Maternal Isoflavone‐S Improve Offspring Intestinal Homeostasis Through Maternal Metabolome–Microbiome Intestine Interactions in a Pig Model

ABSTRACT Our previous research has shown that maternal dietary 40 mg/kg isoflavone‐S (ISO‐S) improves sow reproductive and offspring growth during late gestation and lactation. However, the mechanism by which maternal ISO‐S improves intestinal homeostasis in offspring remains unknown. The results showed that maternal ISO‐S reduced the depth of the jejunal crypt and increased the villous height to crypt depth ratio in both the ileum and jejunum of the offspring. Furthermore, we found that maternal ISO‐S increased the levels of T‐SOD, CAT, and GSH‐Px in the jejunum, as well as the levels of T‐SOD and CAT in the ileum, and the expression of SOD1 and SOD2 mRNA in the offspring's jejunum. Metabolomics analysis identified 56 differentially expressed metabolites in colostrum, with significant changes observed in antioxidant metabolites. Further in vitro studies showed that ISO‐S decreased ROS levels in PMECs under 4‐HNE‐induced oxidative stress. ISO‐S increased the mRNA expression of VADC1 and Atg5 and the protein expression of mitophagy‐related genes. Maternal ISO‐S not only enhanced SIgA production and mRNA expression of SIgA‐related factors in the offspring jejunum, but also affected the gut microbiota composition of the offspring piglets. The relative abundance of the Tenericutes (phylum) and the Bradymonadales (order) was significantly increased. In conclusion, the results indicate that supplementing sows with ISO‐S during late gestation and lactation helps improve offspring intestinal health, likely due to its enhancement of antioxidant enzymes, antioxidant metabolites, and immunoglobulins in colostrum. Furthermore, ISO‐S alleviates 4‐HNE‐induced oxidative stress in mammary epithelial cells by promoting mitophagy.