Abstract Introduction Colorectal cancer (CRC) is one of the leading oncogenic disorders, both in terms of incidence and mortality. The etiology of the disease is certainly multifactorial. Various risk factors like alcohol consumption, smoking, CRC family history, inflammatory bowel disease, hormone therapy, aspirin/nonsteroidal anti-inflammatory drugs use, higher body mass index, consumption of red and/or processed meat, insufficient physical activity, and decreased intake of fruit and vegetables have been pointed out; however, there is not enough support evidence for a single particular causative mechanism. Recently, gut bacterial microbiota has been shown to influence significantly the pathogenesis of CRC. However, little attention is paid to the putative impact of plasmids in gut flora. Material and methods We have designed and tested the workflow for semi-selective isolation and amplification of random circular sequences. The exploitation of rolling circle amplification (RCA) with a random hexamers protocol is crucial for the outcome. Results Our results suggest that it is possible to isolate and amplify plasmid DNA from gut flora and further process, sequence, and identify them. Discussion Little is known about the interactions between bacterial plasmids and human cells. The collection of plasmid sequencing data and the comparison of CRC patients and healthy control sequences can be the first step to elucidating this phenomenon.
32The gut microbes in inflammatory bowel disease: Future novel target option for pharmacotherapy
The gut microbes in inflammatory bowel disease: Future novel target option for pharmacotherapy
18A Systematic Review of Inflammatory Bowel Disease Epidemiology and Health Outcomes in Sexual and Gender Minority Individuals
A Systematic Review of Inflammatory Bowel Disease Epidemiology and Health Outcomes in Sexual and Gender Minority Individuals
Read more31Patterns of NSAIDs Use and Their Association with Other Analgesic Use in CKD.
Avoiding nonsteroidal anti-inflammatory drugs is important for safe CKD care. This study examined nonsteroidal anti-inflammatory drug use patterns and their association with other analgesic use in CKD. The Chronic Renal Insufficiency Cohort Study is an observational cohort study that enrolled 3939 adults ages 21-74 years old with CKD between 2003 and 2008 using age-based eGFR inclusion criteria. Annual visits between June of 2003 and December of 2011 were organized into 15,917 visit-pairs (with an antecedent and subsequent visit) for 3872 participants with medication information. Demographics, kidney function, and clinical factors were ascertained along with report of nonsteroidal anti-inflammatory drug or other analgesic use in the prior 30 days. In our study, 24% of participants reported nonsteroidal anti-inflammatory drug use at baseline or at least one follow-up study visit. Having a 10 ml/min per 1.73 m2 higher eGFR level at an antecedent visit was associated with higher odds of starting nonsteroidal anti-inflammatory drugs at a subsequent visit (odds ratio, 1.44; 95% confidence interval, 1.34 to 1.56). Seeing a nephrologist at the antecedent visit was associated with lower odds of starting or staying on nonsteroidal anti-inflammatory drugs at a subsequent visit (odds ratio, 0.70; 95% confidence interval, 0.56 to 0.87 and odds ratio, 0.61; 95% confidence interval, 0.46 to 0.81, respectively). Starting and stopping nonsteroidal anti-inflammatory drugs were both associated with higher odds of increasing the number of other analgesics (odds ratio, 1.52; 95% confidence interval, 1.25 to 1.85 and odds ratio, 1.78; 95% confidence interval, 1.39 to 2.28, respectively) and higher odds of increasing the number of opioid analgesics specifically (odds ratio, 1.92; 95% confidence interval, 1.48 to 2.48 and odds ratio, 1.46; 95% confidence interval, 1.04 to 2.03, respectively). Nonsteroidal anti-inflammatory drug use is common among patients with CKD but less so among those with worse kidney function or those who see a nephrologist. Initiation or discontinuation of nonsteroidal anti-inflammatory drugs is often associated with supplementation with or replacement by, respectively, other analgesics, including opioids, which introduces possible drug-related problems when taking these alternative analgesics.
Read more262Fungal Signature in the Gut Microbiota of Pediatric Patients With Inflammatory Bowel Disease.
Inflammatory bowel disease (IBD) involves dysregulation of mucosal immunity in response to environmental factors such as the gut microbiota. The bacterial microbiota is often altered in IBD, but the connection to disease is not fully clarified and gut fungi have recently been suggested to play a role as well. In this study, we compared microbes from all 3 domains of life-bacteria, archaea, and eukaryota-in pediatric patients with IBD and healthy controls. A stool sample was collected from patients with IBD (n = 32) or healthy control subjects (n = 90), and bacterial, archaeal, and fungal communities were characterized by deep sequencing of rRNA gene segments specific to each domain. Patients with IBD (Crohn's disease or ulcerative colitis) had lower bacterial diversity and distinctive fungal communities. Two lineages annotating as Candida were significantly more abundant in patients with IBD (P = 0.0034 and P = 0.00038, respectively), whereas a lineage annotating as Cladosporium was more abundant in healthy subjects (P = 0.0025). There were no statistically significant differences in archaea, which were rare in pediatric samples compared with those from adults. Pediatric IBD is associated with reduced diversity in both fungal and bacterial gut microbiota. Specific Candida taxa were found to be increased in abundance in the IBD samples. These data emphasize the potential importance of fungal microbiota signatures as biomarkers of pediatric IBD, supporting their possible role in disease pathogenesis.
Read moreGut Microbes Secretions May Trigger Mononuclear Cell Migration and Offer Comorbidity Mechanism Between Inflammatory Bowel Disease and Diabetic Retinopathy
BackgroundResearches have found that the gut microbiota stimulate inflammation by releasing proinflammatory chemicals, including bile acids (BAs) and L-kynurenine. In the present study, our purpose is to investigate the potential functional roles of gut microbes and their secretions in the comorbidity mechanism between inflammatory bowel disease (IBD) and diabetic retinopathy (DR).MethodsSpecific existing gut microbes among IBD and diabetes mellitus (DM) patients were gained and analyzed to figure out the proinflammatory chemicals secreted by specific existent microbes. The expression data of peripheral blood mononuclear cells (PBMCs) were obtained and underwent differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) to find out potential effects of microbes secretions on PBMCs. Single-cell analysis was conducted to elucidate the underlying cytological comorbidity mechanisms.ResultsThe results of the study showed that the secretions of abnormal gut microbes in IBD and DM patients, such as BAs and L-Kynurenine, can stimulate abnormal immune response. PBMCs can be activated, mobilized, and disrupt vascular endothelial barriers upon exposure to proinflammatory substances generated by Veillonella and Clostridium, the dysbiotic gut microbiota in IBD, which exacerbate retinal inflammation and worsening DR pathological conditions. Furthermore, genes related to PBMC migration, such as RSU1, FN1, and CD9, are activated in PBMCs after exposure to pro-inflammatory chemicals from abnormal gut microbes, offering a genetic comorbidity mechanism for IBD and DR. We also unraveled that IBD can promote the proliferation and activation of effector memory T (Tem) cells, which also showed elevation in DR patients, thereby providing a cellular basis for the comorbidity between IBD and DR.ConclusionThe aberrant gut bacteria in IBD patients might secrete proinflammatory substances, such as L-kynurenine and BAs, which may activate mononuclear cells, especially the Tem. The mononuclear cells subsequently migrated into the retina, exacerbating the situation of DR. This finding underscores the potential of comorbidity mechanism for better treatment of DR in the future.
Read more19Inflammatory bowel disease, a dysregulated host‐microbiota interaction: Are probiotics a new therapeutic option?
Inflammatory bowel disease, a dysregulated host‐microbiota interaction: Are probiotics a new therapeutic option?
S0829 Vitamin D Deficiency Associated With Clostridioides difficile Infection in Inflammatory Bowel Disease Admissions: Insights From the National Inpatient Sample Database
INTRODUCTION: Clostridioides difficile infection (CDI) is an important cause of morbidity and mortality in inflammatory bowel disease (IBD) population. Well established risk factors for CDI include recent hospitalization, long term use of antibiotics, and chronic immunosuppression. Additionally, recent reports suggest that vitamin D-deficiency plays an important role in CDI susceptibility. This study aimed to evaluate the relationship between vitamin D deficiency and CDI in patients admitted with IBD exacerbation. METHODS: We queried the National Inpatient Sample database 2006–2014. We selected patients with a primary diagnosis of ulcerative colitis (UC), Crohn’s disease (CD), or IBD-related complications using the appropriate ICD-9 codes. We identified patients with the diagnosis of intestinal CDI. Categorical variables were compared using Chi-square. Predictors of Vitamin D deficiency and CDI were evaluated by multivariate logistic regression. RESULTS: A total of 1,000,218 weighted discharges with a primary diagnosis of UC, CD, or IBD-related complications were analyzed. 36.3% of the cases had UC, 64% had CD and 0.7% had undetermined IBD. Among all the cases 6.1% had a diagnosis of CDI. Patients with CDI were older (53.8 years vs 45.9 years, P < 0.001) and predominantly female (59.5% vs 40.5% P < 0.001). Older age, female gender (aOR: 1.18, P < 0,001), diagnosis of UC, vitamin D deficiency (aOR: 1.73, P < 0,001), long-term use of steroids (aOR: 1.2, P < 0,001), and antibiotics (aOR: 3.02, P < 0,001) were independent predictors of CDI among the IBD population. Patients with CD (aOR: 0.66, P < 0,001), long-term use of ASA (aOR: 0.93, P = 0.006) and non-steroidal anti-inflammatory drugs (aOR:0.52, P < 0,001) were less likely to have CDI during hospitalization. CONCLUSION: Vitamin D is involved in innate and acquired immunity and plays an important role on gut health. The deficiency of vitamin D in IBD patients has been associated with increased disease activity and poor outcomes. Only a few studies have examined an association between vitamin D levels and susceptibility to CDI in the IBD population. The proposed mechanism is decreased levels of cathelicidin, an antimicrobial peptide that inhibits the effect of C difficile toxin, which production is stimulated by vitamin D. Our study showed that vitamin D deficiency is a predictor of CDI in patients admitted with IBD exacerbation. Its main implication is the potential impact vitamin D supplementation can play in reducing the rates of CDI among the IBD population.Figure 1.: Percentages of the type of IBD among discharges for IBD exacerbation from 2006 to 2014.Table 1.: Summary of demographic characteristics of all cases with a primary discharge diagnosis of IBD: Nationwide Inpatient Database from 2006 to 2014Table 2.: Independent predictors of CDI in patients with a primary discharge diagnosis of IBD: multivariate logistic regression analysis in the Nationwide Inpatient Database in 2006–2014
Read more133Exacerbation of inflammatory bowel diseases associated with the use of nonsteroidal anti-inflammatory drugs: myth or reality?
Nonsteroidal anti-inflammatory drugs (NSAIDs), conventional and selective cyclooxygenase-2 (COX-2) inhibitors, are among the most widely used medications for the treatment of various inflammatory conditions. There is strong evidence of a possible association between the use of these drugs and the relapse of inflammatory bowel diseases (IBD). Our objective was to examine the literature regarding the exacerbation of IBD associated with the use of conventional NSAIDs and selective COX-2 inhibitors and the underlying pathogenetic mechanisms. We reviewed articles, including original papers, controlled trials, case reports, reviews, and editorials published in English at the PubMed, Scopus Database, and Science Direct database, searching with the following keywords: nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, Coxibs, inflammatory bowel diseases (IBD), ulcerative colitis (UC), Crohn's disease (CD). There is substantial evidence that exacerbation of IBD happens after treatment with NSAIDs, but the available data remain conflicting, and it is not clear whether selective COX-2 inhibitors are safer than traditional NSAIDs. However, there is some evidence that selective COX-2 inhibition and COX-1 inhibition (with low-dose aspirin) appear to be well-tolerated in the short term. Regarding the mechanisms of relapse, the reduction of prostaglandins appears to be the hallmark of the NSAIDs adverse effects. Further randomized, double-blind, controlled trials should be performed to address this issue, and more in vitro studies to identify the pathways involved are required.
Read moreThis Month in Gastroenterology
This Month in Gastroenterology
Figure 3 from Prospective Analysis Reveals Associations between Carbohydrate Intakes, Genetic Predictors of Short-Chain Fatty Acid Synthesis, and Colorectal Cancer Risk
<p>Multivariable-adjusted hazard ratios (95% CI) for intake of carbohydrates and fiber and colorectal cancer risk separated by genetically predicted host short-chain fatty acid production for butyrate (<b>A</b>) and propionate (<i>n</i> = 87,417; <b>B</b>). All models are stratified by sex, age at recruitment, adjusted for region of recruitment, first 10 genetic principal components, body mass index, height, physical activity, Townsend deprivation index, education, smoking, alcohol consumption, diabetes status, nonsteroidal anti-inflammatory drug use, red and processed meat intake, fruit and vegetable intake (except when fiber from vegetables and/or fruits, and non-free sugar intake was the exposure), energy intake, and female-specific covariates: menopausal hormone therapy use and menopausal status. Analyses are restricted to white British participants. χ<sup>2</sup> and <i>P</i> value represents improvement of fit obtained from likelihood ratio tests for including an interaction term between butyrate or propionate polygenic score and carbohydrate type/source (modeled as a 5% energy increment) or fiber source (modeled as a 5 gram/day increment) into the model.</p>
Read more58Effects of Cancer Treatment on Inflammatory Bowel Disease Remission and Reactivation
Effects of Cancer Treatment on Inflammatory Bowel Disease Remission and Reactivation
16Alcohol consumption analysis among patients with liver disease in China
Background:Alcohol consumption has been observed to be a contributing factor in liver damage. However, very few studies have tried to decipher the correlation between patients with liver disease and alcohol consumption. Therefore, this study was planned to determine the prevalence of alcohol consumption among patients with liver disease, and to evaluate the risk factors, liver diseases, and chronic medical conditions associated with alcohol drinking.Methods:A cross-sectional study was conducted among patients with liver disease in 30 provinces, autonomous regions, and municipalities across China. All participants answered the questionnaire, which led to the calculation of Alcohol Use Disorders Inventory Test (AUDIT) score for each patient. Based on this score, low-risk drinkers, hazardous drinkers, and harmful drinkers were defined as having AUDIT score of <8, between 8 and 15, and ≥16, respectively.Results:A total of 1489 participants completed the questionnaire. Based on this information, 900 (60.44%) participants were classified as alcohol drinkers. Among these, 8.66% were ex-drinkers, 22.10% were low-risk drinkers, 17.13% were hazardous drinkers, and 12.56% were harmful drinkers. Further investigation of the association between alcohol consumption and other baseline characteristics of patients with liver disease revealed that usually men <40 years old, participants having higher family annual income, having college degree or higher education, living alone, having higher body mass index (BMI), current smokers, and ex-smokers had significant association with higher risk of alcohol consumption. In addition, among the 18.07% of the participants with cirrhosis, it was observed that risk of cirrhosis increased with higher alcohol consumption. Furthermore, harmful drinkers showed greater odds of hypertension and heart diseases, while hazardous drinkers and harmful drinkers, both had greater odds of hyperlipidemia.Conclusions:Overall our analyses indicated that among the patients with liver disease in China, there was high rate of alcohol consumption and dependence. Alcohol consumption usually associated with men <40 years old, higher family income, education level, living alone, high BMI, and smoking. Increased alcohol consumption not only increased the risk of cirrhosis, but also enhanced the risk of hypertension, heart diseases, and hyperlipidemia.
Read more2P1264 Metabolic dysfunction-associated steatotic liver disease (MASLD) in patients with Inflammatory Bowel Disease (IBD). A prospective single-center study
Background Inflammatory bowel disease (IBD) has been linked to an increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD). This study assesses MASLD prevalence in IBD patients and its associations with demographic, clinical, and laboratory features. Methods This prospective study included 113 adult IBD outpatients [Crohn’s disease (CD): 63, ulcerative colitis (UC): 49, unclassified colitis: 1; male/female: 68/45; mean age: 47.8 years (SD: 15.06); mean age at IBD diagnosis: 35.84 years (SD: 15.57)] derived from the Gastroenterology Division, University Hospital of Patras, Greece. Of these, 95 patients underwent ultrasound, clinical evaluation, and laboratory testing to diagnose MASLD. Results Among the 95 patients evaluated, 22 (23.2%) were diagnosed with MASLD, 8 (9.4%) with alcoholic liver disease (ALD), and 65 (68.4%) had no steatotic liver disease (No-SLD). MASLD patients were predominantly male (n = 11), with a CD to UC ratio of 16:6, a mean age of 46.4 years (SD:10.80), and a mean IBD diagnosis age 34.82 years (SD:14.20). Patients with MASLD had significantly increased rates of central obesity (p = 0.001, OR = 5.90, CI: 2.10-16.58), overall obesity (p = 0.001, OR = 4.2, CI:1.15-15.22), higher body mass index (BMI) (p = 0.001, OR-1.25, CI:1.10-1.42), elevated SGOT (p=0.019, OR=1.06, CI=1.01-1.117), SGPT (p=0,027, OR=1.03, CI=1.003-1.059), and greater waist circumference (p=0.04, OR=1.05, CI:1.01-1.09) compared to non-MASLD patients. No significant differences were observed between groups regarding age (p = 0.787), age at IBD diagnosis (p = 0.723), sex distribution (p = 0.277), disease type (p = 0.312), smoking status (p = 0.335), γ-GT (p = 0.896) and ALP (p = 0.440). Lastly, no significant differences were found regarding IBD clinical activity markers (CDAI, p = 0.698; Trulove-Witts, p = 0.764), CRP (p=0.798), IBD-related surgery(p=0.734), or extraintestinal manifestations(p=0.059). Conclusion MASLD is prevalent among IBD patients and is significantly associated with central and overall obesity, increased BMI, liver enzymes, and waist circumference. These findings suggest MASLD could be an early indicator of metabolic syndrome in IBD patients, preceding other cardiometabolic disorders. Further research is needed to clarify the relationship between MASLD and IBD and guide early intervention strategies.
Read more121Risk of myocardial infarction, ischemic stroke, and cardiovascular death in patients with atopic dermatitis
Risk of myocardial infarction, ischemic stroke, and cardiovascular death in patients with atopic dermatitis
39Comparison of Speaking Fundamental Frequency between Premenopausal Women and Postmenopausal Women with and without Hormone Therapy
Objective: The purpose of this study was to investigate the speaking fundamental frequency (SFF) in pre- and postmenopausal women with and without hormone therapy (HT) and with low and high body mass index (BMI). Patients and Methods: The SFF of premenopausal women with low BMI (n = 22) was compared with the SFF of premenopausal women with high BMI (n = 13), postmenopausal women with HT and low BMI (n = 35), postmenopausal women with HT and high BMI (n = 19), postmenopausal women without HT and with low BMI (n = 28) and postmenopausal women without HT and with high BMI (n = 12) using ANCOVA and post hoc tests. Results: A significantly lower SFF of the voice was only found in postmenopausal women without HT and with a low BMI. Conclusion: The results of this study suggest that the menopause lowers the voice with approximately 14 Hz and that HT and adipose tissue (high BMI) might counteract the menopausal drop in SFF.
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