Persistent Benefits of Early Gestational Chenodeoxycholic Acid Supplementation on Late Pregnancy in Sows via Sustained Modulation of the Gut-Metabolism Axis.

BACKGROUND

Our previous studies in pigs have identified chenodeoxycholic acid (CDCA) as a potent metabolic regulator during early gestation, capable of enhancing embryo implantation by optimizing maternal metabolic status and gut microbiota-host interactions, whereas the long-term impacts of early gestational CDCA on late pregnancy remain largely unexplored.

OBJECTIVES

This study investigated whether supplementation with CDCA during early gestation (gestational day 0-28) exerts a sustained metabolic modulation effect on maternal health and reproductive outcomes in late gestation in a sow model.

METHODS

Multiparous sows (n = 24) were randomly assigned to receive either a control diet or a diet supplemented with 0.15% CDCA during early gestation. The reproductive performance, oxidative stress, inflammatory status, gut microbiome, and serum metabolome in late gestation were subsequently evaluated.

RESULTS

Results showed that early CDCA intervention significantly increased the total and live litter sizes (P < 0.05). Furthermore, CDCA treatment alleviated maternal oxidative stress and systemic inflammation and improved insulin sensitivity in late gestation (P < 0.05). Untargeted metabolomics revealed a distinct metabolic remodeling, characterized by the enrichment of beneficial metabolites, such as L-ornithine, and the depletion of proinflammatory and oxidative markers, including 1-palmitoylphosphatidylcholine, 2-lysophosphatidylcholine, 3-hydroxyanthranilic acid, and N-carboxymethyllysine. 16S rRNA sequencing indicated that CDCA exerted a targeted modulation rather than a global reconstruction of the gut microbiota. Specifically, CDCA suppressed potentially harmful bacteria, including NK4A214_group, Clostridium_sensu_stricto_1, and Turicibacter, whereas it enriched beneficial genera such as Subdoligranulum. Multiomics integration identified NK4A214_group as a key driver associated with exacerbated inflammatory status and unfavorable metabolic profiles.

CONCLUSIONS

Collectively, these findings demonstrate that early gestational CDCA supplementation elicits a long-term protective effect on maternal metabolism via optimizing specific gut microbe-metabolite interactions, thereby ensuring optimal gestational outcomes.