Search Results (1,292)

Background: Intestinal failure-associated liver disease (IFALD) is a serious complication in patients receiving parenteral nutrition, often exacerbated by inflammation, lipid overload, and oxidative stress. Nobiletin (NOB), a polymethoxylated flavone, is known for its anti-inflammatory and lipid-regulating properties. Methods: We employed an in vitro model using THLE-2 human hepatocytes and primary human cholangiocytes exposed to Intralipid (INT) and lipopolysaccharide (LPS) to simulate IFALD conditions. NOB was tested at non-toxic concentrations (10 and 25 µM) to assess its protective effects. MTT viability assays, multiplex bead-based immunoassays (MAGPIX), RT-qPCR, and Western blotting were used to evaluate changes in inflammation markers, gene expression, and protein signaling. Moreover, ALT and AST activities were used to assess hepatocellular injury. Results: NOB maintained high cell viability in THLE-2 hepatocytes and cholangiocytes, confirming its low cytotoxicity. NOB normalized ALT and AST activities in both tested cell lines, but the effect reached statistical significance only for ALT in cholangiocytes. Under IFALD-like conditions (LPS+INT), NOB significantly preserved metabolic activity in both cell types. In THLE-2 and cholangiocytes, NOB markedly reduced the phosphorylation of pro-inflammatory proteins JNK, NF-κB, and STAT3, indicating a broad inhibition of inflammatory signaling. Moreover, in THLE-2 cells, NOB upregulated lipid metabolism-related genes (PRKAA2, CYP7A1, and ABCA1) and decreased oxidative stress, thereby enhancing the nuclear translocation of Nrf2 and increasing SOD1 level, which supports the activation of antioxidant defenses. Conclusions: NOB exhibits hepatoprotective properties under IFALD-like conditions in vitro, likely through modulation of inflammation-related signaling and lipid metabolism pathways. Full article

Background: Ulcerative colitis (UC) is characterized by chronic mucosal inflammation, oxidative stress, and disruption of intestinal metabolic homeostasis. Immunomodulatory nutrients such as arginine, glutamine, and β-hydroxy β-methylbutyrate (HMB) have shown potential benefits; however, their combined molecular effects on UC remain insufficiently defined. Objective: To investigate the individual and combined effects of arginine, glutamine, and HMB on inflammatory and metabolic gene expression, oxidative stress markers, and histopathological outcomes in a dextran sulfate sodium (DSS)-induced colitis model. Methods: Female Sprague Dawley rats were assigned to six groups: control, DSS, DSS + arginine, DSS + glutamine, DSS + HMB, and DSS + mixture. Colitis was induced using 3% DSS. Colon tissues were examined histologically, serum MDA, MPO, and GSH levels were quantified, and mRNA expression of IL6, IL10, COX2, NOS2, ARG2, CCR1, and ALDH4A1 was measured by RT-qPCR. Pathway enrichment analyses were performed to interpret cytokine and metabolic network regulation. Results: DSS induced severe mucosal injury, elevated MDA and MPO, reduced GSH, and significantly increased IL6, COX2, NOS2, ARG2, and CCR1 expression. Glutamine demonstrated the strongest anti-inflammatory and antioxidant effects by decreasing IL6 and COX2 and restoring GSH. Arginine primarily modulated nitric oxide–related pathways, whereas HMB increased ALDH4A1 expression and metabolic adaptation. The combination treatment produced more balanced modulation across inflammatory, chemokine, and metabolic pathways, consistent with enrichment results highlighting cytokine signaling and amino acid metabolism. Histopathological improvement was greatest in the mixture group. Conclusions: Arginine, glutamine, and HMB ameliorate DSS-induced colitis through coordinated regulation of cytokine networks, oxidative stress responses, and metabolic pathways. Their combined use yields broader and more harmonized therapeutic effects than individual administration, supporting their potential as targeted immunonutritional strategies for UC. Rather than targeting a single inflammatory mediator, this study was designed to test whether combined immunonutrient supplementation could promote coordinated regulation of cytokine signaling, oxidative stress responses, and metabolic adaptation, thereby facilitating mucosal repair in experimental colitis. Full article

Background/Objectives: Gut dysbiosis in Chronic Fatigue Syndrome (CFS) drives low-grade inflammation and shifts tryptophan metabolism toward neurotoxic pathways. The causal link between bacterial translocation, kynurenine pathway dysregulation, and symptom severity remains under-defined. We evaluated the impact of a high-concentration multi-strain probiotic on the “gut-kynurenine axis” and clinical status in CFS patients with co-morbid IBS-U and confirmed dysbiosis. Methods: Forty female patients with confirmed dysbiosis (GA-map™ Dysbiosis Index > 2) received the CDS22 formula (450 billion CFU/day) for 12 weeks. We compared urinary tryptophan metabolite profiles (LC-MS/MS), gut dysbiosis markers (3-indoxyl sulfate), and fatigue severity (FSS) against 40 age-matched healthy controls. Results: Baseline analysis revealed profound metabolic perturbations: elevated bacterial proteolytic markers (3-IS), substrate depletion (low tryptophan), and a neurotoxic signature (high quinolinic acid [QA], low kynurenic acid [KYNA]). Following the intervention, fatigue scores declined by 40.3%, with 97.5% of patients reaching the remission threshold (FSS < 36). Biochemically, 3-IS levels decreased to the range observed in healthy controls and attenuated xanthurenic acid levels. Although absolute QA concentrations remained elevated compared to controls, the neuroprotective KYNA/QA ratio increased significantly (+45%). Increased systemic tryptophan availability correlated directly with clinical symptom reduction (Spearman’s rho = −0.36, p = 0.024). Conclusions: The CDS22 formulation was associated with a restoration of intestinal eubiosis and functional tryptophan partitioning. Clinical remission coincides with a metabolic shift favoring neuroprotection (increased KYNA/QA ratio), validating the gut–kynurenine axis as a modifiable therapeutic target. Peripheral metabolic improvement relative to the healthy baseline appeared sufficient for symptom relief in this specific phenotype, despite incomplete clearance of neurotoxic metabolites. Full article

Probiotics, prebiotics, and postbiotics are of interest for their potential gastrointestinal and immunological benefits in pet health. This study aimed to assess whether a unique blend of Bacillus subtilis, Bacillus clausii, Bacillus coagulans (Weizmannia coagulans), FOS, GOS, and a postbiotic yeast extract could provide beneficial gut and immunological effects when fed to healthy, adult dogs. Twenty-four healthy adult beagle dogs (mean age 5.17 yrs) were fed the probiotic, prebiotic, and yeast chew (PPYC) or control chew (CC) supplement for 31 days, accompanied by fecal and blood sampling. Following 31 days, PPYC fed dogs had decreased (p < 0.05) fecal calprotectin concentration, a biomarker indicative of reduced intestinal inflammation, compared with dogs receiving the CC. In the PPYC group, blood C-reactive protein levels, an indicator of tissue inflammation, tended (p = 0.11) to be reduced. In addition, dogs receiving the PPYC supplement showed an increase in the IL-17a cytokine (p < 0.05). Despite dogs being in a clinically healthy state, changes in some dysbiosis-related bacterial strains were observed. There was an increase (p < 0.05) in the % of total bacteria of Blautia in the PPYC group by the end of the study, as well as an increase in the percent change from Day 0 of C. hiranosis (p < 0.05). Increased alpha diversity, a measure related to the resilience to environmental change, was observed in the PPYC group (p < 0.05). These results suggest that after consuming a supplement containing probiotics, prebiotics and a postbiotic yeast extract, markers of gut and systemic health were improved in otherwise healthy dogs. Full article

Since there is currently no cure for Parkinson’s disease, pharmacobiotic approaches based on gut microbiota—capable of producing pharmacologically active compounds—are under development. In this study, we propose LfU21, derived from the strain Limosilactobacillus fermentum U-21, as a candidate pharmacobiotic. To evaluate its efficacy, a combined LPS- and lactacystin (LAC)-induced Parkinson’s disease model was established in Wistar rats. Effects were assessed using behavioral, biochemical, immunomodulatory, and transcriptomic biomarkers. LfU21 administration reduced α-synuclein levels, altered motor performance in the “Rung ladder” test, and modulated bdnf gene expression in the right and left striata. Under LPS exposure, LfU21 prevented alterations in immune response markers, GSH levels, drd2 and bdnf gene expression, and intestinal goblet cell counts. In LAC and LAC + LPS groups, LfU21 mitigated the rise in α-synuclein, the decline in bdnf expression, and behavioral deficits in the “Open Field” and “Rung ladder” tests, respectively. The multifunctional activity of LfU21 in a combined Parkinson’s disease model underscores its therapeutic potential and helps identify a target patient cohort for future clinical trials. Full article

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling clinical condition, whose hallmark characteristic is post-exertional malaise (PEM). It can affect many organs and systems, leading to severe impairment of patients’ quality of life. Although numerous post-infectious, immunological, neurological, metabolic, and endocrine alterations have been documented, neither a definitive diagnostic marker nor approved treatments are available. The etiology and pathophysiology remain incompletely understood; however, emerging evidence suggests that the gut microbiome plays a role in immune responses and the development of ME/CFS. It is hypothesized that specific disturbances in gut microbiome composition, known as dysbiosis, may compromise the integrity of the intestinal barrier. This consequently leads to translocation of microbial components, which further triggers an immune response and systemic inflammation complicating the clinical presentation of ME/CFS. Furthermore, in terms of the so-called gut–brain axis, microbiome changes may lead to distinct neurocognitive impairments observed in ME/CFS patients. This review offers the readers a broad perspective on the topic on ME/CFS, with a particular emphasis on the interplay between the gut microbiome and disease mechanisms. Last but not least, recent data on potential treatment strategies for intestinal dysbiosis in ME/CFS patients have been included. Full article

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a chronic liver disease characterized by abnormal lipid metabolism. The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor involved in regulating multiple physiological processes. Recent studies have demonstrated that AHR exerts a multifaceted regulatory role in liver diseases by integrating metabolic and immune signaling pathways; however, the specific role of AHR in MAFLD is not clear. In our work, a rat model of MAFLD was established by feeding wild-type (WT) and AHR knockout (AHR^−/−) rats with a high-fat, high-fructose, and high-cholesterol diet (HFHFrHCD) for 10 weeks, and then the liver injury markers, lipid-related biochemical indices and liver histopathology were examined to elucidate the effect of AHR on MAFLD progression. We discovered that AHR deficiency can elevate plasma transaminase levels, increase hepatic triglyceride (TG) and total cholesterol (TC), and exacerbate insulin resistance (IR) under an overnutrition environment. Subsequently, liver transcriptome and RT-qPCR were performed to investigate the underlying mechanism, which revealed that the hepatic bile acid synthesis was inhibited because of lower Cytochrome P450 Family 7 Subfamily A Member 1 (CYP7A1) expression in the liver when AHR was knockout. Additionally, intestinal flora dysbiosis occurred in AHR^−/− rats fed with HFHFrHCD, which might also contribute to the hepatic cholesterol accumulation. Taken together, our results suggested that AHR might play an important role in regulating cholesterol metabolism by inhibiting bile acid synthesis and breaking the steady state of the gut microbiota during the MAFLD progression. Full article

Inflammatory bowel disease (IBD) involves chronic inflammation and disruption of the intestinal barrier, often accompanied by alterations in gut microbiota composition. This study examined the protective potential of a prebiotic mixture extract (PME) prepared from Vigna radiata (mung bean), Vigna angularis (red bean), and Foeniculum vulgare (fennel) using the HT-29 cell and colitis animal model. PME exhibited concentration-dependent antioxidant activity, with greater radical-scavenging capacity in the ABTS assay than in the DPPH assay. In LPS-stimulated HT-29 epithelial cells, PME reduced the mRNA expression of inflammation-associated genes (TNF-α, IL-1β, NF-κB) and upregulated tight junction markers (CLDN1 and OCLN), demonstrating its anti-inflammatory and supportive effects on the intestinal barrier. Vitexin, a C-glycosylated flavonoid, was detected in PME and is expected to mediate these protective effects. In a DSS-induced colitis mouse model, PME administration alleviated disease severity by increasing colon length, reducing serum levels of inflammatory cytokines and COX-2/PGE2, and restoring intestinal permeability. Furthermore, PME modulated the gut microbiota by enhancing beneficial bacteria such as Bifidobacterium and Faecalibaculum while suppressing inflammation-associated taxa, including Escherichia, Bacteroides, and Mucispirillum. These improvements collectively suggest that PME reinforces epithelial barrier integrity and promotes intestinal homeostasis through both anti-inflammatory and microbiota-regulating actions. Full article

Pomegranate peel, a rich agro-industrial by-product, contains abundant phenolic compounds with strong antioxidant and antimicrobial properties. However, the low stability and bioavailability of these compounds limit their efficacy in animal nutrition. This study investigated the effects of pomegranate peel phenolic extract (PE), either in raw form (PE300) or nano-encapsulated using gum–gelatin nano-capsules (NPE300), on health and growth parameters in newly weaned rabbits. Fifty-four male rabbits (40 days old) were assigned to three treatment groups: PE0 (control), PE300 (300 mg PE/L drinking water), and NPE300 (300 mg nano-encapsulated PE/L drinking water). Over six weeks, growth performance, hematological and immunological profiles, antioxidant status, microbial populations, and carcass traits were evaluated. NPE300 treatment demonstrated superior antimicrobial activity in vitro, with larger inhibition zones against all tested pathogens compared to PE300. In vivo, NPE300 significantly improved body weight gain (945.8 g) and feed efficiency, while also enhancing immune function, evidenced by higher white and red blood cell counts, phagocytic activity, and increased plasma IgG and IgM levels. Antioxidant markers showed that NPE300 significantly reduced malondialdehyde levels and tended to improve total antioxidant capacity. Furthermore, intestinal Clostridia counts were reduced, and beneficial microflora significantly increased in the NPE300 group. Carcass weight with edible parts, fur weight, kidney weight, and cecum length were also elevated under NPE300 treatment. In conclusion, nanoencapsulation of PE using gum–gelatin carriers enhanced its bio-efficacy, supporting better redox balance, immunity, gut health, and growth performance in rabbits. These findings support the application of nano-encapsulated PE as a promising natural growth promoter in rabbit production. Full article

Iron is essential for numerous physiological processes, including oxygen transport, energy metabolism, and immune function. This study evaluated the efficacy and safety of three iron formulations combining heme and non-heme iron, comparing them with existing market products and the original form of iron. The formulations tested were GlobiFer^® Forte, a combination of heme and non-heme iron containing 18 mg of elemental iron (hereinafter referred to as nutraceutical product 1); GlobiFer^®, a combination of heme and non-heme iron containing 14 mg of elemental iron (hereinafter referred to as nutraceutical product 2); and a double dose of nutraceutical product 2. Using an in vitro 3D intestinal barrier model, all three formulations significantly increased tight junction protein expression and TEER values, indicating preserved barrier integrity. Iron absorption analysis revealed that all three iron formulations had higher absorption rates than controls. Nutraceutical product 1 showed the highest absorption, associated with increased expression of the iron transporters such as the primary non-heme iron transporter, DMT1, and the leading apical heme transporter, HCP-1. All three new formulations increased ferritin and ferroportin levels, markers of systemic iron storage and regulation. Nutraceutical product 1 was found to be the most effective, based on percentage. Overall, combining heme and non-heme iron improved intestinal absorption and supported iron metabolism, with Nutraceutical Product 1 proving the most promising in terms of efficacy and safety. These results support the development of optimised dual-source iron supplements to improve bioavailability and maintain intestinal barrier integrity, prerequisites for better efficacy and tolerability in clinical use. Full article

The intestinal epithelium maintains tissue homeostasis through a dynamic balance of stem cell proliferation and differentiation. This process is spatially regulated along the crypt–villus axis, with intestinal stem cells in the crypt regions proliferating and progenitor cells differentiating as they migrate toward the villus tips. Because the lumen of the gut contains very low levels of oxygen (i.e., hypoxia), an oxygen gradient is established within the crypt–villus axis, placing the crypt regions under normoxic conditions while the villus tips reside under hypoxic conditions. Hence, intestinal epithelial cells encounter distinct oxygen microenvironments throughout their life span as they migrate along the crypt–villus structures during their proliferation and differentiation process. To investigate how oxygen availability influences intestinal stem cell proliferation and differentiation, we cultured patient-derived human ileum organoids (i.e., enteroids) under normoxic (20% oxygen) or hypoxic (1% oxygen) conditions. Under hypoxia, enteroid growth was reduced, and expression of several stem cell markers, such as OLFM4 and LGR5, was decreased. Bulk and single-cell RNA sequencing revealed that hypoxia suppressed Wnt signaling pathways and reduced stem cell activity. Importantly, pharmacological stabilization of HIF-1α under normoxic conditions recapitulated the hypoxia-induced loss of stemness, demonstrating that HIF-1α is a key mediator of oxygen-dependent stem cell regulation in enteroids. These findings establish that physiological hypoxia in the intestinal epithelium directly regulates stem cell fate through HIF-1α stabilization, providing mechanistic insight into how oxygen availability along the crypt–villus structures controls intestinal homeostasis. Full article

Chronic stress is a major risk factor contributing to cellular changes in the brain that precipitate the emergence of various behavioral changes, including anxiety and anhedonia—symptoms relevant to mood disorders including major depression—however the sequence and trajectory of early molecular changes is poorly characterized. Using the chronic restraint stress (CRS) model in mice (N = 6–8/sex/group), we assessed the impact of 0, 7, 14, 21, 28, or 35 days of CRS at the behavioral level on the emergence of anxiety-like and anhedonia-like phenotypes. While 7 days of CRS was sufficient to induce anxiety-like behaviors in the PhenoTyper test, anhedonia-like deficits in the sucrose consumption test were only observed after 35 days of CRS. We also investigated the underlying molecular changes in the prefrontal cortex, a limbic brain region highly sensitive to stress, using Western blot and qPCR. We found that protein or RNA levels of several markers known to be implicated in the pathology of depression, and markers of synapses (post synaptic density protein 95 (PSD95), synapsin-1 (SYN1), vesicular glutamate transporter-1 (VGLUT1), and gephyrin (GPHN)); GABAergic inhibitory interneurons (somatostatin (SST), parvalbumin (PV), glutamic acid decarboxylase-67 (GAD67), and vasoactive intestinal peptide (VIP)); and astroglia (glial fibrillary acidic protein (GFAP), glutamate transporter-1 (GLT1), and glutamine synthase (GS)) were gradually reduced by CRS. Interestingly, all three astroglial markers were negatively correlated with anhedonia-like behaviors, while SYN1 and GPHN negatively correlated with anxiety-like behaviors. GLT1, VGLUT1, SYN1, and GAD67 negatively correlated with Z-emotionality scores. Exploratory between-marker correlations and integrative network analyses revealed that CRS effects might be driven by different compartments (synaptic, GABAergic and astroglial) depending on sex. Our study demonstrates that CRS induces dynamic changes that can be observed at the behavioral and molecular levels, and that male and female mice, while exhibiting similar symptoms, may experience different underlying pathologies. Full article

Background: Gastrointestinal (GI) mucosal injury is a frequent complication of long-term nonsteroidal anti-inflammatory drug (NSAID) use. Effective mucosal healing requires coordinated epithelial migration, proliferation, and angiogenesis, which may be influenced by focal adhesion kinase (FAK). This study aimed to determine whether our newly developed FAK activators promote intestinal mucosal healing by enhancing angiogenesis and whether FAK activation increases resistance to reinjury. Methods: Ischemic jejunal ulcers were induced in C57BL/6 mice. After 24 h, mice received intraperitoneal injections of the FAK activator ZINC40099027 (ZN27, 900 µg/kg every 6 h) or vehicle for 2, 4, or 14 days. Ulcer areas were quantified, and liver and kidney function were assessed. Ulcer and adjacent tissues were analyzed by immunofluorescence staining for angiogenesis and proliferation markers. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with ZN27 to evaluate proliferation, migration, angiogenesis, and intracellular signaling. In a reinjury model, male C57BL/6J mice received continuous infusion of the FAK activator M64HCl (25 mg/kg/day) or vehicle for 7 days, with a single subcutaneous injection of indomethacin (10 mg/kg) on day 1 to induce GI injury. Fourteen days after the first dose of indomethacin, the mice received a second indomethacin challenge, and one day later, total ulcer areas in the pyloric opening and small intestine were quantified. Results: Ulcer areas were significantly smaller in ZN27-treated mice compared with vehicle-treated controls at 3 and 5 days, accompanied by increased expression of angiogenesis and proliferation markers. In vitro, ZN27 enhanced HUVEC migration via FAK activation in an ERK1/2-dependent manner and increased the number of angiogenic sprouts. In the reinjury model, treatment with M64HCl during the initial indomethacin-induced injury resulted in significantly smaller ulcer areas in both the pyloric opening and small intestine after the second indomethacin challenge compared with controls. Conclusions: FAK activation accelerates ischemic ulcer healing, in part by enhancing angiogenesis. Moreover, FAK activation during an initial injury reduces susceptibility to recurrent NSAID-induced intestinal injury, perhaps because it promotes initial higher-quality ulcer repair. Full article

Insulin resistance develops when skeletal muscle (SM), adipose tissue (AT), and the liver fail to respond adequately to insulin, a dysfunction closely intertwined with chronic low-grade inflammation. This combination leads to compensatory hyperinsulinemia, dysglycemia, and metabolic stress, driving major disorders such as type 2 diabetes, metabolic syndrome, metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular disease. Both adipokines and myokines are central modulators of this metabolic–inflammatory axis. In obesity, diabetes, MASLD, and thyroid dysfunction, alterations in myokines such as myostatin, irisin, fibroblast growth factor 21 (FGF-21), apelin, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and interleukin-15 (IL-15) influence glucose uptake, lipid oxidation, mitochondrial function, and systemic inflammation. Exercise-induced myokines exert insulin-sensitizing and anti-inflammatory effects, whereas myostatin and tumor necrosis factor-alpha (TNF-α) promote metabolic impairment. These pathways reveal extensive crosstalk between SM and key metabolic organs—including the liver, pancreas, AT, intestine, heart, and thyroid gland. In metabolic disease, inflammation-driven changes in deiodinase activity and triiodothyronine (T3) availability further link muscle dysfunction with thyroid imbalance. The aim of this narrative review was to elucidate the complex interplay between myokines, adipokines, inflammation, and insulin resistance, and to clarify their clinical relevance in metabolic and thyroid disorders. Given this integrative role of SM, sarcopenia should be recognized as a clinical marker of metabolic or thyroid dysregulation, and preserving muscle mass through structured physical activity should be a core therapeutic target. Full article

Background/Objectives: Intestinal ultrasound (IUS) is increasingly used to monitor ulcerative colitis (UC), but its predictive value remains unclear. This systematic review evaluated the ability of IUS parameters and scores to predict short- and long-term treatment response, remission, and adverse outcomes in hospitalized and outpatient UC populations. Methods: A systematic review was conducted according to Cochrane and PRISMA guidelines. MEDLINE and Embase were searched for prospective studies assessing IUS as a predictor of clinical or endoscopic response, remission, relapse, or adverse outcomes in adult UC. Two reviewers independently performed screening, data extraction, and QUADAS-2 assessment. Results: Eighteen prospective studies were included: eleven outpatient studies and seven involving hospitalized patients treated with intravenous corticosteroids (IVCS). In hospitalized patients, bowel wall thickness (BWT) was the most consistent predictor of treatment failure, rescue therapy, colectomy, and clinical response. Baseline BWT showed variable performance, but once IVCS was initiated, early BWT change within 48–72 h was the strongest marker of disease trajectory. Non-responders had higher BWT and smaller reductions. A BWT ≥ 4 mm, absolute reduction ≤ 1 mm, or relative reduction ≤ 20% at 48 h reliably identified patients needing rescue therapy (area under the curve (AUC) values of 0.77 (95% confidence interval (CI) 0.71–0.74), 0.71 (95% CI 0.56–0.86), and 0.74 (95% CI 0.60–0.88)). Colectomy risk was similarly predicted: BWT < 3 mm at 48 h was associated with no colectomies, whereas BWT ≥ 4 mm or persistently elevated BWT at day 6 markedly increased risk (Odds ratio (OR) 9.5-fold (95% CI 1.4–64.0) and OR 8.3 (95% CI 1.7–40.0), respectively). Other sonographic features (loss of haustration, increased vascularity) added supplementary but less consistent value. In outpatients, BWT also demonstrated the strongest predictive accuracy. BWT ≤ 3.6 mm at 2 weeks and <3.0 mm at 6 weeks were associated with early endoscopic remission (area under the receiver operating characteristic (AUROC) of 0.87 (95% CI 0.71–1.00) and 0.82 (95% CI 0.63–1.00), respectively). Dynamic changes with ≥23–25% relative reduction predicted clinical or endoscopic response (AUROC of 0.81 (95% CI 0.61–1.00) and OR of 13.9 (95% CI 1.13–1986.85), respectively). Persistent BWT > 3.5 mm or minimal reduction (<20% or <1 mm) indicated a low likelihood of long-term remission. Composite vascularity-based indices, particularly the Milan Ultrasound Criteria (MUC), strengthened prediction: MUC ≤ 4.3 or ≥2-point reduction at 12 weeks predicted long-term remission (AUROC 0.88 (95% CI 0.750–0.952) and 0.82 (95% CI 0.68–0.91), respectively), while MUC ≥ 7.7 indicated high risk of treatment failure or colectomy (AUROC 0.77 (95% CI: 0.73–0.82)). Conclusions: Across clinical settings, BWT consistently emerged as the strongest IUS predictor of UC treatment outcomes. Early BWT change within 48–72 h in hospitalized patients and absolute BWT values at 2–6 weeks in outpatients showed high predictive accuracy for response, remission, and colectomy. Composite indices incorporating vascularity further improved prediction. These findings support the incorporation of IUS into early treatment-response algorithms and underscore the need for standardized cut-offs and multicenter validation. Full article