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Baseline Luminal Narrowing is Associated with Ileal Microbial Shifts and Gene Expression Programs and Subsequent Transmural Healing in Pediatric Crohn’s Disease

Ta, Allison D, M.D.
http://orcid.org/0000-0002-3403-5629
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1617105155605576

Abstract Details

2021, MS, University of Cincinnati, Medicine: Clinical and Translational Research.
Background: Transmural healing (TH) is associated with better long-term outcomes in Crohn’s Disease (CD), while pre-treatment ileal gene signatures encoding myeloid inflammatory responses and extracellular matrix production are associated with stricturing. We aimed to develop a predictive model for ileal transmural healing (TH), and to identify ileal genes and microbes associated with baseline luminal narrowing (LN), a precursor to strictures. Methods: Baseline small bowel imaging obtained in the RISK pediatric CD cohort study was graded for LN. Ileal gene expression was determined by RNASeq and the ileal microbial community composition characterized using 16S rRNA amplicon sequencing. Clinical, demographic, radiologic, and genomic variables were tested for association with baseline LN and future TH. Results: After controlling for ileal location, baseline ileal LN (Odds Ratio (95%CI): 0.3 (0.1,0.8)), increasing serum albumin (4 (1.3,12.3)), and ASCA IgG serology (0.97 (0.95,1)) were associated with subsequent TH. A multivariable regression model including these factors had excellent discriminant power for TH (AUC of 0.86, PPV of 80%, NPV of 87%). Patients with baseline LN exhibited increased Enterobacteriaceae and inflammatory and extracellular matrix gene signatures, coupled with reduced levels of butyrate producing commensals and a respiratory electron transport gene signature. Taxa including Lachnospiraceae and Roseburia were associated with increased respiratory and decreased inflammatory gene signatures, while Aggregatibacter and Blautia were associated with reduced extracellular matrix gene expression. Conclusions: Pediatric CD patients with LN at diagnosis are less likely to achieve TH. The association between specific microbiota, wound healing gene programs, and LN may suggest future therapeutic targets.
Patrick Ryan, Ph.D. (Committee Chair)
Lee Denson, M.D. (Committee Member)
Nicholas Ollberding (Committee Member)
83 p.
Surgery
Microbiome; Gene Expression; Luminal Narrowing; Magnetic Resonance Enterography; Transmural Healing; Crohns Disease

Recommended Citations

Citations

  • Ta, M.D., A. D. (2021). Baseline Luminal Narrowing is Associated with Ileal Microbial Shifts and Gene Expression Programs and Subsequent Transmural Healing in Pediatric Crohn’s Disease [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1617105155605576

    APA Style (7th edition)

  • Ta, M.D., Allison. Baseline Luminal Narrowing is Associated with Ileal Microbial Shifts and Gene Expression Programs and Subsequent Transmural Healing in Pediatric Crohn’s Disease. 2021. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1617105155605576.

    MLA Style (8th edition)

  • Ta, M.D., Allison. "Baseline Luminal Narrowing is Associated with Ileal Microbial Shifts and Gene Expression Programs and Subsequent Transmural Healing in Pediatric Crohn’s Disease." Master's thesis, University of Cincinnati, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1617105155605576

    Chicago Manual of Style (17th edition)

ucin1617105155605576
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This open access ETD is published by University of Cincinnati and OhioLINK.