Search Results (88)

Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder, often accompanied by low-grade inflammation, visceral hypersensitivity and gut microbiota dysbiosis. In this study, the therapeutic potential of Lactiplantibacillus plantarum LPPerfectus001 (L. plantarum 001) was investigated to alleviate IBS symptoms. Using an Lipopolysaccharides (LPS)-induced RAW264.7 macrophage model, L. plantarum 001 demonstrated significant anti-inflammatory properties by inhibiting Nitric Oxide production and downregulating pro-inflammatory cytokines. Furthermore, in a mouse model of IBS induced by Citrobacter rodentium infection and water avoidance stress, L. plantarum 001 intervention reduced fecal moisture, improved intestinal barrier integrity via up-regulating of ZO-1 and MUC2, and attenuated visceral hypersensitivity. Transcriptomic analysis combining with RT-qPCR revealed that L. plantarum 001 modulated the NF-κB signaling pathway and Th1/Th2 cell differentiation, reducing expression of key inflammatory genes. Additionally, 16S rRNA sequencing showed that L. plantarum 001 restored gut microbiota diversity, enriched beneficial butyrate-producing Odoribacter, and suppressed pro-inflammatory Pseudomonadota. These findings suggested that L. plantarum 001 alleviates IBS through multi-targeted mechanisms involving barrier repair, microbiota modulation, and anti-inflammatory signaling, highlighting its potential as a probiotic therapy for IBS. Full article

Suillus luteus is a highly prized edible fungus and demonstrates significant potential in the field of bioremediation, particularly for soil restoration and pollution mitigation. However, systematic research on the structural characteristics of the bioactive polysaccharides and regulatory effects on gut microbiota metabolism remains scarce. In this study, S. luteus polysaccharide (SLP) was obtained by hot water extraction and the structural characteristics were systematically determined, as well as the regulatory function on gut microbiota metabolism in a tumor-bearing mice model. Results showed that SLP exhibited an average molecular weight of approximately 1.90 × 10⁶ Da with Fuc:Man:Glc:Gal molar ratio of 0.37:1.00:0.72:0.54. The polysaccharide predominantly employed β-(1→4)-Manp as the backbone with α-(1→3)-Fucp, α-(1→6)-Glcp, and α-(1→6)-Galp as side chains. SLP administration of 200 mg/kg in tumor-bearing mice exerted enrichment effects of intestinal probiotics, including Lactobacillus and Odoribacter, which were associated with alterations in glyoxylate and dicarboxylic acid metabolism, ultimately enhancing CD4⁺ T cell immunity and resulting in a tumor suppression rate of 53.14%. This study provides a theoretical foundation and supporting data for the development of S. luteus polysaccharide in the functional food field. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is associated with altered maternal gut microbiota and increased risk of large-for-gestational age (LGA) births. The contribution of gut microbiota to fetal overgrowth in GDM, independent of glycemic control, remains unclear. Methods: In this pilot longitudinal study, the gut microbiota of 18 women with GDM was followed from the second (2T) to the third trimester (3T). Maternal fecal samples were analyzed by 16S rRNA gene sequencing, and associations between microbial profiles and infant birth weight were examined. In addition, these associations were adjusted for pre-pregnancy body mass index (BMI) and gestational weight gain (GWG). Results: Maternal gut microbiota of LGA infants exhibited consistently lower microbial diversity, a reduced Bacillota/Bacteroidota ratio, and enrichment of pro-inflammatory taxa including Prevotella, Sutterella, and Bilophila. Short-chain fatty acids (SCFAs)-producing genera such as Acinetobacter, Odoribacter, Faecalibacterium, and Lachnoclostridium were depleted. Although Bilophila was identified as a third-trimester biomarker with LEfSE approach, its association with LGA disappeared after adjusting for BMI and GWG. Conversely, Nitrospirota, Polaromonas, Acinetobacter, and Aeromonas correlated negatively with LGA even after BMI and GWG adjustment. Conclusions: These findings suggest that specific maternal microbiota signatures, together with pre-pregnancy adiposity, influence fetal overgrowth in GDM and may serve as early biomarkers or targets for preventive interventions. Full article

Background/Objectives: Ulcerative colitis (UC) incidence has risen alarmingly worldwide, posing significant clinical challenges due to limitations of therapeutic efficacy and side effects of current drugs. While Polygonatum kingianum polysaccharides (PKPs) exhibit anti-inflammatory and antioxidant properties, their anti-colitis potential remains unexplored. This study aimed to validate the protective effects of PKPs against dextran sulfate sodium (DSS)-induced colitis and elucidate its mechanisms. Methods: Acute UC was induced in C57BL/6J mice by 3% DSS. PKPs (125 mg/kg) were administered via gavage for 10 days. Integrated approaches included histopathology, tight junction protein (ZO-1/Occludin/Claudin-1) immunohistochemistry, inflammatory/oxidative markers (ELISA), Nrf2 pathway proteins (Western blot), 16S rRNA gut microbiota sequencing, fecal untargeted metabolomics (UHPLC-MS), short-chain fatty acids (SCFAs) analysis and combined analysis. Results: PKPs significantly alleviated colitis phenotypes: reduced weight loss, lowered disease activity index (DAI), and attenuated colon shortening. They restored intestinal barrier integrity by upregulating tight junction proteins and reducing plasma Diamine Oxidase (DAO)/D-lactate (D-Lac)/Endotoxin (ET). PKPs suppressed pro-inflammatory cytokines (TNF-α/IL-1β/IL-6) while elevating IL-10, activated the Nrf2/HO-1/NQO1 antioxidant pathway, and reduced oxidative stress (MDA decreased, SOD/GSH increased). Multi-omics revealed PKPs enriched beneficial bacteria (Blautia, Odoribacter, Rikenellaceae_RC9_gut_group), restored SCFAs (acetate/propionate/butyrate), and modulated metabolic pathways (sphingolipid/linoleic acid metabolism). Conclusions: PKPs ameliorate DSS-induced colitis through multi-target mechanisms: (1) preserving intestinal barrier function, (2) suppressing inflammation and oxidative stress via Nrf2 activation, (3) restoring gut microbiota balance and SCFA production, and (4) regulating host-microbiota metabolic interactions. These findings support PKPs as a promising dietary supplement for UC management. Full article

Background/Objectives: Gut microbiota has been implicated in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular disease (CVD). This study aimed to identify associations between gut dysbiosis and MASLD, regarding body mass index (BMI) and subclinical coronary atherosclerosis (SCA). Methods: We conducted a cross-sectional study of 202 patients with MASLD who had no previous history of CVD. The severity of MASLD was evaluated using a magnetic resonance imaging-based method, and SCA was measured by assessing coronary artery calcification (CAC). Gut microbiota was assessed in fecal specimens using sequencing targeting the V4 region of the 16S rRNA gene. Results: Our results demonstrated that gut microbial profiles between low- and high-BMI groups (<30 vs. ≥30 kg/m²) differed significantly in beta-diversity, but not in alpha-diversity indices. At the genus level, we identified Megamonas, Sutterella, Catenibacterium, and Odoribacter, enriched in the high BMI group. Compared to the low CAC group (<100 AU), MASLD patients with high CAC scores (≥100 AU) exhibited enrichment in Ruminococcus gnavus, Bacteroides, and Lachnoclostridium, along with depletion of several short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibacterium. Multivariate analysis demonstrated that older age, the presence of diabetes, high BMI, fibrosis stage F3-F4, and high plasma trimethylamine oxide (TMAO) levels were independently associated with a high CAC score in patients with MASLD. Conclusions: These data indicated that gut dysbiosis and related metabolites, in association with advanced liver disease, were potential contributors to the progression of SCA in obese patients with MASLD. Full article

Pre-, pro-, and post-biotics have been used with success in several commercially grown insect species to increase yields and improve health outcomes. However, few studies have been published evaluating the use of nutritional supplements in Acheta domesticus. For this study, we fed day-old, farm-raised, A. domesticus a Saccharomyces cerevisiae postbiotic product at one of three different inclusion rates (0, 0.25, and 0.5%) for 32 days. Crickets were analyzed for differences in average weights, total biomass, percent survival, nutritional analyses, viral qPCR, and 16S/18S microbiomes. Crickets receiving the 0.5% inclusion feed trended towards having a higher total biomass (F = 3.823, p = 0.052) and a higher percent survival per bin (F = 3.667, p = 0.057) than the crickets receiving lower inclusion feeds. No significant differences were found in viral prevalences or loads. Significant changes to the microbiomes were mostly defined by increased abundances of presumed beneficial bacteria (Akkermansia, Catenibacillus, and Odoribacter) in the groups receiving postbiotics rather than by losses of harmful bacteria. For the 18S results, there was an increased abundance of a Gregarian apicomplexan, Leidyana erratica in the treatment groups. Overall, the 0.5% inclusion feed appeared to be beneficial and further study investigating other forms of feed additives is warranted. Full article

Background: Chronic alcohol intake impairs intestinal function, while L-theanine (LTA) may support intestinal health. However, the protective effects of LTA to chronic alcoholic intestinal injuries remain unclear. Methods: SD rats were administered LTA for 8 weeks and then co-administered Lieber–DeCarli liquid alcohol feed and LTA for 4 weeks to establish a chronic alcoholic intestinal injury model and investigate the mitigating influence of LTA on chronic alcoholic intestinal injury. Results: LTA alleviated duodenal pathology and intestinal permeability injury and reduced intestinal oxidative stress and inflammatory response, thereby mitigating chronic alcoholic intestinal injury. Additionally, LTA ameliorated disturbances in the gut microbiota induced by chronic alcohol intake by increasing the beneficial bacteria abundance (Ruminococcus and Odoribacter) and decreasing the harmful bacteria abundance (Enterococcus). Moreover, LTA altered the metabolic profiles associated with ethanol and linoleic (LA) and arachidonic acid (AA) metabolism. ADH6, ALDH2, and ACSS1 mRNA and protein levels were upregulated by LTA, whereas those for CYP2E1, FADS2, ALOX-5, and COX-1 were downregulated. Concurrently, LTA increased the levels of metabolites, such as acetyl-CoA, and decreased the levels of ethanol, acetaldehyde, acetic acid, LA, AA, PGE2, 13-HPODE, and LTB4. Conclusions: L-theanine mitigates chronic alcoholic intestinal injury by regulating intestinal alcohol and LA-AA metabolism. Our findings support the functional potential of the dietary supplement LTA and highlight its potential for addressing chronic intestinal injury caused by chronic alcohol intake. Full article

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder whose precise etiology remains unclear, though growing evidence implicates gut microbiota in its pathogenesis. This study aimed to investigate the role of gut microbiota in the onset and progression of RA by employing fecal microbiota transplantation (FMT) in a collagen-induced arthritis (CIA) mouse model using DBA/1J and Aire⁻/⁻ strains. Mice received FMT from healthy donors, treatment-naïve RA patients, or treated RA patients in relapse, followed by assessment of microbiota composition via 16S rRNA sequencing, arthritis severity scoring, histological evaluations, and systemic inflammatory markers. The findings revealed distinct microbiota clustering patterns post-FMT across experimental groups, highlighting strain-specific colonization effects. Notably, genera such as Bifidobacterium and Paraprevotella correlated positively with arthritis severity in DBA/1J mice, whereas Corynebacterium, Enterorhabdus, and Odoribacter exhibited negative correlations, suggesting potential protective roles. Despite these microbial differences, minor variations in arthritis scores, paw inflammation, or systemic inflammation were observed among FMT groups. This indicates that although gut microbiota alterations are associated with RA pathogenesis, further investigation with larger cohorts and comprehensive sequencing approaches is essential to elucidate the therapeutic potential of microbiome modulation in autoimmune diseases. Full article

Background/Objectives: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is treated using a combination of multiple antimicrobial agents and prolonged therapy; however, recurrence and reinfection rates remain high. Susceptibility to NTM-PD is not fully understood. We aimed to investigate the association between NTM-PD and gut microbiota and determine the impact of antimicrobial therapy on the composition of the gut microbiota. Methods: We analyzed the gut microbiota of 20 Japanese females with NTM-PD (mean age: 67.9 years; range: 50–80 years) at different treatment stages—before, during, and at recurrence—alongside 20 healthy individuals, using 16S rRNA gene amplicon sequencing. Results: Subgroup A (pre-treatment) showed a small difference in β-diversity when compared with the healthy control (HC) group, while no significant differences in α-diversity were observed. Subgroup B (during treatment) exhibited a larger difference in β-diversity compared with the HC group, along with a decrease in α-diversity. The α-diversity of the gut microbiota in Subgroup C (at recurrence) was lower than that in Subgroup A but higher than that in Subgroup B. In Subgroups A and C, the bacterial taxa Sutterella, Adlercreutzia, Odoribacter, and Prevotella had decreased relative abundance, while Erysipelatoclostridium, Massilimicrobiota, Flavonifractor, Eggerthella, and Fusobacterium had increased relative abundance compared to those in the HC group. Conclusions: The loss of normal resident gut bacteria may hinder reacquisition. Treatment may be associated with the persistence of a dysbiotic gut microbiota, fostering susceptibility to NTM-PD. Gut microbiota dysbiosis may heighten susceptibility to NTM-PD, complicate treatment outcomes, and increase the risk of microbiological recurrence following therapy. Full article

Objectives. The relationships among neuropathic pain, gut microbiota, microbiome-derived metabolites, and neuropathology have received increasing attention. This study examined the effects of two dosages of gingerol-enriched ginger (GEG) on mechanical hypersensitivity, anxiety-like behavior, gut microbiome composition and its metabolites, and neuropathology markers in female rats in the spinal nerve ligation (SNL) model of neuropathic pain. Methods. Forty female rats were assigned to 4 groups: sham-vehicle, SNL-vehicle, SNL+GEG at 200 mg/kg BW, and SNL+GEG at 600 mg/kg BW via oral gavage. All animals were given an AIN-93G diet for 5 weeks. Mechanical hypersensitivity was assessed by the von Frey test. Anxiety-like behavior was assessed by the open field test. Fecal microbiota composition and metabolites were determined using 16S rRNA gene sequencing and GC-MS, respectively. Neuropathology gene expression profiling of the amygdala was assessed by an nCounter^® Neuropathology pathway panel. Results. Both GEG-treated groups showed decreased mechanical hypersensitivity and anxiety-like behavior in the SNL model. Gut microbiome diversity in both GEG groups was decreased compared with untreated SNL rats. In the SNL model, phyla such as Bacteroidota, Proteobacteria and Verrucomicrobiota were decreased. Compared with the untreated SNL group, both GEG groups exhibited increased abundance of the phyla Bacteroidota (i.e., Rikenella, Alistipes, Muribaculaceae, Odoribacter), Firmicutes (i.e., UBA1819, Ruminococcaceae, Oscillospiraceae, Roseburia), and Verrucomicrobiota (i.e., Victivallis). GEG groups had higher levels of nine hydrophilic positive metabolites [val-glu, urocanic acid, oxazolidinone, L-threonine, L-norleucine, indole, imino-tryptophan, 2,3-octadiene-5,7-diyn-1-ol, and (2E)-3-(3-hydroxyphenyl) acrylaldehyde] and two hydrophilic negative metabolites [methylmalonic acid and metaphosphoric acid], as well as lower levels of five hydrophilic metabolites [xanthine, N-acetylmuramic acid, doxaprost, adenine, and 1-myristoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine]. Among the 770 neuropathology genes, 1 gene (PLA2G4A) was upregulated and 2 genes (CDK5R1 and SHH) were downregulated in SNL rats. GEG caused the upregulation of nine genes (APC, CCNH, EFNA5, GRN, HEXB, ITPR1, PCSK2, TAF9, and WFS1) and downregulation of three genes (AVP, C4A, and TSPO) in the amygdala. Conclusions. GEG supplementation mitigated pain-associated behaviors in female rats with neuropathic pain, in part by reversing the molecular neuropathology signature of the amygdala. This was associated with changes in the gut microbiome composition and fecal metabolites, which could play a role in mediating the effects of GEG on neuropathic pain. Full article

As an important intestinal microorganism, Odoribacter splanchnicus frequently appears in high-throughput sequencing analyses, although pure culture research on this microorganism is not as advanced. It is widely present in the mammalian gut and is closely associated with the health status of the host and the incidence of various diseases. In recent years, changes in the abundance of O. splanchnicus have been found to be positively or negatively correlated with health issues, such as obesity, metabolic syndrome, diabetes, and intestinal inflammation. It may exhibit a dual protective or promotional role in specific diseases. Thus, it may play an important role in regulating host metabolism, immune response, and intestinal homeostasis. Additional research has revealed that O. splanchnicus can synthesize various metabolites, especially short-chain fatty acids (SCFAs), which play a key role in promoting intestinal health, enhancing energy metabolism, improving insulin resistance, and regulating immune responses in the host. Therefore, O. splanchnicus is a strong candidate for “next-generation probiotics”, and its potential probiotic function provides novel ideas for the development of functional foods and the prevention and treatment of metabolic and intestinal inflammatory diseases. These findings can help develop new biological treatment strategies and optimize health management plans. Full article

Ulcerative colitis (UC) is a chronic and recurrent gastrointestinal disease that affects millions of humans worldwide and imposes a huge social and economic burden. It is necessary to find safe and efficient drugs for preventing and treating UC. The aim of this study was to determine whether ganoderic acid (GA), the main bioactive components of Ganoderma lucidum, has preventive and therapeutic effect on UC in a dextran sulfate sodium (DSS)-induced UC mouse model. Our experimental results showed that GA significantly ameliorated the body weight loss and disease activity index (DAI) of UC mice. GA significantly restored 11% of the colon length and 69% of the spleen index compared to UC mice. GA significantly decreased the intestinal inflammatory response and improved the barrier function of the intestine by upregulating the tight junction proteins Zonula occludens-1 (ZO-1), occludin and claudin-1. A co-housing experiment showed that gut microbiota accounted for the therapeutic activity of GA on UC, which was confirmed by fecal microbiota transplantation from GA-treated mice to the UC mice. Furthermore, 16S rDNA high-throughput sequencing of fecal bacteria showed that GA significantly enriched the abundance of Lactobacillus, Oscillospira, Odoribacter and Ruminococcus, which were positively correlated with colon length. Furthermore, this study found the functional metabolites, including Indole-3-acetaldehyde (IAAld), Glutamine (Gln) and Glutathione (GSH), reduced barrier damage in the Caco-2 cell model. In conclusion, this study suggests that GA could ameliorate UC by improving intestinal barrier function via modulating gut microbiota and associated metabolites. Full article

Different dietary fibers have distinct structures, leading to significant variations in their laxative effects. To explore how these structural differences impact constipation intervention, a 14-day study was conducted on loperamide-induced constipated mice using five dietary fibers: soluble dietary fiber from steamed sweet potato (SDF-S), oat β-glucan (OB), polydextrose (PD), arabinogalactan (AG), and inulin (IN). The results showed that four fibers, excluding PD, significantly improved gastrointestinal (GI) transit rate (p < 0.05), although PD had the highest fecal moisture, it was significantly different from the lowest IN (p < 0.05). AG and IN resulted in higher 6 h fecal weights compared to other fibers. SDF-S and OB were more effective in modulating serum levels of gastrointestinal hormones. The different monosaccharide compositions and glycosidic bonds of these fibers led to distinct changes in gut microbiota composition and SCFA profiles. Galactose and arabinose in AG were linked to increased abundance of Lachnospiraceae_UCG-006, Bacteroides, and Odoribacter, promoting butyrate fermentation, which is positively correlated with GI transit rate. Glucose in SDF-S, OB, and PD favored acetate fermentation positively correlated with fecal moisture. Fructose in IN encouraged the proliferation of Muribaculaceae_unclassified and Ruminococcus, associated with butyrate fermentation and increased 6 h stool weight, respectively. The β-glycosidic bonds in OB may lead to high butyrate production through the selective proliferation of Lachnospiraceae_unclassified. Minor components like fucose, rhamnose, and ribose were positively correlated with the abundance of Oscillospiraceae_unclassified, Anaerotignum, and Lachnospiraceae_unclassified. In conclusion, the unique monosaccharide compositions and glycosidic bond differences in dietary fibers selectively promote the proliferation of fiber-degrading and butyrate-producing bacteria, resulting in varied effects on constipation relief. Full article

Ulcerative colitis (UC) is a chronic and progressive inflammatory gastrointestinal disease closely associated with gut microbiota dysbiosis and metabolic homeostasis disruption. Although targeted microbial therapies are an emerging intervention strategy for inflammatory bowel disease (IBD), the mechanisms by which specific probiotics, such as Lactobacillus fermentum 016 (LF), alleviate UC remain unclear. The current study evaluated the effects of LF supplementation on gut health in a basal model using C57BL/6 mice. Subsequently, the preventive effects and mechanisms of LF supplementation on DSS-induced UC were systematically investigated. According to our findings, LF supplementation revealed immunoregulatory capabilities with significantly altered gut the composition of microbiota and metabolic activities, particularly enhancing tryptophan metabolism. In the UC model, LF supplementation effectively mitigated weight loss, increased the disease activity index (DAI), and alleviated diarrhea, rectal bleeding, and colon shortening. Moreover, it reduced colonic pathological damage and histological injury scores. LF intervention improved antioxidant markers and intestinal mucosal barrier function with the activation of the Nrf2–Keap1 signaling pathway and regulation of systemic inflammatory markers, i.e., IL-1β, IL-6, TNF-α, IFN-γ, IL-4, and IL-10. Importantly, LF supplementation reversed metabolic disturbances by significantly increasing the abundance of beneficial genera (e.g., g_Dubosiella, g_Faecalibaculum, g_Odoribacter, g_Candidatus_saccharimonas, g_Roseburia, and g_Eubacterium_xylanophilum_group) and elevating tryptophan metabolites (e.g., melatonin, kynurenic acid, 3-indoleacetic acid, 5-methoxytryptophan, and 5-hydroxyindoleacetic acid). In conclusion, Lactobacillus fermentum 016 exhibits potential for regulating gut microbiota homeostasis, enhancing tryptophan metabolism, and alleviating UC, providing critical insights for developing probiotic-based precision therapeutic strategies for IBD. Full article

Background/Objectives: Inflammatory bowel disease (IBD) is a persistent inflammatory condition affecting the gastrointestinal tract, distinguished by the impairment of the intestinal epithelial barrier, dysregulation of the gut microbiota, and abnormal immune responses. Cajanus cajan (L.) Millsp., traditionally used in Chinese herbal medicine for gastrointestinal issues such as bleeding and dysentery, has garnered attention for its potential therapeutic benefits. However, its effects on IBD remain largely unexplored. Methods: In this study, the major compounds from Cajanus cajan leaf extract (CCLE) were initially characterized by LCMS-IT-TOF. The IBD model was developed in C57BL/6 mice by administering continuous 4% (w/v) dextran sodium sulfate (DSS) aqueous solution over a period of seven days. The body weight, colon length, disease activity index (DAI), and histopathological examination using hematoxylin and eosin (H&E) staining were performed in the IBD model. The levels of the main inflammatory factors, specifically TNF-α, IL-1β, IL-6, and myeloperoxidase (MPO), were quantified by employing enzyme-linked immunosorbent assay (ELISA) kits. Additionally, the levels of tight junction proteins (ZO-1, Occludin) and oxidative stress enzymes (iNOS, SOD1, CAT) were investigated by qPCR. Subsequently, flow cytometry was employed to analyze the populations of various immune cells within the spleen, thereby assessing the impact of the CCLE on the systemic immune homeostasis of IBD mice. Finally, 16S rDNA sequencing was conducted to examine the composition and relative abundance of gut microbiota across different experimental groups. In addition, molecular docking analysis was performed to assess the interaction between the principal components of CCLE and the aryl hydrocarbon receptor (AHR). Results: We identified seven bioactive compounds in CCLE: catechin, cajachalcone, 2-hydroxy-4-methoxy-6-(2-phenylcinyl)-benzoic acid, longistylin A, longistylin C, pinostrobin, amorfrutin A, and cajaninstilbene acid. Our results demonstrated that oral administration of CCLE significantly alleviates gastrointestinal symptoms in DSS-induced IBD mice by modulating the balance of gut-derived pro- and anti-inflammatory cytokines. This modulation is associated with a functional correction in M1/M2 macrophage polarization and the Th17/Treg cell balance in splenic immune cells, as well as shifts in the populations of harmful bacteria (Erysipelatoclostridium and Staphylococcus) and beneficial bacteria (Odoribacter, unidentified Oscillospiraceae, Lachnoclostridium, and Oscillibacter) in the gut. Furthermore, cajaninstilbene acid, longistylin A, and longistylin C were identified as potential AhR agonists. Conclusions: The present results suggested that CCLE, comprising stilbenes like cajaninstilbene acid, longistylin A, and longistylin C, protects the epithelial barrier’s structure and function against DSS-induced acute IBD by restoring gut microbiota balance and systemic immune response as AhR agonists. Overall, CCLE represents a promising natural product-based therapeutic strategy for treating IBD by restoring gut microbiota balance and modulating systemic immune responses. Full article