Chronic Inflammatory Bowel Disorder Research Articles

Perianal fistulizing Crohn's disease: Current perspectives on diagnosis, monitoring and management with a focus on emerging therapies.

Crohn's disease (CD), a chronic inflammatory bowel disorder, manifests in various phenotypes, with fistulizing perianal CD (CD-PAF) being one of its most severe phenotypes. Characterized by fistula formation and abscesses, CD-PAF impacts 17% to 34% of all CD cases and with a significantly deleterious impact on patient's quality of life, while increasing the risk for anorectal cancers. The pathogenesis involves a complex interplay of genetic, immunological and environmental factors, with cytokines such as tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) playing pivotal roles. Diagnostic protocols require a multi-disciplinary approach including colonoscopy, examination under anesthesia and magnetic resonance imaging. In terms of treatment, biologics alone often prove inadequate, making surgical interventions such as setons and fistula surgeries essential. Emerging therapies such as mesenchymal stem cells are under study. The South Asian context adds layers of complexity, including diagnostic ambiguities related to high tuberculosis prevalence, healthcare access limitations and cultural stigma toward perianal Crohn's disease and ostomy surgery. Effective management necessitates an integrated, multi-disciplinary approach, especially in resource-constrained settings. Despite advances, there remain significant gaps in understanding the disease's pathophysiology and a dearth of standardized outcome measures, underscoring the urgent need for comprehensive research.

P1104 Shifting Surgical Landscape in Crohn's Colitis: Laparoscopic Supremacy and Robotic Upsurge

Abstract Background Crohn's disease (CD) is a chronic inflammatory bowel disorder that can cause transmural inflammation throughout the digestive tract. When CD affects the colon, it is known as Crohn's colitis (CC), a serious condition often requiring surgical resection. Surgical trends in CC have changed significantly over the past decade, shifting towards minimally invasive surgery, with laparoscopic and robotic procedures becoming increasingly common. This study examines how surgical trends in CC have changed in recent years and predicts how they may change. Methods We conducted a retrospective analysis using the ACS-NSQIP database, focusing on patients who underwent colonic resections for CC between 2012 and 2021, including 20,109 patients. Our main goal was to examine trends in open, laparoscopic, hand-assisted, and robotic surgery. We utilized time series analysis, specifically quarter and year of admission data, and employed Vector Autoregressive (VAR) models to explore the dynamic relationships among these surgical techniques. To analyze the time trends, we reported the quarter (Q) and year of admission. These models enabled us to forecast future trends, accompanied by 95% confidence intervals, extending our predictions up until Q2 of 2025. Results As shown in Figure 1, open surgery has been the most common approach to CC since Q1 2012, accounting for 52.3% of all procedures. Laparoscopic surgery was the next most common approach, at 33.3%, followed by hand-assisted laparoscopy at 14.4%. Laparoscopy rapidly expressed market supremacy, by steadily becoming the most widespread approach by Q2 of 2017, representing 42.2% of CC surgery and peaking in Q2 2020 at 43.5%. This growth in laparoscopy came at the expense of open surgery, which experienced a significant decline, reaching its lowest point of 28.5% in Q2 2021. Hand-assisted procedures gradually increased in popularity over the years but remained less popular than open and laparoscopic methods, peaking at 24.0% in Q4 2019. Robotic procedures experienced slow but steady growth, from 1.9% in Q1 2013 to 10% in Q2 2021. Future trends suggest that laparoscopy will continue to grow steadily, reaching 45% (95% CI 28.2-61.7%) by the end of our prediction period. Robotic surgery is poised to significantly shift CC surgery trends, with resections expected to reach 12.6% (95% CI 9.3-15.8%) by Q2 2025, while a subsequent decline in open procedures to 20.8% (95% CI 0-43%). Conclusion Laparoscopic surgery has emerged as the favored surgical approach in CC and is expected to maintain its supremacy into the near future. Open colonic resections are anticipated to decline, making way for the increasing prevalence of robotic surgery.

Orbital myositis in a patient with Crohn's disease: A case report of two episodes

To describe a case report of a 34 years-old patient with Crohn's Disease and two episodes of Ocular Myositis. The research methodology employed in this study consisted of a retrospective review of the patient's complete medical history. Crohn's Disease is a chronic inflammatory bowel disorder known to be associated with a wide range of extraintestinal manifestations. Ocular abnormalities, such as episcleritis and uveitis, are commonly observed. However, orbital myositis is an extremely rare ocular extraintestinal manifestations characterized by acute ocular pain that worsens with eye movements and is often accompanied by diplopia. In this case report, we present the case of a 34-year-old woman with a confirmed diagnosis of Crohn's Disease, who experienced two episodes of acute orbital pain exacerbated by ocular movements and diplopia. The diagnosis was established through clinical evaluation and radiologic imaging, with confirmation after a good response to systemic corticosteroids. She responded favorably to systemic corticosteroid therapy on both episodes, and no additional treatment was required. As of now, she remains stable without any ocular sequelae. It is important to note that orbital myositis is an uncommon ocular manifestation associated with Crohn's Disease, and prompt recognition and management are crucial to achieve successful outcomes.

Advances in natural compound-based nanomedicine and the interaction with gut microbiota in ulcerative colitis therapy.

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder of the large intestine. Previous studies have indicated that the gut microbiota plays an important role in the triggers, development, and treatment response of UC. Natural active molecules and their nanoformulations show huge potential for treating UC. The nanoparticles can regulate the gut microbiota and metabolites, whereas gut microbiota-mediated effects on nanomedicines can also bring additional therapeutic benefits. Therefore, this review aims to integrate current research on natural active molecule-based nanomedicines for UC therapy and their interaction with the gut microbiota. Here, this discussion focuses on the effects and functions of gut microbiota and metabolites in UC. The use of active molecules and the nanoformulation from natural compounds for UC therapy have been provided. The interactions between the gut microbiota and nanomedicines are derived from natural products and elucidate the possible biological mechanisms involved. Finally, the challenges and future directions for enhancing the therapeutic efficacy of nanomedicine in treating UC are proposed.

Functional properties and health benefits of finger millet (Eleusine coracana L.): A review

In India, ragi is the colloquial name for finger millet (Eleusine coracana L.). It is sometimes recognised as poor man’s food. Ragi flour is used to baked items to create calcium and iron-fortified biscuits. Calcium deficiency may cause birth abnormalities and dental problems. Ragi is good source of iron, which is crucial for the production of haemoglobin in red blood cells. Nutritionally, finger millets are rich in calcium, potassium, dietary fibres and polyphenolic constituents. Some individuals are allergic to protein gluten causing immune reaction. Gluten intolerance leads to chronic inflammatory bowel disorder. An ongoing strict diet (GFD) is the only solution available for these illnesses. Gluten-free products have less nutritional content and to be more expensive other lactose food products. They are well known for their health benefits like antidiabetic, antioxidant and antimicrobial properties. Hence, finger millets are naturally gluten free, these can be consumed by both gluten intolerant as well as diabetic individuals.

Selective oxidative protection leads to tissue topological changes orchestrated by macrophage during ulcerative colitis

Ulcerative colitis is a chronic inflammatory bowel disorder with cellular heterogeneity. To understand the composition and spatial changes of the ulcerative colitis ecosystem, here we use imaging mass cytometry and single-cell RNA sequencing to depict the single-cell landscape of the human colon ecosystem. We find tissue topological changes featured with macrophage disappearance reaction in the ulcerative colitis region, occurring only for tissue-resident macrophages. Reactive oxygen species levels are higher in the ulcerative colitis region, but reactive oxygen species scavenging enzyme SOD2 is barely detected in resident macrophages, resulting in distinct reactive oxygen species vulnerability for inflammatory macrophages and resident macrophages. Inflammatory macrophages replace resident macrophages and cause a spatial shift of TNF production during ulcerative colitis via a cytokine production network formed with T and B cells. Our study suggests components of a mechanism for the observed macrophage disappearance reaction of resident macrophages, providing mechanistic hints for macrophage disappearance reaction in other inflammation or infection situations.

Predictors of bowel damage in the long-term progression of Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory bowel disorder that progresses to bowel damage (BD) over time. An image-based index, the Lémann index (LI), has been developed to measure cumulative BD. To characterize the long-term progression of BD in CD based on changes in the LI and to determine risk factors for long-term progression. This was a single-center longitudinal cohort study. Patients who had participated in prospective studies on the accuracy of magnetic resonance imaging using endoscopy as a gold standard and who had a follow-up of at least 5 years were re-evaluated after 5-12 years. Seventy-two patients were included. LI increased in 38 patients (52.8%), remained unchanged in 9 patients (12.5%), and decreased in 25 patients (34.7%). The small bowel score and surgery subscale significantly increased (P = 0.002 and P = 0.001, respectively), whereas the fistulizing subscale significantly decreased (P = 0.001). Baseline parameters associated with BD progression were ileal location (P = 0.026), CD phenotype [stricturing, fistulizing, or both (P = 0.007, P = 0.006, and P = 0.035, respectively)], disease duration > 10 years (P = 0.019), and baseline LI stricturing score (P = 0.049). No correlation was observed between BD progression and baseline clinical activity, biological markers, or severity of endoscopic lesions. BD, as assessed by the LI, progressed in half of the patients with CD over a period of 5-12 years. The main determinants of BD progression were ileal location, stricturing/fistulizing phenotype, and disease duration.

Gut-Brain Axis: Insights from Hippocampal Neurogenesis and Brain Tumor Development in a Mouse Model of Experimental Colitis Induced by Dextran Sodium Sulfate.

Chronic inflammatory bowel disorders (IBD) are idiopathic diseases associated with altered intestinal permeability, which in turn causes an exaggerated immune response to enteric antigens in a genetically susceptible host. A rise in psych cognitive disorders, such as anxiety and depression, has been observed in IBD patients. We here report investigations on a model of chemically induced experimental colitis by oral administration of sodium dextran sulfate (DSS) in C57BL/6 mice. We investigate, in vivo, the crosstalk between the intestine and the brain, evaluating the consequences of intestinal inflammation on neuroinflammation and hippocampal adult neurogenesis. By using different DSS administration strategies, we are able to induce acute or chronic colitis, simulating clinical characteristics observed in IBD patients. Body weight loss, colon shortening, alterations of the intestinal mucosa and fecal metabolic changes in amino acids-, lipid- and thiamine-related pathways are observed in colitis. The activation of inflammatory processes in the colon is confirmed by macrophage infiltration and increased expression of the proinflammatory cytokine and oxidative stress marker (Il-6 and iNOS). Interestingly, in the hippocampus of acutely DSS-treated mice, we report the upregulation of inflammatory-related genes (Il-6, Il-1β, S-100, Tgf-β and Smad-3), together with microgliosis. Chronic DSS treatment also resulted in neuroinflammation in the hippocampus, indicated by astrocyte activation. Evaluation of stage-specific neurogenesis markers reveals deficits in the dentate gyrus after acute and chronic DSS treatments, indicative of defective adult hippocampal neurogenesis. Finally, based on a possible causal relationship between gut-related inflammation and brain cancer, we investigate the impact of DSS-induced colitis on oncogenesis, using the Ptch1+/−/C57BL/6 mice, a well-established medulloblastoma (MB) mouse model, finding no differences in MB development between untreated and DSS-treated mice. In conclusion, in our experimental model, the intestinal inflammation associated with acute and chronic colitis markedly influences brain homeostasis, impairing hippocampal neurogenesis but not MB oncogenesis.

Invasive squamous cell carcinoma arising from long‐lasting enterocutaneous fistula due to Crohn's disease

Chronic inflammation led to squamous cell carcinoma. We experienced squamous cell carcinoma from Crohn’s disease. A 53-year-old woman with Crohn's disease (CD) diagnosed more than 30 years earlier was referred to us because of a 4 month history of abdominal tumors. She underwent a total colectomy, small intestinal resection, and an eternal enterostomy 24 years earlier and had two enterocutaneous fistulous tracts with repeated inflammation on the lower-right side of her abdomen for 13 years. She had been treated with 5-aminosalicylic acid for more than 15 years, but did not receive immunosuppressants or tumor necrosis factor alpha inhibitors. Physical examination revealed a 6 × 3.5 cm reddish ulcerative tumor on the lower-right side of her abdomen surrounded by brownish pigmentation with indurations (Figure 1A). Histopathological examination of the tumor revealed atypical squamous cell proliferation with marked keratinization (Figure 1B,C). Histological continuity between the epidermis and atypical cells was not observed, and immunostaining of the cells was negative for human papillomavirus. Computed tomography and positron emission tomography/computed tomography demonstrated a large mass involving the abdominal walls and enlargement of the inguinal and right external iliac lymph nodes (Figure 1D). Her serum squamous cell carcinoma (SCC) antigen level was also elevated (5.4 ng/ml; normal range, <2.5 ng/ml). The patients were then diagnosed with SCC arising from an enterocutaneous fistula (ECF) related to CD. She was treated with radiation therapy (30 Gy) for a skin tumor and bilateral inguinal lymph nodes, followed by chemotherapy with pepleomycin. Unfortunately, her disease slowly progressed and she died 5 months after her initial visit. Crohn's disease is a chronic inflammatory bowel disorder characterized by transmural inflammation and fistula formation.1 Perianal fistulas are common complications of the disease, and patients with anal and/or perianal CD have a high risk of perianal fistula-related cancer.2 Fistula-related carcinoma develops in approximately 1% of patients with fistulizing perianal CD. More than half of these carcinomas are adenocarcinoma; most of the rest are SCC. Compared with perianal fistulas, ECF is rare, but it is associated with significant morbidity and mortality due to various complications.3 Late complications, such as late onset of malignancy, have been given little attention in the literature, with a limited number of patients with cancers arising from ECF and only one fistula-associated SCC patient, who was treated with long-lasting azathioprine followed by infliximab, being reported.4 The causes of malignancies arising from chronic fistulas are unclear, but chronic inflammation and immunosuppression are considered mechanisms of carcinogenesis in CD patients. Chronic inflammation, a feature of CD, induces constant epithelial regeneration, ulceration, and high cell turnover rates, leading to dysplasia and subsequently carcinoma. Our patient was not treated with immunosuppressants or biologics; however, so it is likely that her chronic inflammation led to carcinogenesis. The onset of malignancies arising from ECF in CD patients may increase in future because of the expanding use of immunosuppressants and/or biologics and improvements in the treatment of acute complications of ECF. Therefore, diagnosticians should be alert to early signs of fistula-associated malignancies. The authors declare no conflict of interest. Approval of the research protocol: N/A. Informed Consent: The written informed consent was obtained from the patient. Registry and the Registration No. of the study/trial: N/A. Animal Studies: N/A.

Traditional Chinese Medicine Alleviates Ulcerative Colitis via Modulating Gut Microbiota.

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by relapsing and remitting inflammation of the bowel. In recent decades, traditional Chinese medicine (TCM) has been widely used in the therapy of UC. However, its underlying mechanisms have not been sufficiently elucidated. Accumulating studies indicate that the gut microbial dysbiosis is closely related to UC. It has been demonstrated that TCM could alter the composition of intestinal microbiota by enriching beneficial and SCFA-producing bacteria and reducing pathogenic bacteria. In this review, we discussed recent evidence regarding the TCM and its role in modulating gut microbiota for the treatment of UC.

Alterations of Gut Microbiota in Patients With Intestinal Tuberculosis That Different From Crohn's Disease.

Intestinal tuberculosis (ITB) and Crohn’s disease (CD) are chronic inflammatory bowel disorders that are associated with dysregulated mucosal immunity. The gut microbiota plays an important role in the regulation of host immunity and inflammatory response. Although mounting evidence has linked CD with the dysbiosis of gut microbiota, the characteristic profiles of mucosal bacteria in ITB remain unclear. The aim of this study was to assess the alterations of the gut microbiota in ITB and compare the microbial structure of ITB with CD. A total of 71 mucosal samples were collected from patients with ITB, CD, and healthy controls (HC), and then, 16S rRNA gene sequencing was performed. The overall composition of gut microbiota in ITB was strikingly different from HC, with the dominance of Proteobacteria and reduction of Firmicutes. Of note, the short-chain fatty acids (SCFAs)-producing bacteria such as Faecalibacterium, Roseburia, and Ruminococcus were decreased in ITB relative to HC, while Klebsiella and Pseudomonas were enriched. Multiple predictive functional modules were altered in ITB, including the over-representation of lipopolysaccharide biosynthesis, bacterial invasion of epithelial cells, and pathogenic Escherichia coli infection that can promote inflammation. Additionally, the microbial structure in CD was distinctly different from ITB, characterized by lower alpha diversity and increased abundance of Bacteroides, Faecalibacterium, Collinsella, and Klebsiella. These four bacterial markers distinguished ITB from CD with an area under the curve of 97.6%. This study established the compositional and functional perturbation of the gut microbiome in ITB and suggested the potential for using gut microbiota as biomarkers to differentiate ITB from CD.

P471 Predictors of bowel damage in long term progression of Crohn’s disease

Abstract Background Crohn’s disease is a chronic inflammatory bowel disorder that progresses to bowel damage over time. An image-based index, the Lémann Index, has been developed to measure the cumulative bowel damage. AIMS To characterize the long-term progression of bowel damage in Crohn’s disease based on changes in the Lémann Index and to determine risk factors for long term progression. Methods This was a single-center longitudinal cohort study. Patients who had participated in prospective studies on the accuracy of magnetic resonance imaging using endoscopy as gold standard and had a follow-up of at least 5 years were reevaluated after 5–12 years. Results Seventy-two patients were included. Lémann Index increased in 38 patients (52.8%), remained unchanged in 9 patients (12.5%) and decreased in 25 patients (34.7%). Small bowel score and surgery subscale significantly increased (p=0.002 and p=0.0001), whereas fistulizing subscale significantly decreased (p=0.001). Baseline parameters associated with bowel damage progression were ileum location (p=0.026), phenotype (stricturing, fistulizing or both with p=0.007, p=0.006 and p=0.035), disease duration &amp;gt;10 years (p=0.019) and baseline Lémann Index stricturing score (p=0.049). No correlation was observed between bowel damage progression and baseline clinical activity, biological markers or endoscopic lesions. Need of surgery during follow-up was a major determinant of bowel damage progression (p=0.0001). Baseline stricturing Lémann Index score was associated with the risk of future surgery (p=0.02). Conclusion Bowel damage, assessed by the Lémann Index, progresses in half of the patients with Crohn’s disease over a period of 5–12 years. The main determinants of bowel damage progression are ileum location, stricturing/fistulizing phenotype and disease duration.

Function of intestinal barrier protected by regulating the miR-199a-3p in ulcerative colitis: Modulation of IL-23/IL-17A axis.

Ulcerative colitis is a chronic inflammatory bowel disorder, which is having higher mortality rate. The present report evaluates the protective effect of miR-199a-3p oligomer for the treatment of Ulcerative colitis (UC). Ulcerative colitis was induced by administration of dextran sulfate sodium [DSS (3%)] with drinking water for the duration of one week in mice and miR-199a-3p oligomer was treated for the same duration. Effect of miR-199a-3p oligomer was determined by estimating the body weight, blood stool and length of colon in UC mice. Inflammatory cytokines, oxidative stress parameters and Treg/Th17 ratio was determined in the serum, intestinal and spleen tissue of UC mice. mRNA expression of TGFβ, Foxp3, RORγt and STAT3 was estimated in the intestinal tissue of UC mice. Moreover, permeability of intestine was determined by estimating the expression of FITC-dextran in the serum and expression of junction protein in the tissue of UC mice. The data of the study suggest that treatment with miR-199a-3p oligomer ameliorates the altered condition in ulcerative colitis mice. There was reduction in the level of cytokines and parameters of oxidative stress in the intestine of miR-199a-3p oligomer than UC group. Moreover, intestinal permeability was enhanced in miR-199a-3p oligomer treated UC mice. The level of Th17 in the serum and mRNA expression of TGFβ, Foxp3, RORγt and STAT3 was attenuated in miR-199a-3p oligomer treated UC mice. In conclusion, the data of the study suggest that treatment with miR-199a-3p oligomer ameliorates intestinal barrier in ulcerative colitis by down regulating the IL-17A/IL-23 axis.

Apprehending Ulcerative Colitis Management With Springing Up Therapeutic Approaches: Can Nanotechnology Play a Nascent Role?

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder that causes inflammation in the colon and rectum and can be lethal to the patients. The dysbiotic intestinal microbiome is considered a major factor of UC, yet it needs more evidences. As there is no cure for UC, anti-inflammatory drugs, potent steroids, immunomodulatory drugs, or even surgery is used to manage the disease. The purpose of this review is to focus on the underlying factors involved in the disease pathogenicity, including host gut microbiome and novel therapies for treatment of UC. Due to disruption of intestinal epithelial layers, the intestinal microflora interacts with immune cells in the lamina propria, which in turn provokes an inflammatory response, which is subsequently exacerbated in the colon. Anti–tumor necrosis factor (anti-TNF), anti-integrin, Janus kinase inhibitors, siRNA, fecal microbiome transfer, synbiotics, and many other small molecules such as ozanimod are emerging as potential therapy for UC. Moreover, a nanoparticle-based drug delivery system enhances localized delivery of the drug to the inflammatory sites. Additionally, herbal-derived nanoparticles are also emerging as a novel drug delivery system in disease management. The homeostasis of gut microbiota is crucial for both prevention and remission of UC. Synbiotics and fecal microbiome transfer is emerging as potential treatment strategies for management of UC. The combination of multiple therapies may have durable therapeutic outcomes against the debilitating condition of UC. The outcome of the ongoing clinical trials of novel drugs will define the new therapeutic approaches in the treatment of UC for long-term remission.

Diet Advice for Crohn's Disease: FODMAP and Beyond.

Crohn’s disease (CD) is a chronic, progressive, and destructive granulomatous inflammatory bowel disorder that can involve any part of the gastrointestinal tract. It has been presumed that different types of diet might improve gastrointestinal symptoms in CD patients. The aim of this review was to clarify the efficiency and indications of a low-“fermentable oligo-, di-, mono-saccharides and polyols” (FODMAP) diet (LFD) in CD and to further analyze the available data on other types of diets. PubMed, Cochrane Library, EMBASE and WILEY databases were screened for relevant publications regarding the effect of FODMAP diets on CD. Our search identified 12 articles analyzing the effect of an LFD in CD, 5 articles analyzing the effect of a Mediterranean diet (MD), 2 articles analyzing the effect of a vegetarian diet (VD), and 2 articles analyzing the effect of a low-lactose diet (LLD). The majority of the studies included in this review show the significant efficiency of the LFD in CD patients. We found significant evidence demonstrating that the LFD has a favorable impact on gastrointestinal symptoms in CD patients. Notwithstanding the evidence, it remains to be established if an LFD is more efficient than other types of diets in the short term and especially in the long term.

Intestinal Tuberculosis versus Crohn's Disease: Evaluating the Role of Computed Tomography Enterography in Differentiating the Two

AbstractIntestinal tuberculosis (ITB) and Crohn's disease (CD) are chronic inflammatory bowel disorders that are frequently misdiagnosed due to overlapping clinical, radiologic, endoscopic, and histologic resemblance. Recent trends indicate a change in the epidemiology of inflammatory bowel diseases, with previously low-incidence areas now reporting a continuous rise in incidence. The rising incidence of CD in countries such as India where TB continues to be endemic has made the differentiation of these two disorders a diagnostic challenge. Misdiagnosis leads to delays in initiating effective therapy with increased morbidity and mortality, hence the importance of making an accurate diagnosis at the earliest possible stage. This study aimed to evaluate the diagnostic value of computed tomography enterography findings in the differential diagnosis between ITB and CD.

Glucocorticoids Impair Phagocytosis and Inflammatory Response Against Crohn's Disease-Associated Adherent-Invasive Escherichia coli.

Crohn’s disease (CD) is a chronic inflammatory bowel disorder characterized by deregulated inflammation triggered by environmental factors. Notably, adherent-invasive Escherichia coli (AIEC), a bacterium with the ability to survive within macrophages is believed to be one of such factors. Glucocorticoids are the first line treatment for CD and to date, it is unknown how they affect bactericidal and inflammatory properties of macrophages against AIEC. The aim of this study was to evaluate the impact of glucocorticoid treatment on AIEC infected macrophages. First, THP-1 cell-derived macrophages were infected with a CD2-a AIEC strain, in the presence or absence of the glucocorticoid dexamethasone (Dex) and mRNA microarray analysis was performed. Differentially expressed mRNAs were confirmed by TaqMan-qPCR. In addition, an amikacin protection assay was used to evaluate the phagocytic and bactericidal activity of Dex-treated macrophages infected with E. coli strains (CD2-a, HM605, NRG857c, and HB101). Finally, cytokine secretion and the inflammatory phenotype of macrophages were evaluated by ELISA and flow cytometry, respectively. The microarray analysis showed that CD2-a, Dex, and CD2-a + Dex-treated macrophages have differential inflammatory gene profiles. Also, canonical pathway analysis revealed decreased phagocytosis signaling by Dex and anti-inflammatory polarization on CD2-a + Dex macrophages. Moreover, amikacin protection assay showed reduced phagocytosis upon Dex treatment and TaqMan-qPCR confirmed Dex inhibition of three phagocytosis-associated genes. All bacteria strains induced TNF-α, IL-6, IL-23, CD40, and CD80, which was inhibited by Dex. Thus, our data demonstrate that glucocorticoids impair phagocytosis and induce anti-inflammatory polarization after AIEC infection, possibly contributing to the survival of AIEC in infected CD patients.

Small bowel imaging in Crohn's disease patients.

Crohn’s disease (CD) is a lifelong, chronic inflammatory bowel disorder. The small bowel (SB) is involved to varying extents, and the clinical course may vary from an inflammatory type to a more complicated one with stricture, fistula, and abscess formation. Esophagogastroduodenoscopy and ileocolonoscopy with biopsies are the conventional endoscopic techniques that usually establish the diagnosis. On the other hand, CD may affect SB segments that cannot be reached through these procedures. Video capsule endoscopy and enteroscopy are additional endoscopic techniques that may allow further SB evaluation in such circumstances. Computed tomographic enterography, magnetic resonance enterography, and ultrasonography are radiologic techniques that serve as a crucial adjunct to endoscopic assessment. They enable the assessment of parts of the bowel that may be difficult to reach with conventional endoscopy; this allows for the detection of active inflammation, penetrating or stricturing disease, and the appreciation of extraintestinal complications. Both endoscopic and radiologic modalities play a role in establishing the diagnosis of CD, as well as determining the disease extent, activity and response to therapy. This review is intended to evaluate these modalities in terms of specificity, sensitivity, potential side-effects, and limiting factors. This should serve as a guide to the clinician for establishing the most appropriate and reliable test within a particular clinical context.

Antibiotic-induced microbiota perturbation causes gut endocannabinoidome changes, hippocampal neuroglial reorganization and depression in mice

The microbiota-gut-brain axis (MGBA) regulates the reciprocal interaction between chronic inflammatory bowel and psychiatric disorders. This interaction involves multiple pathways that are highly debated. We examined the behavioural, biochemical and electrophysiological alterations, as well as gut microbiota composition in a model of antibiotic-induced experimental dysbiosis. Inflammation of the small intestine was also assessed. Mice were exposed to a mixture of antimicrobials for 2weeks. Afterwards, they received Lactobacillus casei DG (LCDG) or a vehicle for up to 7days via oral gavage.Perturbation of microbiota was accompanied by a general inflammatory state and alteration of some endocannabinoidome members in the gut. Behavioural changes, including increased immobility in the tail suspension test and reduced social recognition were observed, and were associated with altered BDNF/TrkB signalling, TRPV1 phosphorylation and neuronal firing in the hippocampus. Moreover, morphological rearrangements of non-neuronal cells in brain areas controlling emotional behaviour were detected. Subsequent probiotic administration, compared with vehicle, counteracted most of these gut inflammatory, behavioural, biochemical and functional alterations. Interestingly, levels of Lachnospiraceae were found to significantly correlate with the behavioural changes observed in dysbiotic mice. Our findings clarify some of the biomolecular and functional modifications leading to the development of affective disorders associated with gut microbiota alterations.

Pathogenic T cell subsets in allergic and chronic inflammatory bowel disorders

Homeostasis in the gastrointestinal tract relies on a sensitive equilibrium between permissive and protective functions. This is closely reflected in the regulation of the intestinal immune system and especially T cells in the gut. This balance, however, is susceptible to disturbances as demonstrated by pathological conditions like food allergy, celiac disease, or inflammatory bowel disease. In these allergic and chronic inflammatory bowel disorders, luminal antigens get access to the lamina propria where they trigger a dysregulated immune response with crucial involvement of different T cell subsets. We will begin this review with some comprehensive remarks on current concepts on the pathogenesis of these diseases before taking a closer look at the life cycle of intestinal T cells consisting of priming, homing, differentiation and proliferation and apoptosis respectively. Subsequently we will discuss the specific implication of distinct T cell subsets in allergic and chronic inflammatory conditions of the gastrointestinal tract in detail and comment on current and future approaches to targeted therapy in this context.