Shared more. Cited more. Safe forever.
    • advanced search
    • submit works
    • about
    • help
    • contact us
    • login
    View Item 
    •   MOspace Home
    • University of Missouri-Columbia
    • Graduate School - MU Theses and Dissertations (MU)
    • Theses and Dissertations (MU)
    • Dissertations (MU)
    • 2020 Dissertations (MU)
    • 2020 MU dissertations - Access restricted to MU
    • View Item
    •   MOspace Home
    • University of Missouri-Columbia
    • Graduate School - MU Theses and Dissertations (MU)
    • Theses and Dissertations (MU)
    • Dissertations (MU)
    • 2020 Dissertations (MU)
    • 2020 MU dissertations - Access restricted to MU
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    advanced searchsubmit worksabouthelpcontact us

    Browse

    All of MOspaceCommunities & CollectionsDate IssuedAuthor/ContributorTitleIdentifierThesis DepartmentThesis AdvisorThesis SemesterThis CollectionDate IssuedAuthor/ContributorTitleIdentifierThesis DepartmentThesis AdvisorThesis Semester

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular AuthorsStatistics by Referrer

    Interactions between helicobacter-induced inflammation acute changes in the gut microbiota, and colorectal cancer in Smad3-/- mice

    Wolfie, Annie E.
    View/Open
    [PDF] WolfeAnnie.pdf (4.024Mb)
    Date
    2020
    Format
    Thesis
    Metadata
    [+] Show full item record
    Abstract
    [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI--COLUMBIA AT REQUEST OF AUTHOR.] Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide, accounting for 551,269 deaths in 2018 alone. One subset of CRC, colitis associated CRC (CAC), develops as a sequela to chronic inflammatory diseases of the bowel. The underlying mechanism of CAC is poorly understood, but prognosis is poor due to difficulty of detection. Surveillance strategies are invasive and expensive. Risk factors of CAC include inflammatory bowel disease (IBD), diet, smoking, environment, and obesity--all of which impact or are impacted by the gut microbiota (GM), making the GM a prime target for understanding the etiology of CAC in order to develop preventative measures. Using the Smad3-/- CAC model, which requires inoculation of pathobiont Helicobacter spp., we tested the ability of the Th17-enhancing commensal Candidatus Savagella, more commonly denoted as Segmented Filamentous Bacteria (SFB), to influence the incidence and severity of CAC. To document the composition of the gut microbiota during CRC development and identify taxa associated with disease, fecal samples were collected before and throughout disease development and characterized via 16S rRNA sequencing. While there were no significant SFB-dependent effects on disease incidence or severity, SFB were found to exert a sex-dependent protective effect in male mice. Furthermore, SFB stabilized the GM against Helicobacter-induced changes post inoculation, resulting in a shift in disease association from Helicobacter spp. to Escherichia coli. These data support sex-dependent SFB-mediated effects on CRC risk, and highlight the complex community dynamics within the GM during exposure to inflammatory pathobionts. In order to artificially modulate disease severity, we repeated the above experiments using Smad3-/- mice rederived onto different GM backgrounds, using a technique called complex microbiota targeted rederivation (CMTR). Smad3-/- mice harboring distinct GM profiles termed GM1, GM2, and GM4 were similarly inoculated with Helicobacter spp. and followed longitudinally through disease development or lack thereof. We hypothesized that GM1 and 2 would develop the most severe disease, due to lack of richness and diversity. There was no difference in disease penetrance between the GM profiles, and no pre-disposing GM profile was found at pre-inoculation or early timepoints. However, GM2 developed greater disease severity than GM1 and GM4. Looking at static and dynamic differences between CRC- and CRC+ groups of each GM revealed OTUs, genera, and families which differed in disease development. Network construction analysis using overlapping timepoints from early to late, revealed that overall CRC+ bacterial communities had fewer connections than their CRC- counterparts. This was most striking in GM2 CRC+, which could account for the increased disease severity in this GM profile.
    URI
    https://hdl.handle.net/10355/79465
    https://doi.org/10.32469/10355/79465
    Degree
    Ph. D.
    Thesis Department
    Molecular microbiology and immunology (MU)
    Rights
    Access to files is limited to the University of Missouri--Columbia.
    Collections
    • 2020 MU dissertations - Access restricted to MU
    • Molecular Microbiology and Immunology electronic theses and dissertations (MU)

    Send Feedback
    hosted by University of Missouri Library Systems
     

     


    Send Feedback
    hosted by University of Missouri Library Systems