ApoE deficient mice

Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and therosclerotic Plaque Development in ApoE-Deficient Mice

Ida Rune1*, Bidda Rolin2, Christian Larsen1, Dennis Sandris Nielsen3, Jenny E. Kanter4, Karin E. Bornfeldt4, Jens Lykkesfeldt1, Karsten Buschard5, Rikke Kaae Kirk2, Berit Christoffersen2, Johannes Josef Fels2, Knud Josefsen5, Pernille Kihl1, Axel Kornerup Hansen1

1Section of Experimental Animal Models, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Thorvaldsensvej 57, 1871 Frederiksberg C, Denmark,
2Global Research, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Måløv, Denmark,
3Department of Food Science, Faculty of Science, University of Copenhagen, Rolighedsvej 26, 1958 Frederiksberg C, Denmark,
4Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA, 98109, United States of America,
5The Bartholin Institute, Rigshospitalet Dept. 3733, Copenhagen Biocenter, Ole Maaløes Vej 5, 2200 København N, Denmark


The importance of the gut microbiota (GM) in disease development has recently received increased attention, and numerous approaches have been made to better understand this important interplay. For example, metabolites derived from the GM have been shown to promote atherosclerosis, the underlying cause of cardiovascular disease (CVD), and to increase CVD risk factors. Popular interest in the role of the intestine in a variety of disease states has now resulted in a significant proportion of individuals without coeliac disease switching to gluten-free diets. The effect of gluten-free diets on atherosclerosis and cardiovascular risk factors is largely unknown.We therefore investigated the effect of a glutenfree high-fat cholesterol-rich diet, as compared to the same diet in which the glutenpeptide gliadin had been added back, on atherosclerosis and several cardiovascular risk factors in apolipoprotein E-deficient (Apoe-/-) mice. The gluten-free diet transiently altered GM composition in these mice, as compared to the gliadin-supplemented diet, but did not alter body weights, glucose tolerance, insulin levels, plasma lipids, or atherosclerosis. In parallel, other Apoe-/- mice fed the same diets were treated with ampicillin, a broad-spectrum antibiotic known to affect GM composition. Ampicillin-treatment had a marked and sustained effect on GM composition, as expected. Furthermore, although ampicillin-treated mice were slightly heavier than controls, ampicillin-treatment transiently improved glucose tolerance both in the absence or presence of gliadin, reduced plasma LDL and VLDL cholesterol levels, and reduced aortic atherosclerotic lesion area.

Plos One          DOI:10.1371/journal.pone.0146439

20 JUNE 2024