Deborah Flomenhoft

Investigating the effect of antibiotics on quorum sensing with whole-cell biosensing systems

Quorum sensing (QS) allows bacteria to communicate with one another by means of QS signaling molecules and control certain behaviors in a group-based manner, including pathogenicity and biofilm formation. Bacterial gut microflora may play a role in inflammatory bowel disease pathogenesis, and antibiotics are one of the available therapeutic options for Crohn’s disease. In the present study, we employed genetically engineered bioluminescent bacterial whole-cell sensing systems as a tool to evaluate the ability of antibiotics commonly employed in the treatment of chronic inflammatory conditions to interfere with QS. We investigated the effect of ciprofloxacin, metronidazole, and tinidazole on quorum sensing. Several concentrations of individual antibiotics were allowed to interact with two different types of bacterial sensing cells, in both the presence and absence of a fixed concentration of N-acylhomoserine lactone (AHL) QS molecules. The antibiotic effect was then determined by monitoring the biosensor’s bioluminescence response. Ciprofloxacin, metronidazole, and tinidazole exhibited a dose-dependent augmentation in the response of both bacterial sensing systems, thus showing an AHL-like effect. Additionally, such an augmentation was observed, in both the presence and absence of AHL. The data obtained indicate that ciprofloxacin, metronidazole, and tinidazole may interfere with bacterial communication systems. The results suggest that these antibiotics, at the concentrations tested, may themselves act as bacterial signaling molecules. The beneficial effect of these antibiotics in the treatment of intestinal inflammation may be due, at least in part, to their effect on QS-related bacterial behavior in the gut.

Correlation of Biomarker Expression in Colonic Mucosa with Disease Phenotype in Crohn's Disease and Ulcerative Colitis.

AbstractBackground Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by chronic intestinal inflammation due to immunological, microbial, and environmental factors in genetically predisposed individuals. Advances in the diagnosis, prognosis, and treatment of IBD require the identification of robust biomarkers that can be used for molecular classification of diverse disease presentations. We previously identified five genes, RELA, TNFAIP3 (A20), PIGR, TNF, and IL8, whose mRNA levels in colonic mucosal biopsies could be used in a multivariate analysis to classify patients with CD based on disease behavior and responses to therapy.AimWe compared expression of these five biomarkers in IBD patients classified as having CD or UC, and in healthy controls.ResultsPatients with CD were characterized as having decreased median expression of TNFAIP3, PIGR, and TNF in non-inflamed colonic mucosa as compared to healthy controls. By contrast, UC patients exhibited decreased expression of PIGR and elevated expression of IL8 in colonic mucosa compared to healthy controls. A multivariate analysis combining mRNA levels for all five genes resulted in segregation of individuals based on disease presentation (CD vs. UC) as well as severity, i.e., patients in remission versus those with acute colitis at the time of biopsy.ConclusionWe propose that this approach could be used as a model for molecular classification of IBD patients, which could further be enhanced by the inclusion of additional genes that are identified by functional studies, global gene expression analyses, and genome-wide association studies.

Atypical Clinical and Diagnostic Features in Ménétrier's Disease in a Child

Ménétriers disease is one of the rarest protein-losing gastropathies in childhood. It is characterized clinically by non-specific gastrointestinal symptoms and edema, biochemically by hypoalbuminemia, and pathologically by enlarged gastric folds. In adults, this disease can be devastating with significant morbidity and mortality. In childhood, it is a self-limiting, transient and benign illness. Its treatment is largely supportive with total parenteral nutrition (TPN) while oral intake is encouraged. Acute onset of vomiting in healthy school age children can be initially explained by acute viral gastroenteritis. However, persistent vomiting associated with hematemesis and severe abdominal pain should warrant further work-up. This case report illustrates a self-limiting and rare cause of protein-losing enteropathy called Ménétriers disease that presented with several variant clinical features not typically described in association with this entity.

Predictors of Chronic Opioid Use in Newly Diagnosed Crohn's Disease

Background and Aims: Patients with Crohns disease (CD) are often prescribed opioids chronically to manage pain associated with their disease. However, little evidence exists to support this practice. Here, we examine newly diagnosed patients with CD with and without chronic opioid use (COU) and sought to identify predictors and consequences of COU. Methods: A nationally representative administrative health care claims that data set identified newly diagnosed patients with CD. Their data were examined during the periods 6 months before and 2 years after diagnosis. Multivariable logistic regression was used to assess predictors of COU at diagnosis. Results: The final study cohort consisted of 47,164 patients with CD. Of them, 3.8% were identified with new COU. Chronic opioid users were more likely women, older, and likely who had more surgeries, endoscopies, admissions, and medication usage compared with other patients. Features detected before CD diagnosis that correlated with COU after diagnosis included previous opioid use (odds ratio [OR] = 6.6), chronic pain (OR = 1.36), arthritis (OR = 1.95), and mental disorders (OR = 1.58). Interestingly, emergency department visits before CD Dx increased the risk of COU (OR = 1.11), whereas endoscopy reduced COU risk (OR = 0.88). Conclusions: This study presents a nationally representative assessment of COU in newly diagnosed patients with CD. The results may be used to determine the impact of COU in this population and to alert clinicians to those patients with CD at high risk of COU. Chronic opioids are consistently associated with indicators of more severe disease; however, additional research is needed to determine whether COU drives disease severity or vice versa.

Helicobacter pylori & beyond: pediatric peptic ulcer disease

The word peptic implies ‘gastric-, pepsin- or acid-related’. Peptic ulcer disease (PUD) denotes the presence of gastric and/or duodenal ulceration or erosion. In clinical practice, the term encompasses gastric or duodenal infl ammation due to any etiology, and may be more common in childhood than ulcerative disease. PUD occurs across the pediatric age group. Although etiopathology of PUD is typically related to that of Helicobacter pylori infection, other etiology for PUD is not uncommon in children and requires a different approach in evaluation and therapeutic decisions. Evaluation of PUD includes endoscopy with mucosal biopsy. Noninvasive testing, such as urea breath test, has a role in the follow-up of H. pylori eradication following therapy. Better understanding of pathogenic factors innate to H. pylori infection has enhanced our understanding of associated PUD. This review describes the management of both H. pylori and non-H. pylori PUD.

Superior mesenteric artery-duodenal fistula secondary to a gunshot wound.

Arterioenteric fistulas are a rare cause of massive gastrointestinal hemorrhage. We present a patient who developed a fistula between a middle colic artery pseudoaneurysm, a proximal branch of the superior mesenteric artery (SMA), and the third part of the duodenum 2 weeks after a self-inflicted gunshot wound to the abdomen. The patients presentation, evaluation, treatment, and prognosis are discussed. All prior published cases of SMA-duodenal fistulas are reviewed.