Astragalus polysaccharides ameliorate perinatal metabolic syndrome in sows via enhancing butyrate-producing bacteria

Astragalus polysaccharide (APS), a bioactive phytomacromolecule from Astragalus membranaceus , exhibits anti-inflammatory, antioxidant, and immunomodulatory activities. Given mammals’ lack of endogenous glycosidases for APS catabolism, this study hypothesizes its bioactivity stems from gut microbial interactions, investigating APS-mediated microbiome remodeling and therapeutic effects on perinatal metabolic syndrome (PeriMS) in sows. In vitro fermentation showed that APS significantly increased short-chain fatty acid (SCFA) production, with acetate (44.51 mmol/L), propionate (17.37 mmol/L), and butyrate (22.04 mmol/L) levels notably elevated and enriched canonical butyrate-producing taxa ( g_norank_f_Muribaculaceae , g_Monoglobus , g_unclassified_f_Lachnospiraceae , P < 0.05). In vivo , gestational APS supplementation (from day 90) improved piglet weaning weight, reduced maternal backfat loss during lactation, shortened post-weaning estrus interval, elevated intestinal butyrate, alleviated systemic inflammation/oxidative stress, and mitigated PeriMS. Mechanistic analysis associated PeriMS improvement with butyrate-producing bacteria, with butyrate playing a key role in gut health enhancement. These findings establish APS as a prebiotic, highlighting the gut microbiota-SCFA axis as a therapeutic target for PeriMS. This study provides targeted mechanistic evidence that the gut microbiota-SCFA axis mediates PeriMS improvement by APS. Mechanistic analysis linked PeriMS improvement to butyrate-producing bacteria, with butyrate playing a key role in gut health enhancement, which was verified by a sodium butyrate rescue experiment. These findings establish APS as a prebiotic, highlighting the gut microbiota-SCFA axis as a therapeutic target for PeriMS. This work provides novel evidence for microbiota-SCFA axis involvement in sow perinatal metabolic health, offering translational strategies to improve livestock metabolic health through APS supplementation. IMPORTANCE In intensive pig farming, 40% of multiparous sows develop perinatal metabolic syndrome (PeriMS) around farrowing, causing $150–$200 annual loss per sow due to inflammation (e.g., higher IL-6), oxidative stress, and extended weaning-to-estrus intervals (2.1 days). Gut dysfunction—marked by fewer butyrate-producing bacteria and increased endotoxin—triggers barrier damage and inflammation. Supplementing with Astragalus polysaccharides (APS, 10 g/day) enhances beneficial bacteria like Muribaculaceae and butyrogenic Bacteroides, raising butyrate in vitro . In sows, APS lowers endotoxemia and gut inflammation (calprotectin), correlating with reduced postpartum IL-6 and reactive oxygen species. It also improves productivity: less backfat loss and heavier weaned piglets. By targeting gut-barrier crosstalk, APS breaks the inflammation-metabolism cycle, providing a sustainable alternative to antibiotics to enhance peripartum sow health and profitability.