Signs Of Colitis Research Articles

Bacterial and viral enterocolitis in horses: a review.

Enteritis, colitis, and enterocolitis are considered some of the most common causes of disease and death in horses. Determining the etiology of these conditions is challenging, among other reasons because different causes produce similar clinical signs and lesions, and also because some agents of colitis can be present in the intestine of normal animals. We review here the main bacterial and viral causes of enterocolitis of horses, including Salmonella spp., Clostridium perfringens type A NetF-positive, C. perfringens type C, Clostridioides difficile, Clostridium piliforme, Paeniclostridium sordellii, other clostridia, Rhodococcus equi, Neorickettsia risticii, Lawsonia intracellularis, equine rotavirus, and equine coronavirus. Diarrhea and colic are the hallmark clinical signs of colitis and enterocolitis, and the majority of these conditions are characterized by necrotizing changes in the mucosa of the small intestine, colon, cecum, or in a combination of these organs. The presumptive diagnosis is based on clinical, gross, and microscopic findings, and confirmed by detection of some of the agents and/or their toxins in the intestinal content or feces.

Magnetic resonance colonography assessment of acute trinitrobenzene sulfonic acid colitis in pre-pubertal rats.

Pre-pubertal murine models of acute colitis are lacking. Magnetic resonance colonography (MRC) is a promising minimally invasive tool to assess colitis. We aimed to: 1/ Adapt a model of acute experimental colitis to pre-pubertal rats and determine whether MRC characteristics correlate with histological inflammation. 2/ Test this model by administering a diet supplemented in transforming growth factor β2 to reverse inflammation. Twenty-four rats were randomized at weaning to one of 3 groups: Trinitrobenzene Sulfonic Acid (TNBS) group (n = 8) fed a standard diet, that received an intra-rectal 60 mg/kg dose of TNBS-ethanol; Control group (n = 8) fed standard diet, that received a dose of intra-rectal PBS; TNBS+MODULEN group (n = 8) that received a dose of TNBS and were exclusively fed MODULEN-IBD® after induction of colitis. One week after induction of colitis, rats were assessed by MRC, colon histopathology and inflammation markers (Interleukin 1β, Tumor necrosis factor α, Nitric Oxide Synthase 2 and Cyclooxygenase 2). TNBS induced typical features of acute colitis on histopathology and MRC (increased colon wall thickness, increased colon intensity on T2-weighted images, target sign, ulcers). Treatment with MODULEN-IBD® did not reduce signs of colitis on MRC. Inflammatory marker expression did not differ among study groups.

Volcanic ash-driven worsening of mucosal inflammation in an experimental colitis model

Particulate matter exposure and related chemical changes in drinking water have been associated with health problems and inflammatory disorders. This study aimed to examine the effect of orally administered ash-water dilution on the gut of mice under normal and inflammatory conditions.Balb/c mice received ash-released soluble and dust-suspended components in the drinking water for 14 days. On day 7, animals were intrarectally instilled with TNBS in ethanol or flagellin from Salmonella typhimurium in PBS. At sacrifice, colon segments were collected and histologic damage, mRNA expression and cytokine levels in tissue were evaluated. In addition, these parameters were also evaluated in IL-10 null mice.We found that mice that received 5% w. fine-ash dilution in the drinking water worsened colitis signs. Weight loss, shortening of the colon, tissue edema with mucosa and submucosa cell infiltration and production of pro-inflammatory cytokines and chemokines were enhanced compared to control mice. A more pronounced inflammation was observed in IL-10 null mice. In addition, markers of NLRP3-dependent inflammasome activation were found in animals exposed to ash.In conclusion, ingestion of contaminated water with dust-suspended particulate matter enhanced the inflammatory response in the gut, probably due to alteration of the gut barrier and promoting an intense contact with the luminal content. This study critically appraises the response for fine particulate matter in uncommon illnesses reported for volcanic ash pollution. We suggest actions to enable better prediction and assessment the health impacts of volcanic eruptions.

<i>Сlostridium difficile</i> Infection in a COVID-19 Patient

Aim. The clinical observation highlights plausible compound origins of diarrhoea, fever and neutrophilic leucocytosis in COVID-19 and the rationale to exclude Clostridium difficile infection in such patients.Key points. A 57-yo female patient was admitted in May 2020 with the complaints of 39 °C fever, general weakness, polymyalgia, diarrhoea to 3–4 times a day (mushy stool, no morbid inclusions). Initial diarrhoea was non-severe and likely triggered by the coronavirus infection. A background antibiotic and putative-immunosuppressive therapy proceeded with watery diarrhoea to 7–8 times a day and C. difficile toxins A and B detected in stool. The C. difficile infection relapsed on day 10 of vancomycin withdrawal and associated with elevated body temperature, diarrhoea and neutrophil leucocytosis; signs of colitis determined in ultrasound and CT. Exacerbation was successfully treated in a repeated metronidazole-combined vancomycin course.Conclusion. Patients with COVID-19 are at risk of clostridial colitis due to massive antibiotic, systemic glucocorticoid and biologics-based therapy they receive. The opportunistic bacterial infection of C. difficile often proceeds undetected due to its potential mirroring of COVID-19 presentation. A screening algorithm in COVID-19 patients with diarrhoea should imply steps for C. difficile detection.

Butyrate functions in concert with myeloid-derived suppressor cells recruited by CCR9 to alleviate DSS-induced murine colitis

Ulcerative colitis (UC) is a precancerous disease caused mainly by a combination of genetic susceptibility, environmental factors and microbiota dysbiosis. As a kind of short-chain fatty acid (SCFA), butyrate has been shown to be closely related to the progression of colitis. However, the exact regulatory mechanism of butyrate in colitis needs to be further elucidated. In our current research, the effects of butyrate were examined in a dextran sulfate sodium (DSS)–induced murine colitis model, which simulates human UC. The administration of butyrate significantly reversed the signs of colitis and alleviated colonic histological damage in DSS‑induced colitis. The transcription levels of the main proinflammatory mediators, including tumor necrosis factor–α, interleukin–6 and interleukin–12, were also reduced, as determined by reverse transcription–quantitative polymerase chain reaction (RT-qPCR). This indicates that butyrate could alleviate DSS-induced colitis by inhibiting proinflammatory mediators. In addition, we found that myeloid-derived suppressor cells (MDSCs), which have an inflammation-relieving effect, did not effectively alleviate DSS‑induced colitis but showed a compensatory increase in the DSS group. However, the compensatory increase in MDSCs in the DSS group significantly decreased after butyrate treatment. Moreover, the chemokine receptor CCR9, which mediates the homing of intestinal immune cells, also showed consistent changes similar to MDSCs. Butyrate alone did not have the aforementioned effects on mice. Thus, butyrate may effectively relieve DSS‑induced colitis by synergistic regulatory effects with MDSCs, which migrate and gather through CCR9 recruitment.

Canagliflozin, an SGLT-2 inhibitor, ameliorates acetic acid-induced colitis in rats through targeting glucose metabolism and inhibiting NOX2

BackgroundInflammatory bowel disease is defined as chronic noninfectious inflammation of the gastrointestinal tract, including ulcerative colitis and Crohn’s disease. Its incidence and predominance have increased globally, with no effective agents for preventing its recurrence or treatment until now. AimThe current study aimed to investigate the possible role of canagliflozin (CANA), a sodium-glucose co-transporter-2 inhibitor (SGLT-2), to prevent and treat acetic acid (AA)-induced colitis in a rat model. MethodsColitis was induced in male Wistar rats by intrarectal instillation of 1 ml of 4% (v/v) AA. Rats were treated orally with either CANA (30 mg/kg/day, p.o.) for 10 days before or after colitis induction or sulfasalazine (360 mg/kg/day, p.o.) for 10 days before colitis induction. ResultsAA resulted in a significant increase in disease activity index, colonic weight over length ratio, colon macroscopic damage score, and histological signs of colitis. All of these effects were significantly decreased by CANA administration. Additionally, CANA markedly inhibited AA-induced oxidative stress and inflammatory responses by significantly reducing the up-regulated levels in malondialdehyde, total nitrite, NF-κB, interleukin-1β, and TNF-α, and significantly increasing the down-regulated levels in reduced glutathione, superoxide dismutase, and interleukin-10. CANA significantly inhibited caspase-3 level while rescued survivin expression in colons. Finally, CANA reduced the elevated levels of pyruvic acid and G6PDH activity, as well as the levels of p22phox and NOX2 in the AA-induced colitis. ConclusionOur findings provide novel evidence that CANA has protective and therapeutic effects against AA-induced colitis by the impact of its antioxidant, anti-inflammatory, and anti-apoptotic effects.

Multi-detector computed tomography (MDCT)-based severity score as a prognostic tool in patients with suspected immune checkpoint inhibitor therapy associated colitis.

This study aimed to assess MDCT as a diagnostic and prognostic tool in patients with suspected immune checkpoint inhibitor (ICI)-related colitis. This retrospective cohort study included patients receiving ICIs at three hospitals between 2015 and 2019 who underwent both abdominopelvic MDCT and endoscopic biopsy to workup suspected ICI-related colitis. Two radiologists independently reviewed MDCT images for signs of colitis based on pre-defined features. Diagnostic performance of MDCT was calculated and categorical variables between treatment subgroups were compared. Logistic regression was used to develop proposed MDCT criteria for diagnosis and MDCT severity score based on a combination of MDCT features of colitis to predict the patient outcomes in ICI-related colitis. A total of 118 MDCT scans from 108 patients were evaluated for suspected colitis, with 72 confirmed ICI-related colitis cases. Sensitivity, specificity, PPV, and NPV of MDCT for diagnosis of ICI-related colitis was 81% (58/72), 52 % (24/46), 73% (58/80), and 63% (24/38), respectively. Small bowel involvement was visualized in 25% of cases with ICI-related colitis (18/72). In melanoma patients presenting with diarrhea grade ≥ 2 (n=40), MDCT had the best diagnostic performance for ICI-related colitis (specificity=80% [8/10], PPV=92% [23/25]). MDCT severity scores predicted intravenous steroid use (OR 10.3, p = 0.004), length of stay > 7 days (OR 9.0, p < 0.001), and endoscopic mucosal ulceration (OR 4.7, p = 0.02). MDCT is a useful diagnostic and prognostic tool for evaluating patients with immune checkpoint inhibitor-related colitis. An MDCT-based severity score enables assessment of disease severity and predicts outcome. • MDCT is useful for the diagnosis of colitis in patients receiving immune checkpoint inhibitor (ICI) therapy, and an MDCT-based severity score allows for prognostication of patient outcomes. • MDCT yielded moderate sensitivity (81%) for diagnosis of ICI-related colitis but limited specificity (52%). However, in symptomatic melanoma patients (grade 2-4 diarrhea) with a high pretest probability, MDCT proved useful for diagnosis with a high PPV (92%). • For ICI-related colitis, our proposed MDCT severity score has prognostic value in predicting intravenous steroid use, prolonged length of stay during inpatient admission (> 7 days), and endoscopic mucosal ulceration.

Granulomatous colitis in a patient with metastatic melanoma under immunotherapy: a case report and literature review

BackgroundImmune checkpoint inhibitors (ICPIs) have changed the way advanced malignancies are currently confronted, improving cancer patients’ outcomes but also generating distinct immune-related (ir) adverse events. ICPIs-induced colitis is a common complication showing different clinical and histological manifestations. In the literature review, 14 cases with ICPIs related colon granulomas have been reported in 5 studies with either limited or unavailable information regarding histology. Granulomatous reactions can be mistakenly perceived as disease recurrence or progression. Better understanding and identification of this infrequent histological display can help to avoid misdiagnosis and mismanagement.Case presentationA 63-year-old female patient with metastatic melanoma was admitted to the hospital with symptoms of nausea, persistent diarrhea and shivering fever under consecutive treatments with ICPIs, initially pembrolizumab and subsequently ipilimumab. Sigmoidoscopy was performed revealing mucosal edema, hyperemia and erosions of the rectum and sigmoid colon. Histological evaluation of sigmoid colon mucosa biopsies revealed an unusual colitis pattern characterized by multiple intracryptal granulomas attributed to ICPIs therapy. Steroids were administered and the patient recovered. ICPIs treatment was discontinued. The patient was subsequently treated with chemotherapy but follow up radiology showed disease progression. A re-challenge with another ICPI regimen was decided and the patient is currently under immunotherapy with stable disease regarding melanoma status and without any sign of colitis recurrence.ConclusionsThe present report provides detailed histological description of a distinctive ICPIs-induced granulomatous colitis and highlights the need for awareness of the distinct adverse events and reaction patterns in the context of immunotherapy.

Novel polyurethane based particulate formulations of infliximab reduce inflammation in DSS induced murine model of colitis – A preliminary study

Our recent study showed that novel infliximab (INF) loaded polyesterurethane (INF-PU) and INF-PU-PEG particulate formulations reduced inflammation in an in-vitro epithelial inflammation model. In this study we investigated therapeutic potential of novel INF-PU and INF-PU-PEG particulate formulations to reduce inflammation in a dextran sodium sulfate (DSS) induced murine model of colitis. Severity of colitis was assessed by measurement of disease activity index (DAI) score, inflammatory markers (neutrophil infiltration, TNFα) and histological score. Treatment groups orally administered with INF-PU and INF-PU-PEG particulate formulations showed improvement in the clinical signs of colitis, similar to that observed with intraperitoneally administered INF, in both, moderate and severe DSS induced colitis model. This was related to a significant reduction in inflammatory cytokines, resulting in a significant reduction in histological score (ANOVA; p < 0.05), indicative of mucosal healing, a key goal of IBD therapy. This could be attributed to its targeted delivery to the inflamed colon and higher permeation of these particulate formulations across the inflamed colonic mucosa, as observed by the confocal images, resulting in local inhibition of TNFα at its site of production. These promising preliminary results warrant further investigation of orally administered INF and its novel particulate formulations in a wider preclinical study.

Changes in expression of NLRP3 inflamasome and IL-1β in the development of oxazolone-induced colitis in rats and on the background of administration of simvastatin and interleukin-1β receptor antagonist

The aim. To study the expression of mRNA of the NLRP3 inflammasome and proinflammatory cytokine IL-1β in the inflamed colon of rats with experimental oxazolone-induced colitis and against the background of the introduction of simvastatin and antagonist of interleukin-1 receptors. Materials and methods. Experiments were carried out on male Wistar rats aged 8 months (body mass 120–150 g). Tissue samples were obtained from rats with experimental oxazolone-induced colitis (n = 20), rats with oxazolone-induced colitis treated with simvastatin (n = 20); rats with oxazolone-induced colitis treated with interleukin-1 receptor antagonist (n = 20) and control animals (n = 10). Clinical signs of colitis were evaluated by the clinical index of disease activity on the following parameters: weight loss, stool consistency and animal behavior. For macroscopic assessment of the development of colitis areas of inflammation and ulceration were investigated. For histological evaluation of lesions, sections of the intestine were stained with hematoxylin and eosin and cellular inflammatory infiltrates, epithelial hyperplasia, ulceration and loss of intestinal glands were studied. IL-1β and NLRP3 inflammasome mRNA expression was analyzed by real-time reverse transcriptase-polymerase chain reaction. Results. Animals treated with oxazolone rapidly developed colitis marked by weight loss and diarrhea peaking by day 2 after oxazolone administration and leading to death of 40 % of the rats by day 4. The histological observation showed inflammatory cell infiltration, including polymorphonuclear leukocytes and multiple erosive lesions in the large intestine. We determined that the expression level of the proinflammatory cytokine IL-1β is increased in colon samples of rats with oxazolone-induced colitis. IL-1β expression is increased 3.5‐fold in inflamed colon compared to uninflamed tissue. Administration of simvastatin and an interleukin-1 receptor antagonist to rats with oxazolone-induced colitis resulted in a 30 % and 2-fold decrease expression of IL-1β in colon samples. In addition, we examined NLRP3 expression in these tissues. RT‐PCR analysis demonstrates a 71‐fold increased expression of NLRP3 mRNA expression in colon samples tested. Administration of simvastatin and an interleukin-1 receptor antagonist to rats with oxazolone-induced colitis resulted in a 2.5- to 3.0-fold decrease expression of NLRP3 mRNA in colon samples. Conclusions. IL-1β and NLRP3 mRNA expression levels were elevated in the inflamed colon of rats with experimental oxazolone-induced colitis. Administration of simvastatin and an interleukin-1 receptor antagonist against the background of colitis caused a decrease in the expression levels of IL-1β and NLRP3 mRNA in the tissues of the intestine. Detection of abnormal expression of IL-1β and NLRP3 mRNA could provide insights into pathogenesis of Crohn's disease, and may help to identify future potential targets for therapeutic strategies in people with inflammatory bowel disease.

Potential Mechanisms Mediating the Protective Effects of Tricholoma matsutake-Derived Peptides in Mitigating DSS-Induced Colitis.

Intestinal barrier dysfunction and inflammatory cytokine secretion play crucial roles in inflammatory bowel disease (IBD). Herein, we investigated the protective effects of Tricholoma matsutake-derived peptides SDIKHFPF and SDLKHFPF against dextran sulfate sodium-induced colitis. Both peptides alleviated colitis signs, including diarrhea, weight loss, bloody stools, colon shortening, and histopathological changes, while reducing mucus destruction, goblet cell exhaustion, and intestinal permeability. SDIKHFPF and SDLKHFPF protected the barrier function by promoting the expression of tight junction (TJ) zonula occludens-1 and occludin within the colon, as well as attenuating colonic inflammation through myeloperoxidase and pro-inflammatory cytokine suppression. Western blotting indicated that the peptides suppressed myosin light chain kinase (MLCK) and nuclear factor kappa B (NF-κB) levels, inhibiting MLC phosphorylation. SDLKHFPF was more potent than SDIKHFPF. These findings suggest that peptide SDLKHFPF mitigates colitis by regulating TJ protein expression and pro-inflammatory cytokine production via NF-κB/MLCK/p-MLC signaling, improving the barrier function.

Effects of Combined Inulin and VSL#3 on Susceptibility to Dextran Sodium Sulfate‐Induced Colitis

Inflammatory bowel disease (IBD) is a chronic intestinal disease that includes Crohn's disease and ulcerative colitis. Previous studies have found alterations in the microbiome in IBD and in animal models of IBD, underscoring the role of the intestinal microbiota in IBD pathogenesis. Prebiotics are molecules in foods that support the growth or activity of beneficial microbes. Inulin, a soluble fiber molecule, is a commonly available prebiotic, and previous studies suggest that it can reduce symptoms in dextran sodium sulfate (DSS)-induced colitis in mice. VSL#3 is a commercially available mixture of 8 probiotic species that has shown beneficial effects in models of intestinal inflammation. This study aimed to determine whether pretreatment with 1% inulin for 1 week, followed by 7 days of 3% DSS administration with inulin plus VSL#3 treatment, altered the severity of disease in C57Bl/6 mice. Clinical signs of colitis, including weight loss, fecal occult blood, and fecal consistency, were monitored daily during the DSS treatment period. At the end of the experiment, samples were collected for histological scoring, and for RNA isolation and analysis of colonic pro-inflammatory cytokine expression by RT-PCR. At the end of DSS treatment, the disease activity index was not different between control colitic mice or those treated with inulin and VSL#3. In addition, colon length and colon wet weight were similar in the two groups. Treatment with inulin+VSL#3 did not significantly alter expression of mRNA for COX-2, TGF-beta, or KC in the colon of mice with DSS colitis. In conclusion, a combination of inulin + VSL#3 treatment did not significantly alter susceptibility to DSS-induced colitis.

MicroRNAs in Colon Tissue of Pediatric Ulcerative Pancolitis Patients Allow Detection and Prognostic Stratification.

Prevalence of inflammatory bowel disease has been on the rise in recent years, especially in pediatric populations. This study aimed to provide precise identification and stratification of pediatric patients with diagnosed ulcerative colitis (UC) according to the severity of their condition and the prediction for standard treatment according to the specific expression of candidate miRNAs. We enrolled consecutive, therapeutically naïve, pediatric UC patients with confirmed pancolitis. We examined formalin-fixed paraffin-embedded specimens of colonic tissue for the expression of 10 selected candidate miRNAs. We performed receiver operating characteristic curve analysis, using area under the curve and a logistic regression model to evaluate the diagnostic and predictive power of the miRNA panels. Sixty patients were included in the final analysis. As a control group, 18 children without macroscopic and microscopic signs of inflammatory bowel disease were examined. The combination of three candidate miRNAs (let-7i-5p, miR-223-3p and miR-4284) enabled accurate detection of pediatric UC patients and controls. A panel of four candidate miRNAs (miR-375-3p, miR-146a-5p, miR-223-3p and miR-200b-3p) was associated with severity of UC in pediatric patients and a combination of three miRNAs (miR-21-5p, miR-192-5p and miR-194-5p) was associated with early relapse of the disease. Nine patients out of the total were diagnosed with primary sclerosing cholangitis (PSC) simultaneously with ulcerative colitis. A panel of 6 candidate miRNAs (miR-142-3p, miR-146a-5p, miR-223-3p, let-7i-5p, miR-192-5p and miR-194-5p) identified those patients with PSC. Specific combinations of miRNAs are promising tools for potential use in precise disease identification and severity and prognostic stratification in pediatric patients with ulcerative pancolitis.

A23 DIETARY PROTEIN AND AMINO ACID COMPOSITIONS INFLUENCE MICROBIOTA, INTESTINAL PERMEABILITY, AND SUSCEPTIBILITY TO COLITIS

Abstract Background Environmental factors, such as alterations in diet and microbiota, have been linked to inflammatory bowel diseases (IBD). The incidence of IBD is rising, particularly in Canada and other industrialized nations that consume western-style diets high in fat and protein. While most dietary proteins and amino acids are absorbed in the small intestine, substantial amounts can enter the colon for microbial metabolism and to exert effects on intestinal tissue and immune cells. Prospective cohort studies suggest that diets high in protein are associated with an increased risk of IBD. However, the role of excess dietary protein and amino acids in IBD pathogenesis is not clear. Aims To study whether and how consumption of diets high in protein or amino acids influences intestinal inflammation, colitis severity, and intestinal microbiota. Methods To assess the influence of dietary protein composition on colitis severity, specific pathogen-free C57BL/6 mice were fed isocaloric casein-based purified diets containing low (7%), normal (14%), or high (35%) protein (HPD). Mice were also fed an amino acid-defined diet (AAD) with amino acid and ingredient composition matched to the normal protein diet. Following three weeks of diet consumption ad libitum, mice were continued on the same diet and mucosal injury was induced with 2% dextran sulfate sodium (DSS; 5 days) followed by water (2 days) before sacrifice. Mice were monitored daily for clinical signs of colitis. Susceptibility to colitis was assessed by analysing stool consistency and blood, microscopic scoring (Cooper score), and by immunohistochemistry of colon tissue. Fecal microbiota (16S rRNA Illumina), intestinal permeability (Ussing chambers), proinflammatory gene expression (NanoString and RT-qPCR), and bacterial translocation (plating) were analysed. Results Following DSS exposure, mice fed HPD and AAD experienced greater weight loss, bacterial translocation to the spleen, stool blood, and diarrhea compared to mice fed the normal protein control diet. While all DSS-treated mice developed colitis, HPD and AAD fed mice also developed greater histologic damage, intestinal permeability, and innate immune cell infiltration. Cytokine profiling revealed that AAD is associated with significant up-regulation of IL-18 during colitis. Principle coordinates analysis based on Bray-Curtis dissimilarities demonstrates distinct shifts in the fecal microbiota of mice fed HPD and AAD. Conclusions These results suggest that excess dietary protein and amino acids are associated with more severe colitis and microbiota alterations in the DSS model. Previous studies demonstrate that IL-18 is up-regulated in IBD patients. Its overexpression may incite inflammation by stimulating cytokine signalling through NFκB and modify microbial community structure by regulating antimicrobial peptides. Funding Agencies CIHRFarncombe Family Digestive Health Research Institute, Douglas Family Chair in Gastroenterology Research

Saccharomyces cerevisiae Fermentation Product Did Not Attenuate Clinical Signs, but Psyllium Husk Has Protective Effects in a Murine Dextran Sulfate Sodium-Induced Colitis Model.

ABSTRACTBackgroundYeast products and psyllium husk may provide relief from clinical signs of colitis due to their ability to promote gut integrity, modulate gut microbiota, or positively affect immune responses, which have been demonstrated in several species.ObjectiveThe objective of this study was to investigate the effects of a Saccharomyces cerevisiae fermentation product (SCFP) and psyllium husk (PH) on cecal and fecal microbiota, colonic gene expression and histopathology, and mesenteric lymph node (MLN) immune cells in a dextran sulfate sodium (DSS)–induced colitis model.MethodsMale C57BL/6J mice (n = 54) were assigned to a control, 5% SCFP, or 5% PH diet. After 2 wk of diet adaptation, mice were provided distilled water or 3% (wt:vol) DSS for 5 d ad libitum. Body weight, food and water intakes, and disease activity index (DAI) were recorded daily during the treatment period. Fresh fecal samples were collected before and during treatment for microbial analyses. After treatment, mice were killed, followed by tissue collection. Tissues were stored in proper solutions until further analyses. Data were analyzed using the Mixed Models procedure of SAS 9.4 (SAS Institute).ResultsConsumption of SCFP increased (P < 0.05) species richness of the gut microbiota and relative abundance of Butyricicoccus in fecal and cecal samples compared with control or PH mice. PH mice had greater (P < 0.05) gene expression of claudin (Cldn) 2, Cldn3, Cldn8, and occludin(Ocln) compared with control mice. DAI, MLN immune cell populations, colonic histopathology, and colonic gene expression were not affected (P > 0.05) by SCFP in DSS mice. DSS mice consuming PH had lower (P < 0.05) DAI compared with control or SCFP mice.ConclusionsResults suggest that, despite the modest changes it had on cecal and fecal microbiota, SCFP did not attenuate clinical signs associated with DSS-induced colitis in mice, while PH showed protective effects.

S1623 Chronic Norovirus Gastroenteritis in a Patient With Common Variable Immunodeficiency Enteropathy: A Case Report

INTRODUCTION: Norovirus gastroenteritis is a self-limiting illness that is treated with supportive care. In immunocompromised patients, however, it is known to cause prolonged illness. Treatment remains controversial. We present a case of an immunocompromised patient with chronic norovirus gastroenteritis. CASE DESCRIPTION/METHODS: A 45–year-old Caucasian male presented to the emergency room with nausea, vomiting, loose stools up to 8/day, and 15-pound weight loss. He had a past medical history of common variable immune deficiency (CVID) with CVID associated enteropathy, vitiligo, history of extra-nodal marginal B-cell lymphoma, and celiac disease. Five months prior, he had a CVID enteropathy flare up and was prescribed oral steroids. Post steroids, he developed acute organizing pneumonia and was hospitalized. He had diarrhea which was treated with supportive care. Stool studies were positive for Norovirus 2. On admission, he was hemodynamically stable, and physical examination was remarkable for hypopigmented patches secondary to vitiligo. Abdomen had positive bowel sounds and was soft, non-tender, and non-distended. Laboratory workup was as shown in Table 1. Stool studies were positive for fecal lactoferrin and Norovirus 2. The rest of the infectious workup was negative. The patient was diagnosed with CVID enteropathy flare and was started on intravenous methylprednisolone 20 mg three times a day. He had mild improvement in his symptoms. Colonoscopy was performed and was grossly unremarkable. Random colon biopsies revealed active cryptitis but did not show a paucity of plasma cells or intraepithelial lymphocytosis, as shown in Figure 1. There were no histological signs of inflammatory bowel disease and staining for cytomegalovirus infection was negative. The patient was discharged on prednisone 40 mg once a day and nitazoxanide 500 mg for 14 days. Steroids helped only minimally, but after starting nitazoxanide, he had significant improvements in his symptoms and the frequency of his bowel movements decreased to 2-3 per day. At six months, he has been doing well with no reported adverse effects. DISCUSSION: This case demonstrates that immunocompromised patients with gastrointestinal manifestations can have prolonged norovirus infection, which might cause flare-ups of underlying gastrointestinal conditions. Hence, treatment of norovirus infection in such patients should be considered, with nitazoxanide a potentially effective treatment.Table 1.: Serum Laboratory Results.Figure 1.: Hematoxylin and eosin stain of a random colon biopsy revealing active neutrophilic infiltration of the crypts with no significant architectural abnormality.

S1620 A Case of Cocaine-Induced Ischemic Colitis With Increased Fecal Calprotectin

INTRODUCTION: Ischemic colitis can be caused by a wide variety of factors and is most often seen as an atherosclerotic event in the elderly. We report a case of a healthy young male who presented with multiple episodes of hematochezia and was found to have ischemic colitis due to cocaine use. CASE DESCRIPTION/METHODS: A healthy 27 year old male presented to the emergency department with one day history of left lower quadrant abdominal pain and over 10 episodes of hematochezia. He denied recent travel, sick contacts or family history of inflammatory bowel disease. His exam revealed diffuse abdominal tenderness. Laboratory data was significant for hemoglobin of 16 g/dL on arrival, which decreased to 12.7 g/dL after ongoing hematochezia. A CT of his abdomen/pelvis revealed diffuse circumferential wall thickening of sigmoid and descending colon with adjacent pericolonic fat stranding, suggestive of colitis. A GI PCR for infectious diarrhea was negative. Fecal calprotectin was greater than 1,250 μg/g. A colonoscopy demonstrated diffuse, erythematous and friable mucosa in the sigmoid and transverse colon with discontinuous areas of nonbleeding ulcerated mucosa. Biopsies showed surface ulceration, regenerative epithelial changes and superficially injured and withered crypts as seen with ischemia. Once pathology results returned, the patient disclosed using intranasal cocaine prior to the onset of the abdominal pain and his hematochezia was the result of cocaine induced ischemic colitis. DISCUSSION: Our patient was a young male presenting with hematochezia, diffuse abdominal pain, signs of colitis on imaging and had an elevated fecal calprotectin. Because of this, inflammatory bowel disease was high on the differential diagnosis. However his biopsies revealed pathology consistent with ischemia. A study by Hsieh et al, evaluated ten patients with ischemic colitis and found that each of them had an elevated fecal calprotectin. The levels were not indicative of severity or prognosis. Cocaine induced ischemic colitis is well described, especially in young patients with severe abdominal pain and hematochezia, as in our patient. Early suspicion and a careful history are essential to avoid significant morbidity and mortality. This case highlights the importance of maintaining high suspicion of cocaine abuse in young patients with ischemic colitis despite an elevation in fecal calprotectin levels.Figure 1.: Visualized splenic flexure ulcerated mucosa, erythematous (hyperemic mucousa), friable mucosa.Figure 2.: Visualized descending Colon with ulcerated mucosa, erythematous (hyperemic mucousa), friable mucosa.Figure 3.: Visualized descending colon with ulcerated mucosa, erythematous (hyperemic mucousa), friable mucosa.

Discordant Clostridioides difficile diagnostic assay and treatment practice: a cross-sectional study in a tertiary care hospital, Geneva, Switzerland.

ObjectivesTo determine the proportion of patients who received a treatment for Clostridioides difficile infection (CDI) among those presenting a discordant C. difficile diagnostic assay and to identify patient characteristics associated with the decision to treat CDI.DesignCross-sectional study.SettingMonocentric study in a tertiary care hospital, Geneva, Switzerland.ParticipantsAmong 4562 adult patients tested for C. difficile between March 2017 and March 2019, 208 patients with discordant tests’ results (positive nucleic acid amplification test (NAAT+)/negative enzyme immunoassay (EIA−)) were included.Main outcome measuresTreatment for CDI.ResultsCDI treatment was administered in 147 (71%) cases. In multivariate analysis, an abdominal CT scan with signs of colitis (OR 14.7; 95% CI 1.96 to 110.8) was the only factor associated with CDI treatment.ConclusionsThe proportion of NAAT+/EIA− patients who received treatment questions the contribution of the EIA for the detection of toxin A/B after NAAT to limit overtreatment. Additional studies are needed to investigate if other factors are associated with the decision to treat.

Prostaglandin E receptor EP4 stimulates lymphangiogenesis to promote mucosal healing during DSS-induced colitis

In the intestine, the formation of new lymphatic vessels from pre-existing lymphatic vasculature (lymphangiogenesis) is related to the progression of inflammatory bowel disease (IBD). However, it remains unclear whether lymphangiogenesis contributes to mucosal repair after acute colitis. Prostaglandin E receptor EP4 suppresses the development of experimental colitis. In this study, we investigated whether EP4 exerts this effect by contributing to lymphangiogenesis, in turn promoting mucosal tissue repair, following acute colitis. We elicited experimental colitis in male C57/BL6 mice by administering dextran sulphate sodium (DSS) via the drinking water for 5 days, followed by normal water for 9 additional days. From Day 5 through Day 13, the experimental mice received a daily dose of EP4-selective agonist, EP4-selective antagonist, or vehicle. On Day 14, mice treated with vehicle had recovered 95 % of body weight and exhibited moderate increases in disease activity and histological score relative to untreated controls. Compared with vehicle, post-treatment with EP4 antagonist increased signs of colitis, colonic tissue destruction, and CD11b+ cell infiltration, associated with elevated lymphatic vessel density (LVD) and reduced percentage of lymphatic vessel area (LVA%). By contrast, post-treatment with EP4 agonist improved disease activity, suppressed CD11b+ infiltration, and decreased levels of inflammatory cytokines; these changes were associated with upregulation of lymphatic growth factors and lymphangiogenesis, as evidenced by increases in LVA% and lymphatic drainage function. Inhibition of vascular endothelial growth factor receptor 3 (VEGFR3) caused a delay in mucosal repair, accompanied by impaired lymphangiogenesis. These results suggest that EP4 stimulation aids in mucosal repair from DSS-induced acute colitis by promoting lymphangiogenesis.

Effects of prebiotic inulin pre‐treatment on susceptibility to DSS‐induced colitis in mice

Inflammatory bowel disease (IBD) is a chronic intestinal disease that includes Crohn’s disease and ulcerative colitis. Previous studies have found alterations in the microbiome in IBD and in animal models of IBD, underscoring the role of the intestinal microbiota in IBD pathogenesis. Prebiotics are molecules in foods that support the growth or activity of beneficial microbes. Inulin, a soluble fiber molecule, is a commonly available prebiotic, and previous studies suggest that it can reduce symptoms in dextran sodium sulfate (DSS)‐induced colitis in mice. This study aimed to determine whether pretreatment with 1% inulin for 1 week, followed by 7 days of 3% DSS administration with continued inulin treatment, altered the severity of disease in C57Bl/6 mice. Clinical signs of colitis, including weight loss, fecal occult blood, and fecal consistency, were monitored daily during the DSS treatment period. At the end of the experiment, samples were collected for histological scoring, and for RNA isolation and analysis of colonic pro‐inflammatory cytokine expression by quantitative PCR. Unexpectedly, inulin pre‐treated, DSS‐exposed mice were positive for blood in the stool a day sooner than mice given DSS only. However, by the end of DSS treatment, the disease activity index was not different between the two groups. In addition, colon length and colon wet weight were similar in inulin‐treated mice and non‐inulin treated mice. Histological scoring of colitis showed no difference between inulin‐treated and non‐inulin‐treated colitic mice. In conclusion, 7 days of pre‐treatment with inulin followed by induction of acute DSS‐induced colitis did not significantly alter susceptibility to colitis.Support or Funding InformationSupported by the Missouri Western State University PORTAL program