Lactic acid, a metabolic by-product of host and intestinal microbiota, has been recovered as an active signal molecule in the immune system. In this study, a lactic acid biosynthesis pathway that directly produces lactic acid from glucose rather than ethanol with high production was reconstructed in Saccharomyces cerevisiae. The engineered S. cerevisiae showed anti-inflammatory activity in dextran sulfate sodium (DSS)-induced mice with improved histological damage, increased mucosal barrier, and decreased intestinal immune response. Lactic acid regulated the macrophage polarization state and inhibited the expression of pro-inflammatory cytokines in vivo and in vitro. Increasing the macrophage monocarboxylic acid transporter-mediated active lactic acid uptake suppressed the excessive activation of the NLRP3 inflammasome and the downstream caspase-1 pathway in macrophages. Moreover, lactic acid promoted histone H3K9 acetylation and histone H3K18 lactylation. Meanwhile, the engineered S. cerevisiae altered the diversity and composition of the intestinal microbiota and changed the abundance of metabolic products in mice with colitis. In conclusion, this study shows that the application of engineered S. cerevisiae attenuated DSS-induced colitis in mice via suppressing macrophage pyroptosis and modulating the intestinal microbiota, which is an effective and safe treatment strategy for ulcerative colitis.

Scope: Gut microbiome-derived metabolites are the major mediators of diet-induced host-microbial interactions. Aryl hydrocarbon receptor (AHR) plays a crucial role in glucose, lipid, and cholesterol metabolism in the liver. In this study, we aimed to investigate the role of indole-3-acetic acid (IAA) and AHR in sulforaphane (SFN) alleviates hepatic steatosis in mice fed on a high-fat diet (HFD).Methods and Results: The HFD-fed male C57BL/6 mice were intervened with SFN for 6 weeks. HFD-mice showed classical pathophysiological characteristics of hepatic steatosis. The results showed that SFN significantly reduced body weight, liver inflammation and hepatic steatosis in HFD-fed mice. SFN reduced hepatic lipogenesis by activating AHR/SREBP-1C pathway, which was confirmed in HepG2 cell experiments. Moreover, SFN increased hepatic antioxidant activity by modulating Nrf-2/NQO1 expression. SFN increased serum and liver IAA level in HFD mice. Notably, SFN manipulated the gut microbiota, resulting in reducing Deferribacteres and proportions of the phylum Firmicutes/Bacteroidetes and increasing the abundance of specific bacteria that produce IAA. Furthermore, SFN upregulated Ahr expression and decreased the expression of inflammatory cytokines in Raw264.7 cells.Conclusions: SFN ameliorated hepatic steatosis not only by modulating lipid metabolism via AHR/SREBP-1C pathway but regulating IAA and gut microbiota in HFD-induced NAFLD mice.

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Gastric intestinal metaplasia (IM) is a precancerous lesion that increases the risk of subsequent gastric cancer (GC) development. Therefore, the mechanism of IM has been the focus of basic and clinical research. Helicobacter pylori (H. pylori) infection has been recognized as the main pathogenesis of gastric IM. However, more and more studies have shown that chronic inflammation of gastric mucosa caused by bile reflux is the key pathogenic factor of gastric IM. Bile reflux activates the expression of IM biomarkers via the bile acid receptor. In addition, microRNAs, exosomes, and epigenetics are also involved in the occurrence and development of bile acid-induced gastric IM. Currently, the relevant research is still very few. The molecular mechanism of the phenotypic transformation of gastrointestinal epithelial cells induced by bile acids has not been fully understood. This article mainly reviews the physiology and pathology of bile acid, mechanism of gastric IM induced by bile acid, bile acid receptors, and so on, in order to provide reference for further research.

Background: Accurate assessment of lymph node status in gastric cancer (GC) patients can help to select appropriate treatment strategies for GC, but the diagnostic accuracy of conventional methods needs to be improved. The aim of this study was to investigate the predictive value of preoperative hemoglobin and albumin levels and lymphocyte and platelet counts (HALP) on lymph node status in GC patients and to construct a risk prediction model. Methods: This study retrospectively analyzed the clinicopathological characteristics of 349 patients with GC who underwent radical gastrectomy, among which 250 patients were recruited in the training cohort and 99 patients in the independent validation cohort. Significant risk factors in univariate analysis were further identified as independent variables in multivariate logistic regression analysis, which were then incorporated and presented in a nomogram. ROC curves, Calibration curve and DCA curves were used to evaluate the discrimination, prediction accuracy and clinical effectiveness of the model Results: Multifactorial logistic regression analysis showed that alcohol use (OR =2.203, P=0.036), Depth of invasion (OR =7.756, P<0.001), differentiation (OR =2.252, P=0.018), CEA (OR =2.443, P=0.017), CA199 (OR =2.715, P=0.008) and HALP (OR =2.276, P=0.032) were independent risk factors for lymph node metastasis (LNM) in GC. We used these factors to construct a nomogram for predicting LNM in GC patients, and the ROC curves showed good discrimination of the model with AUC values of 0.854 (training cohort) and 0.868 (validation cohort), respectively, and the calibration curves showed good predictive ability of the nomogram, in addition to the DCA curves results showed the clinical usefulness of the model. Conclusions: In conclusion, we established a nomogram for predicting LNM in patients with GC.