Sex-driven differences in the rumen microbe-metabolite-epithelial transport axis: an integrated multi-omics study of rumen function in male and female Zhongwei goats

Sex is a critical regulatory factor affecting rumen microecology, substance metabolism, and epithelial transport function in ruminants. Nevertheless, potential molecular clues underlying sex‑associated differences of the ruminal microbe‑metabolite‑epithelial transport axis remain poorly understood. The present study aimed to elucidate the sex-specific regulatory characteristics and functional differences in rumen functions of Zhongwei goats. A total of 12 six-month-old Zhongwei goats with an average body weight of 22.5 ± 1.8 kg (6 males and 6 females) were selected for multi-omics analysis, including 16 S rRNA sequencing, volatile fatty acid (VFAs) determination, untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics, and qPCR detection of transporter genes. The results showed that male goats had significantly higher concentrations of butyric acid, branched‑chain volatile fatty acids, caproic acid and total VFAs in the rumen ( P < 0.05), with significant enrichment of Firmicutes, Butyrivibrio and Succinibacterium , as well as remarkably upregulated expression of the AE2 gene ( P < 0.05). In contrast, female goats had higher abundances of Fibrobacteres, Fibrobacter and Prevotella , accompanied by significantly higher expression of the DRA gene ( P < 0.05). A total of 491 sex-related differential metabolites were identified. Antioxidant metabolites (pallidol and tiliroside) were significantly enriched in female goats, whereas differential metabolites in male goats were mainly annotated to steroid saponin metabolism and neuroactive substance metabolic pathways. Sex shapes two distinct rumen functional patterns in Zhongwei goats. Males possess stronger protein fermentation capacity relying on the AE2- mediated transport system, while females exhibit efficient fiber degradation function dependent on the DRA gene. This study provides correlative molecular clues for developing sex‑specific precise nutritional strategies in ruminants.