Elena F. Verdu

McMaster University | McMaster · Division of Gastroenterology

Background Patients with IBD are increasingly experiencing treatment failures on frontline therapies. While corticosteroids are an effective frontline intervention, 16% of patients fail to respond, and 20%–30% show only partial responses. Bacteriophages have recently garnered attention as a potential adjunctive therapy for IBD to target bacterial s...

Background Celiac disease (CeD) is an autoimmune condition driven by gluten in individuals expressing celiac-specific genes (HLA-DQ2 and/or DQ8). A strict gluten-free diet (GFD) is currently the only treatment. 30-40% of celiac patients exhibit persistent symptoms despite following a GFD ampersand:003E1 year and are considered non-responsive. Trypt...

Background Recent evidence has linked ultra-processed foods, which are high in salt, to increased risk of inflammatory bowel disease (IBD). A high salt diet (HSD) was also shown to be colitogenic in specific pathogen-free mice, in part, through modulation of the microbiota. We recently described high microbial proteolytic activity (PA) in feces fro...

Background IBD is characterized by relapsing episodes of tissue-damaging inflammation in the gastrointestinal tract. Abdominal pain is common in IBD and often persists in the absence of overt inflammation. The treatment has limited efficacy, in part due to our partial understanding of its pathophysiology, and thus commonly leads to dependency on op...

Background Celiac disease (CeD) is a T-cell mediated enteropathy driven by gluten in genetically susceptible individuals. Mucosal inflammation persists for years even when treated with a gluten-free diet (GFD). Although patients may be advised to increase dietary fibre, some fibres are poorly tolerated leading, potentially, to suboptimal fibre inta...

Background Patients with self-perceived gluten sensitivity often undergo double-blinded, placebo-controlled (DBPC) challenge studies to determine whether gluten or wheat trigger their symptoms. However, it is unknown whether the result disclosure impacts patients’ beliefs and dietary choices. Aims To evaluate the impact of disclosing results of DB...

Background Many patients living with IBD identify diet as a key factor in managing their disease, symptoms and general health, and many report implementing dietary restrictions in response to disease activity and symptoms. Despite increasing data on the role of diet, IBD patients face a variety of challenges that can compromise adherence to dietary...

Background A strict gluten-free diet (GFD) is currently the only treatment for celiac disease (CeD), but a GFD can be inconvenient and expensive. CeD patients who are food insecure (FI) face threats to GFD adherence, overall health, and quality of life. Aims To evaluate the prevalence of FI in patients with CeD attending a dedicated Adult Celiac D...

Background Chronic abdominal pain is the key symptom in IBS. Gut microbiota produces a large variety of molecules that can regulate pain perception, including bioactive lipids. LPC and LPA are phospholipids, known to generate and maintain neurogenic pain in mammals, by directly activating multiple channels and G-protein coupled receptors on sensory...

Background Patients with celiac disease (CeD) reported increased COVID-19 vaccine hesitancy due to a fear of adverse events (AEs). However, the risk of AEs post-COVID-19 vaccination in patients with CeD is unknown. Purpose To assess whether the rate of common side effects (SEs) and AEs due to COVID vaccines are higher in patients with CeD compared...

Background Patients with irritable bowel syndrome (IBS) often report gastrointestinal symptoms after consuming wheat and gluten-containing foods. It is, however, unclear whether gluten is the main driver of symptoms, as other immunogenic peptides, such as amylase trypsin inhibitors (ATI), poorly digestible fiber (inulin, part of FODMAP) or even the...

Background Opportunistic pathogens have been postulated to drive dysregulated inflammation in inflammatory bowel disease (IBD). Indeed, adherent-invasive Escherichia coli (AIEC) isolated from IBD patients have pathobiont and pro-inflammatory characteristics. Current treatments for IBD suppress the immune response and do not target key microbial dri...

Background Accumulating evidence suggests that gut microbiota affects brain development and its function. It is well known that compared with conventional mice (SPF), germ-free (GF) mice display higher exploratory behavior, which normalizes after bacterial colonization. However, little is known about the underlying mechanisms and first critical ste...

Background Bacteria have recently emerged as additional modulators of inflammation in CeD. We have shown that the elastase-like producing opportunistic pathogen, Pseudomonas (P) aeruginosa, partially metabolizes gluten into peptides that translocate the mucosal barrier and retain their immunogenicity. We previously demonstrated that organoid monola...

Background The link between diet, disease activity and symptoms in IBD patients have recently gained attention and recommendations on dietary interventions to manage symptoms are common. Most studies have explored the correlation between dietary patterns and increased risk of IBD or symptom severity. However, there is limited understanding and no r...

Background An imbalance in host proteases has been implicated in inflammatory bowel disease (IBD). Recent evidence implicates microbial proteolytic activity (PA) in ulcerative colitis but whether it also plays a role in Crohn’s disease (CD) remains unclear. Purpose We therefore investigated the colitogenic potential and underlying pathways of prot...

Background Generalized anxiety disorder (GAD) is a debilitating condition with a lifetime prevalence of 4-7% worldwide. We have previously found that compared to healthy controls, GAD patients had lower reported fiber intake, increased gastrointestinal symptoms; and enrichment of Bacteroides genus as well as carbohydrate metabolism pathways (as det...

Background & Aims Genes and gluten are necessary but insufficient to cause celiac disease (CeD). Altered gut microbiota has been implicated as an additional risk factor. Variability in sampling site may confound interpretation and mechanistic insight, as CeD affects primarily the small intestine. Thus, we characterized CeD microbiota along the duod...

Background Natural supplements are widely consumed by the general public, with little evidence of mechanistic support. Tryptophan has gained central attention, being transformed by host and gut microbial enzymes into multiple bioactive metabolites that regulate immunity and mood. Indoles are activators of the aryl hydrocarbon receptor (AhR), crucia...

Background Celiac disease (CeD) is an autoimmune T-cell mediated enteropathy, triggered by gluten, a group of proteins found in wheat, barley, and rye. The defined role of gluten as a dietary trigger, necessary genes (HLA-DQ2 and/or DQ8), and tissue transglutaminase (TG2) as the autoantigen together, are unique features of CeD. Although CeD onset c...

Background Previous studies proposed that the combination of IgA anti-tissue transglutaminase 2 IgA (TTG) and IgG deamidated gliadin peptide IgG (DGP) antibodies increases celiac disease (CeD) detection rates. However, this remains controversial. Aims To evaluate the performance of adding DGP to TTG antibodies, for the diagnosis of celiac disease...

Background Age-related deterioration of cognitive function and memory capacity occur in both humans and rodents. For example, significant memory deficits have been reported in conventionally raised (SPF) old mice compared to conventionally raised young mice submitted to a spatial memory task (Prevot et al., 2019, Mol Neuropsychiatry 5, 84–97). Micr...

NOT PUBLISHED AT AUTHOR’S REQUEST Funding Agencies: CIHR

Background Bacterial infections have been postulated to drive the dysregulated inflammation found in inflammatory bowel disease (IBD). In particular, adherent-invasive Escherichia coli (AIEC) isolated from patients with IBD have pathobiont characteristics and have been implicated in IBD pathogenesis. Aims Our aim was to characterize and compare th...

Background Ulcerative colitis (UC) is one of two forms of inflammatory bowel disease (IBD). The exact cause of IBD is unknown but altered host-microbe interactions and genetic susceptibility are involved in its pathogenesis. Many patients with IBD do not respond to biological therapies targeting single cytokines, therefore new therapies that target...

Background Genes and gluten are necessary, but insufficient to cause celiac disease (CeD), as risk alleles (DQ2 or DQ8) are prevalent in ~30–40% of the healthy population consuming gluten. Gut microbiota shifts and infections have been proposed as risk modulators. Biogeographic characterization of the microbiota in CeD patients and its functional s...

Background Tryptophan, an essential amino acid found in many protein-based foods, has been involved in the pathogenesis of mood disorders and celiac disease (CeD). However, dietary tryptophan consumption has not been investigated in CeD. Aims To estimate 1) differences in tryptophan content in food consumed in CeD patients compared to matched heal...

Background Generalized anxiety disorder (GAD) is a debilitating chronic condition with a lifetime prevalence of 4–7% worldwide. Both diet and gut microbiota have been previously associated with anxiety. Aims To investigate whether bacterial taxa and/or nutrients associate with GAD, and whether they differ from those of healthy controls (HC). Meth...

Background Corticosteroids (CS) have been used extensively to induce remission in Crohn’s disease (CD); however, they are associated with severe side effects. We hypothesized that the administration of an exclusive enteral nutrition (EEN) formula to CS would lead to increased CD remission rates and to decreased CS-related adverse events. We propose...

Background Tryptophan is an essential amino acid that is transformed by host and gut microbial enzymes into multiple bioactive metabolites that regulate immunity, mood and circadian rhythms. In particular, indoles, produced by gut bacterial metabolism of tryptophan, have recently gained central attention. Indoles are activators of the aryl hydrocar...

Background The exact cause for inflammatory bowel disease (IBD) is unknown, however, there is consensus that a combination of genetic, environmental, and immune factors, participate in its pathogenesis. Recently, high salt diet (HSD) has been shown to increase the severity of experimental colitis through depletion of lactobacilli in specific pathog...

Background Age-associated deterioration of cognitive function and memory capacity occur in a variety of mammals, from humans to rodents. For example, significant memory deficits have been reported in conventionally raised (SPF) old mice compared to conventionally raised young mice submitted to a spatial memory task (Prevot et al., Mol Neuropsychiat...

Background Altered gut microbiota composition and function has been associated with inflammatory bowel diseases (IBD) including ulcerative colitis (UC), but causality and mechanisms remain unknown. Most studies have examined patients with active or treated disease and little is known about microbial compositional or functional changes that occur be...

The only current therapy in celiac disease (CeD) is a lifetime gluten-free diet. Although this intervention is safe and effective in most patients, there are limitations that warrant the development of adjuvant therapies to improve clinical outcomes. Recent studies support the hypothesis that viral infections and bacterial opportunistic pathogens p...

The lack of reproducibility of animal experimental results between laboratories, particularly in studies investigating the microbiota, has raised concern among the scientific community. Factors such as environment, stress and sex have been identified as contributors, whereas dietary composition has received less attention. This study firstly evalua...

Bifidobacterium infantis NLS super strain (B. infantis NLS-SS) was previously shown to alleviate gastrointestinal symptoms in newly diagnosed coeliac disease (CD) patients consuming gluten. A high proportion of patients following a gluten-free diet experiences symptoms despite dietary compliance. The role of B. infantis in persistently symptomatic...

Background The only available treatment for celiac disease (CD) is adherence to a strict gluten-free diet (GFD). CD is associated with several nutritional deficiencies, which could be explained by malabsorption when the disease is active. However, the magnitude of nutritional deficiencies in treated CD and how this is influenced by the duration and...

Background Major depressive disorder (MDD) affects approximately 4.4% of the global population. Despite its high prevalence, little is known about the mechanisms underlying this disorder. Recent studies in both humans and rodents have suggested that the intestinal microbiota may play a role in depression. Altered microbiota composition has been fou...

Background A combination of genetics, environmental, and immune factors contribute to the development of ulcerative colitis (UC). Host proteolytic imbalance has been reported in active UC. Preliminary results from our lab suggest microbial proteolytic activity is increased before as well as after onset of UC, and transfer of this activity to mice c...

Background Proteolytic imbalance has been described in patients with inflammatory bowel disease (IBD) and in different models of experimental colitis. Although the proteases reported to be increased are mainly from the host, the role of bacterial proteases has recently emerged, as they can promote inflammation, in part, through activation of Protea...

Background The role intestinal epithelial cells (IECs) play in the breakdown of tolerance to gluten at an early stage in celiac disease (CeD) is unclear. Epithelial stress is a feature of CeD, and although the triggers are largely unknown, it is accompanied by expression of several markers that could be involved in initiation of inflammatory respon...

Background Stressful events in childhood have been associated with the development of functional gastrointestinal (GI) disorders in adulthood, especially irritable bowel syndrome. The influence of early life adverse events in patients with common organic disorders, such as celiac disease and inflammatory bowel disease (IBD), has been poorly investi...

Background Celiac disease (CD) has an estimated prevalence of 1% worldwide, including North America. Barrett’s esophagus (BE) is a complication of chronic gastroesophageal reflux disease (GERD), which predisposes to development of dysplasia, which can transition to esophageal adenocarcinoma (EAC). GERD is commonly found in patients with CD and ther...

Background Lack of experimental reproducibility, particularly in studies investigating the microbiota, is of growing concern to the scientific community. Factors such as environment, stress, and sex have been identified as contributors, whereas dietary composition has received less attention. Aims To profile the use of standard rodent chows in res...

Background Celiac disease is a chronic autoimmune disorder triggered by dietary gluten. The only available treatment for celiac disease is strict compliance to the gluten-free diet. Despite adherence to a gluten-free diet, many celiac patients still experience symptoms which may be mediated by the gut microbiota. Different studies have assessed the...

Background Irritable bowel syndrome (IBS) is one of the most common conditions seen by gastroenterologists for which there is no effective cure. The pathophysiology of IBS is multifactorial and poorly understood, but the condition is characterized by chronic abdominal pain accompanied by altered bowel habits in the absence of an underlying structur...

Background Altered gut microbiota composition has been associated with inflammatory bowel diseases (IBD) including ulcerative colitis (UC), but causality and bacterially-driven mechanisms, are unclear. Proteases within the gastrointestinal tract play a critical role in maintaining homeostasis and are tightly regulated by anti-proteases. Host-derive...

Background Mental disorders are the leading cause of disabilities worldwide, with depression and anxiety among the most common ones, affecting up to 1/3 of the worldwide population at least once in their lifetime. In both preclinical models and clinical studies, gut microbiota has been associated with altered behavior and anxiety or depression, res...

Background Celiac disease (CeD), an autoimmune and chronic inflammatory enteropathy triggered by the ingestion of gluten, is associated with HLA-DQ2 (~90%) and, to a lesser extent, HLA-DQ8. We previously characterized a humanized mouse model of gluten sensitivity that expresses the HLA-DQ8 allele, and that develops mild innate and adaptive immune p...

Eosinophils have emerged as multifaceted cells that contribute to tissue homeostasis. However, the impact of the microbiota on their frequency and function at mucosal sites remains unclear. Here, we investigated the role of the microbiota in the regulation of enteric eosinophils. We found that small intestinal (SI) eosinophilia was significantly gr...

BACKGROUND Life-long removal of gluten from the diet is currently the only way to manage celiac disease (CeD). Until now, no objective test has proven useful to objectively detect ingested gluten in clinical practice. Recently, tests that determine consumption of gluten by assessing excretion of gluten immunogenic peptides (GIP) in stool and urine...

NOT PUBLISHED AT AUTHOR’S REQUEST Funding Agencies: CIHRSupported by a grant by the Farncombe Family Digestive Health Research Institute to EFV.

Background Wheat-related disorders involve a wide spectrum of conditions, triggered by the ingestion of gluten-containing cereals. The induction of gluten-specific immune responses in celiac disease is well established. However, the contribution of gluten and/or non-gluten proteins in the generation of symptoms in other wheat-related disorders is c...

Background Stressful events in childhood have been associated with the development of chronic gastrointestinal disorders in adulthood. However, the role of early life adverse events in patients with celiac disease has been not been investigated. Aims to evaluate the association between early childhood life adverse events (ELE) and gastrointestinal...

Background A low FODMAP (fermentable oligo-, di-, mono-saccharides and polyols) diet is often recommended in patients with quiescent inflammatory bowel disease (IBD) who experience irritable bowel syndrome-like symptoms. Concerns that the diet could exacerbate or re-activate inflammation by modifying microbiota fermentation and short-chain fatty ac...

Background Accumulating evidence suggests that mast cells play an important role in the pathogenesis of Irritable Bowel Syndrome (IBS). Colonic mast cells are increased in patients with IBS, and their products, including histamine and tryptase are putative mediators of visceral hypersensitivity in IBS. Aims To investigate the effect of gut microbi...

Background Anxiety disorders are the most prevalent psychiatric conditions within primary care, affecting up to 29% of people across their lifetime. Generalized Anxiety disorder (GAD) is frequently comorbid with major depressive disorder, resulting in greater functional impairment. Gut microbiota have been shown to modulate brain chemistry and func...

Background The Canadian Institute of Health Research (CIHR) and other scientific organizations have raised concern about the variability and lack of reproducibility of animal experimental results between laboratories. This concern includes studies investigating the microbiota, their metabolites and their impact on the host. Factors such as environm...

Gut immune system, microbiota and diet appear to play important roles in irritable bowel syndrome (IBS). Increased levels of colonic mast cell (MC) located in close proximity to mucosal nerves were reported in IBS patients, correlating with increased abdominal pain. We showed recently that IBS patients’ beneficial response to a low-fermentable diet...

Eosinophils have emerged as multifaceted cells that contribute to tissue homeostasis. However, the factors that control their frequency and function at mucosal sites remain unclear. Here, we investigated the role of the microbiota in regulating enteric eosinophils. We found that small intestinal (SI) eosinophilia was significantly greater in germ-f...

Microbiota-modulating strategies, including probiotic administration, have been tested for the treatment of chronic gastrointestinal diseases despite limited information regarding their mechanisms of action. We previously demonstrated that patients with active celiac disease have decreased duodenal expression of elafin, a human serine protease inhi...

Background & aims: Patients with celiac disease should maintain a gluten-free diet (GFD), excluding wheat, rye, and barley. Oats might increase the nutritional value of a GFD, but their including is controversial. We performed a systematic review and meta-analysis to evaluate the safety of oats as part of a GFD in patients with celiac disease. Me...

Levels of inflammatory mediators in circulation are known to increase with age, but the underlying cause of this age-associated inflammation is debated. We find that, when maintained under germ-free conditions, mice do not display an age-related increase in circulating pro-inflammatory cytokine levels. A higher proportion of germ-free mice live to...

Immune tolerance to dietary antigens is key to preventing undesirable responses to innocuous antigens ingested with food. On page 44 of this issue, Bouziat et al. ( 1 ) report how viral infection may break oral tolerance to dietary proteins. The findings provide an explanation for the known epidemiological association between viral infections and t...

BACKGROUND: Celiac disease (CD) is a widespread autoimmune disease triggered by dietary gluten. Ingestion of gluten often causes severe gastrointestinal symptoms in those afflicted with CD. Because there is no available treatment other than a lifelong gluten-free diet, many patients continue to experience chronic symptoms. The goal of this analysis...

Irritable bowel syndrome (IBS) is a common disorder characterized by altered gut function and often is accompanied by comorbid anxiety. Although changes in the gut microbiota have been documented, their relevance to the clinical expression of IBS is unknown. To evaluate a functional role for commensal gut bacteria in IBS, we colonized germ-free mic...

Stress, anxiety and depression are considered risk factors for Inflammatory Bowel Disease. We have previously shown in mice that early life stress induced by maternal separation (MS) changes host physiology leading to intestinal dysbiosis, which in turns causes anxiety and depression-like behavior. Using this murine model, we investigated the role...

Previous studies demonstrated differences in behavior and brain biochemistry between germ-free and conventional mice. We showed that mono-colonization with E. coli induces similar changes in behavior as with complex microbiota. BDNF and cFos expression in the amygdala and hippocampus regions were also changed after mono-colonization. Furthermore, u...