Crohn's Disease Group Research Articles

Disease- and Medication-Specific Differences of the Microbial Spectrum in Perianal Fistulizing Crohn’s Disease—Relevant Aspects for Antibiotic Therapy

Perianal fistulizing Crohn's Disease (CD) with abscess formation represents an aggressive phenotype in Inflammatory Bowel Disease (IBD) with increased morbidity. Treatment is multidisciplinary and includes antibiotics, but knowledge about the microbial spectrum is rare often resulting in inadequate antimicrobial therapy. In this single center retrospective study, all patients who were operated due to perianal abscess formation were retrospectively analyzed and the microbial spectrum evaluated. Patients were divided into a CD and non-CD group with further subgroup analysis. 138 patients were finally included in the analysis with 62 patients suffering from CD. Relevant differences were detected for the microbial spectrum with anaerobic bacteria being significantly more often isolated from non-CD patients. In a subgroup-analysis of CD patients only, medical therapy had a relevant effect on the microbial spectrum since Streptococcus groups and Enterobacterales were significantly more often isolated in patients treated with steroids compared to those being treated by antibodies. In conclusion, the microbial spectrum of patients suffering from CD varies significantly from non-CD patients and immunosuppressive medication has a relevant effect on isolated pathogens. Based on that, adaption of antibiotic treatment might be discussed in the future.

Fecal fungal microbiota alterations associated with clinical phenotypes in Crohn's disease in southwest China.

Although previous studies reported that gut fungal microbiota was associated with Crohn’s disease (CD), only a few studies have focused on the correlation between gut fungi and clinical phenotypes of CD. Here, we aimed to analyze the association between intestinal fungi and the occurrence of CD, disease activity, biological behaviors, and perianal lesions. Stool samples from subjects meeting the inclusion and exclusion criteria were collected for running internal transcribed spacer 2 (ITS2) high-throughput sequencing. Then, correlation analysis was conducted between intestinal fungi and different clinical groups. There were 45 patients with CD and 17 healthy controls (HCs) enrolled. Results showed that two phyla, Rozellomycota and Mortierellomycota, were not present in patients with CD compared to HCs. At the same time, there was a higher abundance of fungal genera and species belonging to the phylum Ascomycota in patients with CD. SparCC network analysis showed fewer interactions among the fungal communities in patients with CD compared to HCs. Exophiala dermatitidis was positively associated with the clinical active stage and platelet count. The genus Candida was with significantly higher abundance in the non-B1 CD group based on the Montreal classification. Clonostachys, Humicola, and Lophiostoma were significantly enriched in patients with CD with perianal lesions. Our results demonstrated that the composition of the intestinal fungal microbiota in patients with CD and HCs was markedly different, some of which might play a pathogenic role in the occurrence of CD and perianal lesions. Exophiala dermatitidis and genus Candida might be associated with active disease stage and type non-B1 CD (CD with intestinal stenosis or penetrating lesions, or both), respectively.

Evaluation of bone mineral density and body compositions interrelation in young and middle-aged male patients with Crohn's disease by quantitative computed tomography.

BackgroundThe aim of this study was to investigate the characteristics of bone mineral density (BMD) and body compositions, and the impact of body compositions on BMD in young and middle-aged male patients with Crohn’s disease (CD).MethodsPatients with CD (n = 198) and normal controls (n = 123) underwent quantitative computed tomography (QCT) examination of lumbar vertebrae 1–3 (L1–3). The BMD and bone geometric parameters were measured and outputted by QCT post-process software. Meanwhile, body composition parameters, including subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), lean mass (LM), and muscles mass around lumbar vertebrae were also acquired by QCT. Blood indicators [interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), Ca, and P] were collected from clinical medical records. Independent t-test was used to compare these variables between the CD group and the normal control group.ResultsThere was no significant difference in age, height, and weight between the CD group and the control group (p > 0.05), indicating that the sample size was relatively balanced. Mean BMD in the CD group were lower than those in the control group, but the difference was not statistically significant (p > 0.05). The bone geometric parameters of the CD group, including cortical area/density (Ct. Ar, Ct. BMD) and trabecular area/density (Tb. Ar and Tb. BMD), were significantly lower than those of the control group (p < 0.05), so were the body composition parameters including total adipose tissue (TAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), lean mass (LM), and muscles mass (p < 0.05). In addition, the level of plasma IL-6, IL-8, CRP, and TNF-α of the CD group were higher than those of the control group (p < 0.05). On the contrary, the body mass index (BMI) and serum Ca and P levels of the CD group were lower than those of the control group (p < 0.05). Through multiple linear regression analysis, Tb. BMD, VAT, Ct. Ar, LM, Ca, and IL-8 entered the regression model and revealed a significant contribution to BMD.ConclusionsPatients with CD could suffer from reduction in BMD. However, the parameters of bone geometric parameters are more sensitive and accurate than BMD changes. Among them, Tb. BMD, VAT, Ct. Ar, and LM have significant effects on BMD reduction.

Circulating Profile of ECM-Related Proteins as Diagnostic Markers in Inflammatory Bowel Diseases.

The aim of our research was to find new biomarkers that could be potentially used in the diagnosis, differentiation and monitoring of inflammatory bowel diseases (IBD). Since extracellular matrix (ECM) remodeling contributes to the pathological changes occurring in IBD, the serum profile of ECM-related proteins may reflect disease activity in the intestinal mucosa. Serum laminin (LM), fibronectin (FN) and gelatinase-associated lipocalin (NGAL) concentrations were determined in 51 patients with IBD before and after a year of treatment, as well as in 48 healthy individuals. A significant difference in serum concentration of FN (130,56 ± 52.87 vs. 287.93 ± 79.69, p < 0.001) and NGAL (133.34 ± 51.51 vs. 102.37.39, p < 0.05) between patients with ulcerative colitis (UC) and healthy individuals was found. In patients with Crohn’s disease (CD), serum concentrations of LM (1329.5 ± 389.36 vs. 1012.07 ± 260.85, p < 0.005) and NGAL (138.94 ± 51.31 vs. 102.65 ± 37.39, p < 0.05) were increased, while FN (89.26 ± 43.86 vs. 287.93 ± 79.69, p < 0.001) was decreased compared to healthy subjects. Moreover, a significant correlation was found between the Mayo score in patients with UC and the levels of NGAL (r = 0.49, p < 0.01) and LM (r = 0.035, p < 0.005), respectively. Another significant correlation was noted between the Crohn’s Disease Activity Index (CDAI) and LM (r = 0.49, p < 0.05) levels in CD group. The results presented in our studies indicate that ECM-related markers might be potential additional tools helpful in diagnosing IBD, differential diagnosis of UC and CD and monitoring the disease activity.

Altered mean apparent propagator-based microstructure and the corresponding functional connectivity of the parahippocampus and thalamus in Crohn's disease.

Crohn’s disease (CD) is a chronic and relapsing inflammatory bowel disorder that has been shown to generate neurological impairments, which has the potential to signify disease activity in an underlying neurological manner. The objective of this study was to investigate the abnormalities of brain microstructure and the corresponding functional connectivity (FC) in patients with CD, as well as their associations with disease condition. Twenty-two patients with CD and 22 age-, gender-, and education-matched healthy controls (HCs) were enrolled in this study. All subjects underwent mean apparent propagator (MAP)-MRI and resting-state functional magnetic resonance imaging (MRI) (rs-fMRI) data collection. Each patient was evaluated clinically for the condition and duration of the disease. The MAP metrics were extracted and compared between two groups. Pearson’s correlation analysis was conducted to determine the relationship between disease characteristics and significantly abnormal MAP metrics in the CD group. Regions of interest (ROIs) for ROI-wise FC analysis were selected based on their correlation with MAP metrics. Results showed that multiple brain regions, including the parahippocampus and thalamus, exhibited statistically significant differences in MAP metrics between CD patients and HCs. Additionally, CD patients exhibited decreased FC between the left parahippocampus and bilateral thalamus, as well as the right parahippocampus and bilateral thalamus. The findings of this work provide preliminary evidence that structural abnormalities in the parahippocampal gyrus (PHG) and thalamus, as well as decreased FC between them, may reflect the degree of inflammatory of the disease and serve as brain biomarkers for evaluating CD activity.

Establishing a novel inflammatory bowel disease prediction model based on gene markers identified from single nucleotide variants of the intestinal microbiota.

The intestinal microbiota is a crucial environmental factor in the development of inflammatory bowel disease (IBD). The abundance of Faecalibacterium prausnitzii is significantly decreased in IBD patients, which is used as a biomarker for IBD diagnosis. However, this can beobserved in both IBD and colorectal cancer, which would confound the diagnosticresults. Thus, we first established a new model for predicting Crohn's disease (CD) with high precision according to gene characteristics based on single nucleotide variants (SNVs). Next, five gene markers belonging to twospecies, F. prausnitzii and Eubacterium rectale, that were enriched in the CD group were obtained to build a CD prediction model, and high accuracy in distinguishing the CD and control groups was observed in the discovery (area under curve [AUC] = 91.13%) and validation cohorts (AUC = 79.55%). The model still maintained high accuracy after expanding the healthy cohort (AUC = 89.75%). High disease specificity in distinguishing CD and CRC groups (AUC = 95.74%) was also proven. This study establishes a novel diagnostic method for predicting IBD that also provides unprecedented insight for the early, painless diagnosis of other non-communicablediseases.

Adalimumab Efficacy for Management of Inflammatory Bowel Disease in Southwest Region of Iran

Background: In recent years, biological drugs, including antitumor necrosis factors, have revolutionized the treatment of inflammatory bowel disease (IBD); however, there is no consensus about the superiority of adalimumab over infliximab. Objectives: This study was designed to evaluate the efficacy of adalimumab for the management of IBD in the southwest region of Iran. Methods: During this prospective observational study, the patients with active IBD and a history of no response to previous treatments that referred to an IBD clinic were included. Moreover, this study evaluated and compared the effectiveness of treatment, including clinical remission rate, disease activity index (the Mayo score in ulcerative colitis (UC) patients and the Crohn’s disease activity index (CDAI) in Crohn’s disease (CD) patients), clinical response, and side effects related to adalimumab injection in 0, 12th, 24th, and 52nd weeks after treatment. Results: A total of 71 patients, including 42 male and 29 female, with a mean age of 29 years, were included. In this study, 37 and 34 patients were diagnosed with UC (52.1%, 20 male and 17 female) and CD (47.8%, 22 male and 12 female), respectively. The time to remission in the UC group was significantly longer than in the CD group (10.05 and 1.71 months; P &lt; 0.0001). Clinical remission rate (≥ 2 points reduction in the Mayo score) in the 12th week among UC patients after treatment with adalimumab was 67.5% and raised to 100% (all the UC patients) in the 24th and 52nd weeks after treatment. None of the UC patients experienced disease recurrence. In CD patients, the CDAI significantly decreased during the treatment time (P &lt; 0.0001); however, all CD patients (100%) experienced disease recurrence after a mean time of 2.59 ± 0.55 months (within 2 - 4 months) (P &lt; 0.0001). Failure of treatment was observed in 94.1% of CD patients (n = 32); nevertheless, none of the UC patients had treatment failure (P &lt; 0.0001). There were no complications related to adalimumab, and no patients needed colectomy during the study period. Conclusions: Adalimumab has a positive effect on the improvement of clinical symptoms, reduction of disease activity, prevention of disease recurrence, and need for colectomy in moderate to severe UC patients. However, adalimumab has no efficacy in the improvement of CD patients, and failure of treatment was observed in most of these patients. Adalimumab could be a therapeutic option for the management of UC with prior failure of treatment.

Characterization of the Mucosally-Adherent Duodenal Microbiome in Children with and without Crohn's Disease.

Manipulation of the microbiome is a rational treatment strategy for inflammatory bowel disease (IBD). Compared to the colon and terminal ileum (TI), understanding of the microbial composition in the duodenum is sparse. This gap in knowledge is especially significant for children with Crohn’s disease (CD) because the prevalence of duodenal CD is higher in children than in adults. Our aim was to characterize the bacterial composition of the mucosally-adherent duodenal microbiome in children with and without CD as a first step toward development of targeted IBD treatment strategies at this disease location. Fresh-frozen mucosal biopsies were obtained from the duodenum and TI of children with treatment-naïve CD and age- and sex-matched controls. Extracted DNA was analyzed for sequence variation in the 16S ribosomal RNA bacterial gene region V4 (Novogene; Beijing, China). Bacterial relative abundance, alpha and beta composition, and diversity, were compared across duodenal and TI samples from the controls and CD groups with and without chronic active inflammation (118 samples from 73 children total; approx. 50% CD), using UniFrac dissimilarity coefficients (α < 0.05), Linear Discriminant Analysis Effect Size (LEfSe) analysis (LDA score ≥ 2), and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) analysis. The relationships between bacterial abundance, sex, age, concomitant medication use, and villous length were assessed. The microbial composition in the duodenum was significantly different from the TI in the control population(R-value = 0.558, p = 0.001) and in children with active CD (R-value = 0.301, p = 0.001). Significant differences in bacterial abundance were noted between the control and CD duodena (LDA > 4). The duodenum of children without CD was characterized by increased abundance in Pseudomonodales, whereas the actively inflamed duodenum in CD was characterized by increased abundance of Bacteroidales, specifically the family Prevotellaceae. This trend is opposite of previously published observations of microbial composition in the TI, where active inflammation was associated with a relative decrease in the abundance of Bacteroidetes and an increase in Proteobacteria, including Pseudomonadales. No statistically significant correlations were noted between abundance and age, sex, concomitant medication use or villous length, except for Bacteroidetes, which significantly decreased in abundance in the TI with age (p = 0.048). The pediatric duodenal microbiome is distinct from the TI and characterized by an increased abundance of Pseudomonodales and Spirochetes in healthy children, and an increased abundance of Bacteroidales in active CD patients.

Fecal Microbiota in Inflammatory Bowel Disease

Background: Diversity of microbial species is a hallmark of dysbiosis in inflammatory bowel disease (IBD). This study was undertaken to determine whether the diversity of lactobacilli and bifidobacteria, two regulatory microbial genera, is altered in patients with IBD. Methods: DNA from fecal samples of 20 healthy volunteers, 20 patients with ulcerative colitis (UC), and 25 patients with Crohn's disease (CD) was amplified by the polymerase chain reaction (PCR) for 16S ribosomal RNA gene sequences specific to genus Lactobacillus and Bifidobacterium. Real-time PCR was done to quantitate bacterial abundance. Amplified DNA was also bar coded and sequenced on the Roche 454 platform. Individual operational taxonomic units (OTUs) were taken as sequences with at least 97% similarity. Results: Abundance of Lactobacillus was significantly increased in UC compared to controls; no other difference in Lactobacillus or Bifidobacterium abundance was found between the three groups. Median reads for genus Lactobacillus was similar between control (940), UC (994), and CD (960) groups. The median number of OTUs per sample was not significantly different between controls (6), UC (5.5) and CD (7). The Shannon index of community diversity was similar between controls (median 1.12), UC (median 1.13) and CD (median 1.11). The Simpson D index was also similar between controls (median 0.393), UC (median 0.439) and CD (median 0.409). Median reads for genus Bifidobacterium was similar between control (846), UC (1052), and CD (964) groups. The median number of Bifidobacteria OTUs per sample was similar for controls (6), UC (7) and CD (8.5). The Shannon index of community diversity was similar between controls (median 0.75), UC (median 1.0) and CD (median 1.14). The Simpson D index was also similar between controls (median 0.570), UC (median 0.422) and CD (median 0.409). Conclusion: The abundance of Lactobacillus was increased in UC. Diversity of genus Lactobacillus and Bifidobacterium was not altered in either UC or CD.

Clinical value of the expression levels of protein tyrosine phosphatase non-receptor type 22.6 mRNA in peripheral blood mononuclear cells in Crohn's disease.

ObjectiveTo explore the relationship between the expression levels of protein tyrosine phosphatase non-receptor type (PTPN) 22.6 mRNA in peripheral blood mononuclear cells (PBMCs) and the disease activity as well as clinical characteristics in Crohn’s disease (CD) patients.MethodsA total of 480 subjects were enrolled. Data were collected including baseline information, expression levels of PTPN22.6 mRNA in PBMCs for all subjects, C-reactive protein (CRP) levels in serum, clinical characteristics, and disease activity for all patients. Expression levels of PTPN22.6 mRNA in PBMCs, CRP levels in serum, clinical characteristics according to Montreal Classification [8], and Crohn’s disease activity index (CDAI) were the primary observation outcomes.ResultsThe expression levels of PTPN22.6 mRNA (P = 0.032) in PBMCs and serum CRP levels (P < 0.001) were significantly higher in active CD patients than in inactive CD patients (P = 0.032). Correlation analysis showed that there was a positive correlation between expression levels of PTPN22.6 mRNA and CDAI value (r = 0.512, P = 0.003), as well as expression levels of PTPN22.6 mRNA and CRP levels in the CD group (r = 0.456, P = 0.006). There were significantly higher expression levels of PTPN22.6 mRNA in PBMCs in patients with structuring behavior than that in patients with non-stricturing and non-penetrating (NSNP) behaviors (P = 0.018) and penetrating behaviors (P = 0.024).ConclusionsThe expression levels of PTPN22.6 mRNA can be used as an indicator to help predict CD diagnosis, disease activity, serum CRP level, and behavior type of CD disease.

Overexpression of programmed death ligand 1 in refractory inflammatory bowel disease

Programmed death ligand 1 (PD-L1) dysregulation has been implicated in chronic inflammatory diseases, but its role in regulating intestinal mucosa inflammation is still unclear. The aim of this study was to assess PD-L1 expression in the intestinal mucosa of patients with refractory inflammatory bowel disease (IBD) compared to controls. We evaluated PD-L1 expression by immunohistochemistry in colectomy specimens of patients with ulcerative colitis (UC) and Crohn disease (CD) compared to controls. PD-L1 expression was assessed in colonic epithelium and inflammatory cells, along with the location of the inflammatory cells expressing PD-L1. All cases were stained with CD3, CD4, CD8, FOXP3, CD20, CD68, and CD90 immunostains to determine the types of cells expressing PD-L1. The UC group showed significantly higher PD-L1 expression in the colonic epithelium than both CD and control groups (both P<0.001), and CD was also significantly higher than the control group (P=0.004). Both UC and CD groups showed similar PD-L1 expression in the inflammatory infiltrate but significantly higher than the control group (both P<0.001). Among both IBD groups, higher IBD activity was associated with higher levels of PD-L1 expression in the colonic epithelium (P<0.05) and inflammatory infiltrate (P<0.001). When comparing PD-L1 expression to lineage-specific markers, CD3+, CD4+ T cells, CD68+ macrophages, and CD90+ colonic stromal cells appeared to be expressing PD-L1. These findings implicate a role for PD-L1 in the dysregulation of the immune response in refractory IBD. Further studies are warranted to better understand the role of the immune regulatory pathways in intestinal mucosa.

Are EPA and DHA Derivatives Involved in IBD Remission?

Recently, an increase in the incidence of inflammatory bowel disease (IBD) has been observed among children and adolescents. Although the pathogenesis of IBD is not fully elucidated currently, actual research focuses on the occurrence of imbalance between pro- and anti-inflammatory molecules and future identification of the role of cytokines in IBD therapy. The purpose of this study was to compare the concentrations of eicosapentaenoic and docosahexaenoic acid derivatives during both phases of Crohn’s disease (CD) and ulcerative colitis (UC). The study included 64 adolescent patients with CD (n = 34) and UC (n = 30) aged 13.76 ± 2.69 and 14.15 ± 3.31, respectively. Biochemical analysis was performed on a liquid chromatography apparatus. A statistically significant lower concentration of resolvin E1 (RvE1) was observed in the CD group relative to UC. In the active phase of CD, a statistically significantly higher concentration of protectin DX (PDX) was observed relative to remission CD. Comparing the active phase of both diseases, a statistically significantly higher concentration of resolvin E1 (RvE1) was observed in UC relative to CD. Comparing the remission phase of both diseases showed statistically significantly higher PDX levels in CD relative to UC. Our study adds to the knowledge on the involvement of anti-inflammatory lipid mediators in both IBD entities. In conclusion, it seems that the marker differentiating both disease entities in the active phase may be RvE1, while in the remission phase, PDX. In CD remission, the greatest involvement was observed towards PDX, whereas in UC, MaR1, RvE1 and 18RS-HEPE seem to be the most involved in remission.

IBD Subtype-Regulators IFNG and GBP5 Identified by Causal Inference Drive More Intense Innate Immunity and Inflammatory Responses in CD Than Those in UC.

Background: The pathological differences between Crohn’s disease (CD) and ulcerative colitis (UC) are substantial and unexplained yet. Here, we aimed to identify potential regulators that drive different pathogenesis of CD and UC by causal inference analysis of transcriptome data. Methods: Kruskal–Wallis and Dunnett’s tests were performed to identify differentially expressed genes (DEGs) among CD patients, UC patients, and controls. Subsequently, differentially expressed pathways (DEPs) between CD and UC were identified and used to construct the interaction network of DEPs. Causal inference was performed to identify IBD subtype-regulators. The expression of the subtype-regulators and their downstream genes was validated by qRT-PCR with an independent cohort. Results: Compared with the control group, we identified 1,352 and 2,081 DEGs in CD and UC groups, respectively. Multiple DEPs between CD and UC were closely related to inflammation-related pathways, such as NOD-like receptor signaling, IL-17 signaling, and chemokine signaling pathways. Based on the priori interaction network of DEPs, causal inference analysis identified IFNG and GBP5 as IBD subtype-regulators. The results with the discovery cohort showed that the expression level of IFNG, GBP5, and NLRP3 was significantly higher in the CD group than that in the UC group. The regulation relationships among IFNG, GBP5, and NLRP3 were confirmed with transcriptome data from an independent cohort and validated by qRT-PCR. Conclusion: Our study suggests that IFNG and GBP5 were IBD subtype-regulators that trigger more intense innate immunity and inflammatory responses in CD than those in UC. Our findings reveal pathomechanical differences between CD and UC that may contribute to personalized treatment for CD and UC.

A Study on Differences between Professional Endoscopists and Gastroenterologists in Endoscopic Detection and Standard Pathological Biopsy of Inflammatory Bowel Diseases

Objective To assess whether professional endoscopists need additional training on inflammatory bowel disease (IBD) diagnosis. Methods This retrospective study was conducted in patients with IBD, including Crohn's disease (CD) and ulcerative colitis (UC), which were diagnosed and treated for the first time in our hospital between January 2005 and December 2020. Doctors including gastroenterologists (group G) and professional endoscopists (group E) participated in the study. The data divided into CD or UC and group G or group E were compared. Results Patients with CD exhibited higher rates of terminal ileal lesions, reexamined colonoscopy within 6 months, and intestinal stenosis than patients with UC (P < 0.001). The positive endoscopic IBD diagnosis rate was significantly higher in group G than in group E (89.6% vs. 74.0%, P < 0.001). In the subgroup analysis for patients with CD, the positive endoscopic IBD diagnosis rate was significantly higher for group G than for group E (81.5% vs. 41.8%, P < 0.001). However, the two groups exhibited no significant difference in the subgroup analysis for patients with UC (94.1% vs. 86.5%, P = 0.060). Group G exhibited a higher rate of terminal ileal intubation (83.1% vs. 65.3%, P < 0.001) and standard pathological biopsy (72.7% vs. 26.0%, P < 0.001) than Group E. Conclusion Professional endoscopists showed lower rates of terminal ileal intubation, positive endoscopic diagnosis, and standard pathological biopsy than gastroenterologists. Hence, additional training on IBD, particularly on CD, must be provided to professional endoscopists to increase their efficiency for terminal ileal intubation and positive endoscopic diagnosis and to enhance their awareness regarding standard biopsy.

Genome-wide DNA methylation profiling in differentiating Crohn's disease from intestinal tuberculosis.

Differential diagnosis of Crohn's disease (CD) and intestinal tuberculosis (ITB) is still difficult in clinical pratice. DNA methylation has been considered as a favorable area for biomarker exploration and identification. The purpose of the current study was to evaluate DNA methylation changes between CD and ITB. We performed a genome-wide association study to identify differentially methylated positions (DMPs), including 8 CD patients (before the initial of biologics or immunomodulators), 6 ITB patients, and 8 healthy controls (HCs), in whole blood DNA using the Infinium HumanMethylation850 BeadChip. Patients in the CD group and ITB group were all observed with hypo-methylated changes compared with HCs. However, the CD group overlaps with the ITB group in DNA methylation, suggesting a stable epigenetic profile between the two diseases. The pathway enrichment analysis showed the alternation in inflammation-related pathway, immune system, and signal transduction. Focused on the DMPs located in the promoter region, further analysis indicated hypermethylation of cg03122532 (5'UTR of KCNJ15) could be a potential CD-specific biomarker. We identified specific differential methylation loci related to CD and ITB in blood DNA. DNA metylation as a important epigenetic modification could contribute to the pathogenesis study and biomarker exploration of the diseases.

The Predictive Value of Periostin to Diagnose Crohn's Disease.

There is still no sensitive and specific biomarker that can be used in the diagnosis and follow-up of Crohn's disease, so we aimed to assess the diagnostic accuracy of serum periostin levels in Crohn's disease Methods: The study included 40 Crohn's disease patients aged 18-70 years and considered in remission (Crohn's Disease Activity Index < 150) at admission. Forty healthy volunteers were included in the study as the control group. Crohn's patients were divided into 3 main groups as 8 years according to the follow-up period (in the group <4 years, it was subdivided into <2 and 2-4 years). Serum periostin levels were studied by enzyme-linked immunosorbent assay. Forty Crohn's disease patients and 40 control participants were included in the study. In the Crohn's disease group, serum periostin level was 36.55 ng/mL, while it was 21 ng/mL in the control group, P < .001. Periostin levels in the Crohn's disease group were higher in the groups with disease duration 8 years compared to the control group (P < .001, P < .001, P = .038, respectively). For the diagnosis of Crohn's disease independent of disease duration, the cut-off periostin level was determined as 27.8 ng/mL, while the sensitivity and specificity for this value were 72.5% and 77.5%, respectively Conclusion: Serum periostin levels of the patients followed up with the diagnosis of Crohn's disease in remission were found to be significantly higher than the healthy individuals, and cut-off values of serum periostin were obtained to both diagnose Crohn's disease and predict the course of the disease.

A161 MUCOSAL TRANSCRIPTOMICS IN NON-INFLAMED ILEUM OF CROHN’S DISEASE PATIENTS SHOWS DIFFERENTIALLY EXPRESSED GENE PROFILE COMPARED TO ILEUM OF HEALTHY CONTROLS

BackgroundThe terminal ileum is the most susceptible location to develop Crohn’s disease (CD) and therefore is a valuable tissue to investigate biological mechanisms underlying chronic inflammation. Gene expression is highly affected by the level of inflammation, however, data on ileal transcriptomic profile in the absence of active inflammation is limited.AimsTo investigate the ileal mucosal transcriptomic profile of CD patients in endoscopic and histologic remission compared to healthy controls (HC).MethodsIleal biopsies were collected during colonoscopy from patients with CD and HC. Biopsies were classified as non-inflamed based on endoscopic appearance and histologic criteria. Endo-histologic remission (EHR) was defined as simple endoscopic score < 3 and absence of active histologic inflammation. We included CD patients with EHR and HC for the analysis of this study. CD phenotype was divided into isolated colonic CD (cCD) that included Montreal L2 and ileal predominant CD (iCD) that included Montreal L1 and L3. Total RNA was extracted from samples, sequenced using a HiSeq 2500 instrument (Illumina, San Diego, CA, USA) and differential expression analysis was performed in EdgeR. Genes that were differentially expressed at the average of 2-fold-change (FC) in mean expression and False Discovery Rate (FDR) < 0.05 were considered significant.ResultsIleal samples from 14 CD patients in EHR and 29 HC were included in the analysis. CD patients were significantly younger (median age 28.5 years, interquartile range (IQR)=24–40) compared with HC (median age 56 years, IQR=51–64). There were no differences in gender distribution (42.9% males in CD and 55.2% males in HC). We found 101 differentially expressed genes in CD patients compared to HC (99 genes were up-regulated and two were down-regulated). Dual oxidase 2 (DUOX2) and complement C6 were respectively the most significant up-regulated (logFC=4.45, FDR=1.3e-8) and down-regulated (logFC=-2.73, FDR=0.0006) genes in non-inflamed ileum CD group when compared with HC. In a subgroup analysis comparing ileal samples of CD patients with cCD (n=8) versus iCD phenotype (n=6), no differentially expressed genes were identified.ConclusionsThe mucosal transcriptomic profile of patients with inactive endoscopic and histologic ileal CD shows significant differentially expressed gene profile compared to ileal mucosa of HC. The clinical relevance of these findings should be further investigated.Funding AgenciesIBD Genetics Consortium

Alterations of Regional Homogeneity in Crohn's Disease With Psychological Disorders: A Resting-State fMRI Study

Abnormal psychological processing in the central nervous system has been found in Crohn's disease (CD) patients. Resting-state functional magnetic resonance images of 57 inactive and 58 active CD patients, and 92 healthy controls (HC) were obtained. The psychological assessment used a psychological questionnaire that was collected within 1 week before functional MRI examination. We investigated the neural basis of CD patients and the correlation among regional homogeneity (ReHo), clinical features and psychological assessment scores. We found that more severe psychological assessment disorder scores were observed in the active CD group than in the inactive CD group and HC group (P<0.001). Compared with HC, the active CD patients exhibited higher ReHo values in the frontal superior medial, frontal middle and lower values in the postcentral, supplementary motor area, and temporal middle. Meanwhile, inactive CD patients exhibited higher ReHo values in the frontal middle and lower ReHo values in the precentral, postcentral and putamen (all voxel P< 0.001, cluster P<0.01, corrected). The values of the frontal superior medial, postcentral and supplementary motor area were correlation with psychological assessment scores (r = 0.38, −0.41, −0.32, P = 0.001, 0.014, 0.003), and the clinical features of simple endoscopic score for Crohn's disease and erythrocyte sedimentation rate were negatively correlated with psychological assessment scores in active CD patients (r = −0.35, −0.34, P = 0.06, 0.08). These results provide evidence for abnormal resting-state brain activity in CD and suggest that the psychological of CD may play a critical role in brain function.

Body Muscle Mass Metabolic Data Analysis in Association with Crohn’s Disease Activity

Abstract Malnutrition is a common complication of Crohn’s disease (CD) patients and it is correlated with alterations of the body composition and disease activity. Our prospective pilot study included hospitalised CD patients, age ≥ 18 years. Patients were assessed using the Nutritional Risk Score (NRS2002), the Malnutrition Universal Screening Tool (MUST), and body bioelectrical impedance analysis. Twenty-three hospitalised patients (median age 36.5, interquartile range (IQR): 28.5–51.5 years) were enrolled; the median CD activity index was 128 (IQR = 6.0–207.0). The study group comprised 48% (n = 11) patients with low CD activity and 52% (n = 12) with high disease activity. According to NRS2002 and MUST, 70% (n = 16) CD patients had malnutrition risk and were in need of nutritional support. The median BMI was lower for the CD group (21.10 [IQR = 19.2–23.3]) than for the control group (23.4 [IQR = 21.5–25.8]) (p = 0.014). In terms of deviation from standard weight, 39% (n = 9) of CD patients showed reduced % body fat. Reduced muscle mass was observed in 48% (n = 11) of CD patients. CD patients with high disease activity had a noticeably increased risk of malnutrition. Identification of the reduction in soft lean muscle mass in CD patients can be used as an anticipatory indicator of disease activity.

P539 COVID-19 is Associated with Long-term Elevated Fecal Calprotectin Levels in Patients with Crohn’s Disease but not in Ulcerative Colitis

BackgroundData regarding the long-term effects of COVID-19 on patients with Inflammatory bowel disease is scarce. Fecal calprotectin (FC) correlates with IBD clinical and endoscopic activity. We compared fecal calprotectin levels between patients with COVID-19 to a control group tested negative to SARS-CoV-2.MethodsWe gathered data from a large health medical organization in Israel of insured individuals who underwent a SARS-COV-2 PCR test from March 1, 2020, to December 31, 2020. Among patients with IBD, data regarding fecal calprotectin taken 30–365 days before SARS-CoV-2 testing was gathered. We compared fecal calprotectin levels taken at least 30 days following COVID-19 infection to those who tested negative.Results1924 Crohn’s disease (CD) patients and 949 Ulcerative Colitis (UC) patients were tested for SARS-CoV-2. 322 (16.7%) were tested positive in the CD group and 114 (13.7%) in the UC group.Pre-COVID-19 calprotectin levels did not show statistically significant differences between patients who ended up testing positive for SARS-CoV-2 and those who tested negative in CD (377 ±759.08 vs. 451.84±869, p-value = 0.4) and in UC (466.93±766.69 vs. 617.91 ±1243.99 p-value=0.37). Post-COVID-19 fecal calprotectin was higher among patients with CD who were tested positive than those who tested negative for SARS-CoV-2 (617.42±832.68 vs. 355.94±1207.46, p value=0.04). In a multivariate linear regression controlling for age, gender, BMI, smoking status, and pre-COVID-19 fecal calprotectin, SARS-CoV-2 positivity was associated with higher fecal calprotectin levels (p value=0.03). In contrast, there was no statistically significant change in fecal calprotectin levels among patients with UC and SARS-CoV-2 positivity (547.2±1089 vs.458.32± 689 p value=0.9). In a 2:1 propensity score-matched cohort (n=264), calprotectin levels were higher among patients with CD who suffered from COVID-19 compared to controls (657.64 vs. 384.94 p-value = 0.03)ConclusionPatients with CD who had COVID-19 have higher FC levels compared to similar CD patients who did not have COVID-19. This finding was not found in patients with UC.