inflammatory bowel disease

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic relapsing-remitting disorder with a rising global incidence. Infectious agents, particularly Clostridium difficile , are frequently considered during IBD flares. However, the role of other infectious agents during these exacerbations remains unclear.

The objective of the current study was to assess the prevalence of infectious agents, including C. difficile , in stool samples of patients with IBD flares and to assess potential risk factors.

A retrospective review was conducted on medical records of IBD patients admitted for flare-ups at Mount Sinai Hospital, Toronto, from October 2018 to August 2019. Stool testing, including cultures, ova, parasites, and C. difficile , was analyzed. Demographic and clinical data were collected, and chi-square tests were used for statistical analysis.

A total of 96 patients (51 CD, 43 UC, 2 IBD-U) were included. Nine patients (9%) tested positive for C. difficile . No other bacterial or parasitic infections were detected. Testing for Cytomegalovirus was performed in 33 patients, with no positive cases. Risk factors, including IBD phenotype, biologic or steroid therapy, and prior antibiotic use, showed no significant association with C. difficile infection.

Clostridium difficile was the predominant infectious agent in IBD flares, while other bacterial and parasitic infections were rare. Routine stool testing, particularly for non- C. difficile pathogens, has a low diagnostic yield in this population. Further studies with larger, generalized cohorts are needed to explore these associations and identify risk factors for infectious colitis in IBD patients.

Invasive methods such as colonoscopy and tissue biopsy are used to diagnose and differentiate inflammatory bowel disease. In this study, we aimed to use the real-time PCR method to examine changes in SIRT1 and NF-κB gene abundance in IBD patients and healthy individuals and to distinguish IBD. This case-control study was conducted on 30 IBD patients and 30 healthy controls. SIRT1 and NF-κB levels in peripheral blood leukocytes of the samples were measured by real-time fluorescent quantitative PCR. According to this study,  the expression of the SIRT1 gene in blood leukocytes of IBD patients was lower than that of the healthy group. Using the ROC curve, it was found that SIRT1 gene expression could distinguish IBD patients from healthy individuals with a sensitivity and specificity of 83% and 77%, respectively. According to the results of this study, the expression of the NF- kB gene in the blood white blood cells of IBD patients increased compared to the healthy group. According to the ROC curve, NF- kB gene expression can distinguish IBD patients from healthy individuals with a sensitivity and specificity of 86% and 72%, respectively. The results of this study, together with other methods, may help diagnose and analyze the disease in IBD patients.

Biological medications have played a significant role in maintenance therapy for Crohn’s disease (CD), but some cases become refractory to these agents. Methotrexate (MTX) appears to be a cost-effective and readily available drug for enhancing the effectiveness of maintenance therapy when used in combination with anti-tumor necrosis factor (anti-TNF) therapy in such cases. However, its effectiveness is still to be established. We aimed to assess the efficacy of MTX and anti-TNF combination therapy in patients with refractory CD.

A retrospective cohort study was conducted on adult patients with CD who were refractory to anti-TNF therapy and were initiated on weekly intravenous MTX in addition to the anti-TNF therapy. These patients were then followed up for over a year. The primary outcome measured was the clinical response to treatment, based on the Harvey-Bradshaw Index. The secondary outcomes included assessing the adverse events and complications of MTX therapy.

Of 70 patients, 44 were included in the final analysis. Among them, 30 patients (68.2%) achieved complete remission, four patients (9.1%) had a partial clinical response, and 10 patients (22.7%) required surgery. The adverse events and complications of MTX therapy were mild and infrequent (9.1%). None of the demographic or clinical factors were significantly associated with response to treatment (P>0.05).

Combining MTX with anti-TNF therapy appears to be an effective and safe treatment for patients with Crohn’s disease, particularly those with severe disease who are less responsive to monotherapy. However, further studies are needed to confirm these findings.

Since 2019, the Covid-19 pandemic has led to the manufacturing of a wide range of different types of vaccines with different mechanisms of action. The data collected from various studies indicate that complications such as injection site pain, headache, fatigue, fever, and malaise are the most common side effects of Covid-19 vaccination. The most common site-specific complications in the gastrointestinal tract and nervous system in different studies were diarrhea, abdominal pain, nausea, vomiting, dizziness, headache, myalgia, peripheral neuropathy, and demyelinating diseases, respectively. In this study, we report a case that developed complications such as Guillain-Barré syndrome and Crohn’s colitis following Sinopharm/BBIBP COVID-19 vaccination. The course of Crohn’s disease (CD) was also complicated by CMV, and the patient developed fulminant colitis, which led to peritonitis.

The patient was a 36-year-old Caucasian male who presented with severe generalized abdominal pain, nausea, vomiting, fever, dyspnea, and fatigue 4 days prior to admission. He mentioned a recent hospitalization due to bilateral ascending paraparesis, which was diagnosed as Guillain-Barré syndrome and treated with intravenous immunoglobulin. He also complained of watery diarrhea for a few weeks. The mentioned symptoms occurred following the injection of the Sinopharm/BBIBP COVID-19 vaccine. Due to the presence of pneumoperitoneum on chest radiography, the patient was transferred to the operating room with a diagnosis of generalized peritonitis and underwent midline laparotomy. On exploration of the abdominal cavity, the colon was perforated at two points: the sigmoid colon and the transverse colon. Signs of inflammation were observed around the perforated edges, but not elsewhere. The patient underwent an extended left hemicolectomy with end colostomy. The postoperative pathology report was consistent with CD, showing transmural chronic inflammation, deep fissuring ulcers, and cryptitis in the surgical specimen. Additionally, the immunohistochemical study for CMV was positive.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease with a wide spectrum of extraintestinal manifestations. Due to the incidence of IBD and Guillain-Barré syndrome in the mentioned patient following vaccination, there is a possibility of the same pathogenesis for both diseases. The incidence of Guillain-Barré syndrome as one of the extraintestinal complications of IBD has been reported in numerous studies as a result of the coexistence of both diseases. Also, according to the recent history of vaccination in a previously healthy individual, it is possible to justify the association of Guillain-Barré syndrome and IBD with the vaccine. So far, many studies have reported the development of Guillain-Barré syndrome following vaccination, but to the best of our knowledge, no studies have reported IBD following Covid-19 vaccination yet. Another issue in this patient was the complication of Crohn’s colitis with CMV. Despite the 7-8-fold higher incidence of CMV infection in patients with IBD, the role of CMV infection in Crohn’s colitis has not been determined.

Changes in the expression of nucleotide-binding oligomerization domain containing 2 (NOD2) play an important role in the pathogenesis of a variety of autoimmune diseases including inflammatory bowel diseases (IBDs). Epigenetic modifications, including DNA methylation, are considered an important mechanism in the suppression of gene activity. In this study, we investigated the relationship between DNA methylation patterns of the promoter region of the NOD2 gene and the pathogenesis of Crohn’s disease (CD).

Colonic mucosa samples were obtained from 15 Iranian patients with IBD and 15 age- and sex-matched healthy controls with no history of autoimmune disease. After the bisulfite conversion of genomic DNA, the DNA methylation status of three CpG sites in the promoter region of the NOD2 gene was determined by the real-time quantitative multiplex methylation-specific PCR (QM-MSP) assay.

Using this approach, we identified that IBD patients showed a decreased level of methylation of the NOD2 promoter in the colonic mucosa than did the healthy controls. (Unmethylated DNA in Crohn's disease vs. healthy controls; 0.128±0.093 vs. 0.025±0.016, P<0.000).

According to our findings, promoter hypomethylation of the NOD2 gene in the colonic mucosa might contribute to the development and severity of CD. Furthermore, aberrant DNA methylation levels are expected to serve as a clinically useful risk marker.

The possibility of pelvic floor dysfunction (PFD) occurrence seems to be higher in patients with inflammatory bowel disease (IBD) due to the presence of functional gastrointestinal disorders in these patients. Hence, this study aimed to evaluate the association of ulcerative colitis (UC) in women with PFD and its comparison with the healthy (without IBD) population.

The present study was conducted on 150 women with UC and 150 without-IBD individuals. Pelvic Floor Distress Inventory (PFDI-20) was used to evaluate the pelvic floor function.

The results of this study revealed that UC had a significant role in increasing not only the PFD score (Beta=3.04; P<0.001) but also the score of each sub-scale of Pelvic Organ Prolapse Distress Inventory (POPDI)(Beta=6.61; P<0.001), Colo-Rectal-Anal Distress Inventory (CRADI) (Beta=9.37; P<0.001), and Urinary Distress Inventory (UDI) (Beta=5.56; P=0.015). In addition, aging, increased body mass index (BMI) and menopause had significant role in increasing POPDI, UDI, and PFDI scores, respectively (P<0.05).

 The percentage of PFD in women with UC was significantly higher than its percentage in women without IBD. This dysfunction was more visible in the two sub-scales of POPDI and CRADI. In addition to having UC, aging, BMI, and menopause played a significant role in increasing PFD.

Ulcerative colitis (UC) is a commonly recurrent inflammatory bowel disease. T helper 17 (Th17)/regulatory T (Treg) cell balance plays an essential role in UC progression. However, it is unknown whether curcumin chitosan microspheres (CCM) regulate the Th17/Treg cell balance.

The UC mouse model was established by administering 3% dextran sodium sulfate and treated with CCM. The influence of CCM on the Th17/Treg balance was detected using flow cytometry. Cell experiments were conducted to investigate the role and mechanism of IGF2BP1 in Th17/Treg balance.

We revealed that CCM demonstrated a significant therapeutic effect on UC. CCM obviously decreased the Th17 cell percentage but boosted the Treg cell percentage in UC mice. CCM remarkably increased the mRNA expression of Foxp3 but suppressed RORγt and interleukin-10 mRNA expression. PCR array of RNA modification-related genes revealed that the m6A binding protein IGF2BP1 was a key molecule in CCM regulation of Th17/Treg balance. IGF2BP1 overexpression dramatically repressed the CCM-induced balance of Th17/Treg cell differentiation. Mechanically, IGF2BP1 targeted LRP5 and regulated LRP5 through m6A modification. Furthermore, the silencing of LRP5 canceled the suppressive effect of IGF2BP1 on Th17/Treg cell percentage.

CCM modulated the Th17/Treg balance through IGF2BP1-mediated m6A modification, thereby alleviating UC, and providing new ideas for the treatment of UC.

Epigenetic modifications exhibit promising evidence in the etiology and prognosis of important diseases such as inflammatory bowel diseases (IBD). In addition to complex factors involved in IBD, a trend toward better prognosis has been reported in older ages of disease onset, specifically in ulcerative colitis (UC). The gastrointestinal mucous layer is one of the important components that is disturbed in the disease course. The integrity of this layer is maintained with an anti-inflammatory factor called trefoil factors (TFF). We investigated the methylation status of the TFF1 gene in UC patients alongside with correlation of its alteration level with age of disease onset.

We analyzed the promoter methylation status of the TFF1 gene, using the real-time quantitative multiplex methylation specific PCR (QM-MSP). DNA was extracted from colorectal biopsies of 15 ulcerative colitis and 14 healthy controls. Correlation analysis was performed between unmethylated DNA level and age through the Pearson correlation coefficient (PPC) test and simple linear regression models.

Our data provided a significant positive correlation between age and TFF1 hypomethylation in ulcerative colitis patients. However, no significant difference was observed in overall TFF1 methylation status between ulcerative colitis patients and control subjects.

This finding suggests the association between epigenetic upregulation of the TFF1 gene with disease mildness in older patients.

In this multicenter study, we investigated all causes of mortality in hospitalized inflammatory bowel disease (IBD) patients.

The widespread use of biologics and immune suppressive treatments, along with the longer lifespan of patients with IBD, may have changed the cause of death in this population. Knowing this may lead to better preventive and therapeutic strategies for IBD patients.

This cross-sectional study reviewed records of 1926 IBD patients hospitalized in referral hospitals in Isfahan and Shiraz during 2013–2021. In nine years, 84 patients, 39 from Isfahan and 45 from Shiraz, died. We retrospectively gathered data on demographic, clinical, and laboratory information, as well as the cause of death. We extracted the cause of death from the death sheets and classified it using the International Classification of Diseases (ICD-10). Using the Kaplan-Meier model, we estimated the median survival time from disease diagnosis to death.

Males accounted for 47 (55%) of the deceased patients. The mean age of the patients was 48.63 ± 18.7 years. The mortality rates among hospitalized UC and CD patients were 7.2% and 7.8%, respectively. The median duration of admission to death was 8 days, with 19 (22.6%) of IBD patients dying on the first day of their hospital admission. Half of the cohort of deceased IBD patients had survived for 8 years following their disease diagnosis. 32.7% of all recorded causes of death were due to certain infectious diseases. The second and third most common causes of death were diseases of the digestive system and diseases of the circulatory system, including pulmonary embolism, accounting for 30.1% and 14.2%, respectively.

According to this study from Iran, infectious diseases are the leading cause of death among hospitalized IBD patients. Prevention and clinical management of pulmonary embolism in IBD patients require more careful consideration. We strongly encourage population-based cohort studies to enhance the findings.

Iran has been one of the most affected countries in the world by COVID-19. The aim of our study was to determine the outcome of COVID-19 in patients with inflammatory bowel disease (IBD). Furthermore, we analyzed the outcome of SARS-CoV-2 infection in patients with IBD treated with immunosuppressant.

This is a cross-sectional, observational study. This study included all patients with IBD, regularly followed up in our IBD Clinic at a tertiary medical center from February 5th, 2020 to August 5th, 2022. We identified those patients with confirmed SARS-CoV-2 infection either by PCR test or chest computed tomography (CT) imaging.

A total of 401 patients were recruited (n=346 [86.28%] with ulcerative colitis, n=53 [13.22%] with Crohn’s disease, and 2 [0.5%] with indeterminate colitis). Of these patients, 273 (68.08%) developed no symptoms or signs during the follow-up period,128 patients developed symptoms similar to COVID-19, and 76 (18.9%) were diagnosed as confirmed COVID-19 cases. Men comprised 60.5% of the confirmed COVID-19 groups, which shows that men were statistically more likely to have symptoms of COVID-19 during the follow-up period (P=0.04). No significant differences were observed among confirmed and non-COVID-19 cases in terms of concomitant medications: steroids (P=0.6), thiopurines (P=0.23), anti-TNF (P=0.23), and aminosalicylate (P=0.61). Three patients required hospitalization, but there were no admissions to the intensive care unit or deaths related to COVID-19.

The risk of COVID-19-related adverse outcomes and death in patients with IBD is low. Also, patients with IBD under immunosuppressive treatment are not at an increased risk of COVID-19.

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract that affects millions of people worldwide. Since acetylcholine is one of the effective factors in reducing inflammation and considering the benefits of using saliva, in this study, the amount of cholinesterase activity in saliva and serum in patients with IBD and healthy people was investigated.

Thirty patients with IBD who were referred to Imam Reza Hospital, as well as 30 healthy individuals, participated in this study. Saliva and serum samples were collected in the morning. Cholinesterase activity was evaluated using the photometric method, and data were analyzed using an unpaired Student’s t-test or Mann-Whitney test.

The mean activity of cholinesterase and saliva flow rate in saliva and serum were not significantly different between the two groups. Xerostomia inventory score was significantly higher in the IBD group (P<0.05).

It seems that cholinesterase activity does not change in patients with IBD, but patients feel more dry mouth than healthy people.

Ulcerative colitis (UC), a chronic inflammatory condition of the colon with no definitive cure, necessitates the exploration of innovative therapies. Herbal remedies combined with conventional drugs may offer complementary benefits, enhancing treatment outcomes.

This study investigates the therapeutic effects of Heracleum lasiopetalum Boiss in a rat model of acetic acid-induced UC.

Forty-eight adult female Wistar rats were randomly allocated to six groups (n = 8 per group) for each of two experiments. UC was induced by intracolonic administration of 1 ml of 4% acetic acid for 10 minutes. In the treatment groups, female rats received an oral gavage of 5%, 10%, and 40% aqueous plant extract, sulfasalazine (100 mg/kg), and distilled water for 6 days, starting 3 days after acetic acid administration. The protective groups received substances via oral gavage from 7 days before to 3 days after acetic acid administration. The extent of mucosal ulcers, hyperemia, inflammation, and mucosal bleeding was evaluated based on the Gerald Classification System Score (Macroscopic). Pathological assessment was conducted on prepared slides using the modified Wallace method (Microscopic). Changes in body and colon weight, along with food and water intake, were examined.

Significant changes in food intake were observed in both the extract and positive control treatment groups, exhibiting a notable difference compared to the negative control group (P < 0.05). Body weight changes experienced a significant increase in the positive control treatment group compared to the negative control group (P < 0.05), while no significant difference was evident between the extract and negative control treatment groups (P > 0.05). In terms of water and food intake, as well as weight changes, no significant differences were detected among the various protective groups (P > 0.05). Both microscopic and macroscopic examinations revealed a substantial enhancement in the colon of the extract and positive control treatment groups compared to the negative control group (P < 0.05), with no significant difference observed between the protective groups (P > 0.05).

Heracleum lasiopetalum extract demonstrates a dose-dependent reduction in colon hyperemia, mucosal ulceration, inflammation, and fibrosis. This highlights its potential as a supplementary treatment option for UC, emphasizing the need for further investigation.

Inflammatory bowel disease (IBD) is a chronic relapsing disorder characterized by inflammation of the gastrointestinal tract. As its natural progression includes flares and periods of remission, so it requires continuous and personalized follow-up to ensure long-term remission. Self-management education through telehealth applications enables patients with inflammatory bowel disease to actively and independently engage in self-care and increases their responsibility in controlling symptoms and complications.

Inflammatory bowel disease comprising Crohn's disease and ulcerative colitis presents with periods of flares and remission. Many reports have identified different dysregulated miRNAs in patients with IBD. Finding new biomarkers in IBD patients can help to launch a novel non-invasive approach for diagnosis and prognosis for patients with UC and CD. This study aimed to evaluate the plasma expression pattern of the miRNAs panel in IBD patients compared to healthy individuals. 73 plasma samples were included; 58 patients with IBD (33 individuals in flare and 25 in remission phase) and 15 healthy controls were enrolled in the study. The miRNA expression was measured by qRT-PCR using miScript SYBR Green PCR Kit (QIAGEN). Our results showed the expression level of miR-16-5P was significantly increased in the active phase compared to the inactive phase (P=0.0138) and in CD patients compared to UC patients (P=0.0216). There was a significant difference in the expression of miR-29a in Crohn's patients compared to healthy subjects (P=0.04). Measuring the expression of mir-106a; a significant increase was observed compared to healthy individuals (P=0.03) and patients with CD (P=0.0143) in proportion of UC patients’ group. The miR-126 expression significantly increased in patients with active disease compared to patients in the inactive phase (P=0.0413) and healthy controls (P=0.0492). This study showed evidence for differential expression levels of plasma panel of miR-16, miR-29a, miR-106a, and miR-126 in IBD patients compare to healthy individuals. We illustrate that miRNAs in plasma correlate with disease activity and can be used as a practical and non-invasive biomarker for early diagnosis and monitoring of the treatment protocol.

Human cytomegalovirus (HCMV) is classified within the Herpesvirales order and is prevalent in 50%‒80% of the general population. Most carriers experience this infection without noticeable clinical symptoms. HCMV causes a lifelong latent infection that can be reactivated due to immune disorders and inflammation. The reactivation of HCMV becomes particularly significant when it coincides with inflammatory bowel disease (IBD). While cytomegalovirus (CMV) colitis in IBD patients was identified years ago, the role of CMV in triggering flare-ups, acute severe colitis, treatment resistance, and other outcomes in IBD patients experiencing CMV reactivation remains a subject of ongoing debate. In this review, we aim to address an updated insight into aspects related to the CMV colitis in IBD patients including epidemiology, risk factors, clinical features, diagnostic tests, histology, place of immunosuppressants and indications for antiviral treatment. We suggest for personalized and thorough assessment based on the disease phase and colitis severity when prescribing drugs to these patients. Furthermore, we emphasize the importance of regular patient follow-up to monitor drug side effects, ensuring treatment success, and minimizing the risk of colectomy.

 Data on the epidemiology of inflammatory bowel disease (IBD) in the Middle East are scarce. We aimed to describe the clinical phenotype, disease course, and medication usage of IBD cases from Iran in the Middle East.

 We conducted a cross-sectional study of registered IBD patients in the Iranian Registry of Crohn’s and Colitis (IRCC) from 2017 until 2022. We collected information on demographic characteristics, past medical history, family history, disease extent and location, extra-intestinal manifestations, IBD medications, and activity using the IBD-control-8 questionnaire and the Manitoba IBD index, admissions history, history of colon cancer, and IBD-related surgeries.

 In total, 9746 patients with ulcerative colitis (UC) (n=7793), and Crohn’s disease (CD) (n=1953) were reported. The UC to CD ratio was 3.99. The median age at diagnosis was 29.2 (IQR: 22.6,37.6) and 27.6 (IQR: 20.6,37.6) for patients with UC and CD, respectively. The male-to-female ratio was 1.28 in CD patients. A positive family history was observed in 17.9% of UC patients. The majority of UC patients had pancolitis (47%). Ileocolonic involvement was the most common type of involvement in CD patients (43.7%), and the prevalence of stricturing behavior was 4.6%. A prevalence of 0.3% was observed for colorectal cancer among patients with UC. Moreover,15.2% of UC patients and 38.4% of CD patients had been treated with anti-tumor necrosis factor (anti-TNF).

 In this national registry-based study, there are significant differences in some clinical phenotypes such as the prevalence of extra-intestinal manifestations and treatment strategies such as biological use in different geographical locations.