Biomarkers In Inflammatory Bowel Disease Research Articles

Exploration of the biomarkers of comorbidity of psoriasis with inflammatory bowel disease and their association with immune infiltration.

There was evidence that significant bidirectional associations between psoriasis and inflammatory bowel diseases (IBDs), which influences management strategy of the patients, so the investigation on the mechanisms by which these two diseases co-occur is important. The Gene Expression Omnibus (GEO) database was used to download gene expression profiles of psoriasis and IBD. The differentially expressed genes (DEGs) between disease and health control groups for each data set were calculated, and Venn diagram was used to obtain for intersection. We performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the intersection, followed by developing a protein-protein interaction network and module construction, and identified hub genes by cytoHubba. Thereafter, least absolute shrinkage and selection operator algorithms was used to identify the co-biomarkers of psoriasis and IBD from the top 50 hub genes. The biomarkers were used to construct a screening model, the discriminatory capacity of which was verified by receiver operating characteristic (ROC) curves. CIBERSORT algorithm was utilized to estimate the compositional patterns of immune cell infiltration in biomarkers of psoriasis and IBD. Spearman rank correlation analysis was used to further evaluate the correlation between the identified biomarkers and immune cells. A total of 271 shared DEGs were screened. The GO and KEGG enrichment analysis indicated that the shared DEGs were mainly enriched in response to lipopolysaccharide, secretory granule lumen, cytokine activity, and interleukin (IL)-17 signaling pathway. Fifty genes such as IL1B, IL6, were identified as hub genes, based on which, FOS, IFI44, MMP9, MNDA, PTGS2, S100A9, and STAT1 were identified as biomarkers of psoriasis. CCL20, CD274, CTGF, CXCL1, CXCL10, CXCL2, CXCL9, FCGR3B, FOS, GBP1, GZMB, IFI27, IFI6, IL1RN, ISG15, ISG20, LCN2, LILRB2, MMP12, MMP7, S100A8, TLR8, and TNFSF13B were identified as biomarkers of IBD. FOS was the common biomarker of psoriasis and IBD. Screening models were validated in the validation data set (Psoriasis: area under the curve (AUC)=1.000, IBD: AUC=0.870). Immunocyte infiltration analysis showed the macrophages cells, mast cells resting, and T cells CD4 memory activated have the common characteristics in psoriasis and IBD. FOS may play a key role in the occurrence and development of psoriasis complicated with IBD and macrophages cells may be an entrance for treating this comorbidity.

Identifying Key Genes to the Early Diagnosis of Inflammatory Bowel Disease by Integrating Analysis at the Blood and Tissue Levels.

Inflammatory bowel disease (IBD) encompasses Crohn's disease (CD) and ulcerative colitis (UC), is challenging to diagnose, and frequently relapses, significantly affecting patients' quality of life. Despite extensive efforts, the pathogenesis of IBD remains unclear. In this study, we integrated bioinformatics analysis and animal disease model to investigate IBD from two dimensions to identify potential diagnostic biomarkers and explore the pathogenesis of distinct conditions at tissue-specific levels. Firstly, we identified dysferlin (DYSF) and C-X-C motif chemokine ligand 2 (CXCL2) as crucial biomarkers for IBD, with 11 and 13 putative biomarkers for CD and UC, respectively, identified by peripheral blood testing only. CXCL8 and S100 calcium-binding protein A8 (S100A8) were determined to be critical hub genes and validated by real-time polymerase chain reaction (RT-PCR). Secondly, in CD, the differentially expressed genes (DEGs) were mainly associated with immunity based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, while the metabolism of multiple substances and substance transport activity were dominant in UC. Thirdly, essential genes in the pathological progression of CD and UC were identified through protein-protein interaction networks and molecular complex detection (MCODE) analysis. Finally, pathological examination and quantitative analysis of IBD models confirmed the above results. Our findings could contribute to understanding the molecular mechanism of IBD, hold clinical significance for early diagnosis and prevention, and provide effective targets for treating IBD.

Assessing vitamin D as a biomarker in inflammatory bowel disease.

A reliable serum biomarker for inflammatory bowel disease (IBD) activity is needed. Vitamin D is involved in inflammation and has been demonstrated to be low in IBD patients with active disease. It is routinely measured in IBD patients. Therefore, vitamin D may have a role as a serum biomarker in IBD. This study aims to investigate whether serum vitamin D may be useful as a biomarker in IBD in a real-world IBD population. Patients were identified by review of fecal calprotectin (FCP) results, and those who had a clinical review, vitamin D test, and FCP performed within 3 months were included. Clinical scores were calculated from chart review. Nonparametric tests were used to investigate vitamin D and FCP levels, serum biomarkers, and clinical scores. Of 616 patients identified, 325 episodes of matched vitamin D level and biomarker data were obtained. A statistically significant correlation was found between vitamin D levels and FCP levels for all patients (r = -0.19 [s -0.29 to -0.080], P < 0.001]. This remained true when patients were divided into IBD subsets. Low vitamin D was associated with partial Mayo scores and C-reactive protein (CRP) to albumin ratio in ulcerative colitis, and CRP and CRP/albumin ratio in Crohn's disease. Vitamin D level is negatively correlated with FCP and it may be considered as an adjunct biomarker at this stage. A prospective study would be beneficial to investigate further correlations between vitamin D and existing biomarkers of inflammation in IBD.

Today and tomorrow: the use of biomarkers in inflammatory bowel disease

Biomarkers play important roles in clinical care for people with inflammatory bowel diseases (IBD). Biomarkers are also central to the development of new therapies and as endpoints in their evaluation.&#x0D; The recommendations from the STRIDE-II study emphasize the central role of clinical indices and biomarkers such as fecal calprotectin (FC) and C-reactive protein (CRP) in the management of Crohn’s disease (CD) and ulcerative colitis (UC).&#x0D; This review will focus on the established roles for FC and CRP, emerging roles for alternative and composite biomarkers, limitations of current biomarkers, and unmet needs in the field. This is an evolving area, with recent clinical practice guidelines from the American Gastroenterological Association in UC. In addition, updates are expected from the European Crohn’s and Colitis Organisation on their multi-society guideline for IBD monitoring.

Differential expression of serum miR-486 and miR-25 in ulcerative colitis and Crohn’s disease: Correlations with disease activity, extent, and location

Novel reliable biomarkers of inflammatory bowel disease (IBD) are clinically imperative due to potential limitations of endoscopic techniques. MicroRNAs (miRNAs) have emerged as non-invasive biomarkers of IBD; however, the full disease-specific miRNAs signature for IBD subtypes remains elusive. We evaluated the diagnostic role of circulating miR-486 and miR-25 in IBD patients and their potential ability to discriminate IBD subtypes; ulcerative colitis (UC) and Crohn’s disease (CD). Sixty UC patients, 60 CD patients, and 60 healthy controls were recruited. Serum miRNA expression was determined using RT-qPCR. Bioinformatics was employed for target gene and protein-protein interaction (PPI) network analyses. Serum miR-486 was upregulated in CD patients, but didn’t change in UC patients compared to controls. Conversely, serum miR-25 was decreased in both CD and UC patients compared to controls. Only miR-486 was differentially expressed between UC and CD patients. Receiver-operating characteristic analysis revealed that serum miR-486 was superior in CD diagnosis (AUC=0.945) and significantly distinguished CD and UC patients, whereas miR-25 showed discriminative potential for both UC and CD from controls. In the multivariate logistic analysis only miR-486 was associated with the risk of CD diagnosis. Serum miR-486 was correlated with CD activity index and location of disease in CD patients, whereas miR-25 was correlated with the type/extent of UC. PPI network analysis revealed common target genes and signaling pathways for both miRNAs. Conclusively, serum miR-486 and miR-25 might serve as new biomarkers of IBD, with serum miR-486 could be employed in risk stratification of IBD subtypes and has the ground for clinical utility in CD diagnosis, whereas miR-25 has potential for UC and CD diagnosis.

Plasma Extracellular Vesicle LncRNA H19 as a Potential Diagnostic Biomarker for Inflammatory Bowel Diseases.

Inflammatory bowel disease (IBD) is a complex gastrointestinal disease with 2 main subtypes of Crohn's disease (CD) and ulcerative colitis (UC), whose diagnosis mainly depends on the medical history, clinical symptoms, endoscopic, histologic, radiological, and serological findings. Extracellular vesicles (EVs) are now considered an additional mechanism for intercellular communication, allowing cells to exchange biomolecules. Long noncoding RNAs (lncRNAs) that are enriched in EVs have been defined as an ideal diagnostic biomarker for diseases. In this study, we investigated the expression differences of 5 lncRNAs in tissue and plasma EVs of active IBD patients compared with patients in the remission phase and healthy controls to introduce an EV-lncRNA as a noninvasive IBD diagnostic biomarker. Twenty-two active IBD patients, 14 patients in the remission phase, 10 active rheumatoid arthritis (RA) patients, 14 irritable bowel syndrome (IBS) patients, and 22 healthy individuals were recruited in the discovery cohort. In addition, 16 patients with active IBD, 16 healthy controls, 10 inactive IBD patients, 12 active RA patients, and 14 IBS patients were also included in the validation cohort. The expression levels of 5 lncRNAs in tissue and EV-plasma were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) . Machine learning and receiver operating characteristic (ROC) curve analysis were performed to investigate the distinguishing ability of the candidate biomarkers. While the expression levels of lncRNAs CDKN2B-AS1, GAS5, and TUG1 were significantly downregulated, lncRNAs H19 and CRNDE were overexpressed in active IBD lesions. Expression of H19 was detected in plasma EVs whose isolation had been confirmed via dynamic light scattering, microscopy images, and western blotting. The classification results demonstrated the excellent ability of H19 in distinguishing IBD/active from IBD/remission, healthy control, RA, and IBS (area under the ROC curve = 0.95, 0.97,1, and 0.97 respectively). Our study suggests that circulating EV-lncRNA H19 exhibited promising potential for the diagnosis of active IBD.

Elevated Fecal Calprotectin Accompanied by Intestinal Neutrophil Infiltration and Goblet Cell Hyperplasia in a Murine Model of Multiple Sclerosis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system caused by myelin-specific autoreactive T cells. We previously demonstrated intestinal barrier disruption and signs of inflammation in experimental autoimmune encephalomyelitis (EAE), a model of MS. Fecal calprotectin is a disease activity biomarker in inflammatory bowel diseases, released by neutrophils in response to inflammation. We aimed to further investigate EAE manifestations in the gastrointestinal tract and to determine whether calprotectin is a useful biomarker of intestinal inflammation in EAE. Calprotectin was analyzed in feces, cecal contents, and plasma of EAE mice. Infiltrating neutrophils and goblet cells were investigated in different parts of the gastrointestinal tract before the onset of neurological symptoms and during established disease. We found increased calprotectin levels in feces, cecal content, and plasma preceding EAE onset that further escalated during disease progression. Increased neutrophil infiltration in the intestinal tissue concomitant with IL-17 expression and myeloperoxidase activity was found to correlate well with clinical activity. Increased goblet cells in the intestine, similar to irritable bowel syndrome (IBS), were also observed. The results suggest calprotectin as a good biomarker of gastrointestinal inflammation in EAE and the potential of this model as a useful animal model for IBS.

Plasminogen Activator Inhibitor 1 Is a Novel Faecal Biomarker for Monitoring Disease Activity and Therapeutic Response in Inflammatory Bowel Diseases.

Crohn's disease [CD] and ulcerative colitis [UC] require lifelong treatment and patient monitoring. Current biomarkers have several limitations; therefore, there is an unmet need to identify novel biomarkers in inflammatory bowel disease [IBD]. Previously, the role of plasminogen activator inhibitor 1 [PAI-1] was established in the pathogenesis of IBD and suggested as a potential biomarker. Therefore, we aimed to comprehensively analyse the selectivity of PAI-1 in IBD, its correlation with disease activity, and its potential to predict therapeutic response. Blood, colon biopsy, organoid cultures [OC], and faecal samples were used from active and inactive IBD patients and control subjects. Serpin E1 gene expressions and PAI-1 protein levels and localisation in serum, biopsy, and faecal samples were evaluated by qRT-PCR, ELISA, and immunostaining, respectively. The study population comprised 132 IBD patients [56 CD and 76 UC] and 40 non-IBD patients. We demonstrated that the serum, mucosal, and faecal PAI-1 concentrations are elevated in IBD patients, showing clinical and endoscopic activity. In responders [decrease of eMayo ≥3 in UC; or SES-CD 50% in CD], the initial PAI-1 level decreased significantly upon successful therapy. OCs derived from active IBD patients produced higher concentrations of PAI-1 than the controls, suggesting that epithelial cells could be a source of PAI-1. Moreover, faecal PAI-1 selectively increases in active IBD but not in other organic gastrointestinal diseases. The serum, mucosal, and faecal PAI-1 concentration correlates with disease activity and therapeutic response in IBD, suggesting that PAI-1 could be used as a novel, non-invasive, disease-specific, faecal biomarker in patient follow-up.

Serum long noncoding RNA H19/micro RNA-675-5p axis as a probable diagnostic biomarker in inflammatory bowel disease

BackgroundA significant body of research strengthens the starring role of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the pathogenesis of inflammatory bowel disease (IBD). Here, we investigated the diagnostic utility of lncRNA H19 and miRNA-675-5p in IBD.MethodsThis study included 97 participants, thirty-five ulcerative colitis patients, thirty-two Crohn’s disease patients, and thirty IBD-free controls. History, staging, laboratory investigations, and colonoscopy were performed. Also, quantitative real-time PCR (qPCR) for revealing of lncRNA H19 and miRNA-675-5p was done.ResultsThe estimated serum levels for H19 and miRNA-675-5p in the UC and CD groups in comparison to the control group showed a high statistical difference (P = 0.0001 for each parameter). Based upon the severity of UC patients, both biomarkers showed significantly higher values between remission and moderate cases, with p-values 0.022 and 0.02, respectively. Meanwhile, in CD patients, both biomarkers revealed no statistical significance between remission and any active stage of the disease. Additionally, ROC analysis revealed that H19 could discriminate between UC and control subjects with 94.3% sensitivity and 90.0% specificity, and with 87.5% sensitivity, and 88.5% specificity in the CD group. Furthermore, miR-675-5p was able to discriminate between UC and control subjects with 85.7% sensitivity and 97.3% specificity and with 88.4% sensitivity, 95.2% specificity in the CD group. Logistic regression found a significant predictive utility of using miR-675-5p and H19 in IBD.ConclusionH19 and miRNA-675-5p can be used as diagnostic biomarkers in IBD, with superiority in UC patients with moderate activity.

Biosensing Intestinal Alkaline Phosphatase by Pregnancy Test Strips Based on Target-Triggered CRISPR-Cas12a Activity to Monitor Intestinal Inflammation.

With an increasing incidence worldwide, inflammatory bowel disease (IBD) is a chronic inflammatory disease affecting the gastrointestinal tract, which impairs the life quality of patients. Therefore, it is of great significance to construct a sensitive, simple, and convenient biosensor to analyze IBD-associated biomarkers for an auxiliary diagnosis of IBD. Intestinal alkaline phosphatase (IAP), expressed by the intestinal epithelium, is an endogenous protein that is thought to play a vital role in maintaining intestinal homeostasis and is considered a potential biomarker for IBD. Here, an IAP detection method was developed using pregnancy test strips by dephosphorylation. Initially, a double-stranded DNA (dsDNA) was designed to respond to IAP and acted as an activator of Cas12a. In the presence of IAP, the designed dsDNA was not digested by lambda exonuclease (λ exo), which hybridized to the Cas12a-crRNA duplex and resulted in the activation of the trans-cleavage of Cas12a. Further, the activated Cas12a cleaved the single-strand DNA (ssDNA) linker in the MBs-ssDNA-hCG probe, triggering the release of hCG. With magnetic separation, the released hCG could be quantitatively detected by pregnancy test strips. IAP levels were analyzed in feces from colitis and healthy mice by pregnancy test strips. The results showed that the IAP level of colitis mice (3.89 ± 1.92 U/L) was much lower than that of healthy mice (39.64 ± 24.93 U/L), indicating the correlation between IAP and intestinal inflammation. Taken together, a sensitive, user-friendly detection assay based on pregnancy test strips was constructed to monitor IAP and used as an auxiliary diagnostic approach for IBD in a clinical scene.

Serum Calprotectin as a Potentially Sensitive Biomarker for Inflammatory Bowel Disease in Egyptian Patients

Abstract Background Inflammatory bowel disease (IBD) incidence is increasing nowadays. Its diagnosis depends on invasive techniques such as colonoscopy and biopsy which is the gold standard for diagnosis. Its activity is monitored by fecal calprotectin levels which has a low compliance rate. Although it is unlikely for serum biomarkers to replace colonoscopy, a need exists for a serum biomarker that at least decreases the need for such an invasive technique. Aim of the Work The aim of this work was to evaluate serum calprotectin as a biomarker for IBD in Egyptian patients. Patients and Methods The study was conducted on 50 Egyptian IBD patients, 34% were males and 66% were females with their ages ranging from 15 to 62 years. Based on IBD type 60% were diagnosed as ulcerative colitis (UC) half of them were in clinical activity and the other half in remission and 40% were diagnosed as Chron’s disease (CD) half of them were in clinical activity and the other half in remission. IBD patients were recruited from Gastroenterology Clinic, Ain Shams University Hospitals in the period from October 2019 till October 2020. In addition, 20 race-, sex- and age- matched apparently healthy subjects were included in the study as a control group. Serum calprotectin levels were measured by ELISA. Results The results revealed that the serum levels of calprotectin were significantly higher in IBD patients than in the control group and in clinically active patients than those in remission. There was a positive correlation between serum calprotectin levels, CRP and ESR, however the diagnostic value of serum calprotectin was higher than that of CRP and ESR as serum calprotectin had higher sensitivity and specificity. The specificity of serum calprotectin in diagnosing IBD was 95% and the sensitivity was 98%; the specificity of CRP was 85% and the sensitivity was 64%; the specificity of ESR was 85% and the sensitivity was 62%. Our work revealed that there was a direct relationship between serum calprotectin and platelet count and an inverse relationship between serum calprotectin and albumin and hemoglobin levels. Conclusion Serum levels of calprotectin are increased and are associated with clinical activity in IBD patients so it may become one of the clinically valuable indicators of activity of the disease.

The significance of serum marker levels for assessing the status and prognosis of patients with inflammatory bowel disease

Purpose of the work: to analyze the research performed in the last decade on the study of serum markers used to diagnose inflammatory bowel diseases (IBD), differential diagnosis of nosological forms of IBD, to predict the course of the disease, response to ongoing therapy, as well as to predict the recurrence of the disease. Materials and methods. A search was carried out in the text databases “Scopus”, “Web of Science”, “PubMed” using keywords from the literature sources of the last 10 years about blood serum biomarkers used for diagnosis, evaluation of therapeutic efficacy, monitoring of disease activity and evaluation of prognosis in patients with IBD. Results. Information on serological biomarkers of IBD, which are well known and widely used in clinical practice (C-reactive protein), recently discovered biomarkers (cytokines, antibodies and non-coding RNA), as well as recent advances in serological biomarkers (metabolomics, proteomics, oncostatin M, galectins), were analyzed, which are used in various aspects of the diagnosis of IBD. Since intestinal fibrosis significantly affects the prognosis in patients with IBD, data on serum markers of intestinal fibrosis are presented separately. Conclusion. Recently, serum biomarkers in patients with IBD have become the object of close attention, since they are minimally invasive, convenient, and relatively inexpensive than markers in biopsy specimens, other biological fluids, fecal, and respiratory tests. Despite an extensive list of studies conducted over the past 10 years, there are still no ideal serum biomarkers for the diagnosis of IBD. Serum and non-coding RNA profiling techniques are just beginning to develop, but offer great promise for clinical practice. A combination of different biomarkers may be useful to improve the efficiency of IBD diagnosis.

Detection of IL12/23p40 via PET Visualizes Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), which includes both Crohn disease and ulcerative colitis, is a relapsing inflammatory disease of the gastrointestinal tract. Long-term chronic inflammatory conditions elevate the patient's risk of colorectal cancer (CRC). Currently, diagnosis requires endoscopy with biopsy. This procedure is invasive and requires a bowel-preparatory regimen, adding to patient burden. Interleukin 12 (IL12) and interleukin 23 (IL23) play key roles in inflammation, especially in the pathogenesis of IBD, and are established therapeutic targets. We propose that imaging of IL12/23 and its p40 subunit in IBD via immuno-PET potentially provides a new noninvasive diagnostic approach. Methods: Our aim was to investigate the potential of immuno-PET to image inflammation in a chemically induced mouse model of colitis using dextran sodium sulfate by targeting IL12/23p40 with a 89Zr-radiolabeled anti-IL12/23p40 antibody. Results: High uptake of the IL12/23p40 immuno-PET agent was exhibited by dextran sodium sulfate-administered mice, and this uptake correlated with increased IL12/23p40 present in the sera. Competitive binding studies confirmed the specificity of the radiotracer for IL12/23p40 in the gastrointestinal tract. Conclusion: These promising results demonstrate the utility of this radiotracer as an imaging biomarker of IBD. Moreover, IL12/23p40 immuno-PET can potentially guide treatment decisions for IBD management.

Identification and Validation of the Diagnostic Markers for Inflammatory Bowel Disease by Bioinformatics Analysis and Machine Learning.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract which is mediated by the inappropriate immune responses. This study was aimed to identify novel diagnostic biomarkers for diagnosis of IBD and explore the relationship between the diagnostic biomarkers and infiltrated immune cells. GSE38713, GSE53306, and GSE75214 downloaded from the Gene Expression Omnibus (GEO) database were split into training and testing sets. Differentially expressed genes (DEGs) were screened using the "limma" package. Gene Ontology (GO) and KEGG pathway enrichment analysis of DEGs were performed by clusterProfiler package. The LASSO regression and support vector machine recursive feature elimination (SVM-RFE) algorithms were conducted to identify novel diagnostic biomarkers. The receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic value of the candidate biomarkers. The relationship of the candidate biomarkers and infiltrating immune cells in IBD were evaluated by CIBERSOTR. Quantitative Real-Time PCR (qRT-PCR) was applied to measure the expression level of the biomarkers in IBD. A total of 289 dysregulated genes were identified as DEGs in IBD. These DEGs were significantly enriched in chemokine signaling pathway and cytokine-cytokine receptor interaction. RHOU was identified as a critical diagnostic gene in IBD, which was confirmed using ROC curve and qRT-PCR assays. Immune cell infiltration analysis showed that RHOU was correlated with macrophages M2, dendritic cells resting, mast cells resting, T cells CD4 memory resting, macrophages M0, and mast cells activated. Our results imply that RHOU may be a potential diagnostic biomarker for IBD.

Circulating Cell-Free DNA in Inflammatory Bowel Disease: Liquid Biopsies with Mechanistic and Translational Implications.

This review examines the role of circulating cell-free DNA (cfDNA) as potential drivers of inflammation and their potential application as mechanistic biomarkers in Inflammatory Bowel Diseases (IBD). These DNA fragments contain significant information about their origins, the underlying host pathology leading to their release, and possess properties that can fuel the inflammatory process. Recent advances in sequencing and analytical approaches have made the translation of cfDNA into clinical practice a promising prospect. We focus on the functional relevance of cfDNA in the inflammatory process and discuss its potential for future assessments of IBD activity and identification of therapeutic options.

Epigenetics of Inflammatory Bowel Diseases.

Inflammatory bowel diseases are multifactorial, chronic, continuous, relapsing, and immune-mediated diseases of the gastrointestinal tract. It has been believed that mechanisms underlying inflammatory bowel diseases include genetic predisposition, environmental factors, and altered immune response to the gut microbiome. The epigenetic modulation takes place via chromatin modifications, including phosphorylation, acetylation, methylation, sumoylation, and ubiquitination. The methylation levels of colonic tissue were found well correlated to blood samples in inflammatory bowel diseases. Moreover, the methylation level of specific genes was different between Crohn's disease and ulcerative colitis. It has been shown that the enzymes affecting histone modifications like histone deacetylases and histone acetyltransferases do not act solely on histones but also affect the acetylation of many proteins such as p53 and STAT3. It has been already shown that a nonselective histone deacetylase inhibitor, Vorinostat (SAHA), which is currently being used in several cancer treatments, showed anti-inflammatory activities in mouse models. Among epigenetic alterations, long non-coding RNAs and microRNAs play significant roles in T-cell maturation, differentiation, activation, and senility. The long non-coding RNA and microRNA expression profiles can perfectly separate inflammatory bowel disease patients from healthy controls and are remarked as biomarkers of inflammatory bowel diseases. Overall, many studies have shown that epigenetic inhibitors can target significant signal pathways in the pathogenesis of inflammatory bowel diseases, and the impact of epigenetic inhibitors is being studied in clinical trials. In conclusion, exploring more epigenetic pathways regarding inflammatory bowel disease pathogenesis will help us to discover therapeutic targets and new drugs and agents targeting miRNAs in inflammatory bowel diseases. In general, discovering epigenetic targets could improve the diagnosis and treatment of inflammatory bowel diseases.

Pre-Diagnostic Saliva Microbiota of School-Aged Children Who Developed Type 1 Diabetes or Inflammatory Bowel Diseases.

Altered commensal microbiota composition has been associated with pediatric type 1 diabetes mellitus (T1D) and inflammatory bowel diseases (IBD), but the causal relationship is still unclear. To search for potential pre-diagnostic biomarkers for pediatric T1D or IBD, we compared microbiota in saliva samples in a nested case-control design comprising children developing T1D (nchildren = 52) or IBD (nchildren = 21) and controls with a similar age, sex, and residential area (nchildren = 79). The pre-diagnostic saliva microbiota alpha- and beta-diversity of children who would develop T1D (nsamples = 27) or IBD (nsamples = 14) minimally varied from that of controls. The relative abundances of Abiotrophia were higher, while those of Veillonella, Actinomyces, Megasphaera, Butyrivibrio, and Candidatus ancillula were lower in children who would develop T1D. Within 2 years before diagnosis, the metabolic PWY-5677 pathway (converting succinate into butyrate) was lower in pre-T1D samples than in controls (q = 0.034). No significant pre-IBD differences were found. In conclusion, saliva microbiota diversity or composition were not successful predictors for pediatric T1D nor IBD. Intriguingly, the succinate fermentation pathway was predicted to be lowered before the onset of T1D. Thus, investigating functional pathways might provide a better approach in searching for biomarkers for autoimmune disease in the future.

Inflammatory bowel disease (IBD)-specific immune cell recruitment and response can be modulated with anti-TNF-α therapies in the human Colon Intestine-Chip

Abstract Objective: Inflammatory bowel disease (IBD) is a complex inflammatory disease, for which few effective therapies exist. The goal of our current work was to show: i) that such a complex, immune cell-driven pathogenesis could be captured on Emulate’s human Colon Intestine-Chips; and ii) that this could be used as a novel human-centric system to support IBD drug development including anti-TNF-α antibodies. Methods: PBMCs were perfused through the vascular (bottom) channel in untreated ‘resting’ or cytokine-‘primed’ Colon Intestine-Chips. Clinically relevant IBD drugs, including anti-TNF-α antibodies (Humira and Cimzia), as well as dexamethasone and AJM300 were administered through the vascular channel during PBMC administration. Total cell recruitment, effluent biomarker secretion (cytokines, calprotectin, C-reactive protein), and barrier function were analyzed for 72 hours. Results: α4β7 +‘gut-tropic’ PBMCs (monocytes, CD4 +, CD8 +, and NK cells) preferentially adhered and transmigrated in a cytokine priming-dependent manner. These PBMCs released clinically relevant IBD cytokines and biomarkers and induced barrier disruption, a hallmark of IBD. Anti-TNF-α antibodies and AJM300 caused reduced PBMC recruitment, inflammatory response and barrier disruption &amp;gt;90%. Dexamethasone had more modest effects, as expected. Conclusion: The human Colon Intestine-Chip can both model complex immune cell-driven IBD and validate effects of clinically relevant IBD drugs. This system could provide predictive validity for pre-clinical development of new IBD drugs.

Dipeptidyl peptidase 4 (DPP4) in fecal samples: validation of the extraction methodology and stability in short-term storage conditions.

This study assesses the clinical relevance of dipeptidyl peptidase 4 (DPP4) membrane exopeptidase as a biomarker of inflammatory bowel disease (IBD). A spike-and-recovery approach of DPP4 in fecal samples was used to compare two different methods for protein extraction, followed by a stability assessment. Fecal samples of healthy volunteers spiked with known concentrations of recombinant DPP4 were processed using a standard manual extraction protocol and the CALEX® protocol. The two methods were compared by quantification of fecal DPP4 by ELISA, followed by Bland-Altman analysis. For the stability assays DPP4 was extracted from fecal samples and stored under different conditions of temperature and time after collection. In general, the levels of spiked DPP4 in stool samples were lower with the manual protocol than in those obtained with the CALEX® method; this trend was corroborated by Bland-Altman analysis. Nonetheless, variability was within the acceptable limits for both protocols. In the stability assessment, no statistically significant differences were found between the results obtained under the different storage conditions. Both manual and CALEX® protocols provided equal extraction ability of DPP4 from stool samples. In addition, DPP4 provided flexibility in terms of sample storage enabling the accurate assessment of samples delivered up to a week before analysis.

The value of 7 peripheral blood serum ratios in diagnosis and prediction of disease activity of patients within inflammatory bowel disease individuals.

In recent years, a number of studies have suggested that inflammation-based biomarkers can be applied in the diagnostics and prognostic testing of disease. However, the association between these ratios and inflammatory bowel disease (IBD) remains unclear. We aimed to investigate the role of these inflammation-based ratios in patients with IBD. Retrospective analysis of 362 patients with IBD and 100 healthy individuals from January 2016 and December 2021. The receiver operating characteristic curve and logistic regression analysis was applied to explore the diagnostic and predictive performance of the seven ratio markers [neutrophil- to-albumin ratio (NAR), neutrophil-to-pre-albumin ratio (NPAR), albumin-to-alkaline-phosphatase ratio (AAPR), albumin-to-globulin ratio (AGR), albumin-to-fibrinogen ratio (AFR), fibrinogen-to-pre-albumin ratio (FPR), and Prognostic Nutritional Index (PNI)] regarding to disease activity in IBD individuals. Compared with healthy controls, patients with Crohn's disease (CD) or ulcerative colitis (UC) exhibited higher levels of NAR, NPAR, FPR (P < 0.001), lower levels of AAPR, and PNI (P < 0.001). Multivariate logistic regression showed that the level of NPAR (OR = 1.12, 95%CI: 1.02-1.23, P = 0.016) and AGR (OR = 1.01, 95%CI: 1.01-1.12, P < 0.001) was an independent risk factor of IBD. Then, we found the level of NPAR (OR = 1.10, 95%CI: 1.01-1.20, P = 0.02) and PNI (OR = 0.83, 95%CI: 0.71-0.96, P = 0.01) was independently associated with disease activity. Besides, a positive association was observed between the level of NPAR and two clinical scores [Harvey Bradshaw index (HBI) in patients with CD, Mayo score in patients with UC]. Finally, the level of NPAR (P = 0.002) and PNI (P = 0.003) showed a significant difference in the IBD-associated neoplasia group and IBD without neoplasia group. Our data first suggests NPAR as a putative biomarker for diagnosing and predicting disease activity in patients with IBD. Investigations involving a larger number of IBD individuals are necessary to validate its use as an easily obtained peripheral blood biomarker of IBD.