Search Results (286)

Background and Objectives: Poor sleep quality and gut microbiota dysbiosis are independently associated with cognitive decline, yet their effects on cognition in heart failure (HF) patients remain unexamined. To assess the independent associations of sleep quality and gut microbiota diversity with cognition in patients with HF. Methods: This exploratory/pilot cross-sectional study enrolled adults with chronic stable HF from an outpatient cardiology clinic. Participants completed the Pittsburgh Sleep Quality Index (PSQI) and Montreal Cognitive Assessment (MoCA). Fecal samples were analyzed for gut microbiota composition, including Shannon diversity and Simpson indices. Multivariable linear regression analysis of MoCA scores with sleep quality and alpha diversity (Shannon index) as primary exposures, adjusted for age, sex, and left ventricular ejection fraction (LVEF) was conducted. Results: Of 59 enrolled patients (mean age 73.3 ± 10.8 years; 72.7% male; 86.4% White), 40 provided fecal samples. Analysis of microbiota data revealed a composition dominated by Bacillota (63.7%). In multivariable regressions, poor sleep quality was independently associated with lower MoCA scores (β = −3.01 to −3.88, p < 0.01). Similarly, Shannon diversity was also associated with lower MoCA (β = −3.45, p < 0.05). Beta-diversity analyses showed no consistent association between overall microbial community composition and cognition. No significant interactions between microbiota diversity and sleep variables were identified (all p > 0.20). Conclusions: Sleep quality and gut microbiota alpha diversity are independently associated with cognitive function in HF. Microbial pathways favoring short-chain fatty acid production align with better sleep, while lipopolysaccharide-related pathways associate with poorer sleep and cognition. Full article

Ozone (O₃) is a prevalent environmental pollutant that can induce oxidative stress and respiratory epithelial injury. Dysregulation of pulmonary microbiota homeostasis plays an important role in the progression of lung damage and inflammatory responses. However, there remains a lack of systematic research on the effects of O₃ exposure on pulmonary microecology and its potential association with pulmonary inflammation. In this study, twenty-three SPF-grade C57BL/6N male mice (aged 6–7 weeks) were randomly divided into a filtered air control group (n = 11) and an O₃ exposure group (n = 12). Mice in the O₃ group underwent whole-body inhalation exposure to 1 ppm O₃ for 4 h daily over 8 consecutive weeks, while control mice were maintained under identical conditions with filtered air exposure. The 1 ppm concentration (equivalent to 0.2–0.3 ppm in humans) and 8-week daily 4 h exposure regimen was selected to model the 2-month summer high-O₃ season with typical afternoon O₃ peaks. The results showed that the O₃-exposed group exhibited marked inflammatory infiltrates in the lung, as well as significantly elevated macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-alpha (TNF-α) in bronchoalveolar lavage fluids compared with controls. Pulmonary microbiota sequencing revealed that O₃ exposure significantly elevated the Shannon index of pulmonary microbiota in mice, and four differential genera including Deinococcus, Aerococcus, Enterococcus and Proteiniphilum were identified. Correlation analysis revealed that MIP-2 was significantly correlated with Aerococcus. In conclusion, the findings of this study suggest that exposure to O₃ induces inflammation and significant changes in the microbial composition of the lungs, which provides an experimental basis for further investigating mechanisms linking microbiota dysbiosis to lung injury triggered by ambient air pollutants. Full article

Atopic dermatitis (AD) and food allergy frequently coexist during early childhood and are increasingly linked through interactions within the gut–skin axis. We evaluated the clinical outcomes of an integrated nutritional and microbiome-oriented management strategy in children with food allergy-associated AD under real-world conditions. This prospective, two-center, real-world observational cohort study included 85 children (median age, 11 months) with AD diagnosed according to the Hanifin–Rajka criteria and confirmed IgE- and/or non-IgE-mediated food allergy. Participants received individualized nutritional and microbiome-oriented management comprising elimination diets, conventional topical therapy, microbiome-directed interventions, and nutritional supplementation tailored to their clinical, allergological, and microbiological profile. Disease severity was assessed using the Scoring Atopic Dermatitis (SCORAD) index at baseline and after approximately 1 and 3 months of follow-up. Cow’s milk, egg, and wheat were the predominant food allergens, and 69.4% of children were polyallergic. SCORAD decreased significantly during follow-up, with a mean relative reduction of 51.6% and 63.5% of participants achieving a SCORAD50 response. Food allergy burden independently predicted baseline disease severity, whereas documented gut dysbiosis was associated with polyallergy and greater absolute clinical improvement, although this association lost statistical significance after adjustment for baseline disease severity and should therefore not be interpreted as a favorable prognostic effect of dysbiosis. Baseline SCORAD remained the strongest independent predictor of clinical improvement. Integrated nutritional and microbiome-oriented management was associated with substantial clinical improvement and may represent a valuable adjunct to standard care in children with food allergy-associated AD. Because of the observational, uncontrolled design, these findings describe associations rather than causal treatment effects. These findings support further evaluation of personalized nutritional strategies in randomized controlled trials. Full article

Chronic enteropathy (CE) is a common cause of persistent gastrointestinal signs in dogs, and dietary management represents the cornerstone of treatment. Probiotics have been proposed as adjunctive strategies to support intestinal health, although evidence of their efficacy remains limited. This randomised, double-blind crossover trial evaluated the effects of a hydrolysed protein diet supplemented or not with Bacillus velezensis DSM 15544 applied during post-extrusion coating. Thirteen CE dogs were randomly assigned to receive the Diet with Probiotic (DIET+PRO) or the Diet without Probiotic (DIET) during two consecutive 60-day feeding periods, with parameters assessed at baseline (T0) and after 30 (T1) and 60 (T2) days of each dietary treatment. Clinical response was assessed using the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) andfecal core (FS). Gut microbiota was evaluated by the qPCR Dysbiosis Index (DI) and 16S rRNA gene sequencing, including taxonomic composition, alpha and beta diversity analyses. Compared with baseline (CIBDAI: 4.2 ± 1.7; FS: 3.9 ± 1.5), both dietary treatments significantly improved clinical scores (CIBDAI: 1.3–1.5; FS: 2.2–2.3; p < 0.02), irrespective of probiotic supplementation. Neither microbiota composition, alpha diversity, beta diversity, nor the DI (−2.7 ± 2.3 to −2.1 ± 2.3) differed between dietary treatments. Clinical responses to B. velezensis DSM 15544 supplementation varied among dogs. Overall, the hydrolysed diet effectively improved gastrointestinal clinical signs in dogs with CE, whereas the effects of B. velezensis DSM 15544 remain unclear and warrant further investigation, as any additional benefit may have been masked by the marked clinical response to the hydrolysed diet. Full article

Smokeless tobacco (SLT) consumption is a significant risk factor for oral dysbiosis and oral cancer in South Asian countries, including India. However, its impact on oral microbial ecology, functional restructuring, and sex-specific microbial responses remains unclear. The present study aimed to evaluate tobacco-associated oral microbiome dysbiosis across different subject groups (addicted male/AM, addicted female/AF, non-addicted male/NAM, and non-addicted female/NAF) using a controlled sibling-based pooled temporal representative framework. To reduce short-term temporal variability and generate representative oral microbiome profiles, oral gargle samples were collected daily for seven days and pooled within each study group prior to DNA extraction and 16S rRNA gene sequencing. Proteobacteria, Firmicutes and Bacteroidetes were the dominant phyla in all samples. Addicted users showed a higher Firmicutes/Bacteroidetes ratio, fewer cultivable species, and more pathobionts, along with lower Shannon diversity in tobacco addiction and a partial separation in beta diversity between addicted and non-addicted samples. The enrichment of Streptococcus, Gemella, Neisseria, Veillonella, Acinetobacter, and Pseudomonas in tobacco-associated microbiomes and Comamonas, Chryseobacterium, Delftia, Flavobacterium, and related taxa in non-addicted individuals were consistently identified by all three analyses, that is, differential abundance, STAMP, and SIMPER. A shared core oral microbiome and unique “tobacco-associated” microbial signatures were observed. Orotype mapping showed that the transition in the microbial community to a Streptococcus-dominated (S-type) dysbiotic state was driven by tobacco addiction, introducing a novel conceptual framework, the Tobacco-Associated Dysbiosis Index (TDI), which showed higher values in addicted participants. Furthermore, functional prediction analysis revealed increased enrichment of ammonia oxidation, dehalogenation, sulfate reduction, nitrite reduction, chitin degradation, and xenobiotic metabolism pathways, highlighting microbial adaptation towards detoxification. In summary, chronic exposure to smokeless tobacco is linked to ecological imbalance, pathobiont enrichment, loss of microbial diversity, functional dysbiosis, and metabolic reprogramming, suggesting descriptive ecological patterns that may be relevant to chronic inflammation and oral carcinogenesis. Full article

Hidradenitis suppurativa (HS) is increasingly recognized as a disorder of intrinsic dysregulation at the intersection of genetic susceptibility, host–microbial interactions, and hormonal signaling, with select environmental exposures acting as important secondary modifiers. This narrative review synthesizes mechanistic, clinical, and epidemiologic evidence on intrinsic and extrinsic contributors to HS pathogenesis. Genetic susceptibility for HS involves pathways regulating keratinocyte differentiation, epidermal stem cell function, and follicular architecture, including Notch signaling and transcriptional regulators such as SOX9 and KLF5. Microbiome alterations in both lesional and non-lesional skin suggest that early dysbiosis may contribute to follicular occlusion, epithelial disruption, and immune activation. Hormonal signaling, particularly androgen signaling, promotes follicular dysfunction and inflammation during periods of hormonal fluctuation, frequently aligning with the time of disease onset and flares. Environmental exposures vary considerably in the strength of supporting evidence: tobacco use and elevated body mass index have the most robust epidemiologic and mechanistic data, heat and humidity are increasingly recognized as disease activity modifiers, and evidence for air pollution and microplastics is growing. Collectively, these findings support a model in which HS arises from intrinsic follicular dysregulation shaped by genetic, microbial, and hormonal factors, with environmental exposures influencing but unlikely to independently initiate disease. Full article

Background/Objectives: Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal disorder characterized by intestinal inflammation and gut microbiota dysbiosis, but current therapies remain limited by adverse effects and suboptimal long-term efficacy. Methods: Here, using a dextran sulfate sodium (DSS)-induced mouse model of IBD-like colitis, we investigated the protective effects of Yakuchinone B (YB)—a diarylheptanoid derived from Alpinia oxyphylla with reported anti-inflammatory and antioxidant activities—against inflammatory bowel disease (IBD). Results: YB supplementation significantly alleviated colitis symptoms, as evidenced by reduced body weight loss, lower disease activity index scores, attenuated colonic shortening, and ameliorated histopathological damage. YB also decreased the colonic and serum levels of TNF-α, IL-1β, and IL-6. Microbiome profiling showed that YB restored gut microbial diversity and reshaped microbial composition, with increased abundances of Alistipes and Duncaniella and reduced overgrowth of Akkermansia. Untargeted metabolomics revealed that YB modulated colitis-associated pathways, including purine metabolism, alanine, aspartate, and glutamate metabolism, and steroid hormone biosynthesis. Targeted analysis further showed that YB increased acetate, propionate, and butyrate levels. Conclusions: These results collectively suggest that YB ameliorates DSS-induced colitis by attenuating inflammation, associated with modulation of the gut microbiota-host metabolism axis, and promoting short-chain fatty acid production, supporting its potential as a promising functional dietary candidate for IBD management. Full article

Background/Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disease in which gut–skin axis dysregulation is increasingly implicated. We conducted a prospective pilot study to describe the clinical evolution of pediatric AD following individualized, stool-guided microbiota-targeted therapy and to explore whether baseline dysbiosis markers predict outcomes beyond baseline disease severity. Methods: Twenty-one children with AD and laboratory-confirmed gut dysbiosis were enrolled consecutively at a tertiary pediatric center in Romania in a single-arm prospective pilot study. Gut microbiota was assessed using targeted culture-based stool analysis, generating a Flora Index and a binary High Putrefaction Flora classification. Individualized treatment consisted of strain-specific probiotics, prebiotics, and antifungals when indicated. Disease severity was assessed using the Patient-Oriented Eczema Measure (POEM) and Scoring Atopic Dermatitis (SCORAD) at baseline, 30 days, and 90 days. Longitudinal changes were evaluated using repeated-measures ANOVA and hierarchical regression models. Results: High Putrefaction Flora was present in 71.4% of participants. Mean POEM decreased from 14.67 ± 5.22 at baseline to 7.10 ± 3.82 at 90 days, while mean SCORAD decreased from 41.66 ± 15.28 to 17.93 ± 11.68 (both p < 0.001). Approximately 76% of participants achieved a ≥50% reduction in POEM, and 71% achieved a ≥50% reduction in SCORAD. Individualized microbiota-targeted therapy was associated with substantial improvements in both clinical and patient-reported disease severity over the 90-day follow-up. Although children with High Putrefaction Flora exhibited higher disease severity scores in unadjusted analyses, baseline disease severity was the only significant predictor of 90-day outcomes. The Flora Index provided no independent explanatory value. Conclusions: In this exploratory single-arm pilot study, individualized microbiota-targeted therapy was associated with substantial and clinically meaningful improvement in AD severity over 90 days. Dysbiosis markers were associated with disease burden but did not independently predict outcomes, suggesting that they may function primarily as indicators of baseline severity rather than prognostic biomarkers. Because of the uncontrolled study design, causal inferences regarding treatment effects cannot be made, and these findings should be considered hypothesis-generating. Adequately powered randomized controlled trials are required to determine the efficacy of individualized microbiota-targeted interventions in pediatric atopic dermatitis. Full article

Excessive consumption of ultra-processed foods (UPFs) containing non-nutritive sweeteners (NNS) has been implicated in inflammatory bowel disease (IBD), yet the effects of erythritol on intestinal inflammation remain poorly understood. In this study, we assessed NNS-containing UPF exposure in patients with IBD and healthy controls, and then investigated the effects of erythritol in a dextran sulfate sodium (DSS)-induced colitis. Food frequency questionnaire (FFQ) results showed that patients with IBD, particularly those with active disease, had a higher proportion of NNS-containing UPF categories among total UPFs consumed. In mice, erythritol administration exacerbated DSS-induced colitis, as evidenced by sustained body weight loss, increased disease activity index, impaired intestinal barrier integrity, and elevated inflammatory cytokine expression. Transcriptomic analysis revealed significant enrichment of ferroptosis-related pathways in the colonic mucosa of erythritol-treated colitic mice. Furthermore, erythritol markedly altered gut microbial composition, characterized by increased abundance of potentially pathogenic bacteria and enrichment of Alistipes sp. CHKCI003. Untargeted metabolomics demonstrated alteration of tryptophan metabolism. Consistently, erythritol aggravated depression-like behavior in DSS-induced mice. Collectively, these findings suggest that erythritol exacerbates experimental colitis and depression-like behavior, potentially through microbiota dysbiosis, ferroptosis-associated alterations, and disrupted tryptophan metabolism. Full article

(1) Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain and altered bowel habits, linked to dysbiosis and inflammation. Currently available treatments, focused on symptom management, displayed limited efficacy. Recent research highlights microbiota modulation as a potential therapeutic strategy to restore intestinal barrier integrity; (2) A dextran sulfate sodium (DSS)-induced mouse model of post-colitis IBS-like symptoms was performed to evaluate the effect of a novel mixture of Enterococcus lactis SF68^®, butyrate, and folate. Disease activity index and spleen weight were assessed. Markers of gut inflammation, intestinal barrier alterations, and gut butyrate bioavailability were measured. The activity of colonic mitochondria was also analyzed; (3) Supplementation with the novel mixture significantly reduced spleen weight and cytokine levels. The intestinal epithelial barrier was restored through an increase in claudin-1, occludin, and defensin 1–3 and a reduction in LBP plasma level. Treatment with the mixture enhanced the expression of butyrate transporters in mice. Mitochondrial activity markers, including citrate synthase and Cytochrome c oxidase, were improved by treatment; (4) The novel mixture containing Enterococcus lactis, butyrate, and folate exerted a protective effect against post-inflammatory IBS by reducing local inflammation, restoring intestinal barrier integrity, and enhancing butyrate bioavailability, suggesting its potential for managing post-inflammatory IBS symptoms effectively. Full article

Periodontitis, a chronic inflammatory disease affecting approximately 40% of U.S. adults aged 30 years and older, is characterized by dysbiosis of the dental plaque microbiome. However, although scaling and root planing (SRP) is the cornerstone of periodontal treatment, its effects on the taxonomic composition and functional potential of the dental plaque microbiome remain incompletely understood. In this study, we used whole-metagenome shotgun sequencing to characterize taxonomic composition and functional potential in dental plaque microbiomes collected from 39 patients with Stage II or III generalized periodontitis before and 3–4 months after SRP. Consistent with clinical improvement, periodontal therapy significantly reduced probing depth, clinical attachment level, bleeding on probing, and plaque index. Whole-metagenome shotgun sequencing identified 3.18 million non-redundant genes and 12,353 microbial species across 78 samples, revealing increased gene and species richness after treatment, along with a significant restructuring of the microbial community. Established periodontal pathogens, including Porphyromonas gingivalis, as well as the emerging pathogens Escherichia coli and Burkholderia multivorans, decreased following treatment. Tannerella forsythia also showed a marked reduction after treatment, although this decrease was not significant after false discovery rate (FDR) correction. In contrast, health-associated early colonizers, including multiple Actinomyces species and Streptococcus cristatus, increased. Functional annotation using the Carbohydrate-Active Enzymes (CAZy) database identified significant treatment-associated differences in carbohydrate-active enzymes, including multiple glycosyltransferases, indicating remodeling of the predicted functional potential of the dental plaque microbiome. These findings demonstrate that successful SRP promotes coordinated taxonomic and predicted functional remodeling of the dental plaque microbiome and highlight the value of shotgun metagenomic sequencing for characterizing both taxonomic and functional recovery following periodontal therapy. Full article

Background/Objectives: Natural bioactive compounds are promising interventions for obesity-related metabolic dysfunction. Lutein, a xanthophyll carotenoid with antioxidant and anti-inflammatory properties, may improve metabolic health, but its effects on liver function and gut microbiota in high-fat diet (HFD)-induced obesity are not fully elucidated. This study evaluated the effects of lutein supplementation on hepatic function, oxidative status, lipid metabolism, and gut microbiota composition in HFD-fed mice. Methods: Male C57BL/6J mice (6 weeks old) were randomly assigned to four groups (n = 8/group): Ctrl (low-fat diet), model (HFD), low-dose lutein (50 mg/kg/day), and high-dose lutein (100 mg/kg/day). Results: Following a 70-day intervention, lutein supplementation, particularly at the higher dose, reduced the liver index, improved serum lipid profiles, liver injury markers, and hepatic antioxidant capacity by increasing superoxide dismutase, catalase, and glutathione levels while reducing malondialdehyde content, and alleviated hepatic histopathological alterations. Lutein supplementation was also linked to elevated gut microbial richness and shifts in the relative frequency of several bacterial taxa, including partial restoration of Bacteroidota and enrichment of Roseburia and Faecalibaculum. These findings demonstrate that lutein supplementation attenuated HFD-induced metabolic and hepatic alterations, accompanied by improved antioxidant status and modulation of gut microbiota. Conclusions: Overall, lutein alleviated hepatic steatosis, oxidative stress, and metabolic dysfunction, highlighting its potential as a dietary strategy for managing obesity-related liver functions and gut dysbiosis. Full article

Gestational diabetes mellitus (GDM) is a metabolic disorder that is characterized by hyperglycemia developed or first diagnosed during pregnancy, affecting up to 15% of pregnant women worldwide. Although risk factors for GDM such as a family history of diabetes, obesity, and advanced maternal age are well recognized, the underlying pathophysiological mechanisms are complex and remain incompletely understood. Multiple studies indicate that GDM arises from a combination of peripheral insulin resistance and pancreatic β-cell dysfunction, in which insulin secretion fails to compensate for the progressive increase in insulin demand during pregnancy. In recent years, growing attention has been focused on the gut microbiota and its potential influence on the development and progression of many metabolic diseases, including GDM. Studies have shown that women diagnosed with GDM exhibited altered gut microbial composition and reduced microbial diversity, termed as “dysbiosis”, suggesting that gut microbiota dysbiosis may contribute to the pathogenesis of GDM. However, most evidence in humans is associative rather than causal, and findings vary across populations due to differences in study cohort characteristics (GDM diagnostic criteria, ethnicity, lifestyle, dietary habits, pregnancy body mass index, gestational age) and sequencing methods. Current treatment guidelines for the management of GDM are universally standardized, despite the known heterogeneity of the disease etiology. Given the inter-individual differences in gut microbial composition in women with GDM, the gut microbiota has been proposed as a promising source for rapid and specific biomarkers to enable early diagnosis, targeted prevention, and personalized management of GDM. In this narrative article, we first summarize current insights into the pathophysiological mechanisms linking gut microbiota to the development of GDM. Second, we emphasize the importance of gut microbiota analysis (or microbiomics) within multi-omics frameworks for the early detection, prevention and personalized management of GDM. Full article

Background/Objectives: Many HIV-positive (HIV+) males receiving highly active antiretroviral therapy (HAART) experience metabolic complications, including non-alcoholic fatty liver disease (NAFLD); lipodystrophy; and intestinal dysbiosis, often characterized by a Prevotella-rich enterotype. Gut microbial fermentation produces short-chain fatty acids (SCFAs), which play important roles in host metabolism. This study investigated the relationships among HAART, anthropometrics, diet, intestinal permeability, gut microbiota composition, and lipodystrophy in HIV+ males. Methods: Forty males aged 23–60 years were enrolled, including 19 HIV+ participants recruited from the East Tennessee State University (ETSU) Health Infectious Diseases Specialty Clinic and 20 HIV-negative (HIV−) controls recruited through standard methods. Participants provided a stool sample for 16S rRNA gene sequencing, SCFA analysis by gas chromatography, and proximate analysis, and completed a food frequency questionnaire. Lipodystrophy-related measures included body mass index (BMI), hip-to-waist ratio (H:W), and liver health assessment using FibroScan. Blood samples were collected by venipuncture. Serum markers of intestinal permeability, including Claudin-21, flagellin, and intestinal fatty acid-binding protein (IFABP), were quantified by enzyme-linked immunosorbent assay (ELISA). Results: HIV+ males exhibited significantly higher H:W ratios (p = 0.001) and hepatic steatosis (p = 0.0047) than HIV− controls (Welsh’s t-test). Concentrations of isobutyrate (p = 0.0024), isovalerate (p = 0.0008), and valerate (p = 0.0329) were elevated in HIV+ participants, whereas butyrate (p = 0.0014) and total acetate/propionate/butyrate (APB) (p = 0.0046) were higher in HIV− males (Welsh’s t-test). HIV+ participants also showed greater abundances of Prevotella and Lachnospiraceae (Analysis of Compositions of Microbiomes; ANCOM). Retrospective analysis revealed that all HIV+ participants were men who have sex with men (MSM). Conclusions: HIV+ males demonstrated distinct gut microbiome profiles, altered SCFA production, and markers of disrupted lipid metabolism. These findings provide a foundation for future investigations of microbiome-metabolism interactions in HIV+ MSM. Full article

Background/Objectives: Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, is implicated in the pathogenesis of ulcerative colitis (UC). Tryptophan metabolism and its interaction with the aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2–related factor 2 (Nrf2) axis represent a crucial regulatory network in intestinal homeostasis. This study aimed to investigate whether the probiotic fermentation product postbiotic Nagqu4580 alleviates UC by modulating this network to inhibit intestinal epithelial ferroptosis. Methods: An acute UC model was induced in mice using 4% dextran sodium sulfate (DSS). The therapeutic effects of postbiotic Nagqu4580 were evaluated through disease activity index (DAI), colon length, histopathology, inflammatory cytokines, and intestinal barrier function. Ferroptosis was assessed by measuring lipid peroxidation (MDA, 4-HNE), antioxidant capacity (GSH/GSSG), and expression levels of GPX4 and ACSL4. Serum tryptophan metabolites were profiled using targeted metabolomics, the activation of the AhR/Nrf2 pathway was examined by Western blot, immunofluorescence, and qPCR, and gut microbiota composition was analyzed by 16S rRNA sequencing. Results: Postbiotic Nagqu4580 dose-dependently ameliorated DSS-induced UC in mice, as evidenced by reduced DAI scores, mitigated colon shortening and histological damage, decreased inflammatory cytokines (TNF-α, IL-1β, IL-6), and restored intestinal barrier function by upregulating tight junction proteins (Claudin-1, ZO-1, Occludin). Mechanistically, postbiotic Nagqu4580 inhibited intestinal epithelial ferroptosis by reducing MDA and 4-HNE levels, restoring the GSH/GSSG balance, downregulating ACSL4, and upregulating GPX4. Serum metabolomics revealed that postbiotic Nagqu4580 reshaped tryptophan metabolism, increasing beneficial metabolites such as 5-hydroxyindoleacetic acid (5-HIAA) and decreasing potentially harmful metabolites such as 3-indoxyl sulfate (3-IS). 16S rRNA sequencing further revealed that the postbiotic Nagqu4580 partially reversed DSS-induced gut microbiota dysbiosis, with a slight increase in the abundance of beneficial genera and a significant reduction in the abundance of pro-inflammatory genera. Furthermore, postbiotic Nagqu4580 significantly activated the AhR/Nrf2 signaling pathway, enhancing the expression of AhR, Nrf2, and their downstream antioxidant genes HO-1 and GPX4. Conclusions: Postbiotic Nagqu4580 alleviates UC by inhibiting intestinal epithelial ferroptosis. Our data suggest that this protective effect is associated with the remodeling of gut microbiota-related tryptophan metabolism and subsequent activation of the AhR/Nrf2 antioxidant axis. Our findings highlight the therapeutic potential of postbiotic Nagqu4580 as a postbiotic agent for UC. Full article