Fig. 4
Mediation and interaction analyses for linoleic acid, gut microbiota, and metabolic health in early pregnancy. A Effect of linoleic acid microbiota index on metabolic biomarkers. B Mediation analysis of linoleic acid microbiota index for the association of linoleic acid with C-peptide. PIDE and Pinv-IDE were estimated by the bidirectional mediation analysis. PIDE indicates the P value for the indirect effect and Pinv-IDE indicates P value for the inverse indirect effect. The full arrowed lines show the effect of linoleic acid on C-peptide mediated by linoleic acid microbiota index. Inverse mediation was performed to check whether linoleic acid microbiota index can influence C-peptide through linoleic acid. C Interaction between linoleic acid levels and specific gut microbiota for GDM risk. Low and high abundance groups were defined based on the second tertile of relative abundance for LA-related microbial genera. The P value for interaction was derived from the interaction term between LA-related microbial genera and LA levels in the multivariable conditional logistic regression models. All models were adjusted for maternal age (years, continuous), education (primary or middle school, high school, and college or above), gestational age at baseline blood collection (weeks, continuous), parity (nulliparous and multiparous), cigarette smoking (ever and never), alcohol drinking (ever and never), physical activity (continuous, MET-hours/week), pre-pregnancy BMI (< 18.5, 18.5–24, 24–28, and ≥ 28 kg/m2), family history of diabetes (yes and no), and history of GDM (yes and no). GDM, gestational diabetes mellitus; HbA1c, hemoglobin A1 C; HDL, high-density lipoprotein; HOMA-IR, homeostatic model assessment for insulin resistance; IDE, indirect effect; inv-IDE, inverse indirect effect; LDL, low-density lipoprotein