Objective To investigate the expression of short-chain fatty acids (SCFAs)—metabolites of intestinal flora—in gestational complications of gestational diabetes mellitus (GDM), preeclampsia (PE), and intrahepatic cholestasis of pregnancy (ICP), and its clinical significance. Methods Targeted metabonomics was used to detect SCFAs in the serum of 28 GDM pregnant women, 28 PE pregnant women, 29 ICP pregnant women, and 27 healthy pregnant women (NP); their expression changes were observed; the correlation between SCFAs and clinical characteristics was studied; and their potential as biomarkers for clinical diagnosis was evaluated. Results There were significant differences in the SCFA metabolic spectrum between the GDM, PE, ICP, and NP groups. Quantitative analysis showed that the content of isobutyric acid in the three pregnancy complications groups (the GDM, PE, and ICP groups) was significantly higher than that in the NP group (p < 0.05), and other SCFAs also showed significant differences in the three pregnancy complications groups compared with the NP group (p < 0.05). Receiver operating characteristic (ROC) curve analysis of the generalized linear model showed that multiple SCFAs were highly sensitive and specific as diagnostic markers in the pregnancy complications groups, where isobutyric acid was highly predictive in GDM (area under the ROC curve (AUC) = 0.764) and PE (AUC = 1), and caproic acid was highly predictive in ICP (AUC = 0.968), with potential clinical application. Conclusion The metabolic products of intestinal flora, SCFAs, during pregnancy are closely related to pregnancy complications (GDM, PE, and ICP), and SCFAs can be used as potential markers of pregnancy complications.

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

Oncogenic SIRT7 inhibits GATA4 transcriptional activity and activates the Wnt signaling pathway in ovarian cancer.

Hypertensive Disorders in Pregnancy: Global Burden from 1990 to 2019, Current Research Hotspots and Emerging Trends.

Obesity is becoming a worldwide pandemic with over one billion people affected. Of women in the United States, who are of childbearing age, two-thirds of them are considered overweight/obese. Offspring of women with obesity have a greater likelihood of developing cardiometabolic disease later in life, therefore making obesity a transgenerational issue. Emerging topics such as maternal microbial dysbiosis with altered levels of bacterial phyla and maternal obesity programming offspring cardiometabolic disease are a novel area of research discussed in this review. In the authors' opinion, beneficial therapeutics will be developed from knowledge of bacterial-host interactions at the most specific level possible. Although there is an abundance of obesity-related microbiome research, it is not concise, readily available, nor easy to interpret at this time. This review details the current knowledge regarding the relationship between obesity and the gut microbiome, with an emphasis on maternal obesity. 

Microbiome and pregnancy: focus on microbial dysbiosis coupled with maternal obesity

Immune checkpoint inhibitors have limited efficacy in hepatocellular carcinoma (HCC). Macrophages are the most abundant immune cells in HCC, suggesting that a better understanding of the intrinsic processes by which tumor cells regulate macrophages could help identify strategies to improve response to immunotherapy. As signaling lymphocytic activation molecule (SLAM) family members regulate various immune functions, we investigated the role of specific SLAM receptors in the immunobiology of HCC. Comparison of the transcriptomic landscapes of immunotherapy-responsive and non-responsive advanced HCC patients identified SLAMF7 upregulation in immunotherapy-responsive HCC, and HCC patients who responded to immunotherapy also displayed higher serum levels of SLAMF7. Loss of Slamf7 in liver-specific knockout mice led to increased hepatocarcinogenesis and metastasis, elevated immunosuppressive macrophage infiltration, and upregulated PD-1 expression in CD8+ T cells. HCC cell-intrinsic SLAMF7 suppressed MAPK/ATF2-mediated CCL2 expression to regulate macrophage migration and polarization in vitro. Mechanistically, SLAMF7 associated with SH2 domain-containing adaptor protein B (SHB) through its cytoplasmic 304 tyrosine site to facilitate the recruitment of SHIP1 to SLAMF7 and inhibit the ubiquitination of TRAF6, thereby attenuating MAPK pathway activation and CCL2 transcription. Pharmacological antagonism of the CCL2/CCR2 axis potentiated the therapeutic effect of anti-PD-1 antibody in orthotopic HCC mouse models with low SLAMF7 expression. In conclusion, this study highlights SLAMF7 as a regulator of macrophage function and a potential predictive biomarker of immunotherapy response in HCC. Strategies targeting CCL2 signaling to induce macrophage repolarization in HCC with low SLAMF7 might enhance the efficacy of immunotherapy.

Repolarization of immunosuppressive macrophages by targeting SLAMF7-regulated CCL2 signaling sensitizes hepatocellular carcinoma to immunotherapy.

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.

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

Upregulation of CXCL1 and LY9 contributes to BRCAness in ovarian cancer and mediates response to PARPi and immune checkpoint blockade

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

Upregulation of CXCL1 and LY9 contributes to BRCAness in ovarian cancer and mediates response to PARPi and immune checkpoint blockade