The interplay between the gut microbiota and gastrointestinal hormones plays a pivotal role in the health of the host and the development of diseases. As a vital component of the intestinal microecosystem, the gut microbiota influences the synthesis and release of many gastrointestinal hormones through mechanisms such as modulating the intestinal environment, producing metabolites, impacting mucosal barriers, generating immune and inflammatory responses, and releasing neurotransmitters. Conversely, gastrointestinal hormones exert feedback regulation on the gut microbiota by modulating the intestinal environment, nutrient absorption and utilization, and the bacterial biological behavior and composition. The distributions of the gut microbiota and gastrointestinal hormones are anatomically intertwined, and close interactions between the gut microbiota and gastrointestinal hormones are crucial for maintaining gastrointestinal homeostasis. Interventions leveraging the interplay between the gut microbiota and gastrointestinal hormones have been employed in the clinical management of metabolic diseases and inflammatory bowel diseases, such as bariatric surgery and fecal microbiota transplantation, offering promising targets for the treatment of dysbiosis-related diseases.

Malnutrition is prevalent in patients with inflammatory bowel disease (IBD); however, its ability to predict the disease activity in IBD remains unexplored. Therefore, this study aimed to explore the association between malnutrition and disease activity in IBD.

In this retrospective study, we enrolled 1006 patients diagnosed with IBD from the First Affiliated Hospital of Wenzhou Medical University from 2011 to 2022. Malnutrition was assessed based on the prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and controlling nutritional status (CONUT) scores. Logistic regression analyses were performed to identify predictors for disease activity. Restricted cubic spline analysis was performed to evaluate the possible nonlinear relations, and subgroup analysis was performed to explore potential interactions. Additionally, prediction performances were compared through receiver operating characteristic curves, net reclassification improvement, and integrated discrimination improvement.

The prevalence of malnutrition calculated by the PNI, GNRI, and CONUT scores in IBD was 16.9%, 72.1%, and 75.6%, respectively and significant correlations were observed among them. Multivariate logistic regression analysis showed that PNI, GNRI, and CONUT were independent risk factors for disease activity, and no significant nonlinear relationship was observed between disease activity and all three indexes. No statistically significant interactive effect was found in nearly all the subgroups. GNRI showed the highest predictive value compared with PNI and CONUT. Additionally, combining any of the three indexes improved the ability of C-reactive protein to predict IBD activity.

All three nutritional indexes evaluated malnutrition to be an independent risk factor for IBD activity.

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.

A chronic inflammatory condition of the colon called ulcerative colitis (UC) is characterized by mucosal surface irritation that extends from the rectum to the near proximal colon portions. The rationale of this work was to conclude if dulaglutide (Dula) could protect rats from developing colitis caused by exposure to acetic acid (AA). Rats were randomly divided into seven groups (each with eight rats): Normal control, Dula control, AA (received 2 milliliters of 3% v/v AA through the rectum), Sulfasalazine (SLZ); given SLZ (100 mg/kg) orally from day 11 to day 21 then AA intrarectally on day 22 and Dula groups ( pretreated with 50, 100 or 150 μg/kg subcutaneous injection of Dula - once weekly for three weeks and AA on day 22 to induce ulcerative colitis, colon tissues and blood samples were taken on day 23. By generating colonic histological deviations such as inflammatory processes, goblet cell death, glandular hyperplasia, and mucosa ulcers, Dula dropped AA-induced colitis. Additionally, these modifications diminished blood lactate dehydrogenase (LDH), C-reactive protein (CRP), colon weight, and the weight/length ratio of the colon. In addition, Dula decreased the oxidative stress biomarker malondialdehyde (MDA) and increased the antioxidant enzymes (total antioxidant capacity (TAC), reduced glutathione (GSH), and superoxide dismutase (SOD) concentrations). Dula also significantly reduced the expression of transforming growth factor-1 (TGF-β1), phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT) signaling pathway, and the inflammatory cytokines: nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), and interferon-γ (IFN-γ) in colonic cellular structures. In addition, Dula enforced the levels of glucagon-like peptide-1 (GLP-1) and trefoil factor-3 (TFF-3) that were crucial to intestinal mucosa regeneration and healing of wounds. By modulating TGF-β1 in conjunction with other inflammatory pathways like PI3K/AKT and NF-κB, regulating the oxidant/antioxidant balance, and improving the integrity of the intestinal barrier, Dula prevented AA-induced colitis in rats.

Many currently proposed diets for inflammatory bowel disease (IBD) focus on increasing plant-based foods, although a vegetarian diet can still contain products such as emulsifiers and refined grains that are believed to negatively impact IBD incidence and progression. To better inform dietary management in IBD, we investigated the association between plant-based diets and the incidence and complications of IBD.

We leveraged data from the UK Biobank (UKB, 2009-2022) including 187,888 participants free of IBD at baseline and the European Prospective Investigation into Cancer and Nutrition (EPIC, 1991-2010) cohort including 341,539 individuals free of IBD across centres among Denmark, France, Germany, Greece, Italy, the Netherlands, Sweden and UK. Healthy and unhealthy diets were characterised using plant-based diet indexes (PDIs); in individual participants, these were based on the 24-h dietary recalls for UKB and food frequency questionnaires for EPIC. The primary outcome was the incidence of IBD; secondary outcomes evaluated endpoints of disease prognosis (IBD-related surgery, diabetes, cardiovascular diease, and all-cause mortality). Cox regression was applied to estimate hazard ratios (HRs).

In the UKB (925 incident IBD, median follow-up 11.6 years, IQR 1.3 years), higher adherence to healthy PDI was associated with a lower IBD risk (HR 0.75, 95% CI 0.60-0.94), while higher alignment to an unhealthy PDI associated with an increased risk (HR 1.48, 95% CI 1.21-1.82) when comparing extreme quintiles of PDIs. Among individuals with established IBD, healthy PDI was inversely associated (HR 0.50, 95% CI 0.30-0.83) and unhealthy PDI was positively associated (HR 2.12, 95% CI 1.30-3.44) with need for IBD-related surgery. We did not observe significant associations between PDIs and risk of cardiovascular disease, diabetes mellitus or mortality. In the EPIC study (548 incident IBD, median follow-up 14.5 years, IQR 7.0 years), the HR of incident IBD for healthy PDI was 0.71 (95% CI 0.59-0.85) and for unhealthy PDI was 1.54 (95% CI 1.30-1.84).

We provide evidence that the composition of a plant-based diet may be an important determinant of the risk of developing IBD, and of disease course after diagnosis. Further research is needed to explore the mechanistic pathways linking plant-based diets and IBD incidence and prognosis.

National Natural Science Foundation of China, Natural Science Fund for Distinguished Young Scholars of Zhejiang Province, National Undergraduate Training Program for Innovation and Entrepreneurship, CRUK Career Development Fellowship, The "Co-PI" project, Natural Science Fund for Excellent Young Scholars of Hunan Province.

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of cellular defense system against oxidative insults. Directly inhibiting the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 protein-protein interaction (PPI) has emerged as a promising approach to activate Nrf2 for the treatment of diseases associated with oxidative stress. Herein, we identified β-amino acids as privileged structural fragments for designing novel naphthalene sulfonamide-based Keap1-Nrf2 PPI inhibitors. Comprehensive structure-activity relationship (SAR) exploration identified compound 19 as the optimal inhibitor with an IC50 of 0.55 μM for disrupting the Keap1-Nrf2 interaction and a Kd of 0.50 μM for binding to Keap1. Further studies demonstrated that 19 effectively activated the Nrf2-regulated cytoprotective system and provided protective effects against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in both in vitro and in vivo models. These findings highlight the potential of β-amino acid substituted naphthalene sulfonamide Keap1-Nrf2 inhibitor 19 as a prospective therapeutic agent for UC via Keap1 targeting.

Ulcerative colitis (UC) is a recurrent, chronic disease whose main symptoms include weight loss, diarrhea, and blood in the stool. In recent years, the incidence of UC has been increasing year by year, which seriously affects the daily life of patients. Luteolin (Lut), as a flavonoid, is widely found in a variety of vegetables and fruits and has been shown to have a variety of pharmacological activities. This work investigated the effects of Lut on dextrose sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice, with a special focus on the role of endoplasmic reticulum (ER) stress in this. The outcomes demonstrated that colitis symptoms, including disease phenotype, elevated inflammatory factor levels, intestinal barrier damage, and gut microbiota disruption, were considerably alleviated in UC model mice treated with luteolin. Also, Lut alleviated ER stress and apoptosis in UC mice. We then explored the effects of Lut on ER stress and apoptosis induced by thapsigargin (TG) and tunicamycin (TM) in HT29 cells in vitro. It was found that Lut treatment inhibited TM/TG-induced ER stress and apoptosis. However, these inhibitory effects of Lut were attenuated by SIRT1 silencing in TM-treated HT29 cells. In conclusion, our results suggest that Lut supplementation in a mouse model of colitis improves the symptoms of colitis in mice, which provides a theoretical basis for further application of Lut in the prevention of inflammation-related diseases in humans.

Natural polysaccharides (NPs) are sugar chains bound by glycosidic bonds that are composed of at least 10 monosaccharides and have broad biological activity. The human body microbiome is a complex ecosystem that plays a role in host metabolism, immunity, and other important life activities. Numerous studies have demonstrated an obvious relationship between the gut flora and the occurrence of many human diseases. Many studies have reviewed and investigated the effects of polysaccharides on the microbiome, but the underlying mechanisms remain unclear. Most of these studies have focused on the effects of NPs on microbes, as they are important "foods" for the intestinal flora. However, polysaccharides can also affect microbes by improving gut homeostasis. Therefore, the purpose of this review is to introduce recent research that looks at how NPs affect microbiomes by directly acting as fermentation substrates and enhancing gut homeostasis. In addition, this study provides a succinct summary of NP extraction, purification, and structural characteristics, as well as a discussion of their structure‒activity correlations. This study also sheds light on future directions and obstacles in the use of NPs with protective properties, with the aim of providing insights into their potential applications in disease treatment.

Ulcerative colitis is one of the most common sorts of inflammatory bowel disease. This study investigates the protective effects of thymoquinone against sodium dodecyl sulfate (SDS)-induced intestinal damage and elucidates the underlying mechanisms using the Drosophila melanogaster model of ulcerative colitis. We found that Drosophila fed thymoquinone from larval to adult stages were resistant to SDS injury in adulthood. Thymoquinone pretreatment significantly restored the abnormal behaviors and intestinal morphological defects in Drosophila exposed to SDS. Moreover, thymoquinone protected the intestinal barrier function by inhibiting the overactivated c-Jun N-terminal kinase (JNK) pathway in the intestine induced by SDS. Further studies indicated that thymoquinone inhibits the JNK pathway by reducing intestinal reactive oxygen species (ROS) levels. This research provides novel pathological and mechanistic insights into the potential application of thymoquinone in developing functional foods or natural medicines, highlighting its significance in treating ulcerative colitis.

Bile acid metabolism mediated by gut microbiota is significantly related to immunity regulation that plays an important role in the development and treatment of inflammatory bowel disease (IBD). Our previous study has demonstrated that Panax notoginseng saponins (PNS) alleviate colitis due to the regulation of T helper 17/Regulatory T cells (Th17/Treg) balance via gut microbiota. However, the effects and mechanism of PNS on colitis pertinent to bile acid metabolism mediated by gut microbiota remain elusive. This study aims to investigate the anti-colitis mechanism of PNS by regulating the Th17/Treg balance pertinent to gut microbiota-bile acid metabolism. Results showed that PNS significantly decreased the relative abundance of Allobaculum, Dubosiella, Muribaculum, and Alistipes, and up-regulated the relative contents of conjugated bile acids, such as TCA and TCDCA. Fecal microbiota transplantation (FMT) showed that the gut microbiota remodeled by PNS had a regulatory effect on bile acid metabolism, and up-regulated the relative contents of TCA and TCDCA, which alleviated IBD and promoted Treg cell expression in vivo and in vitro. Taken together, PNS could reshape the profiling of gut microbiota to generate more TCA and TCDCA, which improve the balance of Th17/Treg to exert anti-IBD effects.

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition linked to gut microbiota dysbiosis and altered production of bacterial metabolites, including succinate, which is also a key intermediate in human mitochondrial energy metabolism in human cells. Succinate levels in the gut are influenced by microbial community dynamics and cross-feeding interactions, highlighting its dual metabolic and ecological importance. Extracellular succinate acts as a key signaling metabolite linking microbial metabolism to host physiology, with transient rises supporting metabolic regulation but chronic elevations contributing to metabolic disorders and disease progression. Succinate signals through its cognate receptor SUCNR1, which mediates adaptive metabolic responses under normal conditions but drives inflammation and fibrosis when dysregulated. IBD patients display a dysbiotic gut microbiota characterized by an increased prevalence of succinate-producing bacteria, contributing to elevated succinate levels in the gut and circulation. This imbalance drives inflammation, worsens IBD severity, and contributes to complications like Clostridioides difficile infection and fibrosis. Emerging evidence highlights the potential of intestinal and systemic succinate levels as indicators of microbial dysbiosis, with a bidirectional relationship between microbial composition and succinate metabolism. Understanding the factors influencing succinate levels and their interaction with dysbiosis shows promise in the development of therapeutic strategies to restore microbial balance. Approaches such as dietary fiber enrichment, prebiotics, and probiotics to enhance succinate-consuming bacteria, combined with targeted modulation of succinate pathways (e.g. SDH inhibitors, SUCNR1 antagonists), hold promise for mitigating inflammation and improving gut health in IBD.

Ulcerative colitis (UC) is a typical type of inflammatory bowel disease, which is often recurrent and directly related with colorectal cancer. Therefore, early prevention and treatment for UC is very necessary. Therefore, it is necessary to find efficient substances to treat the UC with less side effects than drugs. Exopolysaccharides (EPSs) are important bioactive constituents of lactic acid bacteria. The study evaluated the effects of EPS1 produced by Levilactobacillus brevis M-10 on UC by determining the weight, the disease activity index (DAI) and the physiological and biochemical indexes. The pathological structures of colon were observed. The gut microbiota and the short-chain fatty acids were analyzed. The results demonstrated high dose (HD) of EPS1 (400 mg/kg-BW) that had the best effects on UC mice. The HD group restored body weight, decreased DAI and alleviated shortening of the length of the colon, recovered liver tissue, declined lipopolysaccharide, and myeloperoxidase. Also the HD group showed that the expression of tight junction proteins increased, IL-10 up-regulated, IL-6, IL-1β, and TNF-α down-regulated, and the gut microbiota dysbiosis balanced. The HD group markedly elevated the relative abundance of Lachnospiraceae_NK4A136_group, Unclassified-Lachnospiraceae, and Unclassified- Muribaculaceae. Acetic acid, propionic acid, and n-butyric acid were significantly increased in the HD group (P < 0.05). The study could provide a theoretical basis and material support for the exploration of safe functional food in alleviating and preventing UC.

The pathogenesis of inflammatory bowel diseases (IBD) involves genetic, environmental, immunological, and microbial factors; however, it remains unclear. Pro-inflammatory interleukin 8 (IL-8), encoded by the CXCL8 gene, assumes a crucial chemotactic role in leukocyte migration.

This study aimed to investigate whether an association exists between IBD and two CXCL8 variants, namely, c.-251A>T (rs4073) and c.91G>T (rs188378669), and IL-8 concentration. We analyzed the distribution of both variants among 353 Polish IBD patients and 200 population subjects using pyrosequencing, competitive allele-specific PCR and Sanger sequencing.

The c.91T stop-gained allele was significantly more frequent in IBD patients (2.12%) than in controls (0.25%) (p = 0.0121), while the c.-251T allele frequencies were similar (54% vs. 51.5%, p = 0.4955). Serum IL-8 concentrations, measured using ELISA, were higher in IBD patients with the c.91 GG genotype compared to healthy controls (mean, 70.02 vs. 51.5 pg/ml, p<0.01) and patients with c.91 GT (mean, 61.73 pg/ml). Moreover, clinical data indicated that carriers of the c.91T variant need more often corticosteroids and surgical treatment of the disease than GG homozygous IBD patients.

This suggest that the CXCL8 c.91T allele may influence IBD manifestation and the course of the disorders in Polish patients, potentially serving as a novel target for future studies and therapeutic approaches.

Peroxisome proliferator-activated receptors (PPARs), as nuclear receptors, modulate both lipid metabolism and inflammatory/immune processes. This study examines the impact of modulating the activities of the PPAR subtypes PPARβ/ð and PPARγ on the gut microbiota in inflammatory bowel disease (IBD).

Mice with dextran sulfate sodium (DSS)-induced acute colitis were treated with the PPARγ agonist pioglitazone, PPARβ/δ agonist GW0742, or their respective antagonists (GW9662, GSK3787). Weight loss, diarrhea severity, hematochezia, and disease activity index were assessed daily. Upon study completion, colon length, histopathology, and mRNA levels of the intestinal barrier and inflammatory markers were measured. Occludin and E-cadherin levels were assessed via immunofluorescence analysis, and cecal samples underwent 16S rRNA sequencing for gut microbiota analysis.

Our findings revealed that the agonists pioglitazone and GW0742 effectively suppressed DSS-induced colitis, improved clinical symptoms, reversed colon shortening, and mitigated histological damage. Conversely, their antagonists, GW9662 and GSK3787, failed to alleviate inflammation and sometimes exacerbated disease indicators. Both agonists modulated DSS-induced dysbiosis by reducing the abundance of proinflammatory cytokine-associated microbiota, including Bacteroides, Enterococcus, and Escherichia-Shigella, while enhancing both α-diversity and β-diversity of the gut microbiome, to restore equilibrium.

Our findings reveal that activation of PPARγ and PPARβ/δ can balance the gut microbiota in mice and ameliorate experimental colitis in mice. Thus, PPARγ and PPARβ/δ have protective effects against IBD and could serve as novel therapeutic targets for its treatment.

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.

The immunological effects of treatment with exclusive enteral nutrition (EEN) in Crohn's disease (CD) remain unknown. We characterized the plasma levels of inflammation-related proteins (IRPs) in children with CD and ulcerative colitis (UC) compared with noninflammatory controls (non-IBD) and explored the effect of EEN in CD.

Ninety-two IRPs were quantified using Olink proteomics in children with CD (n = 53), UC (n = 11), and non-IBD (n = 19). For 18 children with active CD, IRPs were measured before and after 8 weeks of EEN. Relationships with disease phenotype and response to EEN were studied.

Compared with non-IBD, patients with active UC and CD had different levels of 27 (24 raised, 3 decreased) and 29 (26 raised, 3 decreased) IRPs, respectively. Exclusive enteral nutrition modified the levels of 19 IRPs (13 increased, 6 decreased including CCL23, interleukin-24, interleukin-6, and MMP-1). More pronounced changes in IRP profile were observed in patients with ileal involvement and a ≥50% decrease in fecal calprotectin during EEN compared with those with colonic involvement and a <50% decrease in fecal calprotectin, respectively. A machine-learning model utilizing baseline IRP profile predicted response to EEN with a sensitivity of 89%, specificity of 57%, and accuracy of 73%. Thymic stromal lymphopoietin was the most important IRP in the model, this being higher in responders.

Inflammation-related proteins may be useful in the differential diagnosis of IBD. Exclusive enteral nutrition extensively modulated IRPs levels in children with active CD with more pronounced effects observed in patients who showed a reduction in FC and had ileal disease involvement.

This study aimed to analyze the gut phageome in Japanese patients with ulcerative colitis (UC) in endoscopic remission. Fecal samples were collected from 35 UC patients and 22 healthy controls. The gut microbiome was analyzed using 16S rRNA amplicon sequencing, and the phageome was profiled through shotgun metagenomic sequencing. Compared to healthy controls, UC patients showed a significant reduction in phageome richness (observed species and Chao1 index). Principal coordinate analysis revealed a significant difference in beta-diversity between UC and healthy controls (p = 0.001). The abundance of temperate phages was higher in UC (15.2%) compared to healthy controls (5.9%), although this was not statistically significant (p = 0.088). Temperate phages associated with Coprococcus sp., Bacteroides sp. KFT8, and Faecalibacterium prausnitzii, as well as virulent phages associated with Ruminococcus gnavus and Lactobacillus farciminis, were increased in UC patients. Conversely, phages associated with Thermosipho affectus, Bacteroides sp. OF03-11BH, and Odoribacter splanchnicus were decreased in UC patients. Phages associated with the genera Odoribacter (p = 0.0004), Ruminococcus (p = 0.009), and Veillonella (p = 0.013) were significantly reduced in UC patients. The gut phageome of inactive UC patients exhibited notable alterations in viral composition compared to healthy controls. These results suggest that changes in the gut phageome might be involved in the pathogenesis of UC.

Accumulating research suggests both eating disorders (EDs) and internalizing disorders (e.g., anxiety, depression) are associated with gastrointestinal disease (e.g., irritable bowel syndrome, inflammatory bowel disease). However, the mechanisms underlying comorbidity with gastrointestinal disease-and whether they may differ for eating and internalizing disorders-remain poorly understood. Addressing these gaps is a critical first step to refining etiologic models of comorbidity and identifying potential targets for intervention.

Participants included female and male twins ages 18-65 from the population-based MSU Twin Registry (N = 5883). Lifetime history of EDs, internalizing disorders, and gastrointestinal disease was assessed via questionnaire. We first examined whether EDs and internalizing disorders were independently associated with gastrointestinal disease phenotypically. We then used trivariate Cholesky decomposition twin models to investigate whether EDs and internalizing disorders were related to gastrointestinal disease through overlapping or distinct genetic/environmental pathways.

Eating (OR = 2.54, p = 0.009) and internalizing (OR = 2.14, p < 0.001) disorders were independently associated with gastrointestinal disease. Conclusions were unchanged after adjusting for important covariates (e.g., body mass index, age) and did not significantly differ across sex. Twin models suggested genetic influences shared by all three conditions explained their co-occurrence, with 31% of the variance in EDs and 12% of the variance in gastrointestinal disease attributable to genetic influences shared with internalizing disorders.

Shared genetic mechanisms may contribute to comorbidity between EDs, internalizing disorders, and gastrointestinal disease. Identifying overlapping molecular pathways could potentially lead to novel interventions that simultaneously address all three conditions.

70 % of the ulcerative colitis (UC) linked gene loci are associated with other autoimmune or immunodeficient diseases. The phosphatase activity of PTPN22 can regulate the development of T cells and contribute to regulate the level of inflammation in autoimmune diseases. We produced PTPN22-CS thymus-specific transgenic mice, which suppressed PTPN22 enzyme activity in the thymocytes. Overexpressed PTPN22-CS facilitated the development of the thymocytes towards CD4+T cells and resulted in an increased proportion of the Th1 and Treg cells in the UC mesenteric lymph nodes. PTPN22-CS promoted the activation of the JAK/STAT signaling pathway in the Th1 and Treg cells that localized in the colon, resulting in an excessive production of inflammatory mediators such as IL-2 and IFN-γ. Consequently, PTPN22-CS contributes to the inflammatory response of ulcerative colitis. In summary, the tyrosine phosphatase activity of PTPN22 plays a role in modulating UC by regulating T cell differentiation and modulating the JAK/STAT signaling pathway, thereby influencing the inflammatory response in colonic. These findings provide new insight into the association between PTPN22 and the pathogenesis of UC.

Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions primarily affecting the gastrointestinal tract. Previous studies established the role of the NF-κB signaling pathway in the development of IBDs, suggesting that anti-inflammatory therapies might offer a viable treatment strategy. Tanshinone IIA and salviadione, both derived from Salviae Miltiorrhizae Radix et Rhizoma, possess anti-inflammatory and anti-oxidative activities. A series of new compounds were synthesized by hybridizing salviadione with tanshinone. Among these compounds, 15a showed beneficial effects in LPS-induced acute lung injury and diabetes-induced renal injury mouse models. The current study explored the therapeutic efficacy of 15a using both acute and chronic colitis models and elucidated the underlying mechanisms. DSS-induced colitis models were established in mice, where acute colitis was treated with compound 15a (5 or 10 mg·kg-1·d-1) for 8 days, while chronic colitis mice received compound 15a (5 or 10 mg·kg-1·d-1, i.g.) during 2.5% DSS administration. The 15a treatment significantly alleviated DSS-induced pathological and inflammatory damages in both acute and chronic colitis mouse models. In mouse intestinal epithelial cell line MODE-K, pretreatment with compound 15a (5 or 10 μM) significantly suppressed LPS + L18-MDP-induced inflammatory responses. The receptor-interacting serine/threonine kinase 2 (RIPK2) was identified as a direct binding target of compound 15a using microarrays and recombinant human proteins. Moreover, 15a could directly bind to and inhibit the phosphorylation of RIPK2, leading to the suppression of the NF-κB and MAPK signaling pathways. Furthermore, LEU153 and VAL32 were identified within the KD domain of RIPK2 as critical amino residues for the binding of 15a. Briefly, the current findings demonstrate that compound 15a holds promise as a therapeutic agent for managing acute and chronic colitis.

Pectin, as a kind of soluble dietary fiber in hawthorns, exhibits a wide range of biological activities. Nevertheless, its role and mechanism in ulcerative colitis (UC) remain unclear. In this study, the effect of hawthorn pectin (HP) against dextran sulfate sodium (DSS)-induced UC in mice and its underlying mechanism were evaluated. HP dramatically alleviated the pathological symptoms related to colitis in mice, displaying an increase in body weight and colon length and inhibition in colon damage. Importantly, HP inhibited the serum levels of inflammation-related factors including tumor necrosis factor-α, IL-1β, and IL-6 as well as decreased the number of F4/80-positive macrophages in the colon. Moreover, the expression levels of ZO-1 and occludin proteins related to intestinal permeability were increased. A significant decrease in a dose-dependent manner at the gut bacterial genus level (such as Alistipes, Colidextribacter, and Blautia) was observed after HP treatment. HP improved the metabolic pathways of gut microbiota and increased the concentrations of short-chain fatty acids in cecal contents of UC mice. Intriguingly, fecal microbiota transplantation intervention with an HP-derived microbiome notably increased the length and relieved histopathological changes of colon in UC mice. Conclusively, our study provided valuable insights into the potential of HP as a prebiotic for maintaining intestinal health and confirmed that HP could ameliorate UC in a gut microbiota-dependent manner.

Inflammatory bowel disease (IBD) represents a group of chronic inflammatory disorders of the gastrointestinal tract. Despite substantial advances in our understanding of IBD pathogenesis, the currently available therapeutic options remain limited in their efficacy and often come with significant side effects. Therefore, there is an urgent need to explore novel approaches for the management of IBD. One promising avenue of investigation revolves around the use of histone deacetylase (HDAC) inhibitors, which have garnered considerable attention for their potential in modulating gene expression and curbing inflammatory responses. This review emphasizes the pressing need for innovative drugs in the treatment of IBD, and drawing from a wealth of preclinical studies and clinical trials, we underscore the multifaceted roles and the therapeutic effects of HDAC inhibitors in IBD models and patients. This review aims to contribute significantly to the understanding of HDAC inhibitors' importance and prospects in the management of IBD, ultimately paving the way for improved therapeutic strategies in this challenging clinical landscape.

The incidence of ulcerative colitis (UC) has been rising rapidly in recent years, and there is currently no effective method to prevent its recurrence. Owing to its long treatment duration, difficulty in treatment, prolonged remission, and high costs, it has attracted global attention. Exploring safe, effective, and sustainable treatment regimens has become an urgent global issue. Traditional Chinese medicine (TCM) has unique advantages such as low cost, low drug resistance, and fewer side effects, and has accumulated rich experience in the treatment of UC.

Ferroptosis, as a new form of non-apoptotic cell death, is characterized by iron homeostatic imbalance and lipid peroxidation in the redox system. Studies have shown that inhibited ferroptosis in intestinal epithelial cells can protect the intestinal mucosa. Targeted intervention in ferroptosis may be a new direction for the treatment of UC.

We conducted a systematic literature search with Google Scholar, PubMed, Web of Science, ScienceDirect and X-mol databases have been utilized to retrieve relevant literature up to October 2024, using keywords included ferroptosis, Inflammatory bowel disease (IBD), UC, Crohn's disease and TCM, Chinese traditional prescription, Chinese medicine extract and active ingredients. The existing literature was comprehensively studied and sorted out.

Currently, UC is mainly treated with drugs, including corticosteroids, amino salicylates, biologics, and immunomodulators, but drug resistance and adverse reactions are common. Increasing evidence suggests that TCM may treat UC by interfering with ferroptosis. Scholars have confirmed that TCM can inhibit ferroptosis, and recent studies have shown that TCM can not only inhibit iron dependent lipid peroxidation in intestinal cells but also enhance the antioxidant and anti-inflammatory abilities of intestinal mucosa, thus playing a role in the treatment of UC. This review explores the relevance of TCM intervention in ferroptosis and the treatment of UC, discusses the possible mechanisms of ferroptosis in UC, and aims to provide a basis for the diagnosis and treatment of UC.

It is revealed that TCM targeted ferroptosis has a good application prospect in the treatment of UC, providing a theoretical basis for elucidating the pathogenesis of UC and the study of TCM targeting ferroptosis regulating lipid metabolism in the treatment of UC, and providing a new perspective for the treatment of IBD in the future.

Crohn's disease (CD) is a complex inflammatory condition with the potential for severe complications. Pyroptosis is an inflammatory form of programmed cell death, and the role of pyroptosis in intestinal epithelial cells of CD remains unclear.

In this study, pyroptosis-related hub genes were identified using datasets from the Gene Expression Omnibus database through differential expression analysis, machine learning algorithms, and single-cell sequencing analysis. Hub gene expression was validated using clinical samples and a trinitrobenzene sulfonic acid (TNBS)-induced colitis rat model.

Six pyroptosis-related hub genes (CASP1, IRF1, ZBP1, MLKL, MMP1, HTRA1) were identified. IRF1 and CASP1 exhibited significant upregulation in CD, including both colonic and ileal subtypes, with good diagnostic value across different CD subtypes. Additionally, these two genes were not elevated in any other intestinal disorders, except for ulcerative colitis. Single-cell sequencing analysis revealed a significant interaction between intestinal epithelial cells (IECs) and monocytes. The clinical samples further confirmed that the mRNA levels of IRF1 and CASP1 were significantly higher in CD patients compared to healthy controls. Additionally, the colitis rat model validated the upregulation of Irf1 and Casp1 at both mRNA and protein levels.

Our findings identified IRF1 and CASP1 as critical pyroptosis-related biomarkers for IECs in CD, contributing to the understanding of pyroptosis in CD pathogenesis.

β-Hydroxy β-Methylbutyrate (HMB), derived from leucine, is known for its role in anti-oxidation and anti-inflammation. But, the application of HMB in IBD treatment is not fully understood, highlighting the requirement for further research.

We aimed to examine the effects of HMB treatment on DSS-induced chronic colitis in mice and explore its underlying mechanisms.

To simulate colonic inflammation, a murine colitis model was generated by using DSS induction. Critical indicators such as body weight, colon length, disease activity index (DAI), and gross pathology were thoroughly monitored. Immunohistochemistry assay was conducted to assess the expression of Occludin and F4/80. Flow cytometry was employed to evaluate the expression levels of CD80 and CD86. qPCR was performed to measure cytokine expression (IL-6, IL-1β, TNF-α, IL-22, CXCL2, iNOS). RNA sequencing was carried out using bone-marrow derived dendritic macrophage cells (BMDMs).

Our study indicates that HMB treatment substantially mitigated colonic damage in murine models of DSS-induced colitis, highlighting its anti-inflammatory potential. Notably, HMB significantly enhanced the expression of Occludin in these mice. Furthermore, HMB downregulated proinflammatory markers such as IL-6, IL-1β, and TNF-α as well as CXCL2 in the colon tissue. In vitro experiments also revealed that HMB reduced production of proinflammatory cytokines induced by DSS and suppressed the expression levels of CD80 and CD86 in macrophage cells. On a mechanistic level, we demonstrated the anti-inflammatory effects of HMB by reducing the phosphorylation of p-ERK and p-p65, thereby limiting cytokine production in both in vivo and in vitro settings.

These findings indicate that HMB possesses anti-inflammation against intestinal inflammation and may hold promise as a potential therapeutic candidate for IBD treatment. There's growing interest in combining traditional anti-inflammatory agents with supplements like HMB to improve outcomes in complex IBD cases. HMB's role in established muscle preservation and reduction of systemic inflammation as described in this study could make it a valuable adjunct in IBD therapy.

Inflammatory Bowel Disease (IBD) is an inflammatory intestinal disease, and with prolonged illness duration, the annual risk of IBD progressing to colitis-associated colorectal cancer (CAC) gradually increases. In recent years, there has been a noticeable trend towards the application of traditional Chinese medicine (TCM) in the treatment of CAC.

This comprehensive review summarizes the pathogenesis of CAC and details the therapeutic benefits of TCM in treating CAC, including various TCM prescriptions and ingredients, establishing the theoretical foundation for the application of TCM in CAC treatment.

We assessed literature published before March 24, 2024, from several databases, including Web of Science, PubMed, Scopus and Google Scholar. The keywords used include "traditional Chinese medicine", "traditional Chinese medicine prescriptions", "traditional Chinese medicine ingredients", "herbal medicine", "colitis-associated colorectal cancer", "inflammatory bowel disease", "colorectal cancer" and "colitis-cancer transformation". We conducted a comprehensive collection and collation of pertinent scientific articles from various databases, focusing on the efficacy of TCM in the prevention and treatment of "colitis-cancer transformation".

This paper provides a concise summary and thorough analysis of twenty-eight prescriptions and ingredients of TCM for the prevention and treatment of CAC, based on existing experimental and clinical research. There are positive signs that TCM can effectively prevent and treat the "colitis-cancer transformation" through repairing the intestinal mucosal barrier, correcting intestinal flora imbalance, and regulating intestinal immune responses.

TCM possesses comprehensive regulatory advantages that are multifaceted, multilevel, and multitarget. It has a definite curative effect in the prevention and treatment of CAC. It is essential to enhance the clinical efficacy of TCM in the prevention and treatment of CAC based on syndrome differentiation and treatment, with the assistance of modern medicine.

Anthocyanins are natural flavonoids derived from plants, widely recognized for their health-promoting effects, specifically to treat inflammatory bowel disease (Crohn's disease and ulcerative colitis). However, certain limitations are associated with their use, including instability, low solubility and permeability, poor gastrointestinal digestion, and low bioavailability. In this review, nano-carriers (e.g., liposome, polymersome, exosome, halloysite nanotubes, dendrimer, and nano-niosome, etc.) were summarized as anthocyanins delivery vehicles to treat inflammatory bowel disease. Recent progress on emerging strategies involved surface functionalization, responsive release, magnetic orientation, and self-assembly aggregation to address intestinal inflammation through nano-carriers and potential mechanisms were discussed. Anthocyanins, water-soluble pigments linked by glycoside bonds have attracted attention to alleviate intestinal inflammation related diseases. Anthocyanins can address intestinal inflammation by exerting their health beneficial effects such as anti-oxidative, anti-inflammatory, regulating the intestinal flora, and promoting apoptosis. Moreover, nano-carriers were discussed as oral delivery system for maximized bioefficacy of anthocyanins and to address concerns related to their low solubility and permeability, poor gastrointestinal metabolism, and low bioavailability were discussed. A future perspective is proposed concerning anthocyanin-loaded nano-carriers, different strategies to improve their efficacy, and developing functional food to treat intestinal inflammation.

Preclinical and clinical observations indicate that the probiotic Lactobacillus rhamnosus GG (LGG) can modulate colonic inflammation. However, the underlying mechanisms have not been explored in depth. Here, we demonstrate that oral administration of live LGG alleviated inflammatory colitis by increasing IL-10 expression in intestinal Ly6C+ monocytes. Mechanistically, LGG induced IL-10 production via the stimulator of IFN genes (STING)/TBK1/NF-κB (RELA) signaling pathway in intestinal Ly6C+ monocytes, enhancing their immune-suppressive function. Elevated IL-10 subsequently activated IL-10 signaling in Ly6C+ monocytes, resulting in an IL-10-based autocrine regulatory loop and inhibition of proinflammatory cytokine production. Furthermore, LGG shifted the gut microbial community and its metabolic functions, leading to intestinal immune responses against colitis. Fecal microbiota transplantation from LGG-colonized mice alleviated immune checkpoint blockade-associated colitis. Our findings highlight the importance of STING signaling in IL-10-dependent antiinflammatory immunity and establish an empirical basis for developing oral administration of live LGG as an efficient and safe therapeutic strategy against inflammatory colitis.

The literature documenting the value of drug-like molecules found in natural products is vast. Although many dietary and herbal remedies have been found to be effective for treating intestinal inflammation, the identification of their active components has lagged behind. In this study, we find that a major ginger component, furanodienone (FDN), is a selective pregnane X receptor (PXR) ligand with agonistic transcriptional outcomes. We show that FDN binds within a sub-pocket of the PXR ligand binding domain (LBD), with subsequent alterations in LBD structure. Using male mice, we show that orally provided FDN has potent PXR-dependant anti-inflammatory outcomes that are colon-specific. Increased affinity and target gene activation in the presence of synergistically acting agonists indicates further opportunities for augmenting FDN activity, efficacy and safety. Collectively, these results support the translational potential of FDN as a therapeutic agent for the treatment and prevention of colonic diseases.

Sanguinarine constitutes the main components of Macleaya cordata, and exhibits diverse biological and pharmacological activities. This study investigated the effects of sanguinarine chloride hydrate (SGCH) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice. Five groups were designed to investigate the effects of SGCH on the pathological symptoms, the mRNA expression levels of inflammatory cytokines, colonic mucosal barrier damage, microbiota composition, and SCFAs metabolism in UC mice. The administration of SGCH in DSS-induced UC mice resulted in the amelioration of pathological symptoms, as evidenced by an increase in body weight, a decrease in disease activity index score, elongation of colon length, reduction in spleen index, and improvement in colon injury. SGCH can regulate the expression of inflammatory cytokines (IL-6, TNF-α, IL-1β and IL-10) and tight junction proteins (ZO-1 and Occludin) associated with UC. SGCH exhibited a significant decrease in NF-κB P65 mRNA expression levels, accompanied by a significantly reduced protein level of NF-κB P-P65/P65. Further studies revealed SGCH effectively reversed the decrease in intestinal microbiota diversity induced by UC, thereby promoting the growth of beneficial bacteria such as Akkermansia, Alistipes, and norank_o_Clostridia_UCG-014. Correlation analysis demonstrated a positive association between butanoic acid, propanoic acid, isobutyric acid, isovaleric acid, valeric acid, hexanoic acid with Colidextribacter, while Coriobacteriaceae_UCG-002 exhibited a negative correlation with butanoic acid, acetic acid and propanoic acid. In conclusion, the administration of SGCH can ameliorate clinical symptoms in UC mice, regulate the expression of inflammatory cytokines and tight junction proteins, modulate intestinal microbiota metabolism and SCFAs production.

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is primarily known for its gastrointestinal manifestations. However, emerging evidence suggests a potential link between IBD and an increased risk of stroke, likely mediated by chronic systemic inflammation, endothelial dysfunction, and a prothrombotic state. Despite this growing recognition, the exact mechanisms and extent of this association remain unclear, highlighting a critical knowledge gap. This review aims to systematically analyze the association between IBD and stroke, exploring the underlying vascular mechanisms and identifying potential risk factors contributing to cerebrovascular events in IBD patients. A comprehensive literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines across PubMed, Scopus, and Google Scholar using keywords such as "IBD," "Stroke," "Chronic inflammation," "Cerebrovascular risk," and "Gut-brain axis." After screening 150 studies and applying inclusion and exclusion criteria, six studies were included in the final synthesis. The findings suggest that chronic inflammation in IBD plays a key role in increasing stroke risk through endothelial dysfunction and a heightened prothrombotic state, with additional risk factors such as atrial fibrillation during active IBD flares further contributing to cerebrovascular events. While biologic therapies, including tumor necrosis factor (TNF)-alpha inhibitors, are effective in reducing systemic inflammation, their impact on mitigating stroke risk remains inconclusive. Given the potential role of IBD as an independent risk factor for stroke, a multidisciplinary approach to management is crucial. Addressing modifiable risk factors through pharmacologic interventions such as biologics, statins, and antiplatelet agents, alongside lifestyle modifications, could help reduce cerebrovascular complications in IBD patients. Further research is needed to explore personalized therapeutic strategies and establish clearer preventive guidelines for this at-risk population.

To assess transmural remission in patients with Crohn's disease using low-dose small bowel computed tomography (CT) perfusion scans.

Forty six patients were divided into active and remission phases based on Crohn's Disease Activity Index (CDAI) and C-reactive protein (CRP). Dual-source CT enterography with low-dose perfusion scans was conducted to generate perfusion parameter maps, including blood flow (BF), blood volume (BV), time to peak (TTP), mean transit time (MTT), and permeability of surface (PS). We compared differences in perfusion parameter values of intestinal walls, mesenteric fat, and lymph nodes between two groups. Receiver operating characteristic (ROC) curves were plotted, and area under the curve (AUC), sensitivity, specificity, and cutoff values were calculated.

The BF, BV, TTP, MTT, and PS values of the intestinal wall were significantly higher in the active phase (P0.05). Additionally, lymph node BF and TTP displayed significant differences (P<0.01).

Dual-source CT enterography with low-dose perfusion scans enables quantitative assessment of Crohn's disease microcirculation in intestinal walls, mesenteric fat, and lymph nodes. These quantitative indicators provide strong diagnostic efficacy and offer insights into whether the disease is in transmural remission.

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), is a chronic condition impacting both the gastrointestinal tract and the immune system. Intestinal inflammation and epithelial injury are the pathological features of IBD. Recent studies have reported that some strategies of dietary restriction (DR) can regulate immune system, correct the immune disorders, and improve some immune-associated diseases such as IBD. However, as a form of DR, the effect of intermittent fasting (IF) on the IBD remains unknown. In this study, we investigated the therapeutic efficacy of two cycles of IF on the IBD mouse model induced by dextran sulfate sodium (DSS). It was found that two cycles of IF significantly decreased the score of the disease activity index (DAI) and alleviated the IBD-related symptoms. In addition, IF reversed the shortening of colon length mediated by DSS, significantly increased the number of colonic crypts, and decreased the colonic histological score. Furthermore, the proportion of CD4+ T cells in both the spleen and mesenteric lymph node was reduced by IF treatment. The expression of serum pro-inflammatory cytokines IL-1β, TNF-α, and IL-6 was restrained by IF intervention. Moreover, IF administration significantly reduced the number of leukocytes and macrophages infiltrating around the crypt base in the colon. In conclusion, these results demonstrated that IF administration can alleviate the symptoms and pathology of IBD in the DSS-induced IBD mouse model by reducing the intestinal inflammation.

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.

Individuals with inflammatory bowel disease (IBD) are at a higher risk of developing mental disorders, such as anxiety and depression. The imbalance between the intestinal microbiota and its host, known as dysbiosis, is one of the factors, disrupting the balance of metabolite production and their signaling pathways, leading to disease progression. A metabolomics approach can help identify the role of gut microbiota in mental disorders associated with IBD by evaluating metabolites and their signaling comprehensively. This narrative review focuses on metabolomics studies that have comprehensively elucidated the altered gut microbial metabolites and their signaling pathways underlying mental disorders in IBD patients. The information was compiled by searching PubMed, Web of Science, Scopus, and Google Scholar from 2005 to 2023. The findings indicated that intestinal microbial dysbiosis in IBD patients leads to mental disorders such as anxiety and depression through disturbances in the metabolism of carbohydrates, sphingolipids, bile acids, neurotransmitters, neuroprotective, inflammatory factors, and amino acids. Furthermore, the reduction in the production of neuroprotective factors and the increase in inflammation observed in these patients can also contribute to the worsening of psychological symptoms. Analyzing the metabolite profile of the patients and comparing it with that of healthy individuals using advanced technologies like metabolomics, aids in the early diagnosis and prevention of mental disorders. This approach allows for the more precise identification of the microbes responsible for metabolite production, enabling the development of tailored dietary and pharmaceutical interventions or targeted manipulation of microbiota.

Ulcerative colitis (UC) is a relapsing disease with an increasing morbidity and prevalence. Dietary polysaccharides have recently become a research hotspot because of their therapeutic effects and safety on UC. Our previous research elucidated that pectic polysaccharide from Phyllanthus emblica L. (PEP-1) could alleviate dextran sodium sulfate-induced UC mice. Herein, metabolomics and transcriptomics were further applied to disclose the underlying mechanisms behind PEP-1's anti-inflammatory effects. PEP-1 intervention altered the serum metabolite contents and pathways represented by decreasing xanthine and sphinganine levels. Changes in gene expressions correlated with metabolite variations led by the suppression of the expression of the inflammatory factors, colorectal cancer promoter, and NF-κB pathway as well as the enhancement of tight junctions. This study demonstrated that the ameliorating effect of chronic UC was partially ascribed to the alteration of the serum metabolites and changes in gene expression.