Written by Marcia J. Egles, MD. Supplementation with the prebiotic inulin-type fructose in ApoE-Knock-out mice fed a PUFA-depleted diet for 12 weeks, totally reversed endothelial dysfunction in their carotid arteries and altered their gut microbiota and liver gene expression.
A recent study from Belgium demonstrated detailed cellular mechanisms by which a change in diet produced alterations in gut microbes which caused an improvement in vascular dysfunction in mice. Inulin-type fructans (ITF), a prebiotic fiber supplement to the diet, improved endothelial dysfunction in mice 1. In the future, similar strategies which target gut microbial populations may offer new therapies to human patients.
The study used a “mouse model” of cardiovascular disease with a special type of mouse known as “ApoE- knock-out mouse” (KO). These KO mice are genetically deficient for apolipoprotein-E which is important in cholesterol metabolism. To further compound the model of cardiovascular disease, the mice are fed an omega-3 polyunsaturated fatty acid (n-3 PUFA) deficient Western type diet. Such mice develop accelerated endothelial dysfunction. The lining of their arteries, the endothelium, does not appropriately relax in response to an endothelial stimulus in these KO mice as compared to wild-type mice. Endothelial dysfunction is considered a key marker of cardiovascular disease. It is thought to be mediated by synthesis and release of nitric oxide (NO) in the endothelium 2,3.
In the study, both wild-type and KO mice were fed omega-3 PUFA deficient diets for 12 weeks with or without ITF supplementation (at 250 mg per mouse per day) for the final 15 days. Past studies had shown that ITF and other dietary fiber supplementation can modulate the composition of the gut microbiota, and thus interact with host physiology 4.
The study then examined the mesenteric and carotid arteries of the mice and measured endothelial function. ITF supplementation was found to totally reverse the endothelial dysfunction in the KO mice via nitric oxide pathways making their endothelial function comparable to that of the normal wild type.
The colonic microorganisms were assessed by gene sequencing which identified not only the species of microorganisms, but also some of the gene expression involved. The changes induced by ITF included increased NO-producing bacteria, increased abundance of Akkermansia and decreased bacteria involved in bile acid synthesis. Also, the ITF treatment in the KO mice produced a threefold increase in glucagon-like peptide-1 as compared to the untreated KO mice. Glycagon-like peptide -1, as well as changes in bile acid production and increased NO, was thought to improve endothelial function.
Weight loss itself can improve endothelial dysfunction 5. However, in this study, this mechanism was ruled out as there was no difference in body weight between the ITF treated and untreated mice.
The researchers concluded that ITF’s effects upon the mice gut microbes, and the resultant alleviation of endothelial dysfunction, warrant the start of testing in human studies.
Source: Catry, Emilie, Laure B. Bindels, Anne Tailleux, Sophie Lestavel, Audrey M. Neyrinck, Jean-François Goossens, Irina Lobysheva et al. “Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction.” Gut (2017): gutjnl-2016.
© The Authors 2017. Creative Commons Attribution Non Commercial (CC BY-NC 4.license. http://creativecommons.org/licenses/by-nc/4.0/
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Posted November 6, 2017.
References:
- Catry E, Bindels LB, Tailleux A, et al. Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction. Gut. 2017:gutjnl-2016-313316.
- Pendse AA, Arbones-Mainar JM, Johnson LA, Altenburg MK, Maeda N. Apolipoprotein E knock-out and knock-in mice: atherosclerosis, metabolic syndrome, and beyond. Journal of lipid research. 2009;50(Supplement):S178-S182.
- Catry E, Neyrinck AM, Lobysheva I, et al. Nutritional depletion in n‐3 PUFA in apoE knock‐out mice: A new model of endothelial dysfunction associated with fatty liver disease. Molecular nutrition & food research. 2016;60(10):2198-2207.
- Delzenne NM, Neyrinck AM, Cani PD. Gut microbiota and metabolic disorders: how prebiotic can work? British Journal of Nutrition. 2013;109(S2):S81-S85.
- Bigornia SJ, Mott MM, Hess DT, et al. Long‐term successful weight loss improves vascular endothelial function in severely obese individuals. Obesity. 2010;18(4):754-759.
