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

Abstract

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 gluten-free high-fat cholesterol-rich diet, as compared to the same diet in which the gluten peptide 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. These results demonstrate that a gluten-free diet does not seem to have beneficial effects on atherosclerosis or several CVD risk factors in this mouse model, but that sustained alteration of GM composition with a broad-spectrum antibiotic has beneficial effects on CVD risk factors and atherosclerosis. These findings support the concept that altering the microbiota might provide novel treatment strategies for CVD.

Cardiovascular health effects of oral and pulmonary exposure to multi-walled carbon nanotubes in ApoE-deficient mice

“…Moreover, the same phylotypes of bacteria have been observed in the oral cavity, gut, and atheromas of patients with atherosclerosis, suggesting an infestation of external bacteria to the systemic circulation (Koren et al 2011). This is supported by observations that treatment with broad spectrum antibiotics alters the composition of the gut microbiota and has a beneficial effect on plaque progression in ApoE -/mice (Rune et al 2016). Furthermore, CNTs have an antimicrobial activity to commensal bacteria in the human gastrointestinal tract in vitro (Chen et al 2013a;Zhu et al 2014).…”

The gut microbiota: An emerging risk factor for cardiovascular and cerebrovascular disease

“…Treatment of ApoE −/− mice with broad-spectrum antibiotics, resulting in sustained alteration in gut microbiota composition, had beneficial effects on cardiovascular disease risk factors and reduced atherosclerotic lesion size [87]. Of note, the ApoE −/− mouse atherosclerosis model is dependent on NK-T cell activation through CD1d [88], a restriction element for many self and microbial lipids in this model.…”

The gut microbiota and its interactions with cardiovascular disease

“…For example, vancomycin and minocycline interventions decreased systolic BP in spontaneously hypertensive rats (Galla, et al , ). Furthermore, ampicillin reduced atherosclerotic risk factors, such as lipoprotein levels (Rune, et al , ). However, the general consensus is that non‐specific antimicrobial approaches may lead to a wide range of side‐effects and that even probiotics with excellent safety records could potentially increase the risk of probiotic translocation into the circulation (Liong, ).…”