Effects of an Antibiotic Alternative Additive on Growth Performance, Intestinal Histomorphology, Multi-Omics Profiles, and Microbiome–Host Interactions in Tibetan Pigs

The ban on antibiotic growth promoters has created an urgent need for effective alternatives to maintain intestinal health and production performance. This exploratory study evaluated the effects of a novel antibiotic alternative additive at graded inclusion levels (control, 1%, 3%, 5%) on growth performance, intestinal histomorphology, gut microbiome ecology, and host metabolome in Tibetan pigs (n = 40). Forty Tibetan pigs were randomly assigned to four dietary treatment groups for a 21-day feeding trial. Growth performance, intestinal histopathology, metatranscriptomic sequencing (bacteria, viruses, fungi), and untargeted metabolomics were analyzed. Tibetan pigs fed the 3% additive diet exhibited the highest numerical average daily gain (0.197 vs. 0.148 kg/d, +33.1%) and lowest feed conversion ratio (2.61 vs. 3.59, −27.3%), with overall treatment effects reaching statistical significance (ADG: p = 0.027; FCR: p = 0.023). Metatranscriptomic profiling revealed fundamentally distinct microbial communities between the duodenum and colon. Multi-omics integration identified 79 significant microbiome-pathology associations in the duodenum and 38 in the colon, with SCFA-producing bacteria positively correlated with mucosal architectural parameters. The multi-omics network revealed a core-periphery architecture with Eubacterium, Lactobacillus, and Escherichia as keystone hubs. Dietary supplementation at 3% showed the most favorable effects on growth performance and metabolic modulation without compromising intestinal structural integrity, supporting its potential as a viable antibiotic alternative.