Dietary index for gut microbiota and odds of gestational diabetes mellitus: associations with inflammatory and metabolic biomarkers.
Su Yi Y, Du Xiuping X, Song Zhiying Z, He Xifeng X
Gestational diabetes mellitus (GDM) is a common metabolic disorder of pregnancy associated with adverse maternal and neonatal outcomes. Emerging evidence suggests that dietary patterns supportive of gut microbial health and associated systemic inflammation may contribute to the pathophysiology of GDM. This study evaluated the association between a dietary index oriented toward gut microbiota (DI-GM)-comprising foods previously linked to beneficial gut microbial composition-and GDM odds, metabolic profiles, inflammatory markers, and pregnancy outcomes. This case-control study included 800 pregnant women (400 GDM cases and 400 controls) at 24-28 weeks of gestation. Dietary intake was assessed using a validated food frequency questionnaire, and DI-GM scores were derived based on intake of microbiota-supportive and disruptive foods. Biochemical measurements included glucose parameters, lipid profile, hs-CRP, IL-6, TNF-α, and lipopolysaccharide. Multivariable logistic regression and structural equation modeling were used for association and mediation analyses. Women with GDM had lower DI-GM scores than controls (7.09 ± 1.64 vs. 9.52 ± 1.83, p < 0.001). In the fully adjusted model (Model 2), women in the highest DI-GM tertile (T3) had 55.4% lower odds of GDM compared with those in the lowest tertile (T1) (OR = 0.446). A significant inverse trend was observed across DI-GM tertiles (P trend = 0.002), indicating a dose-response relationship. Each 1-unit increase in DI-GM score was associated with an 11.0% lower adjusted odds of GDM (OR = 0.890); however, the association appeared to be nonlinear, with the strongest protective effect observed in the highest tertile. These findings suggest a potential threshold effect, whereby clinically meaningful benefits become evident primarily at higher levels of dietary adherence. The highest DI-GM tertile demonstrated lower fasting glucose, HbA1c, HOMA-IR, triglycerides, hs-CRP, and LPS, alongside higher HDL-C (all p < 0.05). Among women with GDM, higher DI-GM scores were strongly associated with lower rates of cesarean delivery, preeclampsia, gestational hypertension, macrosomia, neonatal hypoglycemia, NICU admission, and respiratory distress syndrome (all P-trend < 0.001). However, in the control group, this protective trend was not observed for any outcome except for a paradoxical significant increase in cesarean delivery with higher DI-GM adherence (P-trend < 0.001), while all other outcomes showed no significant trends (p > 0.10). Exploratory mediation analyses suggested hs-CRP may partially explain the DI-GM-glycemic association, but concurrent measurement precludes causal mediation. The negative indirect effects indicate an inconsistent mediation pattern, suggesting hs-CRP may not function as a classical mediator but rather reflects shared metabolic pathways or residual confounding. These findings are exploratory and hypothesis-generating, not confirmatory. Greater adherence to a microbiota-oriented dietary pattern was associated with lower GDM odds and improved maternal-neonatal outcomes. However, without direct gut microbiota measurement, these findings represent associations-not confirmation-of diet-microbiota-inflammation pathways, and require further investigation.