Search Results (2,193)

Fusobacterium nucleatum (F. nucleatum), a key oral pathogen, promotes colorectal cancer (CRC) progression via gut translocation. Although gut probiotics provide colonization resistance against pathogens, antibiotic-induced dysbiosis may facilitate F. nucleatum integration and increase the risk of CRC. The mechanisms underlying probiotic–F. nucleatum antagonism and antibiotic modulation remain unclear. A 33-strain probiotic consortium and F. nucleatum subsp. Polymorphum (F. polymorphum) ATCC 10953 were co-cultured. The inhibitory effects of probiotics on F. nucleatum and the impacts of antibiotics (ABXs) on the microbial community structure in the co-culture system and on the probiotic-mediated inhibition of F. nucleatum were evaluated using spent medium assays, plate confrontation tests, growth curves, qRT-PCR, metagenomic sequencing, and transcriptomics. Hydrogen peroxide/pH/lysine assays and coaggregation models were performed to probe the associated mechanisms. Probiotics strongly inhibited the growth of F. nucleatum in a dose-dependent manner, primarily via organic acids, while F. nucleatum enriched amino acid/vitamin biosynthesis pathways without major growth suppression. Antibiotics weakened probiotic antagonism, shifted species abundance (↓ L. plantarum, ↑ L. paracasei), induced adaptive stress responses in F. nucleatum (↑ nucleotide metabolism, propanediol degradation, pdxS), and reduced lysine biosynthesis. Lysine supplementation restored probiotic abundance and disrupted F. nucleatum coaggregation. Multi-strain probiotics exert potent colonization resistance effects against F. nucleatum, mainly through organic acids and metabolic interference. Antibiotic-induced dysbiosis impairs this protective effect and may promote the persistence of F. nucleatum, which has been implicated in CRC risk. Targeted probiotic strategies may offer novel preventive approaches. Full article

Lentils (Lens culinaris; family: Fabaceae) are increasingly recognized as functional legumes with potential benefits for gut health because they provide bioactive peptides, resistant starch, and polyphenol-rich fractions within a shared food matrix. However, most existing studies have focused on individual lentil-derived compounds, and their matrix-dependent complementary interactions during digestion and fermentation remain insufficiently resolved. This review synthesizes current evidence on lentil-derived peptides, resistant starch, and polyphenols, with particular emphasis on their matrix-dependent complementary relationships, digestion-dependent transformation, microbial co-metabolism, and implications for intestinal barrier function. During gastrointestinal digestion and colonic fermentation, lentil proteins, resistant starch, and phenolic compounds undergo sequential transformation, yielding bioactive peptides, fermentable substrates, short-chain fatty acids (SCFAs), and phenolic metabolites that may collectively influence microbial composition and metabolic activity. Emerging evidence suggests that these interconnected processes may support gut health through microbiota–host crosstalk by modulating tight junction-related markers, reducing intestinal permeability, and maintaining epithelial homeostasis. Mechanistically, these effects have been associated with SCFA-mediated G protein-coupled receptor (GPCR) signaling, suppression of TLR4–NF-κB/MAPK inflammatory cascades, and activation of Keap1–Nrf2 antioxidant defenses, thereby attenuating oxidative stress and pro-inflammatory responses. Current evidence is more consistent with matrix-dependent complementary or convergent actions than with demonstrated synergy. At present, phenolic-rich fractions provide clear pathway-level evidence, whereas fermentation-linked carbohydrate effects are more strongly supported by microbiota- and in vivo-associated outcomes, and protein- or peptide-related mechanisms remain comparatively underdefined. Nevertheless, the evidence base remains limited by the scarcity of integrated studies, well-controlled human intervention trials, and factorial experimental designs capable of distinguishing complementary, additive, and truly synergistic effects among lentil bioactives. This review therefore highlights the need to move from describing coexisting beneficial effects toward formally testing interaction effects within physiologically relevant lentil matrices. Full article

Doxorubicin is an effective chemotherapeutic agent, but it causes gastrointestinal toxicity that impairs treatment efficacy and quality of life. This study investigated the effects of liraglutide, a GLP-1 analog, on acute doxorubicin-induced gut toxicity in rats. Sixty male Wistar rats were assigned to four groups: Control (C), Doxorubicin (D), Liraglutide (L), and Doxorubicin + Liraglutide (DL). Groups L and DL received liraglutide (0.6 mg/kg, s.c.) for two weeks. D and DL were given a single dose of doxorubicin (20 mg/kg, i.p). After 48 h, the distal colon, feces, and blood were collected. Results: Doxorubicin caused crypt disruption, goblet cell loss, apoptosis, and reduced fecal short-chain fatty acids. Levels of TNF-α, NF-κB, Bcl-2, TLR4, and antioxidant enzymes were unchanged among groups. Microbiota analysis showed similar α-diversity but altered β-diversity. Doxorubicin reduced Bacteroidetes and increased Proteobacteria, with higher Arcanobacterium and Clavibacter genera abundance. Liraglutide alone decreased Bacteroidetes and increased Corynebacterium and Actinobaculum genera. Combined treatment showed no significant effects. We conclude that acute doxorubicin administration induces intestinal structural damage, reduces short-chain fatty acids, and changes microbiota composition. Although liraglutide alters microbial profiles, it does not attenuate doxorubicin-induced gut toxicity. Full article

This study focuses on Lacto-N-neotetraose (LNnT), a core component of human milk oligosaccharides. Although LNnT has been demonstrated to promote early intestinal development and maintain gut homeostasis, its protective mechanism against D-galactose-induced intestinal injury and associated cognitive impairment remains unclear. This investigation systematically examined the protective effects and underlying mechanisms of LNnT against D-gal-induced colonic damage and cognitive impairment in mice. The results demonstrated that LNnT not only significantly improved systemic physiological phenotypes and upregulated the expression of colonic tight junction proteins to repair the intestinal barrier, but also effectively enhanced learning and memory abilities in mice. Concurrently, LNnT reduced serum proinflammatory factor levels, elevated the anti-inflammatory factor IL-10, and alleviated oxidative stress. Furthermore, LNnT remodeled the gut microbiome structure by increasing microbial diversity, enhancing beneficial bacteria abundance, and promoting short-chain fatty acid production. Untargeted metabolomics analysis further revealed that LNnT corrected metabolic disturbances by regulating key sphingolipid molecules (ceramide, sphingosine, S1P) and the expression of related metabolic enzymes (ACER2, SphK2). In summary, this study suggests that LNnT mitigates intestinal injury and improves cognitive function, potentially through modulation of the gut microbiota–sphingolipid metabolism axis, although further causal validation is warranted. These findings provide a mechanistic foundation for future studies exploring its potential as a functional dietary ingredient. Full article

This study aimed to investigate the effects of pterostilbene (PTE) on the intestinal barrier function, antioxidant capacity, lipid metabolism, and microbial and metabolite homeostasis of suckling piglets via its action on breast milk. Findings indicate that PTE supplementation enhanced the antioxidant status of mature milk and strengthened intestinal barrier function in piglets. Specifically, PTE enhanced intestinal antioxidant status and fatty acid β-oxidation in piglets by regulating the PI3K-AKT and SIRT1-Nrf2/Keap1 signaling pathways. 16S rDNA sequencing and Liquid Chromatography–Mass Spectroscopy (LC–MS) identified breast milk and gut microbiota and their metabolites, respectively. Results indicate that PTE significantly elevated levels of amino acid derivatives in colostrum (Glutathione Reducedform (GSH) and N-acetyl-L-glutamate (NAG)), whilst concurrently reducing levels of glycerophospholipid-related metabolites in both colostrum and mature milk (p < 0.05). Moreover, PTE supplementation markedly altered the composition of the colonic mucosal microbiota in piglets, with Faecalibacterium, Mucispirillum and Ruminococcus identified as key beneficial microbial markers of the colonic mucosa. Combined multi-omics revealed strong correlations in microbial community composition between mature milk and the colon, identifying glycerophospholipid metabolism as a key metabolic pathway that may be associated with the regulatory effects of PTE on milk and the piglet colon. In conclusion, the PTE supplement can improve the quality of breast milk and have a positive impact on the intestinal homeostasis of the offspring. Full article

Background: Colorectal intraepithelial neoplasia (CR-EN) is a precursor lesion of colitis-associated colorectal cancer (CAC). This study investigated the interventional effects and molecular mechanisms of Rhapontici Radix extract on CR-EN. Methods: An azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mouse model of colonic intraepithelial neoplasia, bioinformatics analysis, organoid models, and HCT116 cell experiments were employed, coupled with histopathological examination, inflammatory cytokine detection, Western blot, immunofluorescence, and HPLC-MS/MS. Results: The results showed that the YAP/AKT-PI3K signaling pathway is aberrantly activated in CRC. Rhapontici Radix extract ameliorated colonic pathology, suppressed inflammatory responses, and remodeled gut microbiota composition in model mice. The extract selectively inhibited the proliferation of CR-EN organoids by downregulating Ki67 and β-catenin while upregulating p53, and suppressed the proliferation, colony formation, and migration of HCT116 cells. Mechanistically, the extract modulated the YAP/PI3K/AKT pathway by upregulating phosphorylated YAP (p-YAP) and downregulating phosphorylated AKT (p-AKT), phosphorylated PI3K (p-PI3K), and their downstream targets p-SRC and c-MYC. Conclusions: This study suggests that Rhapontici Radix extract intervenes in inflammation-associated carcinogenesis through a multi-pathway, multi-target strategy, offering potential therapeutic targets for CAC prevention and treatment. Full article

Background: This study investigated the mechanisms underlying diarrhea induced by a high-fat diet (HFD) under a state of fatigue, focusing on gut microbiota dysbiosis, bile acid metabolic disturbance, and gut–liver injury. Methods: Mice were assigned to a normal control diet (NCD) group, a HFD-induced diarrhea under fatigue (HFDM) group, and a HFD-induced diarrhea with aggravated dysbiosis (HFDMA) group. Histopathology, inflammatory factors, intestinal barrier-related proteins, small-intestinal microbiota, and colonic bile acid profiles were assessed, and correlation analyses were performed among gut microbiota, bile acids, and inflammatory factors. Results: Compared with the NCD group, both the HFDM and HFDMA groups showed diarrhea-like and fatigue-like phenotypes, histopathological injury in the small intestine and liver, increased tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels, and impaired intestinal barrier function. No significant differences in inflammatory factors were observed between the HFDM and HFDMA groups. Zonula occludens-1 (ZO-1) expression decreased in both model groups but reached statistical significance only in the HFDMA group, whereas Claudin-1 expression was significantly reduced in both groups. Gut microbiota analysis showed altered community structure, with downward trends in alpha diversity that did not reach statistical significance but clear separation trends in beta diversity. Proteobacteria and Streptococcus increased, whereas Ligilactobacillus decreased. Total bile acid levels did not differ significantly among groups; however, the ratio of secondary to primary bile acids was significantly reduced in both model groups, particularly in the HFDMA group, with decreases in representative secondary bile acids, including hyodeoxycholic acid (HDCA) and isolithocholic acid (isoLCA). Correlation analysis further supported close associations among gut microbial alteration, bile acid disturbance, and intestinal and hepatic inflammation. Conclusions: Gut microbiota dysbiosis may disrupt bile acid metabolism, impair intestinal barrier integrity, and promote intestinal and hepatic inflammatory responses, thereby contributing to diarrhea progression under fatigue and HFD conditions through the gut–liver axis. Full article

Background: Inflammatory bowel disease (IBD) is a gut-based idiopathic disease characterized by chronic and relapsing inflammatory progression and intricate pathophysiology. It is now known that the key etiologies of IBD include immune dysregulation, imbalances in the gut microbiota, and metabolic disruptions. Probiotics are now the potential treatment for IBD, due to their ability to regulate the host immune system and microbiota of the gut. Methods: The current study analytically tested the preventive benefit of Bacillus licheniformis BL-01 on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and also expounded on its molecular pathogenesis. Results: Our results demonstrate that supplementation with BL-01 effectively mitigates DSS-induced weight loss, an elevated disease activity index (DAI), and colonic tissue injury in mice. Concomitantly, BL-01 rectifies dysregulated inflammatory cytokine profiles, attenuates oxidative stress, and restores the expression of colonic tight junction proteins as well as the number of goblet cells. Furthermore, BL-01 modulates the gut microbiota diversity by increasing the abundance of beneficial bacterial genera such as Duncaniella and decreasing the abundance of pathogenic genera such as Helicobacter. Notably, BL-01 restores DSS-induced microbial metabolic dysregulation, modulates key metabolic pathways including arachidonic acid metabolism and steroid hormone biosynthesis, and regulates associated metabolites to ameliorate UC. Finally, Bacillus licheniformis BL-01 mitigates oxidative stress, reverses gut dysbiosis and metabolic disorders, and has a protective effect on UC. Conclusions: The findings give new information on the development of probiotic-based therapeutics in the prevention and treatment of IBD. Full article

Butyrate, a short-chain fatty acid produced by the fermentation of soluble dietary fiber by gut bacteria, also functions as a histone deacetylase inhibitor known to induce apoptosis and promote differentiation in colon tumor cells. During tumorigenesis, cancer cells undergo metabolic reprogramming to meet energetic and biosynthetic demands, increasing glycolytic metabolism and reducing oxidative metabolism—a phenomenon known as the Warburg effect. This study aimed to evaluate the impact of butyrate on the aggressiveness-related metabolic phenotype of three colon cancer cell lines (LS1034, C2BBe1, and WiDr). Butyrate’s effects were assessed through fluorine-18 fluorodeoxyglucose ([¹⁸F]FDG) uptake, flow cytometry analysis of cytoplasmic and membrane expression of glucose transporters (GLUT1, GLUT3, GLUT5, and GLUT12), lactate production, and analysis of Krebs cycle turnover and glycolysis–Krebs cycle coupling using nuclear magnetic resonance isotopomer profiling. [¹⁸F]FDG uptake decreased in C2BBe1 and WiDr cells, whereas an opposite response was observed in LS1034 cells, which also exhibited reduced GLUT5 expression. These uptake patterns were consistent with lactate production measurements, and an enhancement of oxidative metabolism was detected in C2BBe1 and WiDr cells. Although butyrate was consumed by all three cell lines, its metabolic handling appeared to differ in LS1034 cells, possibly reflecting cytotoxic stress and/or distinct metabolic regulation mechanisms. Overall, these findings indicate that butyrate exerts cell-line-dependent metabolic effects in colorectal cancer cells. In C2BBe1 and WiDr cells, butyrate exposure was broadly consistent with the attenuation of glycolytic/Warburg-associated features, whereas LS1034 cells displayed a divergent response and were interpreted separately. These data support further investigation of butyrate as a modulator of colorectal cancer cell metabolism, while highlighting the heterogeneity of metabolic responses across tumor models. Full article

5-Fluorouracil (5-FU) is a first-line chemotherapeutic agent for solid tumors, but its clinical application is severely limited by dose-dependent intestinal injury that impairs patient quality of life and compromises therapeutic efficacy. Natural polysaccharides, especially marine-derived ones, have become safe and multi-targeted gut-protective candidates due to their excellent biocompatibility and prebiotic-like activities. Larimichthys crocea swim bladder is a characteristic marine biological resource, and its polysaccharides (CIPs) have shown potential bioactivities, yet their protective mechanism against 5-FU-induced intestinal injury remains unclear. Our study explored the protective effects of Larimichthys crocea swim bladder polysaccharides (CIPs) against 5-FU-induced intestinal injury in mice. Following 14-day preventive administration, CIPs alleviated 5-FU-induced body weight loss, diarrhea, colonic shortening, and mucosal injury, and restored goblet cell function. Mechanistically, CIPs enhanced intestinal barrier integrity by upregulating ZO-1, Occludin, and MUC2, suppressed the MyD88/NF-κB pathway to balance inflammatory cytokines, and ameliorated oxidative stress by regulating MDA, GSH, SOD, and CAT. CIPs also restored gut microbial diversity and the Firmicutes/Bacteroidota ratio, and modulated retinol and arginine metabolism. In vitro, CIPs reduced inflammation and oxidative damage in Caco-2 cells and promoted M2 macrophage polarization. Thus, CIPs alleviate 5-FU-induced intestinal injury via multi-targeted regulation of the gut–metabolic axis, showing great potential as a dietary intervention and gut health support agent in food science and oncology nutrition, and boosting the high-value utilization of marine resources. Full article

The dextran sodium sulfate (DSS) colitis model is the most widely used experimental model of inflammatory bowel disease (IBD) due to its simplicity and versatility, with over 7000 PubMed entries in the last decade and an exponential rise in recent years. Since its initial description in 1985, DSS colitis has been extensively evaluated across species, most notably in mice and rats, and has yielded substantial insights into IBD pathogenesis. However, the model’s multifactorial nature poses a dual challenge: it offers an opportunity but complicates study design, interpretation, and translational relevance. This complexity is worsened by inconsistent reporting, which hampers reproducibility and comparability across studies. The broad use of the DSS-induced colitis model yields numerous insights about the model, which help better understand its complexity, characteristics and limitations. Although DSS colitis is induced locally, inflammation in the colon and gut barrier destruction may also affect other organs (such as the liver and brain) and their metabolism and molecular responses, which, in turn, may interfere with colitis-underlying mechanisms and drug response, and may influence the interpretation of results. These intrinsic (intra-experimental) characteristics of the DSS model are summarised in the paper (colitis, gut–brain axis, gut–liver axis). In addition, the DSS model is heavily influenced by numerous extrinsic (inter-experimental) factors (environmental, microbiological, genetic), which may further complicate the colitis model, the study outcomes, and data interpretation, and these are also discussed in the paper. As science advances and new data accumulate, understanding the intricate interplay among internal mechanisms, external factors, and technical variables becomes increasingly essential for the accurate interpretation of DSS outcomes. This review synthesises the complexity and interdependence of factors shaping the DSS model, emphasising the need for meticulous reporting and consideration of methodological nuances to enhance reproducibility, interpretation, and translational value in DSS colitis research. In addition, the review provides practical guidance through a “traps and tricks” subsection and checklist table designed to provide a framework and practical recommendations to better understand, apply, and interpret DSS model results in the context of broader systemic and methodological considerations. Full article

Enterotoxigenic Escherichia coli (ETEC) causes severe intestinal infections in animals and threatens public health under the One Health framework. Most conventional studies focus on acute short-term ETEC infection, while natural persistent colonization oftern induces chronic intestinal mucosal compensatory remodeling in hosts. This study evaluated the protective effects of giant panda-derived Weissella confusa BSP201703 against chronic ETEC-induced intestinal damage using a giant panda fecal microbiota-associated (GPF) mouse model. Seventy-two Kunming mice were divided into six groups: blank control (C1), GPF control (C2), ETEC control (C3), and three W. confusa BSP201703 groups at low (1.0 × 10⁷ cfu/mL, W1), medium (1.0 × 10⁸ cfu/mL, W2), and high (1.0 × 10⁹ cfu/mL, W3) doses. Mice were first subjected to continuous ETEC challenge for 5 days to establish stable chronic intestinal injury, followed by a subsequent 5-day intervention with probiotic or sterile PBS for repairing existing damage. Growth performance, histopathology, serum D-lactate, SIgA, tight junction genes (ZO-1, Occludin, Claudin-1), and gut microbiota were analyzed. Histomorphologically, the chronic ETEC challenge induced compensatory increases in ileal villus height and crypt depth, which differed from typical acute necrotic atrophy. W. confusa BSP201703 mitigated ETEC-induced damage, reduced serum D-lactate (p < 0.05), increased SIgA, and upregulated tight junctions (p < 0.05). Microbial results demonstrated that medium-dose W2 maximized microbial diversity, while W1/W3 selectively enriched beneficial Bacteroidetes, Clostridium cluster IV, and Clostridium cluster XIVa taxa, confirming that moderate doses yielded optimal protection. In conclusion, W. confusa BSP201703 relieves ETEC injury by enhancing intestinal barrier function and regulating gut microbiota, highlighting its potential as a wildlife probiotic for One Health applications. Full article

Background/Objectives: Ulcerative colitis is a chronic inflammatory bowel disease marked by a disrupted intestinal barrier and consequent aberrant immune responses. Pseudoginsenoside RT2, an ocotillol-type ginsenoside abundant in Panax herbs, represents a potential therapeutic candidate, yet its anti-ulcerative colitis efficacy and pharmacokinetic profile remain unclear. This study aimed to elucidate RT2’s therapeutic potential for ulcerative colitis through a parallel evaluation of pharmacodynamic efficacy and pharmacokinetic properties. Methods: The anti-ulcerative colitis efficacy and in vivo disposition of RT2 were investigated in a trinitrobenzene sulfonic acid-induced rat colitis model. An ultra-performance liquid chromatography–tandem mass spectrometry method was employed to delineate its pharmacokinetic characteristics and quantify its distribution in various tissues following oral administration. Results: Pharmacodynamically, RT2 demonstrated significant efficacy in the UC rat model by repairing the intestinal barrier (by promoting goblet cell regeneration and upregulating tight junction proteins and mucin) and restoring immune homeostasis (by correcting T-helper 17/regulatory T-cell imbalance and reducing pro-inflammatory cytokines while elevating anti-inflammatory cytokines). Pharmacokinetically, RT2 exhibited rapid absorption, slow elimination, and high colonic accumulation, with concentrations in the inflamed colon being significantly higher than those in healthy rats. Furthermore, the biphasic concentration–time profile may account for its prolonged systemic residence time and enhanced local exposure. In summary, through parallel efficacy and pharmacokinetic studies, this work systematically reveals its characteristics as a therapeutic agent that exhibits high colonic accumulation and acts via barrier repair and immunomodulation. Conclusions: These findings provide a theoretical foundation for the development of RT2 as a novel gut-selective drug candidate for UC. Full article

The gut microbiota, acting as a critical extrinsic endocrine organ, is profoundly involved in the pathological evolution and therapeutic response of hormone-dependent malignancies. This review elucidates the core mechanisms governing the microbiota, endocrine, and immune triple-axis. Multi-omic and biochemical evidence demonstrates that microbial metabolic networks, comprising the estrobolome, androbolome, and progestobolome/corticobolome, rely on enzymatic systems such as β-glucuronidases (GUS) and steroid-17,20-desmolases to execute hormone deconjugation and structural modification, thereby modulating systemic steroid exposure. Concurrently, microbe-derived metabolites, such as secondary bile acids and purine derivatives, act as inter-kingdom messengers. These metabolites remodel the tumor immune microenvironment by antagonizing hormone receptors and activating specific signaling axes, such as the Inosine-A2AR pathway. By modulating localized immune cells like effector T cells and myeloid cells, they play a pivotal role in tumor immune evasion. Furthermore, pharmacomicrobiomics reveals a bidirectional regulation between anti-tumor agents and the gut microbiota, where endocrine and immunotherapeutic drugs can induce microbial dysbiosis, while specific gut taxa contribute to primary or acquired resistance by enzymatically inactivating drugs (e.g., reductive inactivation of Enzalutamide) or providing hormonal precursors through bypass pathways. Facing translational challenges, such as real-world microbiome complexity and the colonization resistance of indigenous flora, we propose treating the human body as a unified host–microbe holobiont system. Future research should leverage gnotobiotic models and genetic causal inference to establish functional causality. These efforts will facilitate the development of precision tools, including ubiquitin–proteasome system (UPS) modulators, microbial enzyme inhibitors, and engineered live biotherapeutics. Collectively, these systems biology strategies offer a robust framework for overcoming therapeutic resistance in hormone-dependent malignancies. Full article

Background: Astragalus membranaceus Fisch. ex Bunge has long been used in East Asian medicine for gastrointestinal disorders and immune modulation. Astragaloside IV (AS-IV), a major bioactive saponin from its roots, exhibits potent anti-inflammatory and antioxidant activities, yet its protective effects against inflammatory bowel disease (IBD)-associated multi-organ damage via the gut–liver–brain axis remain unclear. Methods: Experimental colitis was induced in C57BL/6N mice by administering 5% dextran sulfate sodium (DSS) in drinking water for seven days. AS-IV (100 mg/kg/day) was orally administered during DSS exposure. Disease severity was evaluated using body weight, colon length, disease activity index, and histopathology. Inflammatory cytokines and oxidative stress markers were measured using ELISA, and NF-κB and MAPK signaling were analyzed through Western blotting and immunohistochemistry in colonic, hepatic, and brain tissues. Results: AS-IV significantly alleviated DSS-induced weight loss, disease activity, and colon shortening, while improving intestinal histopathological damage. AS-IV also reduced systemic pro-inflammatory cytokine levels and oxidative stress. Mechanistically, AS-IV was associated with a reduced expression of phosphorylated NF-κB and MAPK proteins, including p-NF-κB, p-IκBα, p-ERK, p-JNK, and p-p38, across the colon, liver, and brain. Conclusions: AS-IV attenuates DSS-induced multi-organ inflammation via gut–liver–brain axis modulation through NF-κB and MAPK pathway inhibition in experimental colitis models. Full article