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.

Metabolic (dysfunction) associated fatty liver disease (MAFLD) is recognized as the most prevalent chronic liver disease globally. However, its pathogenesis remains incompletely understood. Recent advancements in the gut-liver axis offer novel insights into the development of MAFLD. Polysaccharides, primarily derived from fungal and algal sources, abundantly exist in the human diet and exert beneficial effects on glycometabolism, lipid metabolism, inflammation, immune modulation, oxidative stress, and the release of MAFLD. Numerous studies have demonstrated that these bioactivities of polysaccharides are associated with their prebiotic properties, including the ability to modulate the gut microbiome profile, maintain gut barrier integrity, regulate metabolites produced by gut microbiota such as lipopolysaccharide (LPS), short-chain fatty acids (SCFAs), and bile acids (BAs), and contribute to intestinal homeostasis. This narrative review aims to present a comprehensive summary of the current understanding of the protective effects of polysaccharides on MAFLD through their interactions with the gut microbiota and its metabolites. Specifically, we highlight the potential molecular mechanisms underlying the prebiotic effects of polysaccharides, which may give new avenues for the prevention and treatment of MAFLD.

Background. Patients with prolonged inflammatory bowel disease (IBD) can develop into colorectal cancer (CRC), also called colitis-associated cancer (CAC). Studies have shown the association between gut dysbiosis, abnormal bile acid metabolism, and inflammation process. Here, we aimed to investigate these two factors in the CAC model. Methods. C57BL/6 mice were randomly allocated to two groups: azoxymethane/dextran sodium sulfate (AOM/DSS) and control. The AOM/DSS group received AOM injection followed by DSS drinking water. Intestinal inflammation, mucosal barrier, and bile acid receptors were determined by real-time PCR and immunohistochemistry. Fecal microbiome and bile acids were detected via 16S rRNA sequencing and liquid chromatography-mass spectrometry. Results. The AOM/DSS group exhibited severe mucosal barrier impairment, inflammatory response, and tumor formation. In the CAC model, the richness and biodiversity of gut microbiota were decreased, along with significant alteration of composition. The abundance of pathogens was increased, while the short-chain fatty acids producing bacteria were reduced. Interestingly, Clostridium XlV and Lactobacillus, which might be involved in the bile acid deconjugation, transformation, and desulfation, were significantly decreased. Accordingly, fecal bile acids were decreased, accompanied by reduced transformation of primary to secondary bile acids. Given bile acid receptors, the ileum farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis was downregulated, while Takeda G-protein receptor 5 (TGR5) was overexpressed in colonic tumor tissues. Conclusion. Gut dysbiosis might alter the metabolism of bile acids and promote CAC, which would provide a potential preventive strategy of CAC by regulating gut microbiota and bile acid metabolism.

A novel robust nomogram based on preoperative hemoglobin and albumin levels and lymphocyte and platelet counts (HALP) for predicting lymph node metastasis of gastric cancer Xu Wang, Qijin He, Huixi Liang, Jiani Liu, Xin Xu, Kui Jiang, Jie Zhang

It is essential to determine contributors around impairment in health‐related quality of life (HRQoL) in patients with cirrhosis aiming at improving health care and therapeutic strategy. Studies simultaneously incorporating disease severity based on biochemical parameters and other physical/psychological effects (i.e., sleep disturbance and frailty) are heterogeneous and the subject of the present study. We analyzed and compared HRQoL, using the EuroQol Group 5 Dimension (EQ‐5D) questionnaire and the utility index retrieved, in patients with cirrhosis and across groups stratified by sleep disturbance or frailty phenotype. Sleep disturbance and frailty were determined by the Pittsburgh Sleep Quality Index (PSQI) and Frailty Index, respectively. Multiple linear regression was implemented to clarify contributors of poor HRQoL. In this cohort of 227 patients with mean age of 61.7 years and 47.2% male, more than half of the study population represented impairment in HRQoL in at least one domain, according to EQ‐5D. Furthermore, sleep disturbance and frailty have proved to be independently associated with poor HRQoL in two separate regression models, whereas conventional scoring systems such as Child‐Pugh classification and Model for End‐Stage Liver Disease are not closely relevant. Intriguingly, not all health domains within EQ‐5D correlated well with PSQI and Frailty Index, with the exception of usual activities. Pain and anxiety/depression were the most frequently affected HRQoL domains even in patients without sleep disturbance or frailty. Conclusion: Impaired HRQoL is prevalent in patients with decompensated cirrhosis. Sleep disturbance and frailty are independently associated with poor HRQoL. It is imperative to timely intervene with these symptoms and deliver tailored health care.