ABSTRACT Inflammatory bowel disease (IBD) is a chronic intestinal disorder that is often accompanied by oxidative stress, immune imbalance, disruption of the intestinal barrier, and liver complications linked through the gut‐liver axis. In this study, we explored the protective effects of Medjool date seed polysaccharides (MDSP) in a dextran sulfate sodium (DSS)‐induced colitis mouse model. Structural characterization using transmission electron microscopy (TEM), Fourier‐transform infrared (FTIR), x‐ray photoelectron spectroscopy (XPS), high‐performance liquid chromatography (HPLC), and nuclear magnetic resonance (NMR) analyses showed that MDSP consisted of oxygen‐rich heteropolysaccharide structures with notable antioxidant potential. Oral administration of MDSP (150 and 300 mg/kg) markedly alleviated DSS‐induced colitis by reducing body weight loss, disease activity, and colon shortening, while improving intestinal histological architecture and restoring MUC2 expression. MDSP also reduced the levels of pro‐inflammatory cytokines, including IL‐1β, IL‐6, IL‐17, and IL‐23, and enhanced the expression of anti‐inflammatory cytokines, such as IL‐10 and IL‐4. In addition, MDSP improved antioxidant status by increasing superoxide dismutase (SOD) and glutathione (GSH) levels and lowering myeloperoxidase (MPO), malondialdehyde (MDA), nitric oxide (NO), ALT, and AST levels, indicating significant protection against oxidative stress and colitis‐associated liver injury. Analysis of the gut microbiota further demonstrated that MDSP helped restore microbial balance by suppressing harmful bacteria, including Klebsiella and Desulfovibrio , while promoting beneficial genera such as Lactobacillus and Bifidobacterium . The aforementioned findings suggest that MDSP can effectively reduce intestinal inflammation, improve antioxidant defenses, protect liver function, and regulate gut microbiota composition, highlighting its application prospects as a preventive control for IBD.
ABSTRACT This study was conducted to investigate the protective effect of oolong tea extracts (OTEs) on colitis and explore its underlying mechanism. In the mice model, OTE effectively attenuated the dextran sulfate sodium‐induced colitis by preserving intestinal barrier integrity, reducing oxidative stress, and regulating inflammatory cytokines. 16S rRNA sequencing revealed that OTE altered the gut microbiota structure and composition, as evidenced by the reduction of pathogenic bacteria and the increase in probiotic bacteria. Antibiotic‐treated pseudo‐germ‐free model and fecal microbiota transplantation (FMT) experiment suggested the potential involvement of gut microbiota in OTE's anti‐colitis effect. Further analysis indicated that this protective effect may be mediated by the enrichment of SCFAs‐producing bacteria by OTE, which was associated with elevated IL‐22 secretion via the SCFAs‐mediated AHR/ p ‐STAT3 signaling pathway, thereby alleviating intestinal inflammation. Overall, OTE alleviated colitis potentially through gut microbiota–SCFAs–IL‐22 axis. These findings suggest a promising application of oolong tea and a potential therapeutic strategy for colitis intervention.
ABSTRACT Per‐ and polyfluoroalkyl substances (PFAS) have emerged as a global public health concern owing to their extreme environmental persistence and multisystem toxicity. In recent years, accumulating evidence has highlighted a pivotal role of the gut microbiota in regulating the intestinal accumulation and elimination of PFAS. Specific microbial taxa, including members of the Bacteroidetes phylum and lactic acid‐producing bacteria, have been shown to capture PFAS through mechanisms such as bioaccumulation and microbial binding, thereby facilitating their fecal excretion and ultimately reducing PFAS concentrations in the liver and circulation. Importantly, dietary interventions—such as supplementation with probiotics, prebiotics, dietary fiber, and synbiotics—can reshape gut microbial ecology and further enhance this microbiota‐mediated elimination effect. Emerging evidence from both animal models and human studies provides clues that such interventions may reduce internal PFAS burden and alleviate associated toxicological outcomes. This review systematically summarizes current advances in dietary modulation of the gut microbiota as an intervention strategy for PFAS exposure. We discuss the underlying biological mechanisms, evaluate existing experimental and epidemiological evidence, and outline future research directions and translational prospects. Collectively, these insights may inform the development of safe, accessible, and sustainable strategies for mitigating PFAS‐related health risks.
ABSTRACT Nonalcoholic fatty liver disease (NAFLD) demonstrates an increasing incidence alongside metabolic syndromes. The present study aimed to investigate the effects and underlying mechanisms of alpinetin on hepatic injury using both in vivo and in vitro models. Mice were subjected to a high‐fat diet (HFD) and subsequently treated with either high‐ or low‐dose alpinetin. In vitro experiments employed palmitic acid (PA, 1 mM) to induce lipid deposition in mouse primary hepatocytes, which were then treated with varying doses of alpinetin. We observed that alpinetin mitigated HFD‐induced liver damage in a dose‐dependent manner by regulating triglycerides (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), high‐density lipoprotein (HDL), and low‐density lipoprotein (LDL) levels, along with pathological alterations in liver tissues. Furthermore, alpinetin counteracted the HFD‐induced upregulation of lipid synthesis‐related genes (acetyl CoA carboxylase 1 [ Acc1 ], sterol regulatory element‐binding protein 1c [ Srebp1c ], stearoyl‐CoA desaturase‐1 [ Scd1 ]) and lipid accumulation in liver tissues. HFD‐feeding also induced oxidative stress and ferroptosis in mice, which were significantly reduced by alpinetin administration in a dose‐dependent fashion. Similarly, alpinetin markedly reduced PA‐induced apoptosis, lipid accumulation, mitochondrial dysfunction, oxidative stress, and ferroptosis in a dose‐dependent manner. Mechanistically, alpinetin reversed the downregulation of liver X receptor alpha (LXRα) induced by HFD or PA in mouse liver tissues and hepatocytes. Overexpressing LXRα was found to protect mouse hepatocytes from PA‐induced damage. Rescue assays demonstrated that LXRα deficiency negated the protective effects of alpinetin against PA‐induced hepatocyte injury. In conclusion, alpinetin ameliorates hepatic injury induced by an HFD in mice and PA‐induced damage in mouse hepatocytes by modulating LXRα.
ABSTRACT Aflatoxin B1 (AFB1) is a widespread mycotoxin with severe hepatotoxicity. While the ketogenic diet (KD) is increasingly adopted, long‐term KD feeding can induce hepatic metabolic disturbances. However, the effects of AFB1 exposure under KD conditions remain unclear. We hypothesized that long‐term KD‐induced metabolic stress increases hepatic susceptibility to AFB1 toxicity, thereby aggravating liver injury. In this study, we investigated the effects of AFB1 on liver injury in mice fed a KD for 10 weeks. The results suggested that compared with the AFB1 and KD groups, co‐exposure with KD+AFB1 significantly increased serum ALT levels by 108.21% and 29.85%, (all p < 0.01), and AST levels by 35.57% (p < 0.01) and 25.31% (p < 0.05), respectively. Co‐exposure also aggravated hepatic lipid accumulation, with increased TG, T‐CHO, LDLC, and NEFA levels (all p < 0.01) and decreased HDLC levels (p < 0.01). Oil Red O staining and TEM further confirmed pronounced hepatic lipid accumulation and ultrastructural damage. Co‐exposure also increased oxidative stress, as indicated by elevated ROS (by 34.23% and 24.77%, respectively) and MDA levels (by 14.96% and 2.14%, respectively), and enhanced hepatic inflammation, with increased TNF‐α, IL‐6, and COX‐2 and decreased IL‐10 levels. Untargeted metabolomics revealed marked hepatic metabolic disturbances, particularly in glycerophospholipid, fatty acid, glutathione, and TCA cycle metabolism. Protein expression analysis further supported these metabolic alterations, showing suppressed p‐AMPK, increased mTOR phosphorylation, and upregulated PPAR‐γ expression following KD+AFB1 co‐exposure. In conclusion, AFB1 aggravates long‐term KD‐associated hepatic oxidative stress, inflammation, and glucose and lipid metabolic disturbances. These findings highlight dietary safety during long‐term KD‐induced metabolic disturbances.
