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Increased intake of fermentable carbohydrates induces IBS-like symptoms; a complementary understanding of mechanisms involved.

Kamphuis, Jasper. Increased intake of fermentable carbohydrates induces IBS-like symptoms; a complementary understanding of mechanisms involved. PhD, Pathologie, Toxicologie, Génétique et Nutrition, Institut National Polytechnique de Toulouse, 2019, 237 p.

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Abstract

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) characterized by abdominal pain, bloating, and erratic bowel habits. It is an affliction with a high prevalence of around 11% worldwide. It carries a significant economic cost in lost productivity and work absence, and more importantly, it has a strong negative impact on quality of life. Because it is a functional disorder of which the causes are not well understood, treatment is difficult. In recent years, a low-FODMAP diet (low in Fermentable Oligo-, Di-, Mono-saccharides And Polyols) has been successfully used to reduce symptoms of IBS. The efficacity of this approach is not completely understood, but a reduction in enteric distension by reduced gas production and small intestinal water bulk by osmotic effects are most often cited. The bacterial metabolic toxin hypothesis, proposed by Campbell et al. poses that anaerobic fermentation of unabsorbed carbohydrates by the colonic gut microbiota, producing such metabolites as alcohols, ketones, and aldehydes, are responsible for food intolerances such as lactose intolerance. We hypothesized that this same mechanism could be extended to FODMAPs to explain the efficacity of the low- FODMAP diet. In this thesis, we looked for complementary mechanisms on how FODMAPs could influence IBS symptoms, besides distension related complaints. Our studies in a healthy mouse model show a complex role for FODMAPs in IBS physiopathology; FODMAP treatments cause a visceral and abdominal hypersensitivity, and a mucus barrier dysregulation, characterized using an innovative approach. We hypothesized that this is due to generation of glycating agents by the intestinal microbiota, and the prevention of these effects by co-treatment with pyridoxamine indicates that this hypothesis is correct. Mucosal mast cell counts were increased in FODMAP treated animals, but not in animals co-treated with pyridoxamine. Mast cells are implicated in visceral hypersensitivity, as well as in mucus barrier dysregulation, and increased mucosal mast cell numbers or activity are often linked to IBS. This work thus offers a link between the efficacity of the low-FODMAP diet and the involvement of intestinal mast cells in IBS.

Item Type:PhD Thesis
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Institution:Université de Toulouse > Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE)
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Research Director:
Eutamène, Hélène and Theodorou, Vassilia
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Deposited On:12 Mar 2020 10:42

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