microbiome, serum metabolome, placental proteome, colostrum metabolome, and milk fat globule membrane (MFGM) proteome was performed to systematically characterize RT-associated alterations. A total of 12 postpartum yaks were classified into normal released placenta (RL, n = 6) and retained placenta (RT, n = 6) groups based on placental expulsion within or beyond 12 h after parturition. Fecal, serum, placental, and colostrum samples were subjected to integrated microbiome, metabolome, and proteome analyses, followed by multivariate and multi-omics integration analyses. The results showed that RT was characterized by enhanced oxidative stress, endocrine imbalance, and gut microbiota dysbiosis. It was also accompanied by global suppression of serum metabolic homeostasis and significant activation of inflammatory and immune-related pathways in the placenta. Notably, tryptophan metabolism exhibited consistent and pronounced alterations across multiple omics layers. In maternal serum and placental tissue, tryptophan metabolic flux was suppressed and closely linked to immune activation. In contrast, tryptophan-related metabolites were significantly upregulated in colostrum, suggesting a compensatory metabolic response. Integrative DIABLO analysis further demonstrated that tryptophan-derived metabolites, associated microbial taxa, and immune-related proteins exhibited highly coordinated cross-omics variation. This coordination enabled clear discrimination between RL and RT groups. Mechanistically, tryptophan metabolism acts as a central hub linking gut microbiota remodeling, immune activation, and mammary metabolic reprogramming. This process is further coupled with lipid metabolism suppression, autophagy regulation, and MFGM structural remodeling, ultimately affecting milk quality and functional properties. In summary, this study provides the first multi-omics evidence in yaks linking tryptophan metabolism with RT-associated microbiome, metabolome, and proteome alterations. It systematically elucidates the multi-layered molecular mechanisms underlying RT, which advances the understanding of RT pathophysiology and provides theoretical basis for biomarker discovery and targeted nutritional or metabolic interventions.