Search Results (441)

This study investigated the effects of composite postbiotic preparation on the growth performance, immune function, and microbiota composition of Nubian black goats. Thirty healthy Nubian black goats with similar body weights were randomly assigned to two groups (n = 15 per group): a control group fed a basal diet and a treatment group fed the basal diet supplemented with 0.5% composite postbiotic preparation (equal-ratio co-fermentation of Bacillus subtilis GX15 and Lentilactobacillus buchneri GX0328-6). The results indicated that while compound postbiotic supplementation did not significantly alter the average daily gain (ADG) and the serum biochemical indices (p > 0.05), it significantly increased the concentrations of immunoglobulins (IgG and IgA) compared to the control group (p < 0.05). Despite comparable α- and β-diversity, CPP supplementation selectively enriched Bacteroides, UCG-005, and Ruminococcaceae while reducing Turicibacter (LEfSe LDA > 2.0; STAMP p < 0.05), suggesting targeted modulation of gut microbiota. In conclusion, dietary supplementation with 0.5% composite postbiotic preparation improves immune function and modulates intestinal microbiota composition without significantly affecting growth performance in black goats while improving intestinal microbial composition and promoting overall gut health. Full article

This study systematically compared the effects of dietary supplementation with glutamine (Gln) and its precursors, including glutamic acid (GA) and α-ketoglutarate (AKG), on growth performance, serum antioxidant and immune parameters, and multi-region gastrointestinal microbiota in suckling lambs. Forty healthy suckling Hu lambs with similar body weight (7.37 ± 1.18 kg) and age (7 ± 0.8 d) were selected and randomly allocated into four groups (n = 10 per group): a control group (CON, without additive), and three treatment groups (GA, AKG, and Gln), each receiving 2 g per animal per day of the corresponding additive. The experimental period lasted for 42 d. All three additives showed a tendency to increase the final body weight (p = 0.056) and significantly increased the average daily gain (ADG) of lambs (p < 0.05). GA supplementation increased the dry matter intake throughout the entire trial (p < 0.05), whereas the addition of AKG and Gln increased the dry matter intake only during the later period (d 21–42) (p < 0.05). The feed-to-gain ratios did not differ among all groups (p > 0.05). Compared with the CON group, all three treatment groups showed elevated serum activities of catalase, glutathione peroxidase, and total antioxidant capacity, as well as increased IgA and IgG contents (p < 0.05). In addition, malondialdehyde concentration was decreased in all three treatment groups (p < 0.05). Moreover, GA supplementation reduced the ruminal alpha diversity while increasing the abundance of butyrate-producing bacteria (Ruminococcaceae UCG-014) (p < 0.05). All three interventions consistently decreased the abundance of the intestinal pathogen Escherichia-Shigella in the ileum (p < 0.05). Correlation analyses showed that ruminal Treponema 2 abundance was negatively correlated with ADG, whereas jejunal Methylobacterium and ileal [Eubacterium] coprostanoligenes group were positively correlated with final body weight or ADG. In conclusion, glutamine and its precursors play an important role in modulating gastrointestinal bacterial diversity and composition, enhancing antioxidant and immune functions, and improving the growth performance of suckling lambs. Full article

Background/Objectives: Graves’ disease (GD) is a prevalent autoimmune thyroid disorder marked by thyrotoxicosis, goiter, and Graves’ orbitopathy (GO). Recent studies highlighted its association with dysbiosis. This systematic review aims to update the current literature and clarify the distinctive microbial signatures and dysbiosis associated with GD/GO. Methods: A systematic search for relevant studies was conducted across multiple databases (2000–2023), employing appropriate keywords. Relevant data were extracted from 25 eligible studies. Results: Microbiota analysis from 19 GD studies (713 patients, 546 controls) and eight GO studies (356 patients, 187 controls), primarily conducted in China (21/25), were examined. The gut microbiota richness and evenness were reduced in GD patients compared to controls in 62.5% of fecal samples. No consistent pattern in alpha diversity was observed in GO. Significant taxonomic divergence was observed between GD/GO and controls. At the phylum level, the Firmicutes to Bacteroidetes ratio was consistently decreased in GD patients (66.7%). Most GO patients also exhibited a similar disequilibrium in their gut and orbital adipose microflora. At the genus level, Prevotella (11 studies), genera within the Lactobacillaceae family (three studies), and Streptococcus (three studies) consistently showed an increase. Genera from the families Lachnospiraceae (nine studies), Ruminococcaceae (six studies), and Veillonellaceae (five studies), as well as the genus Bacteroides (three studies), were decreased. Conclusions: GD/GO-associated dysbiosis is characterized by reduced microbial richness and evenness and alterations in gut phyla balance (↓ Firmicutes, ↑ Bacteroidetes, ↑ Proteobacteria). Specific genera—including Lactobacillus, Prevotella, Bacteroides, and members of the Lachnospiraceae family—may plausibly act as contributors to the onset or progression of GD/GO by influencing the Th17/Treg balance, although their exact roles remain uncertain and largely hypothetical. Systematic review registration: PROSPERO identifier CRD42024512007. Full article

Dietary zeaxanthin exhibits low intestinal absorption efficiency, and circulating levels are reduced in individuals with type 2 diabetes, suggesting potential metabolic relevance. However, its role during early-stage diabetes remains incompletely understood. This study examined whether dietary zeaxanthin modulates early metabolic and inflammatory responses and influences host–microbiome interactions during early T2DM progression. Four-week-old male db/db mice and wild-type C57BL/6J mice were fed an AIN-93M diet with or without 0.02% (w/w) zeaxanthin for 4 weeks. Zeaxanthin attenuated body weight gain, adiposity, hyperinsulinemia, and circulating keratinocyte-derived chemokine levels in diabetic mice. These effects were accompanied by reduced ileal membrane localization of Niemann-Pick C1-like protein 1 and decreased hepatic expression of CD36, nuclear factor kappa B p65, and phosphoenolpyruvate carboxykinase 1, without significant improvement in fasting blood glucose or hepatic triglyceride accumulation. Cecal microbiota analysis showed reduced microbial richness in diabetic mice that was not restored by zeaxanthin; however, zeaxanthin induced selective compositional shifts, including enrichment of fermentation-associated taxa (e.g., Ruminococcaceae) and normalization of Clostridium XIVb. Predicted microbial pathways related to fermentation, amino acid biosynthesis, and cofactor metabolism were also altered. Collectively, dietary zeaxanthin modulated early metabolic and inflammatory adaptation and was associated with alterations in intestinal lipid handling, inflammatory signaling, and gut microbiome composition during early T2DM progression. Full article

Colorectal cancer (CRC) is an increasing health concern in low- and middle-income countries (LMICs), especially in Africa, driven by dietary shifts, urbanisation, infections, and limited treatment access. The gut microbiome plays a central role in CRC, while soil-transmitted helminths (STHs) exert complex effects that can promote or mitigate risk depending on species, infection intensity, and host context. This systematic review synthesised 17 human studies (2000–2026) examining helminth impacts on gut microbial diversity, revealing a dualistic pattern. Several studies reported that chronic or moderate helminth infections, such as Ascaris lumbricoides and Trichuris trichiura, were associated with increased bacterial richness and the expansion of beneficial taxa, including Paraprevotellaceae, Parabacteroides, Agathobacter, Ruminococcaceae, and Lactobacillus. These taxa are associated with the production of short-chain fatty acids (SCFAs), protection of the epithelial barrier, and regulation of the immune system, suggesting a potential buffering effect against inflammation-driven carcinogenesis. On the contrary, other studies demonstrated helminth-associated dysbiosis characterised by reduced diversity and enrichment of pro-inflammatory and oncogenic taxa. T. trichiura and Strongyloides stercoralis infections were associated with the expansion of Treponema succinifaciens, Streptococcus gallolyticus, Enterobacteriaceae, and Ruminococcus torques, which are linked to reduced gut microbiome diversity, pro-inflammatory states, and oncogenic processes. Furthermore, A. lumbricoides infections altered the host microbiome at the phylum level, with increased Proteobacteria and reduced Firmicutes and Bacteroidetes, alongside metabolome shifts in amino acid and lipid pathways that have been associated with tumourigenic processes. Collectively, the evidence shows that helminthiasis may either enrich potentially protective microbes or be associated with pro-tumourigenic dysbiosis, with outcomes shaped by species, infection intensity, and host context. Notably, none of the included studies directly assessed CRC, underscoring the fact that current evidence is indirect and mechanistic. Overall, helminths are associated with gut microbiome shifts in both potentially protective and potentially harmful directions. This systematic synthesis of human evidence provides an integrated understanding of how helminth-associated microbiome shifts may influence colorectal carcinogenesis and highlights the need for longitudinal mechanistic studies to clarify causality and inform biomarker discovery and prevention in endemic regions. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is the sixth most diagnosed cancer worldwide and a leading cause of cancer-related mortality. The majority of cases arise in the setting of chronic liver disease, where immune checkpoint inhibitors (ICIs) have emerged as a cornerstone of systemic therapy for advanced disease. However, durable clinical benefit remains limited to a minority of patients, and reproducible biomarkers of ICI response are lacking. The gut–liver axis—encompassing bidirectional exchange of microbial products, metabolites, bile acids, and immune signals—has emerged as a biologically plausible determinant of both hepatocarcinogenesis and immunotherapy response. This narrative review synthesises current evidence on the role of the gut–liver axis in HCC and ICI response and proposes a unifying conceptual framework to resolve discrepancies in the existing literature. Methods: A narrative review was conducted through systematic searches of PubMed/MEDLINE, Embase, and Web of Science. Studies were selected based on relevance to the biological mechanisms, clinical associations, and experimental models underpinning gut–liver–immune interactions in HCC, with particular emphasis on studies providing mechanistic insight, addressing immunotherapy outcomes, or highlighting temporal and context-dependent effects. Results: Observational studies consistently associate higher microbial diversity and enrichment of homeostasis-promoting taxa—including Akkermansia, Bifidobacterium, and short-chain fatty acid-producing Ruminococcaceae—with ICI responsiveness in HCC. Functional microbial outputs, particularly short-chain fatty acids and secondary bile acids, exert mechanistically grounded effects on hepatic immune tone and T cell activity that are biologically proximate to ICI effector pathways. Therapeutic modulation of the gut–liver axis through probiotics, dietary interventions, faecal microbiota transplantation, and antibiotic exposure demonstrates context-dependent effects on immune activation and ICI outcomes, with timing and disease severity emerging as critical determinants. The limited reproducibility of microbiome-immunotherapy associations across cohorts is attributable primarily to the dynamic and treatment-sensitive nature of the gut–liver axis rather than a fundamental lack of mechanistic coupling. Conclusions: The gut–liver axis in HCC is best understood as a dynamic, treatment-sensitive system rather than a static baseline trait. This reframing shifts emphasis from single-timepoint taxonomic signatures toward functional and longitudinal readouts and provides a coherent rationale for the heterogeneity observed across existing studies. Longitudinal clinical studies incorporating mechanistic endpoints and functional biomarker assessment are needed to translate this framework into clinically actionable strategies for patient stratification and microbiota-targeted intervention in HCC immunotherapy. Full article

Salvia sclarea L. extract contains various bioactive components such as flavonoids and fatty acids, exhibiting anti-inflammatory, antioxidant, and antibacterial properties. This study aimed to investigate the effects of Salvia sclarea L. extract on the gut microbiota and serum metabolome in lambs. Sixty 2-month-old Chinese Merino female lambs (body weight 20 ± 2 kg) were randomly assigned to five groups. The control (CK) group received the basal diet only, while the treatment groups received the basal diet supplemented with 0.04 mL/kg (CL1), 0.08 mL/kg (CL2), 0.12 mL/kg (CL3), and 0.16 mL/kg (CL4) of Salvia sclarea L. extract, respectively. The results showed that Firmicutes, Bacteroidetes, Spirochaetes, and Proteobacteria were identified as the dominant phyla across all groups (>90%). Compared with the CK group, CL1 and CL2 groups significantly reduced the relative abundance of Tenericutes (decreased by 38.2% and 32.9%, respectively, p < 0.05); the relative abundance of Patescibacteria in the CL1 group was significantly lower (decreased by 55.2%, p < 0.05). At the genus level, Ruminococcaceae constituted a substantial proportion, including Ruminococcaceae UCG-005, UCG-010, UCG-014, and NK4A214 group. STAMP analysis revealed that Klebsiella was significantly enriched in CL2, CL3, and CL4 groups compared to the CK group (p < 0.05). Correlation analysis between microbiota and immune indices showed that Christensenellaceae R-7 group was significantly negatively correlated with TNF-α (p < 0.05); Ruminococcaceae UCG-005 was significantly negatively correlated with IFN-γ (p < 0.05) and showed a negative correlation trend with immunoglobulins (IgA, IgG, IgM). Conversely, Ruminococcaceae UCG-014 was significantly positively correlated with IL-4 (p < 0.05) but showed a negative correlation trend with IgM. Untargeted metabolomics analysis identified 8, 18, 25, and 20 differential metabolites in CL1, CL2, CL3, and CL4 groups, respectively. Notably, 3-hydroxy-7-methoxyflavone and Gamma-Glu-Cys were significantly upregulated across all treatment groups. KEGG pathway enrichment analysis indicated that these differential metabolites were primarily involved in nucleotide metabolism, fatty acid biosynthesis, and oxidative stress-related pathways. Further Spearman correlation analysis revealed significant associations between gut microbiota and differential metabolites. Specifically, g_Klebsiella was significantly positively correlated with 3-Hydroxycapric acid and 3-hydroxy-7-methoxyflavone (p < 0.05). In conclusion, Salvia sclarea L. extract modulates host energy metabolism by regulating nucleotide metabolism and fatty acid biosynthesis, and enhances immune function by alleviating oxidative stress, through the remodeling of gut microbiota and serum metabolome. Full article

Age-related changes in the gut significantly impact host health, yet the multi-omics dynamics during the maturation of Tibetan pigs remain unclear. This study aimed to investigate the morphological, microbial, metabolic, and transcriptomic transformations in the intestines of aging Tibetan pigs. We analyzed the ileum and colon of 1-year-old and 3-year-old Tibetan pigs using histological evaluation, 16S rRNA sequencing, metabolomics, and transcriptomics. Aging to 3 years significantly improved ileal architecture, notably increasing the villus height to crypt depth ratio. Older pigs exhibited higher colonic microbial diversity, a decreased Firmicutes to Bacteroidota ratio, and enrichment of homeostasis-associated taxa, including Lactobacillus, Prevotellaceae, and Ruminococcaceae. Metabolomics revealed higher abundance of certain metabolites, including docosahexaenoic and arachidonic acids, enriching lipid metabolism and bile secretion pathways. Transcriptomics identified 2363 differentially expressed genes in the ileum, primarily involved in immune regulation and nutrient digestion. Integrated analysis showed strong positive correlations between enriched microbes (Lactobacillus porci) and up-regulated host genes (UGT2B31, CCL28) governing intestinal homeostasis. The transition from 1 to 3 years of age in Tibetan pigs fosters a synergistic host-microbiome environment, enhancing intestinal barrier function, immune capacity, and metabolic efficiency. Full article

Salmonellosis is a global foodborne pathogen with zoonotic importance that seriously threatens livestock breeding and human health. Due to the implementation of an anti-resistance policy, probiotics as an alternative to antibiotics have attracted widespread attention. In this study, the widely used probiotic Escherichia coli Nissle 1917 (EcN) was selected to study its protective effect on mice infected with Salmonella typhimurium. Two mice groups (n = 15) were treated with either EcN and PBS. Flow cytometry showed that the frequency of mature dendritic cells in the Peyer’s patch was significantly increased compared to the PBS group. Previous administration of EcN protected against challenge with Salmonella typhimurium infection as an increased survival rate of the mice, a decreased degree of pathological changes, and the number of live bacteria in the spleen and liver were recorded compared to the control group. The results of 16S rRNA high-throughput sequencing of fecal microbial flora showed that EcN could reduce the abundance of microorganisms in the intestine and reduce the proportion of Lactobacillus, while Ruminococcaceae sp., Rikenella sp. and Bifidobacterium sp. disappeared. In contrast, the abundance of Bacteroides increased, which reduced the effect of Salmonella typhimurium on the distribution of intestinal microorganisms. Our results demonstrated that EcN has a protective effect against Salmonella typhimurium infection and may act as a candidate probiotic bacterium to apply in the future. Full article

As a probiotic lactic acid bacterium, E. faecalis regulates intestinal flora, strengthens the intestinal barrier, and enhances immunity in the host. However, as a new strain isolated from healthy feline gut, E. faecalis HHP003 has an unclear effect on feline intestinal health. Twenty cats with mild diarrhea were randomly assigned to two groups: one group received the standard diet (MD), while the other group received supplemental E. faecalis HHP003 (EF). Meanwhile, 10 healthy cats were enrolled as a healthy control group (CON). After 42 days of intervention, the EF group exhibited significantly reduced serum inflammatory markers (TNF-α and IL-1β), as well as decreased levels of calprotectin and lipopolysaccharide, compared with the MD group (p < 0.05). The intestinal microbial diversity was altered in the EF group, with increased Chao and Shannon indices (p < 0.05). Specifically, the relative abundances of Bacillota, Bacteroidota, and Ruminococcaceae were significantly higher in the EF group than those in the MD group (p < 0.05). Metabolomic analysis identified 697 differential metabolites and nine KEGG metabolic pathways (p < 0.05) between the EF and MD groups. Furthermore, the study identified significant associations between the gut microbiota and selected serum metabolites. In summary, E. faecalis HHP003 supplementation was associated with reduced serum inflammatory responses, improved intestinal inflammation and barrier markers, and altered gut microbiota and serum metabolite levels in cats with mild diarrhea. Full article

The attraction of neonatal piglets to sow feces and their coprophagy suggests that fecal semiochemicals promote nutrient intake and gut colonization, but their microbial origin is poorly understood. This study explored associations between gut microbiota and fecal semiochemical/metabolic profiles in prepartum and postpartum sows. Fecal samples were collected from six crossbred sows at 4 days prepartum and 3 days postpartum. Nutritional components, volatile organic compounds (VOCs), untargeted metabolomics, and gut microbiota were analyzed. Nutritional composition remained largely stable postpartum, except that sodium increased while potassium, magnesium, and cellulose decreased. Skatole and p-cresol concentrations increased postpartum even after dry matter correction. Untargeted metabolomics identified 298 differentially abundant metabolites (250 up, 48 down) postpartum, enriched in nicotinamide/nicotinate metabolism, arginine biosynthesis, and others. Gut microbial alpha diversity (Shannon, Chao1, observed features) decreased postpartum. Fibrolytic and butyrate-producing bacteria (e.g., Ruminococcaceae UCG-005, Lachnospira) were enriched prepartum, whereas Escherichia-Shigella, Christensenellaceae R-7 group and Enterococcus were more abundant postpartum. Spearman correlations showed skatole and p-cresol were strongly negatively correlated with butyrate-producing bacteria and positively correlated with postpartum-enriched genera. This study uncovered prepartum-to-postpartum shifts in sow fecal components and microbiota, revealing a microbial basis for semiochemical production and offering probiotic insights using coprophagy to improve piglet health. Full article

Interactions between the gut microbiota, immune system, and brain seem to be involved in the pathogenesis and disease activity of multiple sclerosis (MS). Some MS disease-modifying therapies (DMTs) have been shown to alter the microbiota, but whether this is related to their specific mode of action or indirectly related to their immune-modulatory effect is unknown. In this longitudinal study, we characterized the effects of two DMTs on the microbiota under similar conditions and populations: the injectable, moderate-efficacy DMT interferon beta-1a (INFβ-1a) and the oral, high-efficacy DMT cladribine tablets (CladT). Taxonomic differences were identified following 6 months of therapy for each DMT, and both were associated with the elevation of short-chain fatty acid (SCFA) producers from the Lachnospiraceae, Lactobacillaceae, and Ruminococcaceae families (Firmicutes), while members of Bacteroidetes and Proteobacteria were reduced. Moreover, a higher abundance of Alphaproteobacteria and Betaproteobacteria at baseline was associated with disease activity within 1–2 years of follow-up, while a higher abundance of Lachnospiraceae, Ruminococcaceae, Bifidobacteriaceae, and Streptococcaceae microbes, among others, was associated with no evidence of disease activity (NEDA). Our results provide supporting evidence that alteration of the microbiota by DMTs is part of their beneficial effect, and while some modifications seem to be DMT-specific, MS-DMTs in general promote SCFA-producing microbes, which positively correlate with a favorable clinical outcome. Future therapeutic strategies for PwMS may benefit from microbiome modulation, contingent upon additional mechanistic and interventional studies. Full article

Growing Angus steers (n = 20) were blocked by weight and randomly assigned to one of two treatment groups: Control group (CON, n = 10) fed a feedlot ration ad libitum, or a ruminally protected hydrogenated fat-embedded calcium gluconate (HFCG) treatment group (HFCG, n = 10), which was fed the control ration top-dressed at 16 g/head/day for 55 days. During the slaughter process, digesta samples were collected from the cecum, colon, and rectum. Acetate concentrations were greater in the cecal and rectal digesta of steers (p ≤ 0.05) in the HFCG treatment group. Propionate concentrations were greater in the cecal, colonic, and rectal (p ≤ 0.05) digesta of steers in the HFCG treatment group. Butyrate concentrations were greater (p = 0.098) in the colon digesta of steers in the HFCG treatment group; however, they were not different in the cecal and rectal digesta. To determine the microbial composition within each section of the hindgut, DNA was extracted, and 16S rRNA gene sequencing was performed. Data were analyzed using a General Linear Model with dietary treatment as the main effect. Species richness in the cecum, colon, and rectum was not different between treatments. Erysipelotrichaceae, Peptostreptococcaceae, and Atopobiaceae abundances were increased (p ≤ 0.05) in the cecal bacterial community of steers in the HFCG group, while a significant decrease (p ≤ 0.05) in Rikenellaceae and Muribaculaceae abundances was recorded within the same bacterial community. In the colon bacterial community of steers in the HFCG group, Ruminococcaceae and Muribaculaceae abundances were elevated (p ≤ 0.05), while there was a reduction (p ≤ 0.05) in Lachnospiraceae, Erysipelotrichaceae, Atopobiaceae, and Peptostreptococcaceae abundances. Paeniclostridium, Romboutsia, and Turicibacter abundances were increased (p ≤ 0.05) in the cecal bacterial community of steers in the HFCG group, while there was a decrease (p ≤ 0.05) in Rikenellaceae_RC9 _gut_group abundance within the same bacterial community. In the colon microbiota of steers in the HFCG group, Turicibacter abundance was decreased (p ≤ 0.05). Supplementing growing steers with HFCG impacted some members of the bacterial populations, which have important roles in gut homeostasis and health, along with the formation of beneficial end-products in the gastrointestinal tract. Full article

Semen quality and fecal microbial composition were compared between native Oula rams reared on the Qinghai–Tibet Plateau and Hu sheep rams introduced from lowland regions. Semen quality was analyzed in eight adult Oula rams and eight Hu rams, and fecal microbial composition was assessed via 16S rRNA sequencing. Results indicated that sperm acrosome integrity was significantly higher in Hu sheep than in Oula sheep (p < 0.001); other semen parameters showed no significant differences. Significant differences were also observed in fecal microbial communities between the two breeds. Compared with Hu sheep, Oula sheep exhibited higher microbial abundance and diversity at the phylum level, particularly Campylobacterota, Euryarchaeota, Planctomycetota, Verrucomicrobiota, Myxococcota, and Deferibacterota (p < 0.05). At the genus level, Oula sheep had significantly higher abundances of Treponema, Campylobacter, Methanobrevibacter, UCG-009, Family_XIII_AD3011_group, [Eubacterium]nodatum group, Candidatus Soleaferrea, Akkermansia, and unidentified_Ruminococcaceae (p < 0.05). Correlation analysis indicated associations between sheep semen quality and the top 30 abundant fecal microbial genera. Six genera showed significant positive correlations with acrosome integrity rate, and eight genera exhibited significant negative correlations (p < 0.05). Two genera were correlated positively with plasma membrane integrity rate (p < 0.05). Prevotellaceae_UCG-004 was positively correlated with sperm motility and Progressive Motility spermatozoa proportion (p < 0.05); Ruminococcus showed a significant positive correlation with sperm linear motility and a significant negative correlation with acrosome integrity rate (p < 0.05). These findings indicate that the microbial groups enriched in Oula sheep fecal samples and exhibiting negative correlations with acrosome integrity—including Ruminococcus, Treponema, Akkermansia, and Euryarchaeota—are associated with sperm quality through physiological adaptation mechanisms specific to high-altitude environments. Full article

Background/Objectives: Xu Chunfu’s Modified Xianglian Pill (XXLP) has been used for centuries in Chinese medicine to treat “diarrhea” and “dysentery,” conditions analogous to modern ulcerative colitis (UC). However, the scientific basis for its efficacy and mechanisms remains unclear. Methods: The chemical composition of XXLP was analyzed via UPLC-ESI-MS/MS. A colitis mouse model was established using DSS, and the therapeutic effects were assessed based on body weight, disease activity index (DAI), colon length, and histopathology. Inflammatory cytokines were measured using ELISA. Proteomic analysis and molecular docking identified key targets, which were validated using LPS-induced HT-29 cells via Western blot (WB), qRT-PCR, immunofluorescence (IF), and transmission electron microscopy (TEM). Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Results: Analysis of XXLP led to the detection of 373 compounds. XXLP significantly improved colitis symptoms, including weight loss and colon shortening, and reduced the concentrations of inflammatory markers IL-1β, IL-18, TNF-α, and IL-6. Proteomics and molecular docking identified NADPH oxidase 2 (NOX2) as a key target of XXLP intervention in mice with colitis. qRT-PCR, WB, IF, and TEM results further confirmed that XXLP effectively suppressed the expression of NOX2 and its associated protein levels. Sequencing analysis of 16S rRNA showed that XXLP significantly increased the relative abundance of beneficial bacterial genera (Muribaculaceae and Ruminococcaceae) while markedly reducing the levels of harmful bacteria (Enterobacteriaceae). Correlation analysis revealed that specific microorganisms were correlated with NOX2-related protein expression and severity of colonic inflammation. Conclusions: XXLP effectively alleviates colitis by suppressing inflammatory responses. Its mechanism involves regulating the NOX2/ROS/mitochondria/NLRP3 axis and altering gut microbiota composition, providing novel insights for colitis treatment. Full article