Inflammatory bowel disease (IBD), including ulcerative colitis (UC), is a chronic inflammatory disorder with a rising incidence in pediatric populations. Immune factors play important roles in the pathogenesis of UC. This study aimed to explore the relationships of intestinal immune molecules CD27, CD20 and myeloperoxidase (MPO) with pediatric UC and their diagnostic values. In this study, gene expression data of 206 new-onset UC children and 20 non-IBD controls obtained from the NCBI Gene Expression Omnibus public database and immunohistochemistry analysis were used to evaluate CD27, CD20 and MPO expression in diseased intestinal tissues of UC children. And the diagnostic potentials of them for UC were analyzed using receiver operating characteristic curve and area under the curve (AUC). We found that CD27, CD20 and MPO mRNA and protein expressions were increased in the diseased intestinal tissues of UC children. CD27, CD20 and MPO showed good diagnostic potential for UC in children, with an AUC of 0.95 for CD27, 0.79 for CD20 and 0.92 for MPO, and combination of them had better diagnostic performance with an AUC of 0.98. Besides, they were associated with immune-related biological processes and pathways, and correlated with genes related to immune factors, intestinal epithelial barrier function, and intestinal fibrosis. In conclusion, our findings demonstrated that CD27, CD20 and MPO were increased in diseased intestinal tissues of UC children, and had good diagnostic performance for UC in children.

Colitis is an inflammatory disorder of the gastrointestinal tract. A widely consumed dietary nutrient, α-ketoglutarate (α-KG) is known to play a crucial role in cellular metabolism and provide protection to intestinal epithelium under various pathophysiological conditions. In this study, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was used to induce colitis in Wistar rats. After 36 hours of TNBS administration, the rats were orally treated with a solution of α-KG at 1 g/kg body weight for 5 days. Development of colitis was confirmed by observable physical symptoms of repeated loose blood-mixed stool, apathy for food and weight loss. Macroscopic inspection revealed an inflamed colonic surface with ulcerations. Histopathological observations included alterations in crypts-structure and disruption in both epithelial and mucosal layers of colon in colitis induced rats. Colitis resulted in elevated levels of pro-inflammatory cytokines, ER stress-mediated cell death and intrinsic apoptosis pathway. The ameliorative effects of α-KG against TNBS-mediated toxicity were confirmed through molecular technics and docking analysis. Additionally, there were no instances of toxicity of α-KG. Therefore, α-KG can be considered as a valuable therapeutic agent for further comprehensive research.

The inflammatory response is the core mechanism of the pathogenesis and symptoms of ulcerative colitis (UC), and inhibiting inflammation is a promising therapeutic approach to improving UC. Curcumin is considered a potential treatment for UC due to its significant anti-inflammatory and antioxidant effects. However, its bioavailability in the post-oral administration is limited. Therefore, the stability, sustained release, and colon targeting of curcumin in the treatment of UC have become a challenge. Herein, curcumin was efficiently filled in the porous structure of University of Oslo 66 (UiO-66). Amino-functionalized UiO-66 (MOF) was bound to hyaluronic acid (HA) via chemical crosslinking and electrostatic interactions. Polydopamine (PDA) layer was then applied to form Cur@MOF@HA-PDA NPs for colon targeting for UC treatment. Cur@MOF@HA-PDA NPs not only enhanced the stability of curcumin but also possessed acid resistance and reactive oxygen species (ROS) responsive properties, enabling it to be effectively delivered to the UC lesion site for curcumin release after oral administration, thereby enhancing the therapeutic effect. In vitro studies revealed that Cur@MOF@HA-PDA NPs possessed the ability to eliminate intracellular ROS, inhibit inflammatory (M1) polarization, and promote anti-inflammatory (M2) polarization. Additionally, in vivo experiments demonstrated that Cur@MOF@HA-PDA NPs could effectively alleviate the intestinal inflammatory symptoms of UC mice, promoting intestinal tissue repair. Furthermore, it was also confirmed that Cur@MOF@HA-PDA NPs achieved the treatment of UC by inhibiting inflammatory responses, modulating intestinal immune functions, and promoting the polarization of M2 macrophages. In short, Cur@MOF@HA-PDA NPs, as colon-targeted drug delivery nanosystems, offer a promising therapeutic strategy for the treatment of UC.

Acute lung injury (ALI) and ulcerative colitis (UC) are common inflammatory diseases with high mortality rates and unsatisfactory cure rates. Studies have indicated that inhibiting the expression and release of inflammatory factors holds potential for the treatment of inflammatory diseases. In this study, we designed and synthesized 28 derivatives of 6,7-disubstituted-4-cis-cyclohexanequinazoline and assessed their anti-inflammatory activities in mouse macrophages RAW264.7, J774A.1, and human monocyte THP-1 cell lines. Among them, derivative c1 was found to significantly inhibit the expression and release of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) induced by lipopolysaccharide (LPS) in the three cells mentioned above. It was also demonstrated that c1 could bind to IRAK4 and affect the expression of these two inflammatory factors by inhibiting the activation of the MAPK pathway. Furthermore, in vivo experiments revealed that c1 effectively ameliorated LPS-induced ALI and dextran sulfate sodium (DSS)-induced UC. Additionally, we evaluated the pharmacokinetic properties and in vivo safety of c1. Therefore, our research has identified the 6,7-disubstituted-4-cis-cyclohexanequinazoline derivative c1 exhibiting promising anti-inflammatory effects as a prospective anti-inflammatory drug candidate.

Polystyrene microplastics (PS-MPs) are common microplastics that pose significant health hazards to humans. Due to multifunctionality in the gut system, MP-associated damage and mechanisms require further exploration. This study was undertaken with the objective of elucidating the impact of PS-MP exposure on colonic inflammation in rats, and to explore its potential mechanisms. Forty-eight specific-pathogen-free Wistar male rats were administered 0, 0.5, 5, and 50 mg/kg/d of PS-MPs for 90 days, after which intestinal flora distribution, inflammatory factor levels in the colon, and TLR4/NF-κB/COX-2 gene levels were examined. To clarify whether PS-MPs directly infiltrate intestinal epithelial cells and induce cytotoxicity, human intestinal epithelial cells (HIECs) were exposed to a range of PS-MP concentrations (0 ∼ 100 μg/mL) for 48 h, and CCK-8 assays were conducted to assess the cell survival rates. In the colon tissue of rats exposed to PS-MP, goblet cells decreased, muscular layer arrangements were disordered, and disrupted and discontinuous crypt structures appeared in colon tissue, while high numbers of inflammatory cells infiltrated the colonic mucosa and submucosa. PS-MPs could accumulate in HIECs, and cell survival rates were decreased. In the colons of rats exposed to PS-MPs, the levels of Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were found to be elevated. Additionally, the mRNA and protein levels of TLR4/MyD88 in the colons of PS-MP-exposed rats exhibited a significant increase. Furthermore, the TLR4/NF-κB/COX-2 signaling pathway in rat colons was activated after MP exposure. When the TLR4/NF-κB/COX-2 signaling pathway was inhibited, the significant increases in IL-6 and TNF-α levels caused by PS-MPs were significantly reversed. PS-MP exposure also altered intestinal flora abundance in rats. Compared with the control group, the proportion of Firmicutes, Proteobacteria and Actinobacteria in PS-MPs exposed group was increased. In contrast, the proportion of Bacteroidetes and Verrucomicrobia decreased. Taken together, our results suggest that PS-MP could exert adverse effects on the gastrointestinal health of rats. Pro-inflammatory cytokine (IL-6, IL-1β and TNF-α) levels increased, and the TLR4/NF-κB/COX-2 signaling pathway was triggered. Thus, flora changes and increased intestinal inflammation may interact with each other.

a series of 6-substituted dihydrobenzophenanthridine alkaloids were synthesized by introduction of different functional groups to C-6 of dihydrobenzophenanthridine backbone. The preliminary anti-inflammatory activities of all compounds were screened by investigating the inhibitory ability on NO production in LPS-stimulated RAW 264.7 cells. Among synthesized compounds, 6-(N-phenyl)-aminocarbonyl methyl dihydrochelerythrine (compound 12b) showed increased anti-inflammatory ability and decreased cytotoxicity and could inhibit the expression of pro-inflammatory factors TNF-α and IL-6 in RAW 264.7 macrophages. The anti-inflammatory ability of compound 12b was further evaluated using DSS-induced mice colitis models based on colonic tissue damage assessment, histopathological assessment and immunohistochemical analysis. In vivoexperiment revealed that compound 12b had good alleviating effect on acute colitis in mice. In conclusion, compound 12b may be a promising anti-inflammatory lead compound.

Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract. Candida albicans, a common commensal fungus in the human gut, has been increasingly implicated in UC pathogenesis. Qi-Huang decoction (QHD), a traditional Chinese herbal formula known for its spleen-invigorating and purgative properties, is commonly used to restore gastrointestinal function.

This study investigates the therapeutic potential of QHD in treating colitis exacerbated by C. albicans and explores the underlying mechanisms of action.

A mouse model of colitis was induced using dextran sulfate sodium combined with gavage of C. albicans. Following QHD treatment, colitis severity was evaluated by measuring survival rate, body weight, disease activity index, colon length, and fungal burden, and through histopathological analysis using hematoxylin-eosin staining. The expression of proinflammatory genes IL-1β and TNF-α was quantified, alongside protein levels of key molecules involved in Dectin-1 signaling, including Syk, CARD-9, NLRP-3, Raf-1, and NF-κB. Barrier integrity markers, such as Occludin and Claudin-1, were also examined. To further elucidate QHD's mechanisms, Dectin-1 was inhibited using laminarin. In vitro experiments assessed QHD's antifungal activity against three Candida strains through microdilution, spot assays, and time-kill tests. RAW 264.7 macrophages were employed to study the exposure of fungal cell wall β-glucan and subsequent phagocytosis. Molecular docking simulations predicted interactions between QHD's active compounds and the Dectin-1 receptor.

QHD significantly mitigated colitis severity and reduced fungal burden in vivo. QHD enhanced β-glucan exposure on the fungal cell wall, thereby stimulating phagocytosis by RAW264.7 macrophages. QHD effectively activated Dectin-1-mediated signaling pathways and increased proinflammatory levels in RAW 264.7 cells. In colitis mice, QHD treatment markedly reduced inflammation and Dectin-1 signaling following fungal clearance. However, Dectin-1 inhibition with LAM neutralized QHD's therapeutic effects, highlighting the pathway's importance in mediating QHD's efficacy. Interestingly, QHD alone elevated Dectin-1, NF-κB, TGF-β, and IL-10 levels, whereas reduced IL-1β and TNF-α expression, suggesting a dual modulatory role in inflammation. Molecular docking confirmed a potential direct interaction between QHD's bioactive components and the Dectin-1 receptor.

QHD demonstrates promising therapeutic potential for managing Candida colitis by modulating immune responses and targeting Dectin-1 signaling pathways in clinical settings.

Traditional Chinese medicines, as a burgeoning field of medication, significantly alleviate ulcerative colitis (UC) by improving intestinal microbiota-metabolism. Our previous studies demonstrated the significant efficacy of Hudi Enteric-coated capsules (HDEC), Qingchang Wenzhong decoction (QCWZ), and Modified Wumei pill (MWMP) using a mouse model of colitis. However, the mechanism of these therapies through the modulation of microbiota-metabolism remains uncertain.

Three multicenter randomized controlled trials were designed to explore the effects of three therapies on the microbiota-metabolism of UC patients with different severity.

A total of 143 patients with different severities of UC were recruited from 10 hospitals. The clinical efficacy of HDEC for mild UC, QCWZ for moderate UC, and MWMP for severe UC (SUCs) was evaluated by colorectal Mayo scores and systemic inflammatory indicators. The 16S rRNA sequencing and metabolomics were used to analyze intestinal microbiota and metabolite profiles.

Three therapies used alone or combined with mesalazine (MS) were comparable to MS alone in improving Mayo scores and hematic inflammatory parameters. Microbial diversities and architectures of SUCs showed the greatest response to MWMP+MS than other medications, as reflected by the enriched Ruminococcus and Anaerostipes together with the reduced Enterococcus, Streptococcus, and Streptococcus anginosus. Furthermore, MWMP+MS boosted the production of the microbiota-derived short-chain fatty acids (SCFAs) of SUCs. These differential microbes and metabolites further displayed significant statistical relationships with clinical parameters.

Herbal therapies, especially MWMP+MS, effectively improve microbiota composition and SCFA metabolism, which correlates with the improvements of serum inflammatory markers and endoscopic findings in patients.

Inflammatory bowel disease (IBD) remains a pressing global health challenge, necessitating novel therapeutic strategies. Succinate, a metabolite known for its role in type 2 immunity and tuft cell activation in the small intestine, presents its potential in IBD management. However, its impact on colonic inflammation has not been explored. Here, we demonstrate that succinate administration induces a type 2 immune response, significantly alleviating dextran sulfate sodium (DSS)-induced colonic inflammation. Succinate enhances antibacterial capacity, reduces intestinal permeability, and reshapes the colonic cytokine milieu. Mechanistically, succinate promotes myeloid cell expansion in peripheral blood, mesenteric lymph nodes, and the colonic lamina propria. The protective effects of succinate were abolished in Ccr2-/- mice, confirming the role of monocyte recruitment, but persisted in Rag1-/- mice, indicating independence from adaptive immunity. Adoptive transfer of monocytes from succinate-treated donors mitigated intestinal inflammation in recipient mice. Transcriptomic analysis revealed heightened expression of Il1b and Il6, and higher lactate production in monocytes upon lipopolysaccharide (LPS) stimulation, highlighting a reprogrammed pro-inflammatory trained immunity phenotype. Finally, we identify the IL-4Rα/Hif-1α axis is critical for succinate-mediated protection. These findings reveal the ability of succinate to reprogram monocytes into protective intestinal macrophages via induction of type 2 response, restoring homeostasis through enhanced barrier function and immune modulation. Our study positions thus uncover succinate as a promising therapeutic candidate for IBD.

Four major types of resistant starch (RS1-4) are present in foods and can be fermented to produce short-chain fatty acids (SCFAs), alter the microbiome and modulate post-prandial glucose metabolism. While studies in rodents have examined the effects of RS4 consumption on the microbiome, fewer have examined its effect on gene expression in the cecum or colon or resistance to bacterial-induced colitis, and those that have, use diets that do not reflect what is typically consumed by humans. Here we fed mice a Total Western Diet (TWD), based on National Health and Nutrition Examination Survey (NHANES) data for 6-7 weeks and then supplemented their diet with 0, 2, 5, or 10% of the RS4, Versafibe 1490™ (VF), a phosphorylated and cross-linked potato starch. After three weeks, mice were infected with Citrobacter rodentium (Cr) to induce colitis. Infected mice fed the 10% VF diet had the highest levels of Cr fecal excretion at days 4, 7 and 11 post-infection. Infected mice fed the 5% and 10%VF diets had increased hyperplasia and colonic damage compared with the control. Changes in bacterial genera relative abundance, and alpha and beta diversity due to diet were most evident in mice fed 10% VF. Cr infection also resulted in specific changes to the microbiome and gene expression both in the cecum and the colon compared with diet alone, including the expression of multiple antimicrobial genes, Reg3b, Reg3g, NOS2 and Ifng. These results demonstrate that VF, a RS4, alters cecal and colonic gene expression, the microbiome composition and resistance to bacterial-induced colitis.

Acalypha australis L. (AAL), a traditional medicinal herb from the Euphorbiaceae family, has been widely used in Chinese medicine for its heat-clearing, detoxifying, and diuretic properties, as well as for treating gastrointestinal disorders such as diarrhea and dysentery. Its reported anti-inflammatory and hemostatic effects are closely linked to inflammatory pathways. While previous studies have demonstrated AAL's efficacy in acute colitis, its therapeutic potential in chronic colitis and the underlying mechanisms remain largely unexplored.

This study aims to investigate the therapeutic efficacy of AAL in dextran sulfate sodium (DSS)-induced chronic colitis and elucidate its anti-inflammatory and barrier-protective mechanisms, with a specific focus on the FABP4/PPARγ/NF-κB signaling pathway.

The chemical composition of AAL was characterized using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Chronic colitis was induced in mice through three cycles of DSS administration, and the therapeutic effects of AAL were evaluated by assessing body weight, Disease Activity Index (DAI), colon length, and pathological alterations. Enzyme-linked immunosorbent assay (ELISA) was used to quantify inflammatory cytokine levels. Immunohistochemistry and Western blotting were performed to assess mucosal barrier proteins, including Mucin 2 (MUC2), zonula occludens-1 (ZO-1), and Occludin, as well as key signaling proteins such as fatty acid-binding protein 4 (FABP4), peroxisome proliferator-activated receptor gamma (PPARγ), and phosphorylated P65 (p-P65). Proteomic analysis combined with Gene Set Enrichment Analysis (GSEA) was conducted to identify differentially expressed proteins and enriched pathways. The role of the FABP4/PPARγ/NF-κB axis was further validated using the PPARγ antagonist GW9662. Additionally, molecular docking and molecular dynamics simulations were employed to identify bioactive components in AAL and their interactions with FABP4 and PPARγ.

UPLC-QTOF-MS analysis identified 47 compounds in AAL, including flavonoids, terpenoids, and polyphenols. Bergaptol and corilagin were identified as major constituents with potential anti-inflammatory properties. AAL treatment significantly alleviated chronic colitis symptoms, as evidenced by reduced DAI scores, restoration of body weight, and improved colon length. Pathological and immunohistochemical analyses demonstrated that AAL preserved intestinal mucosal integrity by upregulating MUC2, ZO-1, and Occludin expression. Proteomic and GSEA analyses identified the FABP4/PPARγ/NF-κB pathway as a key target of AAL. Western blotting confirmed that AAL suppressed FABP4 expression, enhanced PPARγ levels, and reduced p-P65 expression, indicating inhibition of NF-κB activation. Notably, the therapeutic effects of AAL were abolished by GW9662, further validating the involvement of PPARγ signaling. Molecular docking and molecular dynamics simulations demonstrated strong binding affinities of bergaptol and corilagin to FABP4 and PPARγ, suggesting their role as active compounds responsible for AAL's therapeutic effects.

AAL effectively mitigates chronic colitis by preserving intestinal barrier integrity, suppressing inflammatory responses, and modulating the FABP4/PPARγ/NF-κB pathway. The bioactive compounds bergaptol and corilagin may contribute to these therapeutic effects, highlighting AAL as a promising natural therapeutic agent for ulcerative colitis.

Ulcerative colitis (UC) is characterized by chronic relapsing inflammation starting from the rectum and distal colon, which in severe disease cases may affect the entire colon. Intestinal stem cells (ISCs) directly isolated from inflamed UC colonic tissue specimens have been found to present an inflammatory gene expression profile. However, a critical issue is whether these cells retain memory of exposure to inflammation and/or therapeutics. Here, we aimed to investigate whether human intestinal epithelial cells retain the inflammatory state observed in vivo when expanded in vitro as 3D cultured organoids to assess their suitability for therapeutic transplantation. ISCs were isolated from non-inflammatory bowel disease controls (non-inflamed; n = 18), as well as from colonoscopy-obtained biopsies of the sigmoid colon from individuals diagnosed with UC (inflamed), who were glucocorticoid-naïve (n = 19). Moreover, ISCs were collected from all patients with inflammatory bowel disease following prednisolone treatment. Epithelial cells were cultured as 3D intestinal organoids in media to support stem cell maintenance and differentiation. Subsequently, the 3D intestinal organoids were harvested at the end of passage two for bulk RNA sequencing. The data revealed that the cellular phenotype of in vitro-cultured epithelial cells isolated from inflamed tissue did not maintain the hallmarks of inflammation observed in the ulcerated environment from which the cells were initially obtained. Our findings indicate that the autologous reinsertion of in vitro-expanded ISCs in active stages of UC may aid in intestinal healing, which calls for future clinical studies. Additionally, a link between organoid morphology and the inflammatory state of the tissue of origin was identified, as organoids derived from inflamed colon exhibited a lower degree of circularity.

Inflammation and oxidative stress are important features of traumatic ulcerative colitis (UC). Turmeric has been used as a dietary and functional ingredient for its potent anti-inflammatory effects in UC therapy. However, its practical effectiveness is hindered by limited reactive oxygen species (ROS) elimination properties. To address this, we constructed a unique treatment agent by growing cerium oxide (CeO2) nanocrystals on the membranes of turmeric-derived nanovesicles (TNVs), named as TNV-Ce. The resulted TNV-Ce could suppress inflammation and exhibit exceptional ROS-scavenging activity, which was validated both in lipopolysaccharide-induced macrophages and dextran sulfate sodium salt-induced chronic colitis mouse model. Following oral administration, TNV-Ce significantly accumulated at inflamed sites, effectively eliminating ROS and inhibiting pro-inflammatory cytokines for synergistic action against UC.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease. The etiology of UC is multifaceted, and the underlying pathogenesis remains incompletely understood. Pyroptosis, programmed cell death mediated by the gasdermins, is a pivotal driver of UC pathology due to its dual role in epithelial barrier disruption and inflammatory amplification. We previously showed that phenethyl isothiocyanate (PEITC), an isothiocyanate derived from cruciferous vegetables, alleviated acute liver injury in mice by suppressing hepatocyte pyroptosis. In this study we evaluated the therapeutic potential of PEITC in the treatment of UC and the underlying mechanisms. UC mouse models were established by administration of 2.5% (w/v) dextran sulfate sodium (DSS) daily for 7 days. PEITC (5, 10, or 20 mg·kg-1·d-1, i.g.) was given 2 days before the start of modeling, and the dosing lasted for a total of 10 days. We showed that during the progression of DSS-induced UC, the pyroptosis pathway was activated accompanied by elevated expression levels of thioredoxin-interacting protein (TXNIP) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3), as well as the activation of caspase-1, gasdermin D (GSDMD) and interleukin-1β (IL-1β). Treatment with PEITC dose-dependently reduced TXNIP and NLRP3 expression while inhibiting the cleavage of proteins associated with the pyroptosis pathway such as caspase-1, GSDMD, and IL-1β. We confirmed the inhibitory effect of PEITC on colonocyte pyroptosis in an in vitro model established in HT29 cells, where PEITC (0.2, 1, 5 µM) dose-dependently inhibited TXNIP and NLRP3 expression and the activation of pro-caspase-1, GSDMD and pro-IL-1β. We revealed that PEITC is directly bound to TXNIP and disrupted the interaction between TXNIP and NLRP3, leading to diminished cellular inflammation and oxidative stress levels. In conclusion, this study demonstrates that PEITC disrupts the interaction of TXNIP and NLRP3 by binding to TXNIP, inhibits NLRP3 activation and colonocyte pyroptosis, and thus effectively alleviates UC symptoms in mice. This study offers novel drug targets along with potential therapeutic candidates for the clinical prevention and treatment of UC.

Ulcerative Colitis (UC) is a chronic inflammatory condition resulting from an abnormal immune response to gut microbiota, leading to cytokine dysregulation, including elevated interleukin-23 (IL-23) levels. Emerging evidence suggests that vitamin D (VD) plays a crucial role in immune modulation. However, its correlation with IL-23 in UC is not well addressed. This study aims to elucidate the relationship between serum VD and IL-23 levels in UC patients. We included forty-four UC patients and forty-four healthy controls. VD insufficiency was more common in UC patients (n = 14) compared to controls (n = 5). Significant increases in IL-23 levels were observed from remission (46.6 ± 4.3 pg/mL) to severe stages (218.5 ± 62.41 pg/mL), while VD levels did not show a similar trend. IL-23 levels also rose significantly with disease extent, from proctitis to pancolitis. A significant negative correlation was found between VD and IL-23 levels (r = -0.3175; P = 0.035). IL-23 and pulse rate were significant predictors of UC in our cohort. Our findings highlight VD insufficiency to be prevalent in UC patients, with VD levels negatively correlating with IL-23 levels, which increase with disease severity and extent. Further, understanding the interplay between VD and IL-23 will help design therapeutic interventions to modulate immune response and disease progression.

Understanding the molecular mechanisms that regulate intestinal epithelial cell (IEC) renewal provides potential targets for inflammatory bowel disease (IBD). Growing evidence has highlighted the importance of epithelial signals in regulating intestinal stem cell (ISC) differentiation. However, it remains unclear which IEC-derived cytokines can precisely regulate ISC commitment toward specific mature cells. Here we systematically analyze all fibroblast growth factors (FGFs) expression and find that colonic FGF1 levels are inversely correlated with the severity of IBD in mouse models and patients. IEC-specific Fgf1 deletion leads to impaired goblet cell differentiation and exacerbated colitis, while pharmacological administration of recombinant FGF1 (rFGF1) alleviates colitis by enhancing goblet cell differentiation and improving colonic epithelial integrity. Mechanistic studies reveal that rFGF1 directs ISC differentiation toward goblet cells via FGFR2-TCF4-ATOH1 signaling axis. In conclusion, our study identifies an epithelial niche-derived FGF1 that regulates ISC commitment toward goblet cells, shedding light on strategies for treating IBD.

Bangle, a perennial herb belonging to the ginger family with antiinflammatory properties, has been under-researched in ulcerative colitis. This study aimed to investigate the effects of Bangle extract (BaE) on inflammation and autophagy in the colons of mice with dextran sulfate sodium (DSS)-induced colitis. Male C57BL/6J mice were assigned to four groups: control, DSS + 0% BaE, DSS + 1% BaE, and DSS + 3% BaE. The BaE groups were fed BaE diets for 3 weeks, followed by an additional week of BaE diets and 3% DSS in the water. The control group received a standard chow diet and water for 4 weeks. Plasma leucine-rich α2-glycoprotein (LRG) levels, macrophage count, and the levels of nuclear factor kappa B (NFκB) p65, tumor necrosis factor-α (TNF-α), adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), mechanistic target of rapamycin (mTOR), and autophagy markers were analyzed. In the DSS + 0% BaE group, LRG levels, macrophage count, NFκB p65 protein, and TNF-α mRNA levels were significantly higher compared to the control group. However, in the DSS + 3% BaE group, these levels were significantly reduced. Additionally, PGC-1α and phosphorylated AMPK levels were increased, while phosphorylated mTOR levels decreased, and autophagy marker microtubule-associated protein 1 light chain 3B (LC3B)-II levels were increased in the DSS + 3% BaE group. BaE may ameliorate colonic inflammation and upregulate autophagy via the modulation of the AMPK/mTOR/NFκB pathway in DSS-induced colitis.

The KunMingShanHaiTang Formula (KMSHTF), adjusted by Professor Zhong Chuanhua for the treatment of ulcerative colitis (UC), is the work of a renowned veteran practitioner of Chinese medicine. However, its specific mechanism remains unknown. Consequently, it is intriguing to investigate the molecular mechanism by which KMSHTF treats UC. To elucidate the mechanism of KMSHTF in the treatment of UC in rats. Initially, the active ingredients and key target genes of KMSHTF in treating UC were analyzed using network pharmacology. Protein-Protein interaction and gene enrichment analyses were performed to predict key targets and pathways. Subsequently, UC rats were treated with KMSHTF, and the expression proteins in intestinal tissue were detected. Finally, the active compounds of KMSHTF intreating ulcerative colitis were further screened using Molecular Docking, and their pharmacological effects were validated through cell experiments. A total of 47 active compounds and 365 key target genes of KMSHTF for UC treatment were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,along with the GeneCards database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment Analysis revealed that KMSHTF exerted its therapeutic effects on UC through regulating multiple pathways. In this study, the HIF-1α pathway was selected as the main molecular pathway of KMSHTF treating UC, and further validation was conducted through in vivo and in vitro experiments.Animal studies revealed that KMSHTF significantly ameliorated UC symptoms in rats, including diarrhea,rectal bleeding and specific pathological alterations in the intestinal wall. Furthermore, KMSHTF reduced pro-inflammatory cytokines IL-6 and TNF-α, up-regulated IL-4 of M2 macrophages and down-regulated iNOS and IL-1β of M1 macrophages. Additionally, it decreased the expression levels of HKII and GLUT1 related HIF-1α pathway. The three active compounds of KMSHTF, Baicalein, Palmatine and Triptonide-were selected based on their strong binding affinity with HIF-1α and HKII through computational molecular docking. Cellular experiments demonstrated that each of these compounds downregulated the protein expression levels of HIF-1α, HKII, GLUT1 and IL-6 in an intestinal wall cell model. Of Note, Baicalein exhibited the most pronounced effect. However, the overexpression of HIF-1α reversed the Baicalein-induced downregulation of HKII, GLUT1 and IL-6 at the protein level in vitro. KMSHTF may modulate macrophage metabolism to promote M2 polarization through the HIF-1α pathway, thereby contributing to its therapeutic efficacy in ulcerative colitis (UC). Baicalein, Palmatine, and Triptonide are the three core active compounds of KMSHTF that primarily contribute to this hypothesis.

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that poses significant therapeutic challenges due to the intestinal mucus and epithelial barriers. In this study, ultra-small zwitterionic nanoparticles (HC-CB NPs) is developed based on glutathione (GSH)-responsive hyperbranched polycarbonate to enhance the oral delivery of drugs and overcome these physiological barriers. HC-CB NPs demonstrate high colloidal stability across a wide range of pH environments and physiological fluids, preventing premature drug release within the gastrointestinal tract. The ultra-small sized HC-CB NPs demonstrate minimal mucin adsorption and effectively penetrate through the mucus layer, and the zwitterion surface further facilitate epithelial barrier crossing via the proton-assisted amino acid transporter 1 (PAT1) pathway. HC-CB NPs mediate enhanced macrophage uptake via monocarboxylate transporters (MCTs) pathway and ultimately improved therapy efficacy on colitis. The in vivo results reveal that FK506-loaded HC-CB NPs (HC-CB NPs@FK506) significantly reduce inflammatory markers (TNF-α, IL-6) and myeloperoxidase (MPO) levels, while promoting epithelial integrity by increasing E-cadherin expression. This study offers a promising approach to overcoming intestinal barriers in oral UC treatment, offering biocompatibility and potential for clinical translation. STATEMENT OF SIGNIFICANCE: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that poses significant therapeutic challenges due to the intestinal mucus and epithelial barriers. This study explores an oral UC therapy using ultra-small zwitterionic nanoparticles (HC-CB NPs) constructed from GSH-responsive hyperbranched polycarbonate. Compared to existing strategies, HC-CB NPs demonstrate minimal mucin adsorption and effectively penetrate through the mucus layer, and the zwitterion surface further facilitate epithelial barrier crossing via the proton-assisted amino acid transporter 1 (PAT1) pathway. Additionally, HC-CB NPs mediate enhanced macrophage uptake via monocarboxylate transporters (MCTs) pathway, resulting in improved therapeutic efficacy. These findings underscore the potential of HC-CB NPs as a transformative platform for overcoming intestinal barriers in UC treatment.

Inflammatory bowel disease (IBD) patients with sarcopenia are at increased morbidity risk. The aim of this study was to assess the prevalence of sarcopenia in IBD outpatients using both morphological and functional criteria.

In this prospective cohort study, all IBD patients admitted to the day hospital unit between March 01 and 31, 2023 were included. Muscle mass and function were evaluated using bioelectrical impedance analysis and handgrip strength measurement, respectively. Probable sarcopenia was defined as reduced handgrip strength (<16-27 kg). Myopenia was defined by a low appendicular muscle mass index (<5.5-7 kg/m²). Sarcopenia was diagnosed based on the coexistence of reduced muscle strength and muscle mass. Disease activity, therapeutic changes, hospitalizations, and IBD-related surgeries were assessed at month 6.

Sixty patients with either Crohn's disease (CD, 52 %) or ulcerative colitis (48 %), with a median age of 37 years (interquartile range [IQR]: 28-54), were included. Fifty-five percent were women. Most patients were in remission (67 %, n = 40). In CD patients, the involvement was ileocolic (48 %), ileal (35 %), or colonic (16 %). A history of IBD-related digestive surgery was noted in 30 % of cases. The median body mass index [BMI] was 24 (IQR: 21-27). The prevalence of sarcopenia, probable sarcopenia, and myopenia was 10 %, 18 %, and 20 %, respectively. Sarcopenic patients were significantly older (59 vs 36 years, p = 0.01), had a longer disease duration (20 vs 8 years, p = 0.003), were more likely to have associated joint inflammation (27 % vs 6 %, p = 0.01) and CD (80 % vs 49 %, p = 0.36). Myopenia was significantly associated with a history of surgery (67 % vs 21 %, p = 0.004) and a lower BMI (21 vs 24, p = 0.001).

In this prospective cohort of IBD outpatients, 10 % and 20 % of patients had sarcopenia and myopenia, respectively. Screening for sarcopenia therefore seems essential in this population, including in stable outpatients in remission who do not meet malnutrition criteria and in overweight patients, as according to the literature, sarcopenia is associated with poorer clinical outcomes and increased postoperative complications. Interventional studies are needed to assess the impact of multidisciplinary treatment of sarcopenia on quality of life and disease progression.

Pediatric gastroenterology (GI) care in low- and middle-income countries (LMICs) faces substantial challenges due to limited healthcare infrastructure, inadequate resources, and a shortage of specialized healthcare professionals. These challenges lead to delayed diagnoses and treatment, exacerbating the morbidity and mortality associated with pediatric GI diseases, which include both infectious conditions like diarrhea and chronic conditions such as inflammatory bowel disease (IBD) and liver diseases.

The aim of this review is to examine the current state of pediatric GI care in LMICs, identify the key challenges these regions face, and propose strategies to improve healthcare outcomes for children affected by GI disorders.

This review synthesizes existing literature from a range of LMICs, analyzing factors such as the economic burden of healthcare, barriers to access, the availability of diagnostic and therapeutic services, and the state of pediatric hepatology and endoscopy. Studies included in the review were sourced from countries in sub-Saharan Africa, South Asia, and other LMIC regions, focusing on pediatric GI disorders and healthcare delivery.

Economic burden: Families in LMICs face significant economic barriers in accessing pediatric GI care, with treatment costs often exceeding household income, especially in private healthcare settings. Healthcare access: Limited access to healthcare facilities, especially in rural areas, coupled with the shortage of trained pediatric gastroenterologists and necessary medical equipment, leads to delayed diagnoses and inadequate care for conditions like Helicobacter pylori infections and chronic liver diseases. Sanitation and infectious diseases: Poor sanitation and lack of access to clean water contribute to the high prevalence of diarrheal diseases, which can be reduced through better hygiene practices and improved infrastructure. Training gaps: The shortage of trained healthcare workers, particularly pediatric specialists, hinders effective care delivery, with healthcare workers often overburdened due to workforce migration and low salaries. Hepatology and endoscopy: Pediatric hepatology, especially in the context of viral hepatitis, and the availability of pediatric GI endoscopy are severely limited in LMICs, further complicating the management of liver diseases and GI conditions in children.

Improving pediatric GI care in LMICs requires addressing systemic challenges such as inadequate healthcare infrastructure, limited financial resources, and a shortage of trained professionals. Prevention strategies like vaccination, sanitation improvements, and public health education campaigns are crucial for reducing the prevalence of pediatric GI diseases. In addition, enhancing access to specialized training, healthcare services, and diagnostic tools will improve outcomes for children in resource-limited settings. Continued international collaboration and investment in local healthcare systems are essential for creating sustainable solutions and bridging the gap in pediatric GI care.

Differentiating Crohn's disease from ulcerative colitis may be a diagnostic challenge for clinicians due to overlapping features. However, the correct diagnosis may guide treatment options and considerations regarding surgery. This study reviews the common components of diagnostic evaluation of inflammatory bowel disease. Additionally, this article provides a basis of understanding for the more complex aspects of the disease to be discussed in subsequent studies.

Ulcerative colitis (UC) is a refractory inflammatory disease that affects the rectum and colon, with pivotal involvement of the rectal environment in relapse initiation. This study was conducted in two phases to examine the differences in gene expression between the rectum and colon and to identify relapse factors.

In ***Study 1, RNA sequencing was performed on biopsies from the colon and rectum of patients with active UC, those with remission UC, and controls. In Study 2, the mucosal impedance (MI) values reflecting mucosal barrier function and the mRNA expression of tight junction proteins and inflammatory cytokines were examined in 32 patients with remission UC and 22 controls. Relapse was monitored prospectively.

In Study 1, comprehensive genetic analysis using RNA sequencing revealed distinct gene profiles in the rectum and sigmoid colon of patients with remission UC. The rectum of these patients exhibited an enriched immune response and apical junction phenotype with persistent upregulation of CLDN2 gene expression. In Study 2, even in patients with remission UC, the MI values in the rectum, but not in the sigmoid colon, were significantly decreased, whereas they were negatively correlated with CLDN2, IL-1β, and IL-6 expressions.

The status of the rectum in patients with remission UC differs from that of the colon, with microinflammation and impaired mucosal barrier function, which are associated with the upregulation of CLDN2, playing a role in relapse.

Aim: Etrasimod and ozanimod are selective sphingosine 1-phosphate receptor modulators targeting the S1P1,4,5, and S1P1,5 receptors, respectively, for the treatment of patients with moderately to severely active ulcerative colitis (UC). No head-to-head trial data exist between the two treatments. We compared these treatments indirectly using key efficacy outcomes from pivotal trials with induction and maintenance phase data adjusting for differences in clinical trial design and populations. Materials & methods: Individual patient data for etrasimod were matched to published aggregate data of ozanimod by key baseline characteristics. An anchored matching-adjusted indirect comparison (MAIC) was conducted for the induction period. An unanchored MAIC was utilized during the maintenance period due to differences in placebo arms between trials as a result of differing trial designs. Matching characteristics measured at baseline were age, sex, corticosteroid use, duration of UC, biologic exposure, modified Mayo score, and presence of left-sided colitis. Outcomes were clinical response and clinical remission for the induction period, and clinical response and clinical remission among induction phase responders for the maintenance period. Two sensitivity analyses were conducted. The first matched on prior TNFi exposure rather than biologic exposure, the second sensitivity analysis included an induction only etrasimod trial (ELEVATE UC 12). Results: There were no significant differences between etrasimod and ozanimod at the end of the induction period for clinical response and clinical remission, respectively (relative risk [RR] 0.98 [95% confidence interval (CI): 0.76-1.33], RR: 1.25 [95% CI: 0.71-2.92]). At the end of maintenance, etrasimod demonstrated improved outcomes compared with ozanimod for both clinical response (RR: 1.18 [95% CI: 1.05-1.30]) and clinical remission among induction phase responders (RR: 1.33 [95% CI: 1.12-1.55]). In the sensitivity analysis that matched on prior TNFi exposure rather than biologic exposure, there were no notable differences compared with the primary analyses. In the sensitivity analysis pooling ELEVATE UC 12 and ELEVATE UC 52 data, results were similar for clinical response (RR: 0.90 [95% CI: 0.75-1.10]) but etrasimod showed reduced efficacy for clinical remission (RR: 0.72 [95% CI: 0.50-1.12]) compared with the primary analysis, though overall remained not significantly different from ozanimod. Conclusion: MAIC results suggest that patients receiving etrasimod have similar induction results but are more likely to have clinical response and clinical remission at the end of the maintenance phase compared with patients receiving ozanimod. Despite the approach to ensure similarity between the trials by weighting, residual imbalance is possible, and results should be interpreted in the context of the assumptions.

Ulcerative colitis (UC) is a lifelong chronic inflammatory disease that is characterized by the absence of specific markers for diagnosis and prognosis. TPM3 is an integral component of the thin filament, responsible for the structural stability of actin filaments and modulation of cytoskeletal function. This study investigated the regulatory role of TPM3 in UC and its potential mechanisms.

At the clinical level, TPM3 levels were assessed in serum and mucosal tissues of UC and other enteric disease. At the cellular level, the effects of TMP3 overexpressing lentivirus on Caco-2 cell phenotype and the barrier of IL-1β-induced UC model were explored. At the animal level, the effects of TMP3 overexpressing lentivirus on symptoms and colonic damage in a DSS-induced UC model were explored.

TPM3 expression in serum of UC patients was significantly lower than that of other enteric disease, and TPM3 levels in the intestinal mucosa showed a negative correlation with the Mayo score of UC patients. TPM3 overexpression alleviates IL-1β-induced apoptosis and inhibition of invasion and migration in UC model in vitro. In monolayer Caco-2 cells, TPM3 overexpression rescued the IL-1β-induced decrease in transepithelial electrical resistance and tight junction markers (ZO-1 and Occludin) and increase in permeability. In animal experiments, TPM3 overexpression increased body weight and colon length and decreased disease activity index in a DSS-induced UC model. In tissue staining, it alleviated pathological damage and upregulated Occuludin and TPM3 levels in the colon.

TPM3 levels correlated with UC disease course and TPM3 overexpression alleviated symptoms/phenotypes and barrier damage in UC models in vivo and in vitro. TPM3 may serve as a potential novel biomarker for UC diagnosis and prognosis.

Modified Shi Hui San (MSHS) has shown excellent therapeutic effects on ulcerative colitis (UC) patients clinically in China. However, the exact mechanism underlying its effect remains unclear and needs to further investigation.

This study aimed to investigate the therapeutic effects of modified Shi Hui San decoction (MSHSD) in murine experimental colitis and explore its underlying mechanisms.

To examine the effects of MSHSD on UC, a murine model of colitis was induced using 2.5 % dextran sodium sulfate (DSS). The mice were then treated with MSHSD at the doses of 6.25 or 25 g/kg for 10 days. The progression of colitis was evaluated through clinical symptoms, histopathological analysis, evaluation of mucosal barrier integrity, biochemical assays, and analysis of the gut microbiota composition.

MSHSD administration markedly ameliorated experimental colitis in DSS-treated mice by suppressing inflammation, restoring the intestinal mucus barrier, alleviating oxidative stress, and reestablishing immunity. More importantly, it transformed the gut microbiota structure from an imbalanced state to a normal state.

These findings for the first time extend our understanding of the mechanisms, by which MSHSD ameliorates murine experimental colitis, and support the clinical use of MSHS for UC treatment.

Therapeutic drug monitoring is important for optimizing anti-tumor necrosis factor-α (TNF-α) therapy in inflammatory bowel disease. However, the exposure-response relationship has never been assessed in pouchitis.

To explore associations between anti-TNF-α drug concentration and pouchitis disease activity in patients with a background of ulcerative colitis.

A retrospective, multicenter, cross-sectional study was conducted in adult patients with pouchitis requiring anti-TNF-α treatment. Rates of clinical and endoscopic remission were calculated, and drug concentrations during maintenance therapy were compared between remission and non-remission cohorts.

Sixty-three patients were included: median age, 48 years (IQR 36-59) and median time since pouchitis diagnosis, 7 years (IQR 2-13). Patients received infliximab, n = 27 (43%), adalimumab, n = 29 (46%), or both n = 7 (11%). Thirty-two (51%) patients received concomitant immunomodulation. Median infliximab trough concentrations (mg/ml) were similar between patients in clinical remission (n = 21) vs non-remission (n = 11), 5.3 vs. 4.4, p = 0.73. For adalimumab, median drug concentrations did not significantly differ between remission/non-remission groups based on clinical (n = 18/18), 11.4 vs 7.6, p = 0.32, or endoscopic assessment, (n = 7/29), 9.0 vs. 7.8, p = 0.78. Four patients had positive anti-drug antibodies with undetectable drug concentration.

In a cohort of patients with pouchitis, higher anti-TNF-α drug concentrations were not associated with more clinical or endoscopic remission.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD), accompanied by intense inflammation, oxidative stress, and intestinal microbiota dysbiosis. Current treatments using chemotherapeutic drugs or immunosuppressants have limited effectiveness and side effects. Therefore, the development of safe, effective, and multi-targeting therapies for IBD is of great importance. Momordica charantia exhibits antioxidant, anti-inflammatory, and intestinal microbiota-regulating properties, suggesting that Momordica charantia-derived extracellular vesicles (MCEVs) have the potential for UC management.

We extracted MCEVs using differential centrifugation and density gradient centrifugation. The results showed that MCEVs possessed high purity, even particle size, and excellent stability. In vitro, MCEVs were shown to inhibit macrophage inflammatory responses, scavenge reactive oxygen species (ROS), and protect cells from oxidative damage. Transcriptomics analysis revealed that MCEVs may alleviate mitochondria-dependent apoptosis by safeguarding the integrity of the mitochondrial structure and regulating the expression of apoptosis-related proteins. Furthermore, all components of MCEVs contributed to their pharmacological activity. In vivo, MCEVs had better retention in the inflamed colon and significantly alleviated UC through a comprehensive renovation of the intestinal microenvironment.

These findings suggested that MCEVs own considerable potential as natural nanotherapeutics for UC treatment.

Oxidative stress, dysbiosis, and immune dysregulation have been confirmed to play pivotal roles in the complex pathogenesis of inflammatory bowel disease (IBD). Herein, we design copper ion-luteolin nanocomplexes (CuL NCs) through a metal-polyphenol coordination strategy, which plays a multifaceted role in the amelioration of IBD. The fabricated CuL NCs function as therapeutic agents with exceptional antioxidant and anti-inflammatory capabilities because of their great stability and capacity to scavenge reactive oxygen species (ROS). It can effectively modulate the inflammatory microenvironment including facilitating the efficient reduction of pro-inflammatory cytokine levels, protecting intestinal epithelial cells, promoting mucosal barrier repair and regulating intestinal microbiota. In addition, CuL NCs have been found to enhance cellular antioxidant and anti-inflammatory capacities by regulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) oxidative stress pathway and nuclear factor kappa B (NF-κB) signaling pathway, respectively. Notably, CuL NCs demonstrate significant prophylactic and therapeutic efficacy in mouse models with typical IBD, including ulcerative colitis (UC) and Crohn's disease (CD). This study provides a new approach for building multifaceted therapeutic platforms for natural products to treat IBD.

While metformin has been shown to alleviate dextran sulfate sodium (DSS)-induced colitis in murine models, the mechanisms underlying its anti-inflammatory and barrier-restorative effects remain poorly defined. This study investigates the role of acetyl coenzyme A (acetyl-CoA)-dependent STAT3 acetylation in mediating metformin's therapeutic actions, with the goal of identifying novel molecular targets for ulcerative colitis (UC) treatment.

Acute colitis was induced in wild-type C57BL/6J mice via oral DSS administration, followed by daily intraperitoneal metformin treatment. Intestinal inflammation, barrier integrity, and STAT3 signaling were assessed using histopathology, western blotting, and transmission electron microscopy. To validate STAT3's critical role in colitis pathogenesis, intestinal epithelium-specific STAT3 knockout mice were employed, enabling targeted investigation of STAT3 acetylation and its regulation by metformin.

Metformin attenuated DSS-induced colitis by suppressing pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), reducing epithelial apoptosis, and restoring tight junction proteins (ZO-1, E-cadherin, Occludin). Mechanistically, metformin reduced acetyl-CoA levels, thereby inhibiting STAT3 acetylation and downstream pathway activation. The pivotal role of STAT3 in colitis progression was confirmed using STAT3 knockout mice, as the therapeutic effects of metformin were significantly diminished in the absence of STAT3-mediated inflammatory signaling.

This study identifies acetyl-CoA-dependent STAT3 acetylation as a novel mechanism through which metformin ameliorates intestinal inflammation and barrier dysfunction. These findings not only advance our understanding of metformin's immunomodulatory properties but also highlight the therapeutic potential of targeting acetyl-CoA metabolism in UC.

Ulcerative colitis (UC) is a chronic autoimmune disease and seriously affects the normal life of patients. Conventional therapeutic drugs are difficult to meet clinical needs. Traditional Chinese medicine (TCM) ingredients could effectively alleviate the symptoms of UC by anti-inflammatory, anti-oxidative, regulating the gut microbiota, and repairing the colonic epithelial barrier, but their low solubility and bioavailability severely limit their clinical application. Nano-drug delivery systems (NDDS) combined with TCM ingredients is a promising option for treating UC, and they could significantly enhance the stability, solubility, and bioavailability of TCM ingredients. The review describes the anti-UC mechanisms of TCM ingredients, systematically summarizes various kinds of NDDS for TCM ingredients according to different routes of administration, and highlights the advantages of NDDS for TCM ingredients in the treatmentof UC. In addition, we discuss the limitations of existing NDDS for TCM ingredients and the development direction in the future. This review will provide a basis for the future development of anti-UC NDDS for TCM ingredients.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by chronic inflammation of the colonic mucosal lining.

This study aimed to examine unmet needs among patients with UC in Spain.

Data were analyzed from the Adelphi Real World IBD Disease Specific Programme™, a cross-sectional survey of physicians and patients with IBD in Spain between October 2020 and March 2021.

Physicians reported patient clinical characteristics, disease severity, treatment patterns and satisfaction, symptoms, and flare and remission status. Patients were then invited to voluntarily self-complete a form reporting health-related quality of life (HRQoL) and work productivity/activity impairment. Analyses were descriptive.

Overall, 57 physicians reported data for 410 patients with UC presenting a high disease severity profile. The mean (standard deviation) patient age was 45 (15) years, with 88% presenting with moderate-to-severe UC at diagnosis. In the survey, 75% and 63% of patients were treated with conventional therapy and biologics, respectively. After treatment initiation, patients had lower disease severity, but 29% of patients had moderate-to-severe disease despite receiving biologics or Janus kinase inhibitors. Overall, 81% of patients and 86% of physicians were satisfied with treatment. Among patients classified as having moderate-to-severe UC, commonly reported symptoms included abdominal pain (41%), bowel urgency (37%), and bloody diarrhea (37%). The mean number of flares experienced in the past year was 1.7, lasting on average >30 days. Consequently, the HRQoL of these patients was impaired.

While disease severity appeared to be lower after the initiation of current treatment, and despite the high prevalence of treatment satisfaction, almost a third of patients remained classified as moderate-to-severe, experiencing symptoms, flares, and impaired HRQoL. Therefore, there is a need for new therapeutic alternatives to target patient unmet needs.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that seriously affects the life expectancy of patients. Although increasingly sophisticated combinations of drugs can alleviate symptoms, 10-20% of patients still do not respond well. Therefore, it is necessary to further explore the pathogenesis and potential biomarkers of UC. Many clues have suggested the important value of mitochondrial metabolism in UC, but its role and related targets need to be further explored. By public database data, we identified differentially expressed mitochondrial metabolism related genes (MMRG) in UC. Subsequently, we identified biomarkers associated with MMRG based on a machine learning approach. After classifying the MMRG-associated molecular subtypes of UC, we comprehensively analyzed the MMRG biomarkers and the relationship between the MMRG molecular subtypes and immune infiltration characteristics. Single-cell sequencing analysis showed significant expression pattern of MMRG signatures in different cell subtypes. qRT-PCR and western blot further confirmed the abnormal expressions of selected genes in vitro. Our findings provided a new perspective on the role of MMRG in UC.

Dahuang Mudan Decoction is a classic Chinese medicine prescription for treating ulcerative colitis (UC). Previous studies have shown that Dahuang Mudan Decoction has preventive and therapeutic effects on mice with dextran sulfate sodium (DSS) induced colitis.

The objective of this research endeavor was to ascertain the most efficacious synergistic blend of Emodin, Luteolin, and Paeonol, the main active ingredients in Dahuang Mudan Decoction, in alleviating UC. Additionally, it sought to elucidate the underlying therapeutic mechanisms and evaluate the safety of the combined components.

Employing Emodin, Luteolin, and Paeonol as starting materials, the optimal combination was selected by orthogonal design. Basic pharmacodynamics was observed in mouse model of UC induced by DSS. The pathological changes of the colon were observed using hematoxylin and eosin (H&E) staining. The changes of cytokines and proteins related to inflammation and intestinal barrier function were detected by WB, Alcian blue staining, immunofluorescence, immunohistochemistry and related kits. Subsequently, 16S rRNA sequencing was used to observe changes in the intestinal flora. To evaluate the therapeutic effect and potential mechanism of the optimal monomer composition on UC mouse model. Finally, we performed toxicity tests as part of the safety assessment of the combination of the three monomers.

The different combinations of Emodin, Luteolin, and Paeonol alleviated DSS-induced colitis to varying degrees. The ELP5 group (Emodin 5 mg/kg + Luteolin 5 mg/kg + Paeonol 15 mg/kg) and ELP9 group (Emodin 15 mg/kg + Luteolin 15 mg/kg + Paeonol 75 mg/kg) had the most significant mitigation effect on UC mice. Mechanistically, the monomeric composition provides a comprehensive treatment for UC by addressing multiple aspects, including anti-inflammatory and antioxidant effects, repairing the damaged intestinal barrier, restoring the intestinal flora structure, and regulating short-chain fatty acid levels. In addition, the combination of Emodin, Luteolin and Paeonol exhibited a more significant effect on DSS-induced colitis compared to the individual components, indicating a synergistic effect among them. In the single-dose toxicity test, no obvious abnormalities were found in the general state or major organs of the mice. In repeated toxicity tests, it was found that the combined use of three monomers had less effect on organ index, hematology and serum biochemical indexes than that of a single compound. Pathological examination showed that the three monomers had certain toxicity to mouse liver, kidney and lung when used alone and in large doses for a long time, and the toxicity was significantly reduced after combined use.

We have determined the optimal combination of three active ingredients in Dahuang Mudan Decoction to alleviate DSS induced colitis in mice by inhibiting intestinal inflammation and oxidative stress, repairing impaired intestinal barrier function, and regulating intestinal flora disturbance. The results of single administration toxicity test proved the safety of the three monomers combined, and repeated administration toxicity test clarified the safe dose range of the combined administration, and also revealed that the combined therapy exhibited superior safety compared to monotherapy.

Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal disease that seriously affects the quality of life of patients around the world. It is characterized by recurrent abdominal pain, diarrhea, and mucous bloody stools. There is an urgent need for more accurate diagnosis and effective treatment of IBD. Accumulated evidence suggests that gut microbiota plays an important role in the occurrence and development of gut inflammation. However, most studies on the role of gut microbiota in IBD have focused on bacteria, while fungal microorganisms have been neglected. Fungal dysbiosis can activate the host protective immune pathway related to the integrity of the epithelial barrier and release a variety of pro-inflammatory cytokines to trigger the inflammatory response. Dectin-1, CARD9, and IL-17 signaling pathways may be immune drivers of fungal dysbacteriosis in the development of IBD. In addition, fungal-bacterial interactions and fungal-derived metabolites also play an important role. Based on this information, we explored new strategies for IBD treatment targeting the intestinal fungal group and its metabolites, such as fungal probiotics, antifungal drugs, diet therapy, and fecal microbiota transplantation (FMT). This review aims to summarize the fungal dysbiosis and pathogenesis of IBD, and provide new insights and directions for further research in this emerging field.

Gut homeostasis is critical for human health, ulcerative colitis (UC) can disrupt gut homeostasis and cause disease. Panax ginseng C.A. Meyer is a widely used traditional herbal medicine known for its anti-inflammatory, antioxidant, and immunomodulatory effects. However, the protective mechanisms of total ginsenosides (TG) in treating UC remain unclear. In this study, we employed Drosophila melanogaster as a model organism to investigate the protective effects of TG on dextran sulfate sodium (DSS)-induced intestinal injury. Our data showed that TG significantly improved survival rates in female flies, restored intestinal length, maintained intestinal barrier integrity, and alleviated oxidative stress. Additionally, TG may protect against intestinal damage by activating the PI3K/Akt signaling pathway and inhibiting the JAK/STAT signaling pathway. These findings suggest that TG alleviates UC symptoms through multi-target regulation, highlighting its potential for developing novel therapeutic strategies for UC.