The Diagnostic Potential of Gut Microbiota-Derived Short-Chain Fatty Acids in Preeclampsia

Abstract

Preeclampsia (PE) is a complex pregnancy-related hypertensive disorder leading to multiorgan dysfunction. It has high maternal, fetal, and neonatal morbidity and mortality rates. The study of gut microbiota and its metabolites in PE deserves further exploration. Thirty-eight pregnant women with PE and 29 healthy pregnant women in the third trimester of their pregnancy were recruited in this study. We used a targeted metabolomics approach to evaluate the short-chain fatty acids (SCFAs) in serum samples. The correlation between SCFAs and clinical characteristics was also explored. The results of mass spectrometry (MS) showed significant differences at the metabolomics level of SCFAs between the PE and healthy control. The metabolic levels of acetate, propionate, isobutyrate, and valerate were significantly increased in the PE group than in the healthy control group. In contrast, caproic acid and butyrate levels were significantly reduced. The correlation analysis showed that urea, systolic, and diastolic blood pressure levels were positively correlated with four types of SCFAs (acetic acid, propionic acid, isobutyric acid, and valeric acid) which increased in the PE group. Furthermore, the neutrophil percentage and the fetal birth weight were negatively correlated with isobutyric acid and valeric acid. In addition, the receiver operating characteristic (ROC) analysis using a generalized linear model showed that multiple SCFAs would be potential diagnostic markers for PE, with high specificity, sensitivity, and area under the curve (AUC). Among them, isobutyric acid (sensitivity: 97.4%, specificity: 100%, AUC = 1.00), propionic acid (sensitivity: 86.8%, specificity: 93.3%, AUC = 0.954) and acetic acid (sensitivity: 86.8%, specificity: 83.3%, AUC = 0.891) depicted significantly higher diagnostic value and potential clinical applications. In summary, the results of this study indicate that SCFAs have the potential to become effective biomarkers for early screening of PE.

Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy

“…In contrast to other SCFAs, this study identified a significant increase in isobutyric acid in the maternal serum of patients with ICP. Your previous research has also noted that the level of isobutyric acid in the peripheral blood circulation of pregnant women with pregnancy complications, such as pre-eclampsia and gestational diabetes, significantly increased compared with the NP group, aligning with the findings of this study[ 5 , 21 ]. This suggests that isobutyric acid plays a pivotal role in promoting the progression of pregnancy complications.…”

Expression and clinical significance of short-chain fatty acids in pregnancy complications

“…Quantitative analysis showed that compared with NP women, the content of isobutyric acid in the pregnancy complications groups was significantly higher, and the levels of other SCFAs were also significantly different from those in the NP group. ROC curve analysis showed that the sensitivity and specificity of acetic, propionic, and isobutyric acids in the PE group were high (AUC > 0.9), which is consistent with a previous study ( Li et al., 2022 ). In addition, we also showed that SCFAs were closely related to the increased risk of ICP, and ROC curve analysis showed that caproic acid and isobutyric acid might be potential biomarkers (AUC > 0.9).…”

The metabolic role of the CD73/adenosine signaling pathway in HTR-8/SVneo cells: A Double-Edged Sword?

“…Furthermore, Sivaprakasam et al reported that MCTs are involved in the uptake of short-chain fatty acids (SCFAs) through the plasma membrane [ 40 ]. Li et al found that several types of SCFAs were increased in patients with preeclampsia and are positively correlated with systolic, and diastolic blood pressure levels [ 41 ]. Our extracellular metabolite profiling pinpointed that the uptake of SCFA increased significantly when extracellular adenosine concentration increased ( Fig.…”