Isomaltodextrin dose-dependently reduces colitis development in HLA-B27 rat colitis model with associated changes to gut microbiota composition and short chain fatty acid production

  • Author / Creator
    Premraj, Nilanjani
  • Prevalence rates for inflammatory bowel diseases (IBD) worldwide have been drastically increasing over recent decades. IBD is characterized by altered intestinal microbiome (i.e. dysbiosis), described by reduced strict butyrate-producing anaerobes versus increased facultative anaerobes in comparison to healthy individuals. Data from preclinical studies and clinical trials show prebiotic inulin-type fibers can prevent/reduce colitis; however, other dietary fibers (e.g. alpha-glucan, α-glucan) are understudied and it is unknown if fiber-induced microbial shifts are protective in experimental colitis. The purpose of this thesis was to assess the efficacy of isomaltodextrin (IMD), a novel highly branched α-glucan, in reducing intestinal inflammation in HLA-B27 transgenic (TG) rat colitis model and to identify the protective mechanisms associated with gut microbial composition and function. HLA-B27 TG rats, 4 weeks of age, were fed standard chow diet supplemented with 7.5% IMD, 15% IMD, 15% cellulose (negative control chow), or 15% fructooligosaccharides (FOS, positive control) for 12 weeks. Body weight and food intake were measured. Cecal and colonic inflammation was assessed by macroscopic scoring and mucosal cytokine (IL-1β and IFNγ) concentrations. Changes in microbial metabolism was evaluated by measuring short chain fatty acid (SCFA) proportions in stool and cecal contents. Endpoint fecal and cecal microbiota composition differences were assessed by 16S rRNA gene sequencing (Illumina MiSeq platform). IMD showed a dose-dependent effect on cecal inflammation. The inflammation reducing effects by IMD was more commonly seen in males but were not universal for either sex, showing individual-specific benefits for the fiber. IMD demonstrated a dose dependent reduction in cecal inflammation, where IMD 15% was more effective than IMD 7.5%, which was confirmed by both gross gut score (GGS) and mucosal IL-1β concentration analyses. Both IMD groups were associated with reduced cecal concentrations of isobutyrate, valerate and isovalerate, with IMD 15% being more effective. Only IMD 15% reduced cecal propionic acid proportions, similar to that of FOS. These specific SCFA also showed a significant positive correlation with cecal IL-1β concentrations, suggesting their use as chronic inflammation markers in HLA-B27 TG rat model. Significant shifts in gut microbial composition were seen, including a decrease in alpha diversity in IMD 15% and FOS groups. Key changes in IMD groups included increased Bifidobacterium, which has previously been shown to have colitis reducing effects, as well as decreased Alistipes, which has previously been associated with colitis. Bifidobacterium and Alistipes were associated negatively and positively with cecal IL-1β concentrations, respectively, suggesting their use as microbial indicators for inflammation in HLA-B27 TG rat model. In conclusion, IMD was dose-dependently effective in reducing chronic cecal inflammation in experimental colitis. Benefits were associated with specific shifts in gut microbiota composition and SCFA production. Results from this preclinical study warrant future microbiota-altering intervention trials using IMD in clinical IBD.

  • Subjects / Keywords
  • Graduation date
    Fall 2021
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.