Higher Fiber Intake is Associated with Reduced Risk of Related Surgery among Individuals with Inflammatory Bowel Disease in a Prospective Cohort Study.

BACKGROUND: Evidence for the effects of dietary fiber on adverse outcomes in individuals with inflammatory bowel disease (IBD) is insufficient and controversial. OBJECTIVES: We aimed to prospectively explore the association between dietary fiber intake and the risk of IBD-related surgery. METHODS: We identified 5580 individuals with diagnosed IBD [Crohn disease (CD, n = 1908) and ulcerative colitis (UC, n = 3672)] at baseline in the UK Biobank via electronic medical records and self-reported information. Dietary fiber intake was estimated by a partial fiber score derived from a valid food frequency questionnaire. IBD-related surgery (enterotomy, perianal surgery, and others) was ascertained via inpatient data. Cox proportional model was applied to estimate hazard ratios with 95% confidence intervals (CIs) of dietary fiber in quartiles for the risk of IBD-related surgery. RESULTS: During a mean follow-up period of 11.2 y, we documented 624 IBD-related surgery among 5580 individuals with IBD (mean age, 57.3; 52.8% females). Compared with individuals in the lowest quartiles, those with second to fourth quartiles of fiber intake were associated with 23% (95% CI: 5%, 38%, P = 0.015), 29% (95% CI: 11%, 43%, P = 0.003), and 28% (95% CI: 10%, 43%, P = 0.005) reduced risk (P-trend = 0.002) of IBD-related surgery. Similar associations were observed in CD (P-trend = 0.005) but not UC (P-trend = 0.131). We observed inverse associations of fiber in vegetables and fruits (P-trend = 0.017 and 0.007) but positive associations of fiber in bread (P-trend = 0.046) with the risk of IBD-related surgery. CONCLUSIONS: Higher intake of fiber is associated with reduced IBD-related surgery risk in patients with IBD with CD but not UC.

The efficacy and safety of endoscopic ultrasound-guided fine-needle biopsy in gallbladder masses.

BACKGROUND: Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is a widely used modality for acquiring various target samples, but its efficacy in gallbladder masses is unknown. The aim of this retrospective study was to evaluate the efficacy and safety of EUS-FNB in patients with gallbladder masses. METHODS: The study samples were composed of patients from March 2015 to July 2019 who needed to identify the nature of gallbladder masses through EUS-FNB. The outcomes of this study were the adequacy of specimens, diagnostic yields, technical feasibility, and adverse events of the EUS-FNB in gallbladder masses. RESULTS: A total of 27 consecutive patients with a median age of 58 years were included in this study. The 22-gauge FNB needle was feasible in all lesions. The median follow-up period of the patients was 294 days. The specimens sufficient for diagnosis account for 89% (24/27) and 93% (25/27) in cytology and histology, respectively. The overall diagnostic yields for malignancy showed the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.45% [95% confidence interval (CI): 75.12%-99.76%], 100% (95% CI: 46.29%-100%), 100% (95% CI: 80.76%-100%), 83.33% (95% CI: 36.48%-99.12%), and 96.30% (95% CI: 80.20%-99.99%), respectively. The subgroup analysis revealed that FNB could obtain sufficient specimens and high diagnostic yields in both gallbladder mass < 20.5 mm group and ≥ 20.5 mm group. One patient experienced mild abdominal pain after the procedure and recovered within one day. CONCLUSIONS: EUS-FNB is a reasonable diagnostic tool for the pretreatment diagnosis of patients with gallbladder masses, especially for patients who may miss the opportunity of surgery and need sufficient specimens to identify the pathological type so as to determine chemotherapy regimens. Further large-scale studies are needed to confirm our conclusion.

Comparison between modified wet suction and dry suction technique for endoscopic ultrasound-guided fine-needle biopsy in pancreatic solid lesions.

BACKGROUND AND AIM: Although endoscopic ultrasound-guided fine-needle biopsy is widely applied, there is no clear consensus on the optimal biopsy technique. We described a modified wet suction technique (MWEST) with the aim to compare the efficacy and safety between MWEST and the dry suction technique (DST). METHODS: In this prospective, randomized, crossover, single-blinded study, patients with suspected pancreatic malignancy were randomized to the DST (group A) or MWEST (group B) for the first pass, and the two techniques were performed alternately. The primary outcome was the comparison of specimen adequacy and diagnostic yield between the techniques. Secondary outcomes included the macroscopic visible core length, blood contamination of specimens, and adverse events of both techniques. RESULTS: From January 2019 to September 2019, 216 passes were performed in 50 patients. The specimen adequacy was significantly higher in "per-lesion" (P = 0.026), "per-pass" (cytology: P = 0.034; histology: P = 0.042), and first-pass analysis (P = 0.034) for MWEST than for DST. In diagnostic yield, MWEST showed significantly superior histological yield (P = 0.014) and first-pass analysis (κ: MWEST: 0.743 and DST: 0.519) compared with DST. The median macroscopic visible core lengths were 8 mm (interquartile range: 3.25-15 mm) and 10 mm (interquartile range: 5.25-15 mm) for DST and MWEST, respectively (P = 0.036). Blood contamination was significantly more serious in DST than in MWEST (cytology: P = 0.021; histology: P = 0.042). CONCLUSIONS: Endoscopic ultrasound-guided fine-needle biopsy with MWEST resulted in significantly better quality of specimen, histological, and first-pass diagnostic yields and comparable safety compared with the DST. MWEST is preferred for endoscopic ultrasound-guided fine-needle biopsy in pancreatic solid lesions.

HIF-1a regulates hypoxia-induced autophagy via translocation of ANKRD37 in colon cancer.

Autophagy is a basic catabolic response that eukaryotic cells use to degrade unnecessary or dysfunctional cellular components in an orderly and regulated manner. It plays important roles in maintaining cellular homeostasis, energy homeostasis, response to environmental stimuli, and the development of cancer. In solid tumors, hypoxia induces an increased HIF-1a that activates autophagy. However, the exact mechanism by which induced HIF-1a stimulates autophagy in cancer cells remains elusive. In the present study, we confirmed that ANKRD37 is upregulated in colon cancer tissue. Moreover, the higher expression level of ANKRD37 is related to a poorer survival rate. Using RNA interference, immunoblot, and immunofluorescence, we discovered that in cancer cell line RKO, hypoxia-induced HIF-1a regulates autophagy activity by increasing ANKRD37 level. In addition, intranuclear ANKRD37 played an important role in the regulation of hypoxia-induced autophagy. The translocation of ANKRD37 into cell nuclear is required for promoting cell growth and HIF-1a induced autophagy. These findings provide new insights to understand the hypoxia regulation mechanisms and the role of autophagy in cancer development.

Down-regulation of SLC35C1 induces colon cancer through over-activating Wnt pathway.

The canonical Wnt signalling pathway is a critical pathway involved in the proliferation of cells. It has been well-established that it plays the central role during colorectal carcinogenesis and development. Yet the exact molecular mechanism of how the canonical Wnt pathway is fine-tuned remains elusive. We found that SLC35C1, a GDP-fucose transporter, negatively regulates the Wnt signalling pathway. We show here that SLC35C1 is reduced in all colon cancer by both immunohistochemistry images and TCGA data, whereas ß-catenin is increased. Down-regulation of SLC35C1 is also detected by real-time PCR in stage 3 and stage 4 colorectal cancer tissues. Moreover, analysing the TCGA database with cBioPortal reveals the negative correlation of SLC35C1 mRNA level to the expression of ß-catenin. Reduced SLC35C1 significantly promotes cell proliferation and colony formation of HEK293 cells. Meanwhile, in HEK293 cells silencing SLC35C1 activates canonical Wnt pathway, whereas overexpressing SLC35C1 inhibits it. Consistently, the reduction of SLC35C1 in HEK293 cells also elevated the mRNA level of Wnt target genes C-myc, Axin2 and Cyclin D1, as well as the secretion of Wnt3a. In conclusion, we identified SLC35C1 as a negative regulator of the Wnt signalling pathway in colon cancer. Decreased SLC35C1 may cause over-activation of Wnt signalling in colorectal cancer.

Increased expression of reticulon 3 in neurons leads to reduced axonal transport of ß site amyloid precursor protein-cleaving enzyme 1.

BACE1 is the sole enzyme responsible for cleaving amyloid precursor protein at the ß-secretase site, and this cleavage initiates the generation of ß-amyloid peptide (Aß). Because amyloid precursor protein is predominantly expressed by neurons and deposition of Aß aggregates in the human brain is highly correlated with the Aß released at axonal terminals, we focused our investigation of BACE1 localization on the neuritic region. We show that BACE1 was not only enriched in the late Golgi, trans-Golgi network, and early endosomes but also in both axons and dendrites. BACE1 was colocalized with the presynaptic vesicle marker synaptophysin, indicating the presence of BACE1 in synapses. Because the excessive release of Aß from synapses is attributable to an increase in amyloid deposition, we further explored whether the presence of BACE1 in synapses was regulated by reticulon 3 (RTN3), a protein identified previously as a negative regulator of BACE1. We found that RTN3 is not only localized in the endoplasmic reticulum but also in neuritic regions where no endoplasmic reticulum-shaping proteins are detected, implicating additional functions of RTN3 in neurons. Coexpression of RTN3 with BACE1 in cultured neurons was sufficient to reduce colocalization of BACE1 with synaptophysin. This reduction correlated with decreased anterograde transport of BACE1 in axons in response to overexpressed RTN3. Our results in this study suggest that altered RTN3 levels can impact the axonal transport of BACE1 and demonstrate that reducing axonal transport of BACE1 in axons is a viable strategy for decreasing BACE1 in axonal terminals and, perhaps, reducing amyloid deposition.

Circulating 25-hydroxyvitamin D concentration can predict bowel resection risk among individuals with inflammatory bowel disease in a longitudinal cohort with 13 years of follow-up.

BACKGROUND: Although the beneficial properties of vitamin D in anti-inflammation and immunity-modulation are promising in the management of inflammatory bowel disease (IBD), data were limited for the critical IBD prognosis. The association between serum vitamin D levels and the risk of bowel resection in individuals with IBD remains largely unknown. MATERIALS AND METHODS: We performed a longitudinal cohort study among 5474 individuals with IBD in the UK Biobank. Serum 25-hydroxyvitamin D [25(OH)D] was measured using direct competitive chemiluminescent immunoassay. Bowel resection events were ascertained via national inpatient data. Multivariable-adjusted Cox proportional hazard regression was used to examine the association between serum 25(OH)D and bowel resection risk, presented with hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline (RCS) was used to evaluate dose-response associations. RESULTS: During a mean follow-up of 13.1 years, we documented 513 incident bowel resection cases. Compared to participants with vitamin D deficiency, non-deficient participants showed a significantly reduced bowel resection risk in IBD (HR 0.72, 95% CI 0.59-0.87, P=0.001), Crohn's disease (CD, HR 0.74, 95% CI 0.56-0.98, P=0.038), and ulcerative colitis (UC, HR 0.73, 95% CI 0.57-0.95, P=0.020). When comparing extreme quintiles of 25(OH)D level, participants with IBD showed a 34% reduced risk of bowel resection (95% CI 11%-51%, P=0.007) and participants with UC showed a 46% reduced risk (95% CI 19%-64%, P=0.003), while this association was not significant in CD (HR 0.93, 95% CI 0.59-1.45, P=0.740). Linear dose-response associations were observed using the RCS curve (all P-nonlinearity>0.05). CONCLUSION: Increased serum level of 25(OH)D is independently associated with reduced bowel resection risk in IBD. This association was significant in UC but may not be stable in CD. Vitamin D deficiency is a risk factor for bowel resection in individuals with IBD, and may be an effective metric in predicting and risk-screening surgical events.

Sedentary lifestyle, physical activity, and gastrointestinal diseases: evidence from mendelian randomization analysis.

BACKGROUND: The causal associations of physical activity and sedentary behavior with the risk of gastrointestinal disease are unclear. We performed a Mendelian randomization analysis to examine these associations. METHODS: Genetic instruments associated with leisure screen time (LST, an indicator of a sedentary lifestyle) and moderate-to-vigorous intensity physical activity (MVPA) at the genome-wide significance (P < 5 × 10-8) level were selected from a genome-wide association study. Summary statistics for gastrointestinal diseases were obtained from the UK Biobank study, the FinnGen study, and large consortia. Multivariable MR analyses were conducted for genetically determined LST with adjustment for MVPA and vice versa. We also performed multivariable MR with adjustment for genetically proxied smoking, body mass index (BMI), waist-to-hip ratio, type 2 diabetes, and fasting insulin for both exposures. FINDINGS: Genetically proxied longer LST was associated with an increased risk of gastrointestinal reflux, gastric ulcer, duodenal ulcer, chronic gastritis, irritable bowel syndrome, diverticular disease, Crohn's disease, ulcerative colitis, non-alcoholic fatty liver disease, alcoholic liver disease, cholangitis, cholecystitis, cholelithiasis, acute pancreatitis, chronic pancreatitis, and acute appendicitis. Most associations remained after adjustment for genetic liability to MVPA. Genetic liability to MVPA was associated with decreased risk of gastroesophageal reflux, gastric ulcer, chronic gastritis, irritable bowel syndrome, cholecystitis, cholelithiasis, acute and chronic pancreatitis. The associations attenuated albeit directionally remained after adjusting for genetically predicted LST. Multivariable MR analysis found that BMI and type 2 diabetes mediated the associations of LST and MVPA with several gastrointestinal diseases. INTERPRETATION: The study suggests that a sedentary lifestyle may play a causal role in the development of many gastrointestinal diseases. FUNDING: Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001), Natural Science Foundation of Hunan Province (2021JJ30999), Swedish Heart-Lung Foundation (Hjärt-Lungfonden, 20210351), Swedish Research Council (Vetenskapsrådet, 2019-00977), Swedish Cancer Society (Cancerfonden), the Wellcome Trust (225790/7/22/Z), United Kingdom Research and Innovation Medical Research Council (MC_UU_00002/7) and National Institute for Health Research Cambridge Biomedical Research Centre (NHIR203312).

Higher dietary fibre intake is associated with lower risk of inflammatory bowel disease: prospective cohort study.

BACKGROUND: Limited prospective studies that have examined the association of dietary fibre with IBD have provided inconsistent evidence. AIM: To examine any associations between dietary fibre intake and subsequent incidence of IBD, Crohn's disease (CD) and ulcerative colitis (UC) METHODS: We conducted a prospective cohort study of 470,669 participants from the UK Biobank and estimated dietary fibre intake from a valid food frequency questionnaire at baseline. Incident IBD was ascertained from primary care data and inpatient data. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between dietary fibre intake and the risk of IBD, CD and UC. RESULTS: During an average follow-up of 12.1 years, we ascertained 1473 incident IBD cases, including 543 cases of CD and 939 cases of UC. Comparing the lowest quintiles, an inverse association was observed between dietary fibre intake and risk of IBD (HR 0.74, 95% CI 0.58-0.93, p = 0.011) and CD (HR 0.48, 95% CI 0.32-0.72, p < 0.001), but not UC (HR 0.92, 95% CI 0.69-1.24, p = 0.595). For specified sources, dietary fibre intake from fruit and bread decreased the risk of CD, while dietary fibre intake from cereal decreased the risk of UC. CONCLUSIONS: Higher consumption of dietary fibre was associated with a lower risk of IBD and CD, but not UC. Our findings support current recommendations to increase the intake of dietary fibre.

Differential expression and bioinformatics analysis of exosome circRNAs in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignant tumor with an unfavorable prognosis. Increasing evidence indicated circRNAs were associated with the pathogenesis and progression of tumors, but data on the expression of serum exosomal circRNAs in PDAC are scarce. This study attempted to explore the prognostic value and function of serum exosomes in PDAC patients. METHODS: Microarray-based circRNA expression was determined in PDAC and paired with normal serum samples, and the intersection of differentially expressed circRNAs (DECs) in serum exosomal samples and GSE79634 tissue samples was conducted. A specific CircRNA database was applied to investigate DECs binding miRNAs. Target genes were predicted using the R package multiMiR. Cox regression analyses were applied for constructing a prognostic model. The immunological characteristics analysis was carried out through the TIMER, QUANTISEQ, XCELL, EPIC, and ssGSEA algorithms. RESULTS: 15 DECs were finally identified, and a circRNA-miRNA-mRNA network was established. A prognostic risk model was developed to categorize patients according to the risk scores. Furthermore, the association between risk score and immune checkpoint genes including CD80, TNFSF9, CD276, CD274, LGALS9, and CD44 were significantly elevated in the high-risk group, while ICOSLG and ADORA2A were upregulated in the low-risk group. CONCLUSIONS: Our results may provide new clues for the prognosis and treatment of PDAC.

Ambient Air Pollution and Risk of Enterotomy, Gastrointestinal Cancer, and All-Cause Mortality among 4,708 Individuals with Inflammatory Bowel Disease: A Prospective Cohort Study.

BACKGROUND: Previous studies indicated that air pollution plausibly increases the risk of adverse outcomes in inflammatory bowel disease (IBD) via proinflammatory mechanisms. However, there is scant epidemiological data and insufficient prospective evidence assessing associations between ambient air pollution and clinical outcomes of IBD. OBJECTIVES: We aimed to investigate the associations between ambient air pollution and clinical outcomes among individuals with IBD. METHODS: Leveraging data from the UK Biobank, we included 4,708 individuals with IBD recruited in the period 2006-2010 in this study. A land use regression model was used to assess annual mean concentrations of ambient air pollutants nitrogen including oxides (NOx), nitrogen dioxide (NO2), and particulate matter (PM) with aerodynamic diameter ≤10µm (PM10) and PM with aerodynamic diameter ≤2.5µm (PM2.5). Individuals with IBD were followed up for incident clinical outcomes of enterotomy, gastrointestinal cancer, and all-cause mortality, ascertained via death registry, inpatient, primary care, and cancer registry data. Cox proportional hazard model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for the magnitude of the associations. RESULTS: During a mean follow-up of 12.0 y, 265 enterotomy events, 124 incident gastrointestinal cancer, and 420 death events were documented among individuals with IBD. We found that each interquartile range (IQR) increase in exposure to PM2.5 was associated with increased risk of enterotomy (HR=1.16; 95% CI: 1.00, 1.34, p=0.043), whereas an IQR increase in exposure to NOx (HR=1.10; 95% CI: 1.01, 1.20, p=0.016), NO2 (HR=1.16; 95% CI: 1.03, 1.29, p=0.010), PM10 (HR=1.15; 95% CI: 1.03, 1.30, p=0.015), and PM2.5 (HR=1.14; 95% CI: 1.02, 1.28, p=0.019) was associated with increased risk of all-cause mortality among individuals with IBD. We did not observe any significant associations between air pollutants and gastrointestinal cancer in the primary analyses. Consistent results were observed in subgroup and sensitivity analyses. CONCLUSIONS: Ambient pollution exposure was associated with an increased risk of enterotomy and all-cause mortality among individuals with IBD, highlighting the important role of environmental health in improving the prognosis of IBD. https://doi.org/10.1289/EHP12215.

Intake of Ultra-processed Foods Is Associated with an Increased Risk of Crohn's Disease: A Cross-sectional and Prospective Analysis of 187 154 Participants in the UK Biobank.

BACKGROUND AND AIMS: Ultra-processed food [UPF] consumption has been linked to globally increasing incidence and prevalence of chronic diseases, including inflammatory bowel diseases [IBD]. We aimed to investigate the association between UPF consumption and IBD incidence, prevalence, and IBD-relevant outcomes. METHODS: We performed a cross-sectional and prospective cohort study in 187 854 individuals included in the national UK Biobank, using 24-h dietary recall questionnaires. Multivariable logistic regression and Cox proportional hazard regression were used to examine the association between UPFs and the prevalence and incidence risk of IBD, respectively. RESULTS: A total of 185 849 participants with a mean age of 56.2 were included, with a mean follow-up of 9.84 years. During follow-up, 841 developed IBD (251 Crohn's disease [CD], and 590 ulcerative colitis [UC]). UPF intake in IBD patients was significantly higher: CD: odds ratio [OR] 1.94 (95% confidence interval [CI]: 1.52, 2.49, p <0.001); UC: OR 1.39 [95% CI: 1.17, 1.65, p <0.001]. Compared with low consumption, higher UPF consumption was significantly associated with incident CD: hazard ration [HR] 2.00 [95% CI: 1.32, 3.03, p = 0.001], but not UC. We also found a significant association between UPF intake and need of IBD-related surgery: HR 4.06 [95% CI: 1.52, 10.86, p = 0.005]. CONCLUSION: Higher intake of UPFs was associated with higher incidence of CD, but not UC. In individuals with a pre-existing diagnosis of IBD, consumption of UPFs was significantly higher compared with controls, and was associated with an increased need for IBD-related surgery. Further studies are needed to address the impact of UPF intake on disease pathogenesis and outcomes.

Metabolic dysfunction-associated fatty liver disease and liver function markers are associated with Crohn's disease but not Ulcerative Colitis: a prospective cohort study.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is recently recognized as a condition featured with metabolic dysfunctions in liver. It has been supposed that MAFLD might contribute to the development of IBD, but evidence from prospective cohort studies is lacking and inconclusive. METHODS: A total of 221,546 females and 183,867 males from the UK Biobank cohort enrolled in 2006-2010 were included to examine whether MAFLD and liver function markers were related to incident IBD. MAFLD was identified based on hepatic steatosis defined by fatty liver index plus the prevalence of overweight, type 2 diabetes mellitus, or at least two metabolic abnormalities. Biomarker related to liver function (albumin [ALB], alkaline phosphatase [ALP], alanine transaminase [ALT], aspartate transaminase [AST]; gamma-glutamyl transferase [GGT], total bilirubin [TB], total protein [TP]) was measured using colorimetric or enzymatic assays. The incidence of IBD was ascertained based on primary care and inpatient records. Cox proportional hazard model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for the magnitude of their associations. RESULTS: With a mean follow-up of 12.1 years, 2228 incident IBD cases were documented. We identified 150,385 individuals with MAFLD at baseline and 86% participants' circulating liver function markers were within the normal range. Participants with MAFLD were associated with a 12% (HR 1.12, 95% CI 1.03, 1.23, p = 0.012) increased risk of IBD compared with those without MAFLD at baseline; the association was stronger (p-Heterogeneity = 0.006) with Crohn's disease (HR 1.35, 95% CI 1.15, 1.59, p < 0.001) than ulcerative colitis (HR 1.03, 95% CI 0.93, 1.15, p = 0.57). As for the serum liver function markers, the HRs of IBD for per 1-SD increment in ALB, ALP, AST, and TB concentration were 0.86 (95% CI 0.83, 0.90, p < 0.001), 1.18 (95% CI 1.13, 1.24, p < 0.001), 0.95 (95% CI 0.91, 0.99, p = 0.027), 0.92 (95% CI 0.87, 0.96, p < 0.001), respectively. We did not observe significant associations of GGT and TP with IBD. CONCLUSIONS: Individuals with MAFLD were at increased risk of developing IBD, especially CD, but not UC. Circulating levels of liver function biomarkers as the surrogate indicators of MAFLD were also associated with IBD risk.

Adverse health effects of emerging contaminants on inflammatory bowel disease.

Inflammatory bowel disease (IBD) is becoming increasingly prevalent with the improvement of people's living standards in recent years, especially in urban areas. The emerging environmental contaminant is a newly-proposed concept in the progress of industrialization and modernization, referring to synthetic chemicals that were not noticed or researched before, which may lead to many chronic diseases, including IBD. The emerging contaminants mainly include microplastics, endocrine-disrupting chemicals, chemical herbicides, heavy metals, and persisting organic pollutants. In this review, we summarize the adverse health effect of these emerging contaminants on humans and their relationships with IBD. Therefore, we can better understand the impact of these new emerging contaminants on IBD, minimize their exposures, and lower the future incidence of IBD.

Azelaic Acid Regulates the Renin-Angiotensin System and Improves Colitis Based on Network Pharmacology and Experimentation.

Inflammatory bowel disease (IBD), which encompasses Crohn's disease and ulcerative colitis, has a complicated etiology that might be brought on by metabolic dysbiosis. Previous metabonomic studies have found a correlation between decreased azelaic acid (AzA) and IBD. Herein, data from the Metabolomics Workbench showed that the content of AzA decreased in IBD patients (PR000639) and dextran sulfate sodium (DSS)-induced mice (PR000837). The effects of AzA on IBD were then examined using a DSS-induced mouse model, and the results demonstrated that AzA alleviated clinical activity, decreased pro-inflammatory cytokine production, and reduced CD4+CD25+Foxp3+Treg percentages in mesenteric lymph nodes. Through network pharmacology analysis, we discovered 99 candidate IBD-associated genes that are potentially regulated by AzA. After the enrichment analysis of the candidate genes, the renin-angiotensin system (RAS) pathway was one of the most substantially enriched pathways. Additionally, AzA reversed the increased expression of important RAS components (ACE, ACE2, and MAS1L) following DSS induction, suggesting that AzA exerts therapeutic effects possibly via the RAS pathway. This study suggests that AzA may be a promising drug for treating IBD.

Fatty acids and lipid mediators in inflammatory bowel disease: from mechanism to treatment.

Inflammatory Bowel Disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract. Though the pathogenesis of IBD remains unclear, diet is increasingly recognized as a pivotal factor influencing its onset and progression. Fatty acids, essential components of dietary lipids, play diverse roles in IBD, ranging from anti-inflammatory and immune-regulatory functions to gut-microbiota modulation and barrier maintenance. Short-chain fatty acids (SCFAs), products of indigestible dietary fiber fermentation by gut microbiota, have strong anti-inflammatory properties and are seen as key protective factors against IBD. Among long-chain fatty acids, saturated fatty acids, trans fatty acids, and ω-6 polyunsaturated fatty acids exhibit pro-inflammatory effects, while oleic acid and ω-3 polyunsaturated fatty acids display anti-inflammatory actions. Lipid mediators derived from polyunsaturated fatty acids serve as bioactive molecules, influencing immune cell functions and offering both pro-inflammatory and anti-inflammatory benefits. Recent research has also highlighted the potential of medium- and very long-chain fatty acids in modulating inflammation, mucosal barriers, and gut microbiota in IBD. Given these insights, dietary intervention and supplementation with short-chain fatty acids are emerging as potential therapeutic strategies for IBD. This review elucidates the impact of various fatty acids and lipid mediators on IBD and delves into potential therapeutic avenues stemming from these compounds.

Adiposity as a risk factor for inflammatory bowel disease and the mediating effect of metabolic and inflammatory status: A population-based cohort study.

BACKGROUND: To examine whether general and abdominal adiposity was a risk factor for the new-onset of inflammatory bowel disease (IBD) and the potential mediating effect of metabolic and inflammation status. METHODS: A total of 492,998 individuals free of IBD recruited from 2006 to 2010 in the UK Biobank were included in our study, with ongoing follow-up linking to the health-related outcome. Multivariable Cox regression models were used to evaluate the associations between general adiposity (body mass index) and abdominal adiposity (waist circumference) and the subsequent risk of IBD and its subtype. We also investigated the potential mediating effects of metabolic and inflammation status by carrying out exploratory mediation analyses. RESULTS: During a median follow-up of 12.5 years, we documented 2954 incident IBD cases (915 Crohn's disease [CD] and 2039 ulcerative colitis). After adjustment for important confounders, body mass index (hazard ratio [HR] highest quintile [Q5] vs. lowest quintile [Q1] = 1.18, 95% confidence interval [CI] 1.04-1.32; P-trend = 0.006) and waist circumference (HR Q5 vs. Q1  = 1.30, 95% CI 1.14-1.49; P-trend <0.001) showed a positive association with the risk of IBD. The associations were partially mediated by metabolic status (24%; 15%), C-reactive protein (36%; 19%) and inflammation score (82%; 46%). CONCLUSIONS: Adiposity bore a risk factor for incident IBD, whereas unhealthy metabolism, especially inflammation, seemed to be an important intermediate condition between the association. Our findings provide evidence for possible mechanisms relating adiposity to IBD from an epidemiological perspective, and experimental studies are needed for further demonstration.

Bacteroides vulgatus alleviates dextran sodium sulfate-induced colitis and depression-like behaviour by facilitating gut-brain axis balance.

Background: Patients with inflammatory bowel disease (IBD) have a higher prevalence of depression. Gut microbiota dysbiosis plays an important role in IBD and depression. However, few studies have explored the characteristic microbiota of patients with IBD and depression (IBDD), or their role in IBDD. Methods: We performed deep metagenomic sequencing and 16S rDNA quantitative PCR to characterise the gut microbial communities of patients with IBDD and patients with IBD without depression (IBDND). We then assessed the effect of the microbiota on colitis and depression in mouse models of dextran sulfate sodium salt (DSS)-induced colitis and lipopolysaccharide (LPS)-induced depression. Furthermore, liquid chromatography-tandem mass spectrometry was used to analyse the microbiota-derived metabolites involved in gut-brain communication. Evans Blue tracer dye was used to assess blood-brain barrier (BBB) permeability. Results: Our results showed that the faecal abundance of Bacteroides vulgatus (B. vulgatus) was lower in patients with IBDD than in those with IBDND. In the DSS-induced colitis mouse model, the B. vulgatus group showed a significantly lower disease activity index score, lesser weight loss, and longer colon length than the DSS group. Moreover, B. vulgatus relieved depression-like behaviour in the DSS-induced colitis mouse model and in the LPS-induced depression mouse model. Furthermore, the key metabolite of B. vulgatus was p-hydroxyphenylacetic acid (4-HPAA), which was found to relieve intestinal inflammation and alleviate depression-like behaviours in mouse models. By increasing the expression of the tight junction protein claudin-5 in the vascular endothelium of the BBB, B. vulgatus and 4-HPAA play critical roles in gut-brain communication. Conclusion: B. vulgatus and B. vulgatus-derived 4-HPAA ameliorated intestinal inflammation and relieved depressive symptoms through the gut-brain axis. Thus, administration of B. vulgatus or 4-HPAA supplementation is a promising therapeutic strategy for treating IBD, particularly IBDD.

Willingness to Undergo Gastroscopy for Early Gastric Cancer Screening and Its Associated Factors During the COVID-19 Pandemic - A Nationwide Cross-Sectional Study in China.

Purpose: This study aimed to investigate the willingness of Chinese adults aged 40 years and older to undergo gastroscopy for gastric cancer (GC) screening during the COVID-19 pandemic in 2020. The secondary purpose was to identify factors influencing willingness to undergo gastroscopy. Methods: A cross-sectional questionnaire survey was conducted in selected cities and counties from nine provinces in China using a multi-stage sampling approach. A multivariate logistic regression model was used to determine the independent predictors of willingness to undergo gastroscopy. Results: This study included 1900 participants, and 1462 (76.95%) responded that they would undergo gastroscopy for GC screening. Participants of younger age, from the eastern region, living in an urban area, with higher educational levels, with Helicobacter pylori (H. pylori) infection, or with precancerous stomach lesions, were more willing to undergo gastroscopy. The top four reasons to reject gastroscopy were fear of pain or discomfort, worry about a possible devastating test result, no symptoms in self-feeling, and concern about the high expense. Of all those who would reject gastroscopy for GC screening, 36.76% (161/438) would be willing to accept painless gastroscopy, while 24.89% (109/438) would be willing to undergo gastroscopy screening if higher medical reimbursement rates were available. Participants considered that gastroscopy was a relatively fearful and unknown procedure, accompanied by high risks and benefits compared to all other life events. Conclusion: In general, 76.95% of participants over 40 years old were willing to undergo gastroscopy for GC screening in China during the COVID-19 pandemic. Participants' willingness to undergo GC screening increased due to medical resource constraints and increased interest in their health. Individuals with H. pylori infection are more likely to undergo gastroscopy, whereas old age individuals, those with lower educational levels, and those living in rural areas are more likely to reject gastroscopy.