Multi-omics analysis reveals Oscillibacter valericigenes gavage increases fetal and placental weights and is associated with altered estrogen-related metabolism and valerate production in mice

Background Our prior work associated Oscillibacter valericigenes and valerate-related features with offspring birth weight in Landrace × Yorkshire sows, but functional evidence was limited. Objectives To test whether O. valericigenes or valerate increases late-gestation fetal weight and characterize maternal metabolic and placental responses. Methods Pregnant mice received 200 μL of sterile culture medium (Control), O. valericigenes bacterial suspension (OV_B; 10 8 CFU/mL), or sterile-filtered culture supernatant (OV_M) by oral gavage every other day from embryonic day (E) 7.5 to E17.5 (n = 7/group). Another cohort received sodium valerate (SV; 0–1.20 mg/mL) in drinking water from E7.5 to E17.5 (n = 8/group). At E18.5, fetal and placental weights, serum hormone concentrations, colonic and serum short-chain fatty acid concentrations, and placental gene expression were measured and analyzed using one-way ANOVA followed by Dunnett’s test. Multi-omics profiling was performed in the Control and OV_B groups. Results Compared with control, maternal gavage with O. valericigenes or its culture supernatant increased fetal weight by 4.56% and 6.81%, respectively (both P < 0.01), and placental weight by 8.57% and 8.25%, respectively (both P < 0.05). Multi-omics analyses revealed that O. valericigenes gavage was associated with altered estrogen-related metabolism and placental proteomic and transcriptional responses related to nutrient transport, angiogenesis, and tight junctions. Compared with the control group, OV_B increased colonic valerate concentration by 53.64% ( P < 0.05) and tended to increase serum estradiol concentration by 34.58% ( P = 0.054). SV supplementation at 0.60 mg/mL increased fetal weight by 6.44% ( P < 0.01), placental weight by 7.30% ( P < 0.05), and serum valerate concentration by 125.25% ( P < 0.05) compared with its respective control. SV supplementation did not significantly alter serum estradiol or progesterone concentrations. Conclusions O . valericigenes increases placental and fetal weights and is associated with altered estrogen-related metabolism and colonic valerate production in mice.