Sows suffer oxidative stress and inflammation induced by metabolic burden during late pregnancy, which negatively regulates reproductive and lactating performances. We previously found that L-malic acid (MA) alleviated oxidative stress and inflammation and improved reproductive performances in sows. However, the mechanism underlying the MA’s positive effects remains unexplored. Here, twenty Large White × Landrace sows with similar parity were randomly divided into two groups and fed with a basal diet or a diet supplemented with 2% L-malic acid complex from day 85 of gestation to delivery. The gut microbiome, fecal short-chain fatty acids, and untargeted serum metabolome were determined. Results showed that Firmicutes, Bacteroidota, and Spirochaetota were the top abundant phyla identified in late pregnancy for sows. Maternal MA supplementation modulated the composition but not the richness and diversity of gut microbiota during late pregnancy. Correlation analysis between gut microbiota and antioxidant capacity (or inflammation indicators) revealed that unclassified_f_Ruminococcaceae, unclassified_f_Lachnospiraceae, UCG-002, norank_f_norank_o_RF3, and Lactobacillus might play a role in anti-oxidation, and Lachnospiraceae_XPB1014_group, Lachnospiraceae_NK4A136_group, UCG-002, unclassified_f_Ruminococcaceae, Candidatus_Soleaferrea, norank_f_UCG-010, norank_f_norank_o_RF39, and unclassified_f_Lachnospiraceae might be involved in the anti-inflammatory effect. The improved antioxidant and inflammation status induced by MA might be independent of short chain fatty acid changes. In addition, untargeted metabolomics analysis exhibited different metabolic landscapes of sows in the MA group from in the control group and revealed the contribution of modified amino acid and lipid metabolism to the improved antioxidant capacity and inflammation status. Notably, correlation results of gut microbiota and serum metabolites, as well as serum metabolites and antioxidant capacity (or inflammation indicators), demonstrated that differential metabolism was highly related to the fecal microorganisms and antioxidant or inflammation indicators. Collectively, these data demonstrated that a maternal dietary supply of MA can ameliorate oxidative stress and inflammation in sows through modulating gut microbiota and host metabolic profiles during late pregnancy.

Fetus loss in early pregnancy is of major concern to both humans and animals, and this issue is largely influenced by embryo implantation. Chenodeoxycholic acid (CDCA), a primary bile acid, contributes to metabolic improvements and protects against intrahepatic cholestasis of pregnancy. However, the effect of CDCA on embryo implantation during early pregnancy has not been investigated. The present study demonstrated that CDCA administration during early pregnancy improved embryo implantation in sows and rats, thereby improving the pregnancy outcomes of sows. CDCA significantly reduced inflammation, oxidative stress, and insulin resistance. The metabolomics analysis indicated significant differences in the fecal metabolome, especially regarding the level of secondary bile acids, between the control and CDCA-treated sows. CDCA also influenced the serum metabolite profiles in sows, and the serum L-Histidine level was significantly correlated with the abundance of 19 differential fecal metabolites. Importantly, L-Histidine administration improved embryo implantation and metabolic health in rats during early pregnancy. Moreover, CDCA administration during early pregnancy also led to long-term metabolic improvements in sows. Our data indicated that CDCA improved embryo implantation by alleviating inflammation and oxidative stress, improving insulin sensitivity, and modulating the interaction between the gut microbiota and host metabolites. Therefore, CDCA intervention is a potential therapeutic strategy regarding embryo loss during pregnancy.