Gut microbiome in immune-mediated inflammatory disease

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dc.contributor.authorForbes, Jessica Dawn
dc.contributor.examiningcommitteeAlfa, Michelle (Medical Microbiology and Infectious Diseases) Bernstein, Charles (Internal Medicine) de Kievit, Teresa (Microbiology) Surette, Michael (McMaster University)en_US
dc.contributor.supervisorVan Domselaar, Gary (Medical Microbiology and Infectious Diseases)en_US
dc.date.accessioned2017-03-30T15:40:14Z
dc.date.available2017-03-30T15:40:14Z
dc.date.issued2016en_US
dc.date.issued2016en_US
dc.date.issued2016en_US
dc.degree.disciplineMedical Microbiology and Infectious Diseasesen_US
dc.degree.levelDoctor of Philosophy (Ph.D.)en_US
dc.description.abstractImmune-mediated inflammatory diseases (IMID) represent a group of ostensibly unrelated, chronic and highly disabling diseases that preferentially affect different organ systems. IMID are assumed to manifest as a result of the accumulation of genetic, environmental and immunological factors. A fundamental commonality between IMID is the idiopathic nature of disease, and moreover, substantial similarities are apparent in disease etiopathogenesis. The complex assemblage of microbes and their genes that exists within and on the human body, collectively known as the microbiome has emerged as a critical factor in human health and, altered microbial populations within the gastrointestinal tract lumen and mucosa have been linked to several IMID. Accordingly, we conducted several studies investigating the association of the gut microbiome with IMID. Our main study investigated differences in the microbial profile and functional potential of multiple IMID utilizing 16S rDNA amplicon sequencing and analysis of stool. We also investigated the mucosal-associated microbiome in IBD to characterize the microbial populations and their functions residing in distinct gastrointestinal compartments from inflamed and noninflamed mucosa. We also explored a potential environmental factor; specifically assessing whether microbes present in drinking water in low or high incidence areas of IBD might contribute to disease etiology. The findings of these studies are manifold. First, we show important differences of the stool microbial profile in IMID. In doing so, we were able to identify distinct states of gut dysbiosis and have revealed numerous microbes that are consistently or uniquely disproportionate between IMID. Second, we have shown the microbial profile associated with inflamed and noninflamed mucosa and have reported that a localized dysbiosis is not observed in the presence of inflammation. Third, we have revealed that distinct gastrointestinal compartments are comprised of similar microbial communities. Lastly, we have reported the drinking water microbiome to differ between low and high incidence areas of IBD, thus suggesting a potential role in IBD etiology. Understanding the role of the gut microbiome in human disease will enable the development and application of more appropriate therapeutic strategies that specifically target microbes within the gut.en_US
dc.description.noteMay 2017en_US
dc.identifier.citationForbes JD, Van Domselaar G, Bernstein CN. 2016. The gut microbiota in immune- mediated inflammatory diseases. Front Microbiol;7:1081. doi: 10.3389/fmicb.2016.01081.en_US
dc.identifier.citationForbes JD, Van Domselaar G, Bernstein CN. 2016. Microbiome survey of the inflamed and noninflamed gut at different compartments within the gastrointestinal tract of inflammatory bowel disease patients. Inflamm Bowel Dis;22(4):817-825. doi: 10.1097/MIB.0000000000000684.en_US
dc.identifier.citationForbes JD, Van Domselaar G, Sargent M, Green C, Springthorpe S, Krause DO, Bernstein CN. 2016. Microbiome profiling of drinking water in relation to incidence of inflammatory bowel disease. Can J Microbiol;62(9):781-793. doi: 10.1139/cjm-2016- 0219.en_US
dc.identifier.urihttp://hdl.handle.net/1993/32175
dc.language.isoengen_US
dc.publisherWolters Kluweren_US
dc.publisherNRC Research Pressen_US
dc.rightsopen accessen_US
dc.subjectmicrobiomeen_US
dc.subjectguten_US
dc.subject16s rRNAen_US
dc.subjectCrohn's diseaseen_US
dc.subjectulcerative colitisen_US
dc.subjectrheumatoid arthritisen_US
dc.subjectmultiple sclerosisen_US
dc.subjectepidemiologyen_US
dc.subjectimmune-mediateden_US
dc.titleGut microbiome in immune-mediated inflammatory diseaseen_US
dc.typedoctoral thesisen_US
local.subject.manitobayesen_US
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