Electroacupuncture at PC6-Induced Gut Microbiota Changes and Potential Suppression of Nausea-Like Behavior: A Preliminary Study in Pregnant Mice

Objectives This study aimed to determine whether electroacupuncture (EA) at PC6 (Neiguan) modulates nausea-like behavior and gut microbiota composition during pregnancy in mice and to explore potential mechanisms involving the gut–brain axis. Methods Pregnant C57BL/6J mice received bilateral EA at PC6 or sham stimulation twice weekly from gestational day (GD) 1. Kaolin intake was measured daily as an index of nausea-like behavior. Fecal samples collected on GD14 were analyzed via 16S rRNA gene sequencing using QIIME2, and functional predictions were generated using PICRUSt2. Plasma growth differentiation factor 15 (GDF15) levels were quantified using ELISA in a separate cohort. Diversity (Chao1, Shannon, weighted UniFrac, and Bray–Curtis) and linear discriminant analysis effect size (LEfSe) analyses were used to identify taxonomic and functional differences. Results EA at PC6 significantly reduced kaolin intake during mid-gestation (GD9–16) without affecting gestational length or litter size. Plasma GDF15 levels increased from GD7 and peaked at GD10–16, mirroring the changes in kaolin intake. Although alpha and beta diversity did not significantly differ between groups, LEfSe analysis revealed enrichment of Bifidobacterium and Dorea in the PC6 group. PICRUSt2 predicted increased superpathway of chorismate metabolism (ALL-CHORISMATE-PWY) and decreased palmitate biosynthesis II (type II fatty acid synthase) (PWY-5971), suggesting a metabolic shift toward aromatic amino acids and anti-inflammatory pathways. Conclusions PC6 stimulation alleviated nausea-like behavior in pregnant mice, potentially through gut–brain axis modulation involving Bifidobacterium -associated metabolic reprogramming. These findings support PC6 stimulation as a safe, non-pharmacological strategy for managing nausea and vomiting during pregnancy (NVP/HG) and provide a preclinical framework integrating behavioral and microbiome analyses.