Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model

Abstract

Humans with metabolic and inflammatory diseases frequently harbor lower levels of butyrate-producing bacteria in their gut. However, it is not known whether variation in the levels of these organisms is causally linked with disease development and whether diet modifies the impact of these bacteria on health. Here we show that prominent gut-associated butyrate-producing bacteria species ( Roseburia sp.) is inversely correlated with atherosclerotic lesion development in a genetically diverse mouse population. We use germ-free apolipoprotein E -deficient mice colonized with synthetic microbial communities that differ in their capacity to generate butyrate to demonstrate that Roseburia intestinalis interacts with dietary plant polysaccharides to (i) impact gene expression in the intestine, directing metabolism away from glycolysis and toward fatty acid utilization, (ii) lower systemic inflammation and (iii) ameliorate atherosclerosis. Furthermore, intestinal administration of butyrate reduces endotoxemia and atherosclerosis development. Altogether, our results illustrate how modifiable diet-by-microbiota interactions impact cardiovascular disease, and suggest that interventions aimed at increasing the representation of butyrate-producing bacteria may provide protection against atherosclerosis.

Butyrate protects against high‐fat diet‐induced atherosclerosis via up‐regulating ABCA1 expression in apolipoprotein E‐deficiency mice

“…In one recent study, gnotobiotic ApoE −/− mice with synthetic microbial communities colonized with butyrate‐producing bacteria Roseburia intestinalis inhibited the progression of atherosclerotic plaque formation in a standard chow diet with high content of plant polysaccharides. Although the exact mechanism was not fully elucidated, the results suggested the athero‐protective effect of R. intestinalis was mediated at least in part by butyrate (Kasahara et al, ). In spite of no significant changes in serum lipid levels in the above studies, however other animal studies have shown promising results of cholesterol‐lowering by butyrate (Gao et al, ; Mollica et al, ).…”

Short-chain fatty acid, acylation and cardiovascular diseases

“…Butyrate inhibits the proliferation of VSMCs by promoting the anti-oxidative effect and anti-inflammatory response [121]. And recent studies reveal that the butyrate plays an atheroprotective role [122,123]. Oral supplementation with 1% butyrate could slow the progression of atherosclerosis by repressing activation of nucleus factor-κB (NF-κB) and decreasing pro-inflammatory cytokines to reduce the adhesion and migration of macrophages, which consequently increased plaque stability in ApoE-knockout mice [124].…”

The Gut Microbiota in Cardiovascular Disease and Arterial Thrombosis

“…This densely colonized microbial ecosystem critically influences the host's immune homeostasis via microbial-associated molecular patterns (MAMPs) and through the signaling of active metabolites [3,4]. For example, stimulation with MAMPs increases the phagocytic capacity and the response to cytokines of macrophages and neutrophils and drives atherogenesis [5][6][7][8]. In contrast, metabolites such as short chain fatty acids (SCFAs) inhibit interferon-γ (IFN-γ) production and protect from mucosal inflammation, but also reduce the development of atherosclerotic lesions [5,6].…”

“…For example, stimulation with MAMPs increases the phagocytic capacity and the response to cytokines of macrophages and neutrophils and drives atherogenesis [5][6][7][8]. In contrast, metabolites such as short chain fatty acids (SCFAs) inhibit interferon-γ (IFN-γ) production and protect from mucosal inflammation, but also reduce the development of atherosclerotic lesions [5,6].…”