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THE EFFECT OF β-FRUCTANS ON INTESTINAL PERMEABILITY IN PATIENTS WITH ULCERATIVE COLITIS IN CLINICAL REMISSION
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- Author / Creator
- Rashed, Reem A
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Introduction: β-fructans are non-digestible fermentable carbohydrates that are metabolized by commensal gut bacteria such as Faecalibacterium prausnitzii and Roseburia spp. By-products of β-fructans fermentation include short-chain fatty acids, shown to improve intestinal epithelial integrity and the mucosal barrier in pre-clinical studies via pH reduction, and homeostasis of energy metabolism and inflammation. Patients with inflammatory bowel diseases exhibit increased paracellular intestinal permeability and tight junction dysfunction (“leaky gut”), which may exacerbate disease progression. In a recent placebo-controlled intervention β-fructans reduced the severity of subclinical relapse in patients with ulcerative colitis (UC). However, it is unknown if this protective effect was mediated by improved intestinal permeability.
Hypothesis: We hypothesized that 6-month supplementation of β-fructans may improve barrier integrity in UC patients with inactive disease.
Methods: Serum samples and colonic biopsies were collected during a randomized placebo-controlled 6-month clinical study with 73 UC patients in remission treated with inulin-type β-fructans (Synergy 1, Beneo GmbH) or maltodextrin (placebo). mRNA expression of tight junction proteins including, claudin-2 and occludin, were quantified using real-time quantitative polymerase chain reaction from colonic biopsies. In addition, serum concentrations of markers for circulating Gram-negative bacteria [lipopolysaccharides (LPS) and LPS-binding protein (LBP)] and Gram-positive bacteria [lipoteichoic acid (LTA)] were assessed at baseline and endpoint by enzyme-linked immunosorbent assay.
Results: Claudin-2 and occludin mRNA gene-expression showed a positive correlation to each other (Placebo: R2=0.604, p=0.001; β-fructans: R2=0.0528, p=0.007). Intergroup analysis showed that tight-junction proteins were down-regulated in patients treated with β-fructans. This was particularly valid for those patients in the β-fructans group who remained in clinical and biochemical remission (one-way ANOVA claudin-2 p=0.0332; occludin p=0.0640). Assessment of the serum LBP, LPS, and LTA showed no difference over the course of the study within treatment and between treatment groups (Placebo: LBP p=0.4939, LPS p=0.6437, LTA p=0.2738; β-fructans: LBP p=0.3092, LPS p= 0.397 LTA p=0.1207; between group differences: LBP p=0.2149, LPS p=0.3176, LTA p=0.0633). Further multivariate analysis including FCP and fecal SCFAs, and markers for intestinal permeability identified that fecal valerate was positively correlated to claudin-2 gene expression (R2=0.413, p=0004).
Conclusion: The efficacy of inulin-type β-fructans was partially mediated by down-regulation in tight-junction proteins claudin-2 and occludin mRNA gene expression in patients with UC who are in clinical remission.
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- Graduation date
- Fall 2023
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- Type of Item
- Thesis
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- Degree
- Master of Science
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- 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.