Ferrous Bisglycinate Supplementation Modulates Intestinal Antioxidant Capacity via the AMPK/FOXO Pathway and Reconstitutes Gut Microbiota and Bile Acid Profiles in Pigs

Multi-omics were applied to compare the risks and benefits of ferrous sulfate (FeSO4) and ferrous bisglycinate (FebisGly) in pigs in the current study. The FebisGly group showed reduced triglyceride (TG) and triglyceride/total cholesterol (TG/CHOL) values in the serum and reduced malondialdehyde (MDA) and increased glutathione (GSH) levels in the duodenum. Transcriptome analysis revealed that differentially expressed genes in the duodenum were enriched in oxidative phosphorylation, AMPK, and FOXO signaling pathways between FeSO4 and FebisGly groups. AMPK phosphorylation and FOXO3 protein expressions were significantly increased in the FebisGly group. Bacterial 16S rRNA gene sequence analysis revealed significantly reduced alpha diversity in the FeSO4 group and increased Firmicutes, reduced Bacteroidetes, and Proteobacteria abundances in the FebisGly group. Targeted metabolome revealed notably increased lithocholic acid (LCA), glycolithocholic acid (GLCA), hyodeoxycholic acid (HDCA), ursodeoxycholic acid (UDCA), and glycoursodeoxycholic acid (GUDCA) in the FebisGly group. RDA analysis indicated that Fusobacteria was positively correlated with TG and TG/high-density lipoprotein in the FeSO4 group while Christensenellaceae_R-7_group, Ruminococcaceae_UCG-002, and Ruminococcaceae_UCG-005 were positively correlated with UDCA and GLCA in the FebisGly group. According to the current study, FebisGly improves serum lipid metabolism, modulates intestinal antioxidant capacity via the AMPK/FOXO pathway, and reconstitutes gut microbiota and bile acid profiles in pigs.