Biomarkerendothelial dysfunctionGut MicrobiotaInflammationInterleukin-1β

Maternal serum trimethylamine-N-oxide is significantly increased in cases with established preeclampsia

  • 2018
  • Yuwen Wen, Linrui Peng, Ruoting Xu, et al.
Why this matters for your gut health

Preeclampsia affects about 5–10% of pregnancies worldwide and is the second leading cause of maternal and perinatal illness and death. Its exact cause is still not well understood. TMAO is a gut-microbiota-derived metabolite already linked to cardiovascular disease, endothelial dysfunction and vascular inflammation. This is reported as the first study to compare serum TMAO in preeclamptic and normal pregnancies and to relate it to disease severity. It suggests a possible gut-microbiome link to preeclampsia and a candidate biomarker, though the authors stress that this needs validation.

Summary

This case-control study at Nanfang Hospital, Southern Medical University (Guangzhou, China), enrolled 86 women in the third trimester between May 2016 and December 2017. There were 43 women with preeclampsia (26 severe, 17 mild) and 43 normotensive controls, matched for age, parity and BMI. Fasting serum TMAO was measured by LC-MS/MS, and IL-1β (inflammation), sVCAM-1 and sFlt-1 (endothelial dysfunction) were measured by ELISA. TMAO was significantly higher in preeclampsia and highest in severe disease. Among the women with preeclampsia, TMAO correlated with blood pressure, urinary protein and all three biomarkers. TMAO did not correlate with kidney function (eGFR), so the authors suggest the elevation was not simply due to impaired renal clearance. They propose that TMAO may promote inflammation (NLRP3/IL-1β) and sFlt-1 overproduction, driving endothelial dysfunction. They note that the study cannot show whether TMAO rises before or after the onset of preeclampsia.

Key findings

  • Median serum TMAO (10th–90th percentile) was 5.9 μM in controls (2.9–15.3), 21.6 μM in mild preeclampsia (5.6–65.8) and 43.5 μM in severe preeclampsia (28.6–96.3). Both preeclampsia groups were significantly higher than controls (P < 0.05), and severe was higher than mild.
  • IL-1β, sVCAM-1 and sFlt-1 were all significantly elevated in preeclampsia compared with controls. sFlt-1 was higher in severe than in mild disease, but IL-1β and sVCAM-1 did not differ significantly between the two severity groups.
  • In women with preeclampsia, TMAO correlated positively with systolic blood pressure (r = 0.602), urinary protein (r = 0.557), IL-1β (r = 0.633), sVCAM-1 (r = 0.719) and sFlt-1 (r = 0.763) (all P < 0.001).
  • TMAO did not correlate with eGFR (r = −0.218, P = 0.15), and renal function did not differ significantly between groups.
  • No significant correlations between TMAO and blood pressure or these biomarkers were seen in the control group (data not shown).
  • Women with preeclampsia had higher blood pressure and proteinuria. They also had earlier delivery (mean 37.1 weeks for mild and 35.1 for severe, versus 39.1 for controls) and lower neonatal birth weight and placental weight.
  • The authors propose a mechanism in which TMAO activates the NLRP3 inflammasome and IL-1β, and may raise sFlt-1 through the Ang II/HIF-1α pathway, causing endothelial dysfunction. This is a hypothesis, not something the study tested.
  • Limitations: blood was taken only after preeclampsia was established, so cause and effect cannot be determined. The sample was small and from a single hospital.
  • The authors suggest lowering TMAO might help as an adjuvant therapy, but this is speculative and was not tested.
  • A few oddities in the PDF’s tables: the text says there were no significant differences “among the three groups” in baseline characteristics (age, gravidity, BMI, urea, eGFR), while gestational age at delivery clearly differed. In Table 2, sFlt-1 for mild preeclampsia is marked as different from the mild group itself. The two statistical references are also cited under one reference number. Check against the original before quoting exact figures.

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Citation

Wen Y, Peng L, Xu R, Zang N, Huang Q, Zhong M. Maternal serum trimethylamine-N-oxide is significantly increased in cases with established preeclampsia. Pregnancy Hypertension. 2019;15:114–117. doi:10.1016/j.preghy.2018.12.001

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