Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), can seriously impact patients' quality of life. Sodium butyrate (NaB), a product of dietary fiber fermentation, has been shown to alleviate IBD symptoms. Some studies have shown that it is related to ferroptosis. However, the precise mechanism linking NaB, IBD, and ferroptosis is not clear.

This study aimed to demonstrate that NaB suppresses ferroptosis, thereby alleviating inflammatory bowel disease (IBD) through modulation of the extracellular regulated protein kinases/signal transducer and activator of transcription 3 (ERK/STAT3) signaling pathway and intestinal flora.

An IBD model was established using 2.5% (w/v) dextran sulfate sodium (DSS). Mice were orally administered low-dose NaB, high-dose NaB , or 5-aminosalicylic acid (5-ASA). Ferroptosis-related molecules were measured using specific kits, and western blotting (WB) and real-time polymerase chain reaction (RT-qPCR) were used to determine the levels of the target molecules.

NaB alleviated symptoms in IBD mice, including reduced weight loss, prolonged colon length, reduced disease activity index (DAI), and reduced spleen index and mRNA expression of inflammatory factors. Additionally, NaB reduced the content of Fe2+ and myeloperoxidase (MPO) and increased the content of GSH and the activity of superoxide dismutase (SOD), which reflected NaB-inhibited ferroptosis. Moreover, western blotting showed that NaB enhanced STAT3 and ERK phosphorylation. In addition, NaB regulates the composition and functions of flora related to IBD.

NaB alleviates IBD by inhibiting ferroptosis and modulating ERK/STAT3 signaling and the intestinal flora.

The pathological mechanisms of ulcerative colitis (UC) are closely related with abnormal memory follicular helper T (mTfh) cell subsets and the Bcl-6/Blimp-1 signaling pathway. Ginsenoside Rg1 (G-Rg1) has been confirmed to exhibit therapeutic effects in obese mice with dextran sulfate sodium (DSS)-induced ulcerative colitis. The aim of this study was to investigate the mechanism of action of G-Rg1 in obese mice with UC by observing mTfh cell subsets and the Bcl-6/Blimp-1 signaling pathway. Obese mice with UC were treated with G-Rg1 at a dose of 200 mg/kg. Disease activity was assessed macroscopically and microscopically, and cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA). Flow cytometry was employed to analyze mTfh cell subsets, and Western blotting to assess protein expression related to the Bcl-6/Blimp-1 pathway. qPCR was used to detect the expression of Bcl-6/Blimp-1, and immunofluorescence was utilized to compare Bcl-6/Blimp-1 expression between different groups. G-Rg1 treatment ameliorated the symptoms of DSS-induced colitis, alleviated the pathological changes in the colonic tissue of obese mice with ulcerative colitis, and reduced the levels of inflammatory cytokines in these mice. Furthermore, flow cytometry analysis indicated that G-Rg1 modulated the balanceof mTfh cells subsets by increasing central memory Tfh (cmTfh) cells and decreasing effector memory Tfh (emTfh) cells, thereby mitigating ulcerative colitis in obese mice. qPCR results revealed the significant upregulation of Bcl-6 and the downregulation of Blimp-1 expression in the DSS group, which was effectively reversed by G-Rg1 treatment. These findings were further confirmed by Western blot and immunofluorescence assays. Collectively, the qPCR, Western blot, and immunofluorescence results demonstrated the pivotal role of the Bcl-6/Blimp-1 signaling pathway in the therapeutic process of G-Rg1 for ulcerative colitis in obese mice. Ginsenoside Rg1 alleviates experimental colitis in obese mice by modulating the proportion of mTfh cell subsets via the Bcl-6/Blimp-1 signaling pathway.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by intestinal barrier dysfunction, oxidative stress, and inflammation. Biochanin A (BCA) is a natural flavonoid found in various plants, known for its anti-inflammatory, antioxidant, and anticancer properties, while its therapeutic role in UC and potential mechanism remains unexplored.

To explores the therapeutic potential of BCA in alleviating UC, focusing on its effects on ferroptosis and the JAK2/STAT3 signaling pathway.

The BCA's therapeutic effects on Dextran sulfate sodium (DSS)-induced colitis model in C57BL/6J mice was investigated. Subsequently, a comprehensive range of techniques was performed to investigate the impact of BCA on intestinal barrier integrity, oxidative stress, inflammation. Besides, the RNA sequencing was performed to explore the potential mechanism. The role of ferroptosis inhibition in BCA's effects in vitro and in vivo was explored by co-treating with the ferroptosis activator Erastin.

Treatment of colitis mice with BCA significantly improved DAI scores and histopathological damage scores, reduced oxidative stress, enhanced intestinal barrier function, and suppress inflammatory responses. RNA sequencing result found that BCA could lead to the inhibition of ferroptosis in mice colon tissue. Moreover, erastin co-treatment negated BCA's effects in vitro and vivo. Mechanistically, BCA exerts these effects by suppressing the JAK2/STAT3 pathway, which plays a pivotal role in ferroptosis and inflammation. Molecular docking studies further confirm the direct binding of BCA to both GPX4 and STAT3.

These results establish BCA as a promising natural compound for UC treatment, offering a novel therapeutic strategy by specifically targeting ferroptosis and its associated molecular pathways, thereby addressing key gaps in current UC management and advancing potential clinical applications.

Ulcerative colitis (UC) is a long-term inflammatory condition impacting the bowel with an unclear cause. It is categorized as a refractory condition due to the limited efficacy and adverse effects of existing treatments. Dihydroartemisinin (DHA), a semi-synthetic derivative and primary active metabolite of artemisinin, exhibits anti-inflammatory and antioxidant properties. To assess the therapeutic effects of DHA on UC and elucidate its possible mechanisms of action. A dextran sulfate sodium (DSS)-induced UC mouse model (2.5% DSS for 30 days) was used to evaluate the therapeutic effects of DHA (20 mg/kg/day) through assessment of disease activity, colon damage, and inflammation. Key targets were identified using network pharmacology, followed by pathway analysis (GO and Kyoto Encyclopedia of Genes and Genomes [KEGG]), molecular docking, and western blotting to validate interactions and signaling modulation. DHA treatment significantly improved disease activity index (DAI) scores, reduced colon shortening, and ameliorated histopathological injury in the DSS-induced UC mouse model. Seven core targets of DHA were identified: EGFR, MMP9, PTGS2, MMP2, mitogen-activated protein kinase 3 (MAPK3), MAPK1, and ERBB2. Enrichment analyses revealed critical mechanisms and pathways implicated in its therapeutic effects. Molecular docking demonstrated robust binding between DHA and its targets, whereas western blot analysis confirmed that DHA mitigated UC via modulation of the MAPK inflammatory signaling pathway. The research highlights DHA's therapeutic potential in UC treatment by identifying its core targets and mechanisms of action, paving the way for future research and drug development in managing UC.

The effectiveness and safety of polyphenols in treating ulcerative colitis remain controversial. This study aimed to evaluate the efficacy and safety of polyphenols in the treatment of ulcerative colitis.

This study followed the preferred reporting items for systematic reviews and meta-analyses 2020 guidelines. A systematic search was conducted across PubMed, Embase, Web of Science, and Cochrane databases to identify relevant articles. The random-effects model was employed to calculate the odds ratio (OR) and corresponding 95% confidence intervals (CIs).

A total of 13 trials involving 742 participants were included in the meta-analysis. The clinical remission rates were higher in the polyphenol group compared to the control group, as demonstrated by both the intention-to-treat (ITT) (OR: 4.71; 95% CI: 2.02-10.99; P = .000) and per-protocol (PP) analysis (OR: 7.14; 95% CI: 3.11-16.39; P = .000). Similarly, the clinical response rate was higher in the polyphenol group compared to the control group, according to the ITT (OR: 5.40; 95% CI: 2.60-11.24; P = .000) and PP analysis (OR: 9.14; 95% CI: 4.25-19.64; P = .000). Moreover, the total endoscopic remission rate was superior in the polyphenol group, as indicated by the ITT (OR: 3.16; 95% CI: 1.20-8.37; P = .020) and PP analysis (OR: 4.92; 95% CI: 2.03-11.93; P = .000). No significant differences were observed regarding side effects between the 2 groups, according to the ITT (OR: 0.99; 95% CI: 0.56-1.76; P = .973) and PP analysis (OR: 0.99; 95% CI: 0.54-1.80; P = .971).

Polyphenols demonstrated effectiveness in inducing clinical remission, clinical response, and endoscopic remission in patients with ulcerative colitis. Furthermore, there was no evidence of a higher incidence of adverse effects associated with their use.

Pediatric inflammatory bowel disease (IBD), encompassing Crohn's disease, ulcerative colitis, and indeterminate colitis, often necessitates surgical intervention in cases of severe or refractory disease. Although biologic therapies have significantly reduced the need for surgery, operative management remains essential for certain patients. The choice between laparoscopic (laparoscopy group [LG]) and open conventional surgery (open group [OG]) continues to be a subject of debate. This meta-analysis aimed to compare the postoperative outcomes of LG and OG in pediatric patients with IBD.

We conducted a meta-analysis of observational studies comparing LG and OG outcomes in pediatric patients with IBD. Key outcomes analyzed included major and minor postoperative complications, reoperations, readmissions, operative time, and length of hospital stay.

Seven studies met the inclusion criteria, analyzing 3417 patients, with 1399 (41%) undergoing OG and 2018 (59%) undergoing LG. Our analysis revealed no significant differences in major postoperative complications, reoperation, and readmissions between LG and OG (P = .114, P = .082, and P = .641, respectively). However, LG was associated with shorter hospital stays (6.04 vs 8.35 days; P < .05). Conversions from LG to open surgery amounted to a total of 153 (7.57%). Open surgery had a significantly shorter operative time (173.8 vs 195.5 min; P = .005).

Both laparoscopic and open conventional surgeries are safe, effective, and reliable in managing pediatric IBD. Although open surgery offers shorter operative times, laparoscopy reduces hospital stay and minor postoperative complications. The choice of approach depends on the surgeon's experience and patient-specific factors.

Ulcerative colitis (UC) is a non-specific inflammatory bowel disease. Unlike any single form of cell death reported previously, macrophage PANoptosis, a unique programmed cell death characterized by inflammation and necrosis, plays a crucial role in the pathogenesis of colitis. Changdiqing Decoction (CDQD), an empirical hospital prescription enema, has been used to treat UC for decades. This study aimed to investigate the multi-target anti-colitic effects of CDQD by examining its impact on intestinal homeostasis and its anti-inflammatory properties.

A dextran sulfate sodium (DSS)-induced mouse model of acute colitis was employed. Interferon-gamma (IFN-γ) and KPT-330 were used to induce macrophage PANoptosis. Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLCHRMS) was utilized to identify the chemical constituents of CDQD. Multi-omics analysis and fecal microbiota transplantation (FMT) were used to explore the therapeutic targets and gut microbiota alterations induced by CDQD.

CDQD treatment significantly alleviated colitis symptoms in mice, with a dose-dependent therapeutic effect. The decoction mitigated PANoptosis in colon tissues and bone marrow-derived macrophages (BMDMs). 16S rRNA sequencing analysis and metabonomics revealed that CDQD administration significantly altered the gut microbiota composition and metabolite profiles. Notably, CDQD-modulated gut microbiota exhibited anti-colitic effects through FMT. Integrated transcriptomics and network pharmacology analysis revealed that CDQD significantly downregulated the PI3K/Akt signaling pathway in colitis. This finding was further validated using the inhibitors LY294002 and MK2206.

CDQD alleviates colitis by suppressing inflammatory macrophage activation and modulating the gut microbiota. Our research provides a novel traditional Chinese medicine strategy for the treatment of UC via enema administration.

Qilian Jiechang Ning (QJN), a traditional Chinese herbal formula, has demonstrated potential therapeutic effects in the treatment of ulcerative colitis (UC). This study aims to investigate the mechanism of QJN in the outer membrane vesicles (OMVs) of Segatella copri (S. copri)-induced colon epithelial cells and UC mice.

Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were utilized to assess the morphology and size of OMVs. Inflammation markers and tight junction protein levels in HCoEpiCs induced by OMVs were monitored using ELISA and western blot. QJN was administered to intervene in HCoEpiCs treated with S. copri OMVs. Additionally, trinitrobenzene sulfonic acid (TNBS)-induced mouse models were conducted to evaluate the therapeutic effects of QJN on UC.

S. copri OMVs treated with QJN demonstrated a significant reduction in particle size, protein concentration, and LPS content. In HCoEpiCs, QJN effectively decreased the expression of inflammation-inducing cytokines (IL-1β, IL-18, IL-6, TNF-α) and proinflammatory proteins (GSDMD-N, NLRP3, ASC, cleaved Caspase-1, cleaved Caspase-4) triggered by S. copri OMVs, while enhancing the expression of tight junction proteins (ZO-1 and Occludin). In the UC mouse models, QJN significantly reduced the Disease Activity Index (DAI), improved colon length, lowered LPS levels, ameliorated colonic tissue damage, and inhibited Caspase-1- and Caspase-11-dependent inflammatory responses.

QJN can alleviate S. copri-OMV-induced inflammatory response in colonic epithelial cells and reduce symptoms of UC in mouse models by modulating the Caspase-1 and Caspase-11 pathways.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is characterized by chronic intestinal inflammation and impaired epithelial barrier function. Emerging evidence highlights the critical role of vascular remodeling and angiogenesis in IBD pathogenesis. This review explores the intricate relationship between blood vessels and the intestinal epithelial barrier, emphasizing how aberrant vascularization contributes to barrier dysfunction and disease progression. In IBD, excessive angiogenesis is driven by hypoxia, immune cell infiltration, and pro-inflammatory cytokines, further perpetuating inflammation and tissue damage. Key angiogenic factors, such as vascular endothelial growth factor (VEGF), angiopoietins, and platelet-derived growth factor (PDGF), are upregulated in IBD, promoting pathological vessel formation. These newly formed vessels are often immature and hyperpermeable, exacerbating leukocyte recruitment and inflammatory responses. Given the pivotal role of angiogenesis in IBD, anti-angiogenic therapies have emerged as a potential therapeutic strategy. Preclinical and clinical studies targeting VEGF and other angiogenic pathways have shown promise in reducing inflammation and promoting mucosal healing. This review summarizes current knowledge on vascular-epithelial interactions in IBD, the mechanisms driving pathological angiogenesis, and the therapeutic potential of anti-angiogenic approaches, providing insights for future research and treatment development.

5-aminosalicylates (5-ASAs) are commonly used in non-surgical patients with Crohn's disease (CD), especially in mild-to-moderate disease, despite current guidelines against their use. Despite this, the evidence regarding their efficacy is mixed, with conflicting findings in systematic reviews (SRs).

We conducted an overview of reviews (umbrella review) to consolidate existing knowledge from published SRs on using 5-ASAs in patients with active or quiescent CD.

We systematically searched for relevant SRs published in English until July 6, 2024, summarizing data on 5-ASAs used in induction, maintenance, or withdrawal trials of CD. We also searched for placebo-controlled RCTs of 5-ASAs published after 2015.

Eight SRs met our inclusion criteria, with the number of included RCTs of 5-ASAs in CD ranging from 2 to 22. Two were network meta-analyses (NMA); 4 were Cochrane SRs. SRs found no evidence of benefit for oral 5-ASAs over placebo for maintaining medically induced remission. The latest NMA in 2017, including 22 RCTs for induction of remission, suggested that high-dose mesalamine (≥ 2.4 g) was more effective than placebo, though ranking lower than systemic corticosteroid and high-dose budesonide. No placebo-controlled RCT of 5-ASAs was published after 2015, only the ongoing STATIC trial is investigating the withdrawal of 5-ASAs in patients with quiescent CD.

This overview of SRs suggests that the evidence does not support the use of 5-ASAs for maintaining medically induced remission. However, high-dose mesalamine may be considered for inducing remission in selected patients with mild luminal CD who prefer to avoid steroids.

Background/Objectives: Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC). The availability of an increasing number of new molecules approved for IBD treatment has increased our ability and aspirations to change the trajectory of the disease. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) II consensus (2018) is the current suggested strategy for IBD management, which recommends a treat-to-target approach. The primary objective of this study is to describe the clinical history of IBD in the post-STRIDE II era and to quantify the burden of IBD in terms of hospitalisation rate. The secondary objective is to estimate the 6-year risk of intestinal resection among IBD patients. Methods: A population-based time series analysis was conducted on administrative data; retrospective data from January 2011 to December 2021 were collected for the Local Health Authority "Roma 1" population (∼1.5 million residents). Hospitalisation and surgical events were prospectively recorded for patients newly diagnosed between January 2018 and February 2022 (n = 556), with follow-up throughout May 2024. A Kaplan-Mayer survivor analysis was performed to estimate the cumulative surgery risk. Results: In 2021, the IBD prevalence was 218.3 cases/100,000 people (77.2 CD, 141.1 UC). The incidence trend slowly increased during the last decade, up to 5.3 (CD) and 9.4 (UC) cases/100,000 ppl/year. The yearly hospitalisation rate remained stable, near 16.5%. The 6-year cumulative risk of surgery was 36% for CD and 20% for UC. Conclusions: The incidence of IBD has increased in the last few decades, with substantial stability in regard to the incidence of surgery and hospitalisations. Thus, the current IBD management approach has only had a small effect on changing the natural history of the disease.

Common mental disorders, including anxiety and depression, are prevalent in patients with inflammatory bowel disease (IBD) and may be associated with adverse outcomes. However, whether increasing psychological co-morbidity, in combination with disease activity, exerts a cumulative effect on prognosis is uncertain.

To assess this in a longitudinal follow-up study.

We collected baseline demographic and IBD-related information, clinical activity using disease activity scores and biochemical activity using calprotectin. Patients were grouped according to the presence or absence of disease activity. Patients in remission or with active disease were subgrouped according to the presence or absence of symptoms of a common mental disorder at baseline. We recorded the occurrence of adverse outcomes over 8.1 years, comparing their occurrence across subgroups using Cox regression.

Among 717 participants with clinical activity data and 187 with clinical and biochemical activity data, rates of adverse outcomes increased with both disease activity and increasing psychological co-morbidity. Rates of flare or glucocorticosteroid prescription, escalation or death were higher with clinical activity (HR 2.89; 95% CI 1.68-4.93 and 2.52; 95% CI 1.55-4.10 and 6.97; 95% CI 2.43-20.0, respectively) or clinical and biochemical activity (HR 7.26; 95% CI 2.86-18.5, 3.62; 95% CI 1.59-8.25 and 57.3; 95% CI 7.58-433, respectively) and two common mental disorders. Rates of hospitalisation (HR 6.20; 95% CI 1.88-20.4) or hospitalisation and/or intestinal resection (HR 7.46; 95% CI 2.41-23.2) were higher with clinical and biochemical activity and two common mental disorders.

Psychological co-morbidity and active disease have a cumulative adverse impact on IBD prognosis.

Disruption of the intestinal epithelial barrier, driven by imbalances in gut mucosal immunity and microbial homeostasis, is central to the onset and progression of inflammatory bowel disease (IBD). This study introduces a CO-releasing polyoxometalates (POMs) nanozyme (PMC), synthesized by coordinating pentacarbonyl manganese bromide with molybdenum-based POM nanoclusters. PMC demonstrates targeted accumulation at IBD-affected sites, efficient scavenging of reactive oxygen species (ROS), and responsive CO release, resulting in multiple therapeutic effects. Extensive in vitro and in vivo studies have validated the exceptional capacity of PMC to repair intestinal barrier, attributed to their potent antioxidant and anti-inflammatory properties, thereby achieving significant therapeutic efficacy in ulcerative colitis treatment. 16S rRNA sequencing indicated that PMC efficiently remodeled the gut microbiota composition. Single-cell RNA sequencing indicates a reduction in pro-inflammatory M1 macrophages, alongside suppressed ROS and inflammatory signaling pathways. Concurrently, an increase in reparative M2 macrophages and intestinal stem cells is observed, in addition to significant activation of the VEGF signaling pathway in macrophages and the NOTCH pathway in stem cells, underscoring the potential of PMC to restore immune balance and promote tissue repair. This study positions PMC as a promising, multifunctional therapeutic agent for IBD treatment owing to its robust intestinal barrier-restoring capability.

Inflammatory bowel disease (IBD) is a chronic, immune-mediated inflammatory disorder of the gastrointestinal tract. In IBD, systemic inflammation and immune dysregulation may also impact extraintestinal organs, such as the thyroid gland. Despite this, little is known about the influence of concomitant hypothyroidism on the clinical course of IBD.

A retrospective analysis was conducted among adult patients with IBD and at least one thyroid stimulating hormone (TSH) measurement within a large healthcare network. Patient charts were reviewed, and baseline demographics, disease characteristics, biomarkers, healthcare utilization, medication use, and other comorbidities were extracted. Patients were stratified by those with IBD only and those with concomitant IBD and hypothyroidism. Multivariable logistic regression was used to identify factors associated with concomitant hypothyroidism. Concomitant disease as an independent predictor for lab abnormalities and increased healthcare utilization was also assessed using multivariable logistic and negative binomial regression.

We identified 287 adult patients with IBD, including 146 (50.9%) with Crohn's disease (CD) and 141 (49.1%) with ulcerative colitis (UC). Among this sample, 178 (62.0%) patients had concomitant hypothyroidism. Concomitant disease was associated with older age (adjOR 1.04, 95% CI 1.02, 1.06), female sex (adjOR 1.78, 95% CI 1.01, 3.16), and the presence of other extraintestinal manifestations (adjOR 2.30, 95% CI 1.06, 5.00). Concomitant disease was also found to be a significant predictor for increased healthcare utilization, specifically, higher number of radiation-based abdominal imaging (RBAI) studies (adjIRR: 1.89, 95% CI 1.08, 3.32).

Patients with both IBD and hypothyroidism have an increased likelihood of other extraintestinal manifestations compared to individuals who have IBD without hypothyroidism. Furthermore, patients with concomitant disease exhibited greater healthcare utilization, specifically, increased rates of RBAI studies. The presence of concomitant hypothyroidism may be associated with a more severe course of IBD.

Serious complications and unplanned healthcare utilization are reported among inflammatory bowel disease (IBD) hospitalizations with associated cytomegalovirus (CMV). The present systematic review and meta-analysis aimed to examine the in-hospital outcomes of CMV-related hospitalization in IBD patients.

Electronic databases were systematically searched in PubMed, Web of Science (ISI), Scopus, Embase, and Google Scholar until February 2024. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Cochran's Q test and I2 statistics were applied to evaluate potential heterogeneity across eligible studies. The random-effects model obtained pooled odds ratio (OR) estimates and associated 95% confidence intervals (CI).

Sixteen articles were included in the meta-analysis, encompassing 5120 IBD patients diagnosed with comorbid CMV infection. Our findings indicated that compared to IBD patients without CMV, those with both CMV and IBD had a longer hospital length of stay (LOS) (8.65 days longer; 95% CI: 6.96, 10.34; P < 0.01), a greater colectomy risk (OR = 2.26; 95% CI: 1.53, 3.34; P < 0.01), and higher in-hospital mortality (OR = 2.83; 95% CI: 1.92, 4.16; P < 0.01). However, the difference in hospital charges between the two groups was not statistically significant (P = 0.78). Sensitivity analysis using the leave-one-out approach revealed significant changes in hospital costs after excluding certain studies. Additionally, subgroup analyses showed significant differences based on IBD subtypes for surgery risk and LOS.

Our findings suggest that CMV infection is associated with poorer outcomes in hospitalized IBD patients, highlighting the importance of early detection and appropriate management of CMV infection in this population to improve clinical outcomes and reduce healthcare resource utilization.

Thlaspi arvense (TA), commonly known as "Ximi" or "Subaijiang," is a traditional Chinese medicinal herb used to prevent and treat ulcerative colitis (UC). However, the precise mechanisms underlying its therapeutic effects remain unclear, necessitating further investigation to identify potential pharmaceutical applications for UC management. This study aims to elucidate the efficacy and mechanisms of TA and its active constituents in UC treatment.

This study first evaluated the effects of varying TA doses on 3% dextran sulfate sodium (DSS)-induced UC. Gut microbiota alterations in UC mice were analyzed via 16S rRNA sequencing, with correlation analyses to reveal the relationship between gut microbiota and cytokines. Then, network pharmacology was utilized to identified potential TA targets for UC treatment. Protein-protein interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were employed to explore TA's mechanisms. Molecular docking and dynamics simulations validated interactions between TA's active compounds and UC-related targets. Finally, TNF pathway modulation by TA and its active component, isovitexin, was verified in vitro and in vivo.

TA alleviated DSS-induced weight loss in a dose-dependent manner, reduced disease activity indices, and preserved intestinal mucosal barrier integrity. Subsequently, fluorescence in situ hybridization (FISH) revealed TA suppressed microbial translocation in intestinal tissues. To further characterize inflammatory responses, ELISA demonstrated that TA modulated levels of key cytokines (TNF-α, IL-1β, IL-6, IL-10) and oxidative stress markers (SOD, MDA), indicating systemic anti-inflammatory effects. Building on these findings, 16S rRNA sequencing analyses showed that TA regulated gut microbiota alpha/beta diversity and inhibited infectious disease-related pathways. Notably, correlation heatmaps highlighted a strong association between TNF-α levels and Escherichia-Shigella abundance, with high-dose TA significantly reducing this pathogenic bacterial genus. To systematically explore molecular mechanisms, network pharmacology identified 220 potential TA targets for UC treatment. Consistent with experimental data, PPI and KEGG analyses implicated TNF-α, IL-6, and AKT as key targets, primarily through TNF signaling pathway modulation. To validate these predictions, molecular docking confirmed stable interactions between TA compounds and identified targets, while dynamics simulations specifically emphasized isovitexin's high affinity for TNF-α. Finally, experiments in vivo demonstrated TA's inhibition of TNF-α-mediated NF-κB pathway activation, and in vitro studies confirmed that isovitexin directly mitigated TNF-α-induced intestinal epithelial damage. Furthermore, TA demonstrated potent inhibition of TNF-α-mediated NF-κB inflammatory pathway activation in intestinal tissues, while its active constituent isovitexin effectively mitigated TNF-α-induced epithelial cell damage, collectively highlighting their complementary anti-inflammatory mechanisms.

Collectively, Thlaspi arvense (TA) ameliorates ulcerative colitis through synergistic mechanisms involving gut microbiota modulation, inflammatory pathway suppression, and intestinal barrier preservation. By remodeling microbial communities to reduce Escherichia-Shigella colonization and microbial translocation. TA concurrently inhibits TNF-α/NF-κB-driven inflammation, and oxidative stress regulation. Furthermore, its active constituent isovitexin directly attenuates TNF-α-induced epithelial damage, demonstrating multi-scale therapeutic efficacy. These findings establish TA's multi-target pharmacology spanning host-microbe interactions and intracellular signaling, while providing a rationale for standardizing TA-based formulations and advancing isovitexin as a precision therapeutic agent for inflammatory bowel diseases.

Up to 30% of patients with acute severe ulcerative colitis (ASUC) will require urgent colectomy despite initiation of intravenous corticosteroids and rescue therapies. Janus kinase inhibitors, such as tofacitinib, have emerged as an effective agent for ASUC; however, there are currently limited data evaluating the risk of postoperative complications among patients who received tofacitinib treatment for an episode of ASUC compared with infliximab.

We conducted a multicenter, retrospective, case-control study of patients hospitalized with ASUC who underwent colectomy, comparing patients treated with tofacitinib prior to colectomy with infliximab-treated controls. The primary outcome was rate of serious postoperative complications within 30 days of colectomy. Outcomes were compared between the tofacitinib-treated cases and infliximab-treated controls using multivariable regression adjusted for open surgery and cumulative corticosteroid exposure.

Forty-one tofacitinib-treated patients were compared with 68 infliximab-treated patients with ASUC. Compared with tofacitinib-treated patients, infliximab-treated patients had higher overall rates of overall (44 [64.7%] vs 13 [31.7%]; P = .002) and serious (19 [27.9%] vs 3 [12%]; P = .019) postoperative complications. No significant different risk for developing serious postoperative complications (odds ratio, 0.28; 95% confidence interval, 0.06-0.96; P = .061) was observed in multivariable analysis; however, a significantly lower rate of overall postoperative complications (odds ratio, 0.38; 95% confidence interval, 0.16-0.87; P = .023) was observed in tofacitinib-treated patients compared with infliximab-treated patients.

We observed a significantly lower rate of overall postoperative complications in ASUC patients treated with tofacitinib compared with infliximab; however, no difference was observed in the risk for serious postoperative complications. Larger prospective trials are needed to confirm these findings.

Myeloid-derived suppressor cells (MDSCs) regulate immune responses in many pathological conditions, one of which is inflammatory bowel disease (IBD), an incurable chronic disorder of the digestive tract and beyond. The pathophysiology of IBD remains unclear, likely involving aberrant innate and adaptive immunity. Studies have reported altered population of MDSCs in patients with IBD. However, their distribution varies among patients and different preclinical models of IBD. The expansion and activation of MDSCs are likely driven by various stimuli during intestinal inflammation, but the in-depth mechanisms remain poorly understood. The role of MDSCs in the pathogenesis of IBD appears to be paradoxical. In addition to intestinal inflammation, suppressive MDSCs may promote colitis-to-colon cancer transition. In this Review, we summarize recent progresses on the features, activation, and roles of MDSCs in the development of IBD and IBD-associated colon cancer.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting millions worldwide. Tofacitinib, an inhibitor of Janus kinase (JAK), has shown considerable potential as an effective treatment option for individuals suffering from moderate to severe UC, aiming to mitigate the risk of colectomy, hospitalization, and disease exacerbation.

We conducted a comprehensive literature review from 2012 to 2024 to assess the study landscape of Tofacitinib in UC. Employing the Web of Science Core Collection database (WOSCC) and the bibliometric tool CiteSpace, we performed an bibliometric analysis to delineate disciplinary evolution and identify research hotspots within the UC Tofacitinib domain.

Our analysis extracted 406 UC Tofacitinib-related articles from WOSCC, indicating a growing body of literature. The United States and Europe are at the forefront of research maturity, with a significant contribution to the field. Here we show that multidisciplinary research is burgeoning, which is crucial for the advancement of UC Tofacitinib studies. We identified 13 highly cited documents and 10 co-cited documents, highlighting Tofacitinib's prominence as a small molecule agent. Keyword analysis revealed that the intestinal barrier, clinical response, remission rate, and safety are the central themes of current research.

By applying bibliometrics, citation analysis, and knowledge mapping, this study provides a snapshot of the current state and trajectory of Tofacitinib research in UC. We have elucidated the knowledge lineage in this field, offering insights that can inform both ongoing and future research endeavors. Our findings underscore the importance of multidisciplinary collaboration in advancing UC therapeutic strategies.

Treat-to-target therapy in inflammatory bowel disease requires longitudinal assessment of disease activity and intestinal ultrasound (IUS) is a promising non-invasive and cheap technology to provide objective read-outs. Vascularization of the bowel wall is one key parameter on IUS. While this is conventionally done with Color doppler imaging, it is currently unclear whether microvascular flow imaging techniques might improve the diagnostic performance of IUS.

To explore the utility of superb microvascular imaging (SMI) for assessing disease activity in Crohn's disease (CD).

We performed a prospective single-center cross-sectional cohort study including 56 patients with CD. IUS was performed on the terminal ileum or sigmoid colon within 30 days of colonoscopy and the International Bowel Ultrasound (IBUS) group Segmental Activity Score (SAS) as well as SMI signals were determined and correlated to established endoscopic, clinical and biochemical read-outs of disease activity.

SMI scores showed superior correlation to endoscopic disease activity than Doppler imaging scores. While this did not further improve the diagnostic performance of the composite IBUS-SAS, SMI scores as a single parameter excellently predicted segmental endoscopic disease activity.

SMI is a highly promising tool to improve or simplify the non-invasive assessment of disease activity in CD that should further be investigated in real-world and multi-center trials.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with significant global prevalence. Despite advancements in medical management, including the widespread use of biologic agents and small molecules, approximately 15-20% of patients eventually require surgery. This study aimed to analyze colectomy and hospitalization rates for UC in Brazil from 2012 to 2022 and assess their temporal trends.

This was a retrospective, observational, population-based study using public database records from January 1, 2012, to December 31, 2022. The study included all patients with one or more diagnostic codes associated with UC (ICD-10) who underwent a UC-related surgical procedure during the study period.

A total of 178,552 unique UC patients were identified. UC prevalence increased significantly, from 17.31 per 100,000 in 2012 to 84.23 per 100,000 in 2022, with an annual average percentage change (AAPC) of 15% (95% CI 14.97-15.11, p<0.001). The Southeastern and Southern regions accounted for the highest number of cases. Among the 1374 surgical procedures identified, 69.4% were total colectomies, and 10.6% were pouch procedures. By the end of 2022, the proportion of surgeries relative to the total number of UC patients was 0.7%, with a declining trend (AAPC -11.8%; 95% CI -13.38 to -10.33, p<0.001). Hospitalization rates also showed a significant decline over time (AAPC -14.3%; 95% CI -14.75 to -14.03, p<0.001).

UC prevalence in Brazil has increased substantially over the past decade. However, colectomy rates remain low and have shown a declining trend over the same period. Additionally, there has been a notable reduction in hospitalization rates, reflecting potential improvements in UC management and disease control.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) that have a negative impact on patient quality of life (QOL).

To evaluate QOL, work productivity, use of healthcare resources, and medical costs in patients with IBD from the RISE-MX trial.

RISE-MX was a non-interventional, multicentric, cross-sectional, retrospective study conducted in a Mexican population with IBD.

The 36-item Short Form Health Survey (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ) were used to assess QOL. The burden of disease was analyzed using the Work Productivity and Activity Impairment Questionnaire (WPAI), healthcare resources use, and medical costs.

Of 326 subjects, 95 (29.1%) had CD, and 231 (70.8%) had UC. In patients with CD, 43 patients (45.3%) showed moderate-to-severe activity, and 42 (18.1%) had moderate-to-severe disease activity in patients with UC. In all SF-36 dimensions, a significant difference between moderate-to-severe and mild activity/in remission groups was observed in patients with UC, while in patients with CD, the difference between activity groups was significant only for physical functioning and social functioning dimensions. In patients with CD, a higher but non-significant IBDQ score difference between activity groups was observed while a statistical difference between activity groups was observed for all dimensions in UC patients. In WPAI, the total percentage for work impairment (absenteeism plus presenteeism) and the percentage of regular daily activity impairment were statistically significant between activity groups only for UC. The annual total costs (direct and indirect) per patient in CD were USD 19,757 (moderate-to-severe activity group) and USD 12,587 (mild activity/in remission group), while in patients with UC were USD 11,702 and USD 9144, respectively.

Moderate-to-severe activity of disease was associated with a substantial impact on QOL, work productivity, and medical costs in Mexican patients with IBD. Total costs were higher for patients with CD than for patients with UC.

The commensal bacterium Alistipes shahii is a core microbe of the human gut microbiome and its abundance is negatively correlated with inflammatory bowel diseases (IBDs). However, its fundamental role in regulating inflammatory response remains unknown. Using a dextran sulfate sodium (DSS)-induced colitis mouse model, we examined the effect of A. shahii strain As360 intervention on host inflammatory response and found that A. shahii As360 alleviated disease activity index, colon shortening, and colonic histopathological lesion. The levels of tight junction proteins (mainly ZO1 and claudin-1) were decreased in DSS-induced colitis mice, whereas the levels of these proteins were elevated in colitis mice with A. shahii As360 treatment. In addition, A. shahii As360 treatment led to alterations in cytokine release, especially an increase of IL10. It also led to reduced expressions of mtor and Nlrp3 and increased expression of mTOR inhibitor Ddit4 at the transcriptional level. 16S rRNA amplicon sequencing found that Bacteroides, a producer of short-chain fatty acids (SCFAs), was enriched in the fecal samples of mice with A. shahii treatment. Metabolic analyses found that, following A. shahii As360 treatment, the SCFAs in the fecal content was increased whereas lactic acid was decreased in the cecal content. These findings suggest that supplementation with A. shahii As360 is a promising strategy to prevent colitis.IMPORTANCEAs one of the core microbes and keystone species in the human gut, Alistipes shahii has the potential to inhibit inflammation and improve inflammatory bowel diseases (IBDs) conditions. In this study, we experimentally demonstrated that oral administration of A. shahii As360 alleviated symptoms of colitis, altered the release of cellular inflammatory factors, reduced the intestinal epithelial barrier damage, and changed gut microbiota and fecal metabolites. These findings provide a deeper understanding of the beneficial effects of A. shahii and its perspective for better strategies to prevent IBD.

Ulcerative colitis (UC) is a recurrent intestinal disease caused by a complex of factors, and there are serious adverse effects and tolerance problems associated with the current long-term use of therapeutic drugs. The development of natural food sources and multi-targeted drugs for the treatment of UC is imminent. Portulaca oleracea L. (PO), as a vegetable, has been shown in studies to have an anti-UC effects. However, the relationship between the abundant active ingredients contained in Portulaca oleracea L. and the improvement of intestinal barrier, gut microbiota and metabolites is unclear. In the present study, Portulaca oleracea L. which was found to be rich in phenolic acid-based active ingredients, were effective in alleviating dextran sulfate sodium (DSS)-induced body weight loss, disease activity index (DAI) score and colon length in mice. It also decreased C-reactive protein (CRP) and myeloperoxidase (MPO) responses, reduced the permeation of fluorescein isothiocyanate (FITC)-dextran, lipopolysaccharide (LPS) and evans blue (EB), and improved histopathological scores. Meanwhile, in vitro and in vivo validation revealed the protective effects of purslane on the intestinal barrier indicators ZO-1, Occludin and Claudin-1, and inhibited the expression of inflammation-associated iNOS and NLRP3 proteins through the NF-κB signaling pathway. In addition, purslane increased the diversity of the intestinal flora, enhancing the proportion of the genera Butyricoccus, Dorea and Bifidobacterium and decreasing the percentage of Bacteroides, Turicibacter and Parabacteroides. Serum metabolomics analysis showed that the imbalance of 39 metabolites was significantly reversed after PO deployment. Enrichment analysis showed that Pentose phosphate pathway and Pyruvate metabolism pathway were the key pathways of PO against UC. Overall, purslane effectively improved the intestinal barrier disruption and intestinal inflammation by inhibiting the NF-κB signaling pathway, and adjusted the disorder of gut microbiota and metabolites to exert anti-UC effects.

Alhagi honey is a light yellow sugar granule formed by concentrating the liquid secreted by Alhagi branches and leaves. It is a traditional Uygur medicine often used to treat abdominal pain, diarrhea, dysentery, and other conditions. Modern research has indicated that the main active components of Alhagi honey are oligosaccharides and polysaccharides. Our previous research had identified that the extract of Alhagi honey exhibits good anti-inflammatory pharmacological activity, however, its efficacy against Crohn's disease (CD) remains to be elucidated.

To determine the efficacy of the extract of Alhagi honey in CD and to explore its potential targets and mechanisms.

Mel (melitriose) is extracted from dried Alhagi honey. In vivo, 2.5% 2,4,6-trinitrobenzenesulfonic acid (TNBS, At a dosage of 100 mg/kg) is used as an enema to induce CD-like changes in the rat colon. Over the subsequent fortnight, the modeled rats were treated with Mel via gavage. The histopathological alterations and repair ability of colonic injury in the colon tissue were evaluated using hematoxylin and eosin (H&E), Masson's trichrome, and immunofluorescence staining. Additionally, the amelioration of inflammatory responses in the colon was assessed using enzyme-linked immunosorbent assay (ELISA). The reparative capacity of Mel on inflammation was evaluated by inducing inflammation in RAW264.7 cells with lipopolysaccharide (LPS). The Drug Affinity Responsive Target Stability (DARTS) experiment was used to explore the relevant targets of action. Furthermore, network pharmacology was used to investigate the mechanism of action of Mel, to further validate its effects at the cellular level.

In the CD rat model, treatment with Mel significantly improved colonic mucosal damage and inflammatory infiltration. It also demonstrated a reduced collagen fiber deposition, thereby ameliorating fibrotic changes in colonic tissue. Furthermore, Mel decreased the expression of pro-inflammatory factors and increased the expression of anti-inflammatory factors in colonic tissue and cell supernatants. Further research confirmed that Mel influences the glycolytic pathway by binding to phosphoglycerate kinase 1 (PGK1) and suppressing its activity, leading to reduced production of adenosine triphosphate (ATP) and its metabolites, 2-phosphoglycerate (2-PG), 3-phosphoglycerate (3-PG); thus, playing a role in anti-inflammation and promotion of repair. This mechanism was further validated using the PGK1 inhibitor NG52, which also demonstrated a reduction in the production of ATP, 2-PG, and 3-PG.

This study revealed that Mel exerts its anti-inflammatory and reparative capabilities in vitro and in vivo by inhibiting the activity of the key glycolytic enzyme PGK1, leading to reduced production of ATP and its products 2-PG and 3-PG, thereby ameliorating the symptoms of CD. It can emerge as a promising candidate for CD treatment.

Inflammatory bowel disease (IBD) is a chronic condition associated with elevated rates of anxiety and depression and ultimately reduces the quality of life. Thus, preventive care addressing both physical and psychological health is essential. In this study we aimed to explore the protective effects of Indoleacrylic Acid (IA) against lipopolysaccharide (LPS)-induced inflammation using human colorectal adenocarcinoma cells (HT-29) and dextran sulfate sodium (DSS)-induced zebrafish to assess its potential as a novel therapeutic agent for IBD. IA exhibited substantial anti-inflammatory properties in HT-29 cells and zebrafish models. It significantly reduced the production of pro-inflammatory mediators, including PGE2, TNF-α, IL-6, and IL-8, while upregulating MUC2, AhR, and tight junction proteins (ZO-1, occludin, and claudin-1), thereby enhancing mucosal barrier integrity. In zebrafish larvae, IA improved survival rates, boosted mucin production, and reduced macrophage infiltration and heartbeat rate. Behavioral analyses of adult zebrafish revealed that IA alleviated anxiety-like behaviors, as shown by increased locomotion and improved performance in zone preference and light-dark transition tests. By targeting inflammation and anxiety-like symptoms, IA demonstrates a dual benefit by addressing both intestinal inflammation and the psychological burden of IBD. These findings highlight IA's potential as a novel therapeutic agent for managing IBD, offering a comprehensive approach to improving patient outcomes.

To understand trends in the risk of all-cause hospitalization for individuals with inflammatory bowel disease, we explored age, period, and cohort effects in Canada.

Repeated cross-sectional survey data from the 2005-2014 Canadian Community Health Survey linked to the Discharge Abstract Database to capture the all-cause hospitalization within 3 years of entry into the study for eligible individuals. Random-effects 2-level models estimated fixed effects for age and random effects for time periods and birth cohorts on the risk of all-cause hospitalization within 3 years entry into the study.

An estimated 197,000 individuals were eligible for study inclusion. From this, an estimated 70,140 all-cause hospitalizations occurred within 3 years postentry into the study. The risk of hospitalization within 3 years increased with age and across birth cohorts, with older cohorts experiencing greater risks of hospitalization. A small temporal effect was identified for both inflammatory bowel disease groups. Within birth cohorts, the risk of hospitalization increased across ages for Crohn's disease, but in individuals with ulcerative colitis, the risk decreased across ages, except for the 2 oldest birth cohorts.

These data support the hypothesis that age effects are primarily responsible for increased risk of hospitalizations. As the prevalence of IBD continues to rise and age distribution of Canadians shifts toward an older-aged population, increasing the allocation of healthcare resources to prevent age-related risks of hospitalizations would be beneficial to reduce hospital burdens.

Ulcerative colitis (UC) is an inflammatory bowel disease in which one-quarter of patients are at risk of developing a severe form of the disease known as acute severe UC (ASUC). This condition exposes patients to serious complications, including toxic megacolon, surgical intervention, and even death. The current therapeutic strategy relies on time-dependent, multi-step algorithms that integrate systemic corticosteroids, calcineurin inhibitors, and biologic agents (specifically infliximab) as medical therapy aimed at avoiding colectomy. Despite this approach, a significant proportion of patients fail to respond to either corticosteroids or infliximab and may require alternative therapeutic options if there is no urgent surgical necessity. These alternatives include other biologics or emerging small molecules, although the evidence supporting these treatments remains extremely low, even considering their well-documented and promising efficacy and safety in moderate-to-severe UC. Conversely, it is necessary to investigate whether infliximab can be effectively replaced or surpassed by other approved biological agents and small molecules as first-line therapy after steroid resistance. This review aims to summarise the available evidence on small molecules, specifically Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators.

Background/Objectives: The solute carrier family 26, member 2 (SLC26A2) gene, which belongs to the family of SLC26 transporters, can be detected in multiple tissues. However, the studies of SLC26A2 in colon-related diseases are still limited and incompletely understood, especially in ulcerative colitis (UC). Methods: In this study, we attempted to search and identify putative UC candidate genes within a large number of known genes by multiple bioinformatics analyses. The potential cellular characteristics and biological functions of SLC26A2 in the pathogenesis of UC were also elucidated. Results: Notably, SLC26A2 was representative and down-regulated in the intestinal mucosa of patients with active UC, compared to healthy controls. Decreased levels of SLC26A2 were proved to have a more value in diagnosis of UC patients, and closely correlated with some UC characteristics, including the Mayo score and Paediatric Ulcerative Colitis Activity Index (PUCAI). Mechanistically, subsequent results from published datasets and our validated clinical data all strongly implied that SLC26A2 was negatively correlated with the IL-17 signaling pathway, and positively associated with the tight junction, which led to abnormal immune cell infiltration and inflammatory injuries. After establishing the UC mice models in vivo by orally administration of DSS in portable water, SLC26A2 was significantly down-regulated at the mRNA or protein level, when compared to that in the control groups. Furthermore, the correlation analyses confirmed that SLC26A2 was positively associated with CLDN3, and negatively correlated with IL-17A expression in colon tissues. In addition, according to the SLC26A2 expression, UC patients were divided into different subgroups. The potential target drugs for UC treatment, such as progesterone, tetradioxin, and dexamethasone, were initially predicted and exerted anti-inflammatory effects via the common molecule-SLC26A2. Conclusions: SLC26A2 might be served as a protective candidate in the UC pathogenesis as well as a potential drug target for UC treatment.

Ulcerative colitis (UC) is an inflammatory bowel disease marked by gut inflammation and microbial dysbiosis. Exopolysaccharides (EPS) from probiotic bacteria have been shown to regulate microbial composition and metabolism, but their role in promoting probiotic growth and alleviating inflammation in UC remains unclear. Here, we investigate BLEPS-1, a novel EPS derived from Bifidobacterium longum subsp. longum XZ01, for its ability to promote the growth of Lactobacillus strains. We then tested a synbiotic formulation of BLEPS-1 and L. acidophilus in a DSS-induced UC mouse model. The combination of BLEPS-1 and L. acidophilus alleviated DSS-induced intestinal inflammation, outperforming either component alone. Administration of BLEPS-1 decreased the proportion of M1 macrophages in the intestine, while M2 macrophages were more abundant following L. acidophilus treatment. Together, BLEPS-1 and L. acidophilus synergistically modulated macrophage polarization toward the M2-type. Administration of BLEPS-1 and L. acidophilus together modulated gut microbiota composition and altered the gut metabolic profile, with BLEPS-1 and L. acidophilus promoting metabolism of short-chain fatty acids and aromatic amino acids, respectively. Our study identified a novel synbiotic formulation with potent immunomodulatory and metabolic activity, laying the groundwork for a promising therapeutic strategy to treat intestinal inflammatory diseases such as colitis.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract (GI) with a high incidence rate globally, and IBD patients are often accompanied by zinc deficiency. This review aims to summarize the potential therapeutic value of zinc supplementation in IBD clinical patients and animal models. Zinc supplementation can relieve the severity of IBD especially in patients with zinc deficiency. The clinical severity of IBD were mainly evaluated through some scoring methods involving clinical performance, endoscopic observation, blood biochemistry, and pathologic biopsy. Through conducting animal experiments, it has been found that zinc plays an important role in alleviating clinical symptoms and improving pathological lesions. In both clinical observation and animal experiment of IBD, the therapeutic mechanisms of zinc interventions have been found to be related to immunomodulation, intestinal epithelial repair, and gut microbiota's balance. Furthermore, the antioxidant activity of zinc was clarified in animal experiment. Appropriate zinc supplementation is beneficial for IBD therapy, and the present evidence highlights that alleviating zinc-deficient status can effectively improve the severity of clinical symptoms in IBD patients and animal models.

Polyacylated anthocyanins are known for their enhanced stability and immunosuppressive properties. Although peonidin-3-O-(3,6-O-dimalonyl-β-D-glucoside) (P3GdM) from black corncobs has demonstrated notable antibacterial and stress-resistance effects in plants, its regulatory role in inflammatory bowel disease (IBD) remains unexplored. In this study, P3GdM was isolated from black corncobs, and its potential as a treatment for dextran sulfate sodium (DSS)-induced colitis in mice was evaluated. The findings revealed that P3GdM significantly mitigated clinical symptoms, reduced the disease activity index (DAI), suppressed the production of pro-inflammatory cytokines and endotoxins, and repaired the intestinal barrier. Furthermore, P3GdM markedly improved DSS-induced gut microbiota dysbiosis, significantly increasing microbial diversity and enhancing the relative abundance of critical bacterial species such as Akkermansia muciniphila and Lactobacillus reuteri, while also stimulating the production of short-chain fatty acids (SCFAs) and lactic acid. Correlation analyses further revealed strong associations between key microbial taxa, pro-inflammatory factors, clinical symptoms, tight junction proteins, and SCFAs. These findings provide support for the potential of P3GdM as an adjunct therapy for intestinal disorders, particularly colitis.

Intestinal mucus, a viscoelastic medium with mucin2 (MUC2) as its main component, covers the surface of intestinal epithelial cells and protects the intestine from invasion, forming the first barrier of the intestinal tract. Unlike the small intestine, where the mucus layer is a single layer, the colonic mucus layer can be divided into a sterile inner layer and an outer layer with bacterial colonization. Many of the substances in the mucus layer have beneficial effects on the intestinal epithelium, but the mucus layer is often affected by a variety of factors, mainly microbiological, dietary, and immunological. Inflammatory bowel disease (IBD) is a disease of increasing morbidity worldwide, with a complex etiology and a high relapse rate. In recent years, the mucus barrier in IBD has received increasing attention and is considered a key factor in the pathogenesis of IBD. Loss of goblet cells (GCs) and changes in the composition and properties of the mucus layer material are commonly found in the colon of IBD patients. Damage to the mucus layer may make it easier for microorganisms to access the intestinal epithelium and cause inflammation. There are currently a number of herbs and other therapies that can be used to treat IBD and repair the damaged mucus barrier. This review highlights the important role of the mucus layer in IBD and the therapies that target the mucus layer in IBD.

Intestinal fibrosis, as a late-stage complication of inflammatory bowel disease (IBD), leads to bowel obstruction and requires surgical intervention, significantly lowering the quality of life of affected patients. SAA3, a highly conserved member of the serum amyloid A (SAA) apolipoprotein family in mice, is synthesized primarily as an acute phase reactant in response to infection, inflammation and trauma. An increasing number of evidence suggests that SAA3 exerts a vital role in the fibrotic process, even though the underlying mechanisms are not yet fully comprehended. This study utilized dextran sulfate sodium (DSS) to establish an IBD mouse model and observed that the SAA3-deficient mice exhibited more severe intestinal fibrosis. Our results further indicated that SAA3 genetic disruption in fibroblasts enhanced cell activation to myofibroblasts through HSPB1/NF-κB/TGF-β1/Smads signaling cascade, exacerbating the pathological phenotype of intestinal fibrosis. Collectively, our results shed novel lights on regulating SAA3 in intestinal fibrosis and indicate the potential to develop therapeutic strategies for IBD patients.

Inflammatory bowel disease is a chronic inflammatory condition predominantly affecting the intestines, encompassing both ulcerative colitis and Crohn disease (CD). As one of the most common gastrointestinal disorders, CD's pathogenesis is closely linked with the intestinal microbiota. Recently, fecal microbiota transplantation (FMT) has gained attention as a potential treatment for CD, with the effective reestablishment of intestinal microecology considered a crucial mechanism of FMT therapy. This article synthesizes the findings of population-based cohort studies to enhance our understanding of gut microbial characteristics in patients with CD. It delves into the roles of "beneficial" and "pathogenic" bacteria in CD's development. This article systematically reviews and compares data on clinical response rates, remission rates, adverse events, and shifts in bacterial microbiota. Among these studies, gut microbiome analysis was conducted in only 7, and a single study examined the metabolome. Overall, FMT has demonstrated a partial restoration of typical CD-associated microbiological alterations, leading to increased α-diversity in responders and a moderate shift in patient microbiota toward the donor profile. Several factors, including donor selection, delivery route, microbial state (fresh or frozen), and recipient condition, are identified as pivotal in influencing FMT's effectiveness. Future prospective clinical studies with larger patient cohorts and improved methodologies are imperative. In addition, standardization of FMT procedures, coupled with advanced genomic techniques such as macroproteomics and culture genomics, is necessary. These advancements will further clarify the bacterial microbiota alterations that significantly contribute to FMT's therapeutic effects in CD treatment, as well as elucidate the underlying mechanisms of action.

The global rise in Crohn's Disease (CD) incidence has intensified diagnostic challenges. This study identified circadian rhythm-related biomarkers for CD using datasets from the GEO database. Differentially expressed genes underwent Weighted Gene Co-Expression Network Analysis, with 49 hub genes intersected from GeneCards data. Diagnostic models were constructed using machine learning algorithms, and biologic therapy efficacy was predicted with advanced regression techniques. Single-cell sequencing showed high gene expression in stem cells, immune, and endothelial cells, with validation confirming significant differences between CD patients and controls. These findings suggest circadian rhythm-related genes as promising diagnostic biomarkers for CD.