Background The gut-liver axis plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC). However, the correlations between the gut microbiome and the liver tumor transcriptome in patients with HCC and the impact of the gut microbiota on clinical outcome are less well-understood. Methods Fecal samples collected from HBV-related HCC patients (n = 113) and healthy volunteers (n = 100) were subjected to 16S rRNA sequencing of the microbiome. After a rigorous selection process, 32 paired tumor and adjacent non-tumor liver tissues from the HCC group were subjected to next-generation sequencing (NGS) RNA-seq. The datasets were analyzed individually and integrated with clinical characteristics for combined analysis using bioinformatics approaches. We further verified the potential of the gut microbiota to predict clinical outcome by a random forest model and a support vector machine model. Results We found that Bacteroides, Lachnospiracea incertae sedis, and Clostridium XIVa were enriched in HCC patients with a high tumor burden. By integrating the microbiome and transcriptome, we identified 31 robust associations between the above three genera and well-characterized genes, indicating possible mechanistic relationships in tumor immune microenvironment. Clinical characteristics and database analysis suggested that serum bile acids may be important communication mediators between these three genera and the host transcriptome. Finally, among these three genera, six important microbial markers associated with tumor immune microenvironment or bile acid metabolism showed the potential to predict clinical outcome (AUC = 81%). Conclusions This study revealed that changes in tumor immune microenvironment caused by the gut microbiota via serum bile acids may be important factors associated with tumor burden and adverse clinical outcome. Gut microbes can be used as biomarkers of clinical features and outcomes, and the microbe-associated transcripts of host tumors can partly explain how gut microbiota promotes HCC pathogenesis.

Studies on the risk factors for intrahepatic cholestasis of pregnancy (ICP) in a population-based cohort are lacking. We assess the prevalence and risk factors of ICP in a Chinese population. In this study, a cohort study was conducted that included 12,200 eligible pregnant women. The overall incidence of ICP in this cohort was 6.06%. With increasing maternal age, the incidence of ICP decreased in women younger than 30 years of age but increased in those older than 30. With increasing pre-pregnancy BMI, the incidence of ICP decreased if the pre-pregnancy BMI was less than 23 kg/m2 but increased if it was 23 kg/m2 or higher. Further analysis showed that the risk of ICP increased when maternal age was < 25 years (Adjusted RR  2.01; 95% CI 1.64–2.47) or ≥ 35 years (Adjusted RR  1.34; 95% CI 1.02–1.76). Furthermore, an increased risk of ICP was associated with pre-pregnancy underweight (adjusted RR  1.27; 95% CI 1.04–1.56), inadequate gestational weight gain (GWG) (adjusted RR  1.58; 95% CI 1.28–1.96), lower maternal education (adjusted RR  2.96; 95% CI 2.35–3.74), multiparity (adjusted RR  1.54; 95% CI 1.23–1.93), and twin/multiple pregnancies (adjusted RR  2.12; 95% CI 1.25–3.58). Maternal age (< 25 or ≥ 35 years), underweight, inadequate GWG, lower maternal education, multiparity, and twin/multiple pregnancies were identified as risk factors of ICP.

Agricultural practices could affect bacterial diversity and community structure by altering soil physical and chemical properties. Straw returning and tillage practices are widely used in agriculture, however, the effects of these agricultural practices on microbiomes are still unclear. In the present study, we compared the 18 bacterial communities of soil with different straw returning and tillage treatment combinations. The V3–V4 regions of the 16S ribosomal RNA were amplified and analyzed by high‐throughput sequencing technology. The results showed that the bacterial communities were consistently dominated by Acidobacteria, Proteobacteria, Actinobacteria, and Chloroflexi. Short‐term straw returning and tillage practices significantly altered the diversity, relative abundance and functions of the soil microbiome. Soil subjected to rotary tillage and straw returning (RTS) combination possessed the highest bacterial diversity and lowest ratio of G+/G‐ bacteria, indicating that RTS could be an efficient integrated management system to improve microbiome in the short term. Double verifications based on relative abundance and network analysis, revealed close relationships of Mycobacterium and Methylibium with RTS, indicating they could serve as biomarkers for RTS. Investigating microbial changes under different agricultural practices will provide valuable foundations for land sustainable utilization and increase crop yields.

Gestational cholestasis is a common disease and is associated with adverse pregnancy outcomes. However, there are still no effective treatments. We investigated the effects of obeticholic acid (OCA) on fetal intrauterine growth restriction (IUGR) during 17α-ethynylestradiol- (E2-) induced gestational cholestasis in mice. All pregnant mice except controls were subcutaneously injected with E2 (0.625 mg/kg) daily from gestational day (GD) 13 to GD17. Some pregnant mice were orally administered with OCA (5 mg/kg) daily from GD12 to GD17. As expected, OCA activated placental, maternal, and fetal hepatic FXR signaling. Additionally, exposure with E2 during late pregnancy induced cholestasis, whereas OCA alleviated E2-induced cholestasis. Gestational cholestasis caused reduction of fetal weight and crown-rump length and elevated the incidence of IUGR. OCA decreased the incidence of IUGR during cholestasis. Interestingly, OCA attenuated reduction of blood sinusoid area in placental labyrinth layer and inhibited downregulation of placental sodium-coupled neutral amino acid transporter- (SNAT-) 2 during cholestasis. Additional experiment found that OCA attenuated glutathione depletion and lipid peroxidation in placenta and fetal liver and placental protein nitration during cholestasis. Moreover, OCA inhibited the upregulation of placental NADPH oxidase-4 and antioxidant genes during cholestasis. OCA activated antioxidant Nrf2 signaling during cholestasis. Overall, we demonstrated that OCA treatment protected against gestational cholestasis-induced placental dysfunction and IUGR through suppressing placental oxidative stress and maintaining bile acid homeostasis.