Gut microbial-related metabolite trimethylamine-N-oxide and its precursor L-carnitine are associated with spontaneous preterm birth: a nested case-control study

Abstract

Background: Gut microbiota has been proven to disease susceptibility and may lead to increased risk of preterm birth. To date, the link of gut microbial-related metabolite trimethylamine-N-oxide (TMAO), L-carnitine, and betaine, with spontaneous preterm birth (sPTB) has not been established. This study aimed to investigate the association of TMAO, L-carnitine and betaine, with sPTB risk. Methods: A nested case-control study was designed including 129 sPTB cases and 258 controls based on Guangxi Birth Cohort Study. TMAO, L-carnitine, and betaine level in maternal serum were determined by liquid chromatography with mass spectrometry. Conditional logistic regression analyses were used to examine the association between maternal serum metabolites and sPTB. Stratified analyses were further conducted according to BMI and preterm prelabor rupture of membranes. Spline analyses were performed to explore the dose-response relationship between the metabolites and sPTB.Results: Statistically significant association with decreased sPTB risk was observed for the highest L-carnitine (OR: 0.47; 95% CI: 0.23, 0.95). In risk analyses stratified by BMI, similar results were observed in normal weight gravida (BMI: 18.5~23.9 kg/cm2). The significant subtype-specific association with TMAO (OR: 0.43; 95% CI: 0.20, 0.93) and L-carnitine (OR: 0.45; 95% CI: 0.21, 0.97) were observed for preterm labor but not PPROM. Spline regression analysis indicated non-linear associations with TMAO and sPTB risk (P for nonlinearity: 0.057). Significant associations of TMAO with sPTB were observed in normal weight gravida (P = 0.028) and preterm labor subtype (P = 0.025). No statistically significant associations with sPTB risk were observed for betaine (P > 0.05).Conclusions: TMAO and L-carnitine levels in maternal serum are inversely linked with sPTB risk. Discovery of the association between gut-microbiota initiated TMAO metabolism and sPTB may open new avenues for diagnose and therapy.