Fecal microbiota transplantation alleviates weaning stress in Tibetan piglets by modulating gut microbiota-metabolite interactions

Jian ZhangMingxuan ZhaoHongliang ZhangMengjia HanZhankun TanPeng Shang^*

• College of Agricultural and Animal Husbandry, Tibet University, Linzhi, China

Weaned piglets are highly stress-vulnerable, with reduced immunity. Conventional use of antibiotics to prevent diarrhea and boost growth carries risks: bacterial resistance, drug residues, and intestinal flora imbalance, threatening food safety and public health.This study systematically evaluated the regulatory effects of fecal microbiota transplantation (FMT) on gut microbiota and host metabolism in weaned Tibetan piglets by integrating 16S rRNA sequencing and metabolomics, with experimental groups including a basal diet (Nor), lincomycin-supplemented (Ant), and FMT-supplemented (Fec) interventions. FMT significantly enhanced gut microbiota alpha diversity (Shannon index), enriching beneficial genera (e.g., Lactobacillus, Prevotella) and functional taxa (e.g., Eubacterium hallii group) to establish a core microbiota dominated by short-chain fatty acid producers and fiber-degrading bacteria, while antibiotics reduced Firmicutes abundance (p < 0.05) and promoted Proteobacteria proliferation. Metabolically, FMT activated tryptophan pathways (e.g., anti-inflammatory 5-hydroxyindole) and bile secretion (ko04976), whereas antibiotics suppressed amino acid metabolism (e.g., N-acetylglycine) and triggered oxidative stress (MAPK signaling). Notably, Streptococcus exhibited dual metabolic roles, positively correlating with phytoestrogens (R-equol) and negatively with biogenic amines (tyramine), highlighting its nichespecific regulatory potential. By reconstructing functional microbiota (e.g., Christensenellaceae) and metabolic networks (tryptophan/riboflavin pathways), FMT achieved comparable growth performance to antibiotics while mitigating dysbiosis and metabolic disturbances. These findings elucidate FMT ' s mechanism in alleviating weaning stress through targeted enrichment of fiberdegrading and anti-inflammatory microbiota, coupled with metabolic synergy, thereby validating its feasibility as a non-antibiotic strategy and providing a theoretical framework for precision gut microbiota modulation in sustainable livestock production.Weaning represents one of the most critical physiological challenges in pig production, profoundly impacting piglet health and farm profitability (Liu, S.et al.,2023;Perez-Palencia.et al.,2022;Winters.et al.,2023.).During this phase, abrupt separation from the sow, a rapid dietary transition from nutrient-rich liquid milk to solid feed, and environmental stressors (e.g., regrouping, handler changes, and novel housing conditions) collectively induce multisystem stress (Camerlink, I.et al.,2021;Kerschaver, C. V.et al.,2023.). Compounded by immature immune and digestive systems in piglets, these stressors synergistically contribute to the development of "post-weaning stress syndrome," characterized by severe diarrhea, weight loss, growth retardation, reduced survival rates, and compromised disease resistance(Moeser, A.