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Investigating the Role of the Microbiota In Chronic Inflammatory Diseases Using Preclinical Models

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Foci: Understanding the organization, composition, and functions of the intestinal microbiota; investigating the role of microbiota in chronic inflammatory GI diseases using preclinical models

Verdu Lab

Twitter: @verdulab

Research summary

The Verdu Lab is a diverse and translational group that investigates host-microbial and dietary interactions in the GI tract as it relates to chronic gastrointestinal diseases. We study how microbial and dietary factors modulate immune responses and host physiology in celiac disease and inflammatory bowel disease (IBD). We are interested in understanding the functional characteristics of the microbiota, with a focus on microbial metabolism and proteolytic activity.

Celiac disease: About 40% of the general population have a genetic predisposition for celiac disease, but only a small proportion will develop this autoimmune disease suggesting a role for environmental factors. Our lab studies how microbes in the small intestine influence metabolism of gluten, the dietary driver of celiac disease.

Ulcerative colitis and Crohn’s disease: The mechanisms by which microbes influence these two chronic intestinal inflammatory conditions are unclear. We focus on microbial proinflammatory proteolytic activity as a marker of disease severity and progression, and on its inhibition using microbial therapeutics, as novel pharmacological strategies in IBD.

Methods, Models and Facilities: We employ translational approaches that include analysis of human patient samples in collaboration with the IBD Clinic and the Celiac Clinic at McMaster University, as well as the IMAGINE and GEM project cohorts. Microbial composition and function are investigated at McMaster’s state-of-the-art Genomics Facility. Clinical findings are functionally validated in gnotobiotic and microbiota-humanized mouse models within the Farncombe Family Axenic Gnotobiotic Facility, and in vitro organoid models.

Click on the following link for a complete PubMed list of publications: www.ncbi.nlm.nih.gov/pubmed/?term=Verdu+EF

Click on the following link to learn more about Verdu Lab activities! www.verdulab.com

The Caminero lab opened in 2019 with the aims to facilitate a multidisciplinary research group that explores microbial metabolism and its various connections to human health.

1. Diet-microbiota interactions in inflammatory bowel disease (IBD) and food sensitivities. The first main research focus is on microbial antigen metabolism in food allergy and other dietary intolerances. We aim to identify microorganisms involved in the proper digestion of prejudicial dietary components and investigate the main dietary triggers in IBD-related food intolerances.

2. Microbial amino acid metabolism in intestinal inflammation. We investigate microbial metabolism of dietary tryptophan, an essential amino acid ingested in our diet, and the conditions that contribute to activation of homeostatic responses in the gut. Recently, impaired tryptophan metabolism was linked to alterations in the microbiota in IBD. We aim to identify beneficial tryptophan-microbiota interactions to generate evidence-based dietary advice for IBD patients and provide more efficient microbiota-targeted therapies such as next-generation probiotics.

 Methodologies: The lab utilizes different gnotobiotic mouse models of intestinal inflammation (spontaneous and chemically-induced) and food sensitivity. Also, the lab hosts equipment for characterization and identification of bacteria, and methodology to study relevant interactions between microorganisms and dietary components in IBD and food sensitivity.

 Sponsors: Dr. Caminero holds a chair in Gastroenterology supported by the Paul Douglas Family. We are also funded by the Canadian Institutes of Health Research (CIHR), Crohn and Colitis Canada (CCC), Natural Sciences and Engineering Research Council of Canada (NSERC), Tri-Agency funding programs and Canada Foundation for Innovation (CFI).

Website: https://www.caminerolab.com

Dr. Caminero’s Google Scholar Page

  1. Grondin JA, Kwon YH, Far PM, Haq S, Khan WI. Mucins in intestinal mucosal defense and inflammation: learning from clinical and experimental studies. Front Immunol. 2020; 11:2054. doi: 10.3389/fimmu.2020.02054.
  2. Kwon YH, Wang H, Denou E, Ghia JE, Rossi L, Fontes ME, Bernier SP, Shajib M, Banskota S, Collins SM, Surette MG, Khan WI. Modulation of Gut Microbiota Composition by Serotonin Signaling Influences Intestinal Immune Response and Susceptibility to Colitis. Cell Mol Gastroenterol Hepatol. 2019;7(4):709-728.

The Coombes lab develops and implements pre-clinical animal models to better understand the microbiological contributions to chronic inflammation associated with Crohn’s disease and the impact of this inflammation on the mucosal immune system. The lab is particularly interested in the expansion of Enterobacteriacae bacteria that is commonly seen during CD and is working to understand where host control of invasive microbes breaks down during CD pathogenesis.

Lab Website: https://www.coombeslab.com