Premysl Bercík

McMaster University | McMaster · Department of Medicine

Imbalances in proteolytic activity have been linked to the development of inflammatory bowel diseases (IBD) and experimental colitis. Proteases in the intestine play important roles in maintaining homeostasis, but exposure of mucosal tissues to excess proteolytic activity can promote pathology through protease-activated receptors (PARs). Previous r...

Background and Aims: Accumulating evidence suggests the microbiota is a key factor in disorders of gut-brain interaction (DGBI), by affecting host immune and neural systems. However, the underlying mechanisms remain elusive due to their complexity and clinical heterogeneity of patients with DGBIs. We aimed to identify neuroimmune pathways that are...

Our recent randomized, placebo-controlled study in Irritable Bowel Syndrome (IBS) patients with diarrhea or alternating bowel habits showed that the probiotic Bifidobacterium longum (BL) NCC3001 improves depression scores and decreases brain emotional reactivity. However, the involved metabolic pathways remain unclear. This analysis aimed to invest...

Background and Aims: Tryptophan is an essential amino acid transformed by host and gut microbial enzymes into metabolites that regulate mucosal homeostasis through Aryl hydrocarbon receptor (AhR) activation. Alteration of tryptophan metabolism has been associated with chronic inflammation, however whether tryptophan supplementation affects the meta...

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 Bacterial translocation is defined as the migration of bacteria from the intestinal lumen into extraintestinal tissues; this process has been implicated in the pathophysiology of gastrointestinal disorders including irritable bowel syndrome (IBS) and central nervous system disorders. In our recent study, we found that gut bacteria from p...

Background Gut microbiota plays a key role in shaping our immune system, producing a myriad of molecules with neuro- and immunomodulatory properties. Many of these bioactive molecules are generated by bacterial metabolism of common dietary components. We have recently found that fecal samples of patients with chronic abdominal pain contain high lev...

Background Intestinal microbiota have been implicated in the expression of irritable bowel syndrome (IBS) as patients present with altered gut microbial profiles and microbial metabolic activity. We have previously identified bacterial histamine to strongly influence mast cell accumulation through only IBS activation of the H4 receptor, leading to...

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 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 Emerging evidence suggests the role of gut microbiome (GMB) in the pathogenesis of schizophrenia (SCZ) and antipsychotic-induced metabolic perturbations. In the present study, we investigated the role of GMB in metabolic alterations associated with SCZ and olanzapine (a prototype antipsychotic) treatment using human fecal microbiota tran...

Background & Aims Although chronic diarrhea and constipation are common, the treatment is symptomatic because their pathophysiology is poorly understood. Accumulating evidence suggests that the microbiota modulates gut function, but the underlying mechanisms are unknown. We therefore investigated the pathways by which microbiota modulates gastroint...

Compositional changes in the microbiota (dysbiosis) may be a basis for Irritable Bowel Syndrome (IBS), but biomarkers are currently unavailable to direct microbiota-directed therapy. We therefore examined whether changes in fecal β-defensin could be a marker of dysbiosis in a murine model. Experimental dysbiosis was induced using four interventions...

Emerging evidence implicates microbial proteolytic activity in ulcerative colitis (UC), but whether it also plays a role in Crohn’s disease (CD) remains unclear. We investigated the effects of colonizing adult and neonatal germ-free C57BL/6 mice with CD microbiota, selected based on high (CD-HPA) or low fecal proteolytic activity (CD-LPA), or micro...

Abdominal pain is common in patients with gastrointestinal disorders, but its pathophysiology is unclear, in part due to poor understanding of basic mechanisms underlying visceral sensitivity. Accumulating evidence suggests that gut microbiota is an important determinant of visceral sensitivity. Clinical and basic research studies also show that se...

Background Irritable bowel syndrome (IBS) is a disorder of gut-brain axis that manifests with chronic abdominal pain, altered bowel habits, and frequent psychiatric comorbidities. Despite mounting evidence showing gut microbiota composition and associated metabolites being altered in IBS, the mechanisms by which they drive the symptoms are unclear....

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 Chronic abdominal pain is the most common complaint of patients with gastrointestinal disorders. Its treatment is of limited efficacy as the pathophysiology is poorly understood. The gut microbiome has been shown to affect host physiology, including the neural system function, and growing evidence suggests that it plays an important role...

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 Chronic gut dysfunction occurs in up to 25% of patients following antibiotic-treated C. difficile infection (CDI). We developed a humanized mouse model in which germ free mice colonized with microbiota from patients with severe constipation post-CDI developed slow colonic transit, as a result of damage to the Interstitial Cells of Cajal...

Background Although intestinal muscle layer macrophages have been suggested to play an important role in the colonic transit by interacting with the myenteric plexus neurons, they have not been fully characterized. CD64 (FcγRI) is one of the most generally used markers for intestinal macrophages, but several studies suggested existence of a subpopu...

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...

Visceral hypersensitivity, a fundamental mechanism of chronic visceral pain disorders, can result from both central or peripheral factors, or their combination. As an important regulator of normal gut function, the gut microbiota has been implicated as a key peripheral factor in the pathophysiology of visceral hypersensitivity. Patients with chroni...

Functional gastrointestinal disorders—recently renamed into disorders of gut–brain interaction—such as irritable bowel syndrome and functional dyspepsia are highly prevalent conditions with bothersome abdominal symptoms in the absence of structural abnormalities. While traditionally considered as motility disorders or even psychosomatic conditions,...

Objective Dietary therapies for irritable bowel syndrome (IBS) have received increasing interest but predicting which patients will benefit remains a challenge due to a lack of mechanistic insight. We recently found evidence of a role for the microbiota in dietary modulation of pain signalling in a humanised mouse model of IBS. This randomised cros...

Both mast cells and microbiota play important roles in the pathogenesis of Irritable Bowel Syndrome (IBS), however the precise mechanisms are unknown. Using microbiota-humanized IBS mouse model, we show that colonic mast cells and mast cells co-localized with neurons were higher in mice colonized with IBS microbiota compared with those with healthy...

The gut microbiota has been implicated in chronic pain disorders, including irritable bowel syndrome (IBS), yet specific pathophysiological mechanisms remain unclear. We showed that decreasing intake of fermentable carbohydrates improved abdominal pain in patients with IBS, and this was accompanied by changes in the gut microbiota and decreased uri...

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...

Loss of oral tolerance (LOT) to gluten, characterized by a T helper 1 (Th1) gluten-specific immune response, is a hallmark of celiac disease (CeD) and can be triggered by enteric viral infections. We hypothesized that certain gut microbes have the capacity to protect against virus-mediated LOT. By using our previously defined reovirus-mediated LOT...

There has been a dramatic increase in clinical studies examining the relationship between disorders of gut-brain interactions (DGBI) and symptoms evoked by food ingestion in the upper and lower GI tract, but study design is challenging to verify valid endpoints. Consequently, mechanistic studies demonstrating biological relevance, biomarkers and no...

GUT MICROBIOTA MODULATES CGRP PRODUCTION BY DRG NEURONS IN FEMALE MICE Julien Pujo, Giada De Palma, Jun Lu, Stephen M. Collins, Premysl Bercik Background: Abdominal pain is a common complaint in patients with chronic gastrointestinal disorders. Accumulating evidence suggests that gut microbiota is an important determinant of gut function, includi...

Irritable bowel syndrome (IBS) patients often resort to dietary interventions to manage their symptoms, as these are frequently exacerbated by various food items. A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) is now considered by many a first‐line treatment option for IBS, as it has been found to...

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 Patients with type 1 Diabetes Mellitus (T1DM) often suffer from dyspeptic symptoms, such as abdominal pain, bloating, early satiety, nausea and vomiting. T1DM shares genetic risk factors (HLA-DQ2 and DQ8) with celiac disease, an autoimmune disorder caused by an immune reaction to gluten. Patients with concomitant T1DM and 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...

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 Granulomatosis with polyangiitis (GPA) is a rare, small-to-medium sized-vessel vasculitis that typically involves the sinus, respiratory, and renal systems. The gastrointestinal (GI) tract is rarely involved, but its exact frequency is poorly characterized. GI symptoms have been reported to occur in up to 10% of acute presentations, and...

Background Recent evidence suggests an increasing prevalence of gut dysfunction following C. difficile infection (CDI). The accompanying prolonged antibiotic (AB) exposure likely contributes to chronic gut dysfunction and our ability to induce gut dysfunction in germ free (GF) mice colonized with microbiota from a patient with severe slow transit p...

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 Abdominal pain is a common complaint in patients with chronic gastrointestinal disorders. Accumulating evidence suggests that gut microbiota is an important determinant of gut function, including visceral sensitivity. Germ-free (GF) mice have been shown to display visceral hypersensitivity, which normalizes after colonization. Thus, gut...

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 Irritable bowel syndrome (IBS) is a complex functional gastrointestinal disorder with likely heterogenous pathophysiology, multiple symptoms, and comorbidities. Growing evidence shows that the gut microbiota composition and function are altered in IBS patients. However, identifying the critical drivers of clinical expression remains chal...

Irritable bowel syndrome is the most common functional gastrointestinal disorder, affecting up to 9% individuals globally. Although the etiology of this syndrome is likely heterogenous, it presents with its hallmark symptoms of abdominal pain and altered intestinal motility. Moreover, it is considered to be a disorder of the gut-brain interaction,...

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...

Introduction Gastrointestinal manifestations of systemic sclerosis affect up to 90% of patients, with symptoms including diarrhea and constipation. Small intestinal bacterial overgrowth is a condition associated with increased numbers of pathogenic bacteria in the small bowel. While currently unknown, it has been suggested that dysregulation of the...

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...

Background Abdominal pain is a common complaint in patients with chronic gastrointestinal disorders. Accumulating evidence suggests that gut microbiota is an important determinant of gut function, including visceral sensitivity. Germ-free (GF) mice have been shown to display visceral hypersensitivity, which normalizes after colonization. Sex also a...

Background Studies of germ-free (GF) mice demonstrate that gut microbiota can influence behaviour by modulating neurochemical pathways in the brain, and that bacterial colonization normalizes behavioural deficits in GF-mice. Since disrupted GABAergic and glutamatergic signaling are reported in mood disorders, this study investigated the effect of g...

Background and aims Altered gut microbiota composition and function have been associated with inflammatory bowel diseases (IBD) including ulcerative colitis (UC), but causality and mechanisms remain unknown. Methods We applied 16S rRNA gene sequencing, shotgun metagenomic sequencing, in vitro functional assays and gnotobiotic colonizations to defin...

Background: Conventionally, patients with functional dyspepsia are subgrouped based on upper gastrointestinal symptoms, according to the Rome criteria. However, psychological co-morbidity and extraintestinal symptoms are also relevant to functional gastrointestinal disorders. Aim: To investigate whether it is possible to subgroup people with fun...

Metabolism of tryptophan by the gut microbiota into derivatives that activate the aryl hydrocarbon receptor (AhR) contributes to intestinal homeostasis. Many chronic inflammatory conditions, including celiac disease involving a loss of tolerance to dietary gluten, are influenced by cues from the gut microbiota. We investigated whether AhR ligand pr...

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...

The World Health Organization declared coronavirus disease-2019 (COVID-19) a global pandemic in March 2020. Since then, there are more than 34 million cases of COVID-19 leading to more than 1 million deaths worldwide. Numerous studies suggest that celiac disease (CeD), a chronic immune-mediated gastrointestinal condition triggered by gluten, is ass...

Introduction Gut microbiome and diet may be important in irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and comorbid psychiatric conditions, but the mechanisms are unclear. We will create a large cohort of patients with IBS, IBD and healthy controls, and follow them over time, collecting dietary and mental health information and b...

Background Gnotobiotic mice colonized with microbiota from patients with irritable bowel syndrome (IBS) and comorbid anxiety (IBS+A) display gut dysfunction and anxiety‐like behavior compared to mice colonized with microbiota from healthy volunteers. Using this model, we tested the therapeutic potential of the probiotic yeast Saccharomyces boulardi...

Background & Aims Many patients with irritable bowel syndrome (IBS) perceive that their symptoms are triggered by wheat-containing foods. We assessed symptoms and gastrointestinal transit before and after a gluten-free diet (GFD) in unselected patients with IBS and investigated biomarkers associated with symptoms. Methods We performed a prospectiv...

Introduction: Many patients with celiac disease (CD) experience persistent symptoms despite adhering to the gluten-free diet. Different studies have assessed the use of probiotics as an adjuvant treatment for CD. We performed a systematic review and meta-analysis to evaluate the efficacy of probiotics in improving gastrointestinal (GI) symptoms an...