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Article: Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe-/- Mice

TitleAkkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe-/- Mice
Authors
Issue Date2016
Citation
Circulation, 2016, 133 n. 24, p. 2434-2446 How to Cite?
AbstractBackground—Altered composition of the gut microbiota is involved in both onset and progression of obesity and diabetes. However, the link between gut microbiota and obesity-related cardiovascular complications has not been explored. The present study was designed to investigate the role of Akkermansia muciniphila, a mucin-degrading bacterium with beneficial effects on metabolism, in the pathogenesis of atherosclerosis in apolipoprotein E-deficient (Apoe-/-) mice. Methods and Results—Apoe-/- mice on normal chow diet or Western diet were treated with A. muciniphila by daily oral gavage for eight weeks, followed by histological evaluations of atherosclerotic lesion in aorta. Real-time PCR analysis demonstrated that the fecal abundance of A. muciniphila was significantly reduced by Western diet. Replenishment with A. muciniphila reversed Western diet-induced exacerbation of atherosclerotic lesion formation without affecting hypercholesterolemia. A. muciniphila prevented Western diet-induced inflammation in both circulation and local atherosclerotic lesion, as evidenced by reduced macrophage infiltration and expression of proinflammatory cytokines and chemokines. These changes were accompanied by a marked attenuation in metabolic endotoxemia. A. muciniphila-mediated reduction in circulating endotoxin level could be attributed to induction of intestinal expression of the tight junction proteins (ZO-1 and occludin), thereby reversing Western diet-induced increases in gut permeability. Chronic infusion of endotoxin to Apoe-/- mice reversed the protective effect of A. muciniphila against atherosclerosis. Conclusions—A. muciniphila attenuates atherosclerotic lesions by ameliorating metabolic endotoxemia-induced inflammation through restoration of the gut barrier.
Persistent Identifierhttp://hdl.handle.net/10722/225632

 

DC FieldValueLanguage
dc.contributor.authorLi, J-
dc.contributor.authorLin, S-
dc.contributor.authorVanhoutte, PMGR-
dc.contributor.authorWoo, WHC-
dc.contributor.authorXu, A-
dc.date.accessioned2016-05-20T08:09:34Z-
dc.date.available2016-05-20T08:09:34Z-
dc.date.issued2016-
dc.identifier.citationCirculation, 2016, 133 n. 24, p. 2434-2446-
dc.identifier.urihttp://hdl.handle.net/10722/225632-
dc.description.abstractBackground—Altered composition of the gut microbiota is involved in both onset and progression of obesity and diabetes. However, the link between gut microbiota and obesity-related cardiovascular complications has not been explored. The present study was designed to investigate the role of Akkermansia muciniphila, a mucin-degrading bacterium with beneficial effects on metabolism, in the pathogenesis of atherosclerosis in apolipoprotein E-deficient (Apoe-/-) mice. Methods and Results—Apoe-/- mice on normal chow diet or Western diet were treated with A. muciniphila by daily oral gavage for eight weeks, followed by histological evaluations of atherosclerotic lesion in aorta. Real-time PCR analysis demonstrated that the fecal abundance of A. muciniphila was significantly reduced by Western diet. Replenishment with A. muciniphila reversed Western diet-induced exacerbation of atherosclerotic lesion formation without affecting hypercholesterolemia. A. muciniphila prevented Western diet-induced inflammation in both circulation and local atherosclerotic lesion, as evidenced by reduced macrophage infiltration and expression of proinflammatory cytokines and chemokines. These changes were accompanied by a marked attenuation in metabolic endotoxemia. A. muciniphila-mediated reduction in circulating endotoxin level could be attributed to induction of intestinal expression of the tight junction proteins (ZO-1 and occludin), thereby reversing Western diet-induced increases in gut permeability. Chronic infusion of endotoxin to Apoe-/- mice reversed the protective effect of A. muciniphila against atherosclerosis. Conclusions—A. muciniphila attenuates atherosclerotic lesions by ameliorating metabolic endotoxemia-induced inflammation through restoration of the gut barrier.-
dc.languageeng-
dc.relation.ispartofCirculation-
dc.titleAkkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe-/- Mice-
dc.typeArticle-
dc.identifier.emailVanhoutte, PMGR: vanhoutt@hku.hk-
dc.identifier.emailWoo, WHC: cwhwoo@hku.hk-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.authorityVanhoutte, PMGR=rp00238-
dc.identifier.authorityWoo, WHC=rp01860-
dc.identifier.authorityXu, A=rp00485-
dc.identifier.doi10.1161/CIRCULATIONAHA.115.019645-
dc.identifier.pmid27143680-
dc.identifier.hkuros257936-
dc.identifier.hkuros259331-

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