Metformin intervention ameliorates AS in ApoE-/- mice through restoring gut dysbiosis and anti-inflammation.

Atherosclerosis (AS) is closely associated with chronic low-grade inflammation and gut dysbiosis. Metformin (MET) presents pleiotropic benefits in the control of chronic metabolic diseases, but the impacts of MET intervention on gut microbiota and inflammation in AS remain largely unclear. In this s...

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Autores principales:	Ning Yan, Lijuan Wang, Yiwei Li, Ting Wang, Libo Yang, Ru Yan, Hao Wang, Shaobin Jia
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e7a17c8b3b494220966b3aacb9fc9c7f
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spelling	oai:doaj.org-article:e7a17c8b3b494220966b3aacb9fc9c7f2021-12-02T20:06:58ZMetformin intervention ameliorates AS in ApoE-/- mice through restoring gut dysbiosis and anti-inflammation.1932-620310.1371/journal.pone.0254321https://doaj.org/article/e7a17c8b3b494220966b3aacb9fc9c7f2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254321https://doaj.org/toc/1932-6203Atherosclerosis (AS) is closely associated with chronic low-grade inflammation and gut dysbiosis. Metformin (MET) presents pleiotropic benefits in the control of chronic metabolic diseases, but the impacts of MET intervention on gut microbiota and inflammation in AS remain largely unclear. In this study, ApoE-/- mice with a high-fat diet (HFD) were adopted to assess the MET treatment. After 12 weeks of MET intervention (100mg·kg-1·d-1), relevant indications were investigated. As indicated by the pathological measurements, the atherosclerotic lesion was alleviated with MET intervention. Moreover, parameters in AS including body weights (BWs), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC) and malondialdehyde (MDA) were elevated; whereas high-density lipoprotein (HDL) and total superoxide dismutase (T-SOD) levels were decreased, which could be reversed by MET intervention. Elevated pro-inflammatory interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and lipopolysaccaride (LPS) in AS were decreased after MET administration. However, anti-inflammatory IL-10 showed no significant difference between AS group and AS+MET group. Consistently, accumulated macrophages in the aorta of AS were conversely lowered with MET treatment. The results of 16S rRNA sequencing and analysis displayed that the overall community of gut microbiota in AS was notably changed with MET treatment mainly through decreasing Firmicutes, Proteobacteria, Romboutsia, Firmicutes/Bacteroidetes, as well as increasing Akkermansia, Bacteroidetes, Bifidobacterium. Additionally, we found that microbiota-derived short-chain fatty acids (SCFAs) including acetic acid, propionic acid, butyric acid and valeric acid in AS were decreased, which were significantly up-regulated with MET intervention. Consistent with the attenuation of MET on gut dysbiosis, decreased intestinal tight junction protein zonula occludens-1 (ZO)-1 in AS was restored after MET supplementation. Correlation analysis showed close relationships among gut bacteria, microbial metabolites SCFAs and inflammation. Collectively, MET intervention ameliorates AS in ApoE-/- mice through restoring gut dysbiosis and anti-inflammation, thus can potentially serve as an inexpensive and effective intervention for the control of the atherosclerotic cardiovascular disease.Ning YanLijuan WangYiwei LiTing WangLibo YangRu YanHao WangShaobin JiaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0254321 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ning Yan Lijuan Wang Yiwei Li Ting Wang Libo Yang Ru Yan Hao Wang Shaobin Jia Metformin intervention ameliorates AS in ApoE-/- mice through restoring gut dysbiosis and anti-inflammation.
description	Atherosclerosis (AS) is closely associated with chronic low-grade inflammation and gut dysbiosis. Metformin (MET) presents pleiotropic benefits in the control of chronic metabolic diseases, but the impacts of MET intervention on gut microbiota and inflammation in AS remain largely unclear. In this study, ApoE-/- mice with a high-fat diet (HFD) were adopted to assess the MET treatment. After 12 weeks of MET intervention (100mg·kg-1·d-1), relevant indications were investigated. As indicated by the pathological measurements, the atherosclerotic lesion was alleviated with MET intervention. Moreover, parameters in AS including body weights (BWs), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC) and malondialdehyde (MDA) were elevated; whereas high-density lipoprotein (HDL) and total superoxide dismutase (T-SOD) levels were decreased, which could be reversed by MET intervention. Elevated pro-inflammatory interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and lipopolysaccaride (LPS) in AS were decreased after MET administration. However, anti-inflammatory IL-10 showed no significant difference between AS group and AS+MET group. Consistently, accumulated macrophages in the aorta of AS were conversely lowered with MET treatment. The results of 16S rRNA sequencing and analysis displayed that the overall community of gut microbiota in AS was notably changed with MET treatment mainly through decreasing Firmicutes, Proteobacteria, Romboutsia, Firmicutes/Bacteroidetes, as well as increasing Akkermansia, Bacteroidetes, Bifidobacterium. Additionally, we found that microbiota-derived short-chain fatty acids (SCFAs) including acetic acid, propionic acid, butyric acid and valeric acid in AS were decreased, which were significantly up-regulated with MET intervention. Consistent with the attenuation of MET on gut dysbiosis, decreased intestinal tight junction protein zonula occludens-1 (ZO)-1 in AS was restored after MET supplementation. Correlation analysis showed close relationships among gut bacteria, microbial metabolites SCFAs and inflammation. Collectively, MET intervention ameliorates AS in ApoE-/- mice through restoring gut dysbiosis and anti-inflammation, thus can potentially serve as an inexpensive and effective intervention for the control of the atherosclerotic cardiovascular disease.
format	article
author	Ning Yan Lijuan Wang Yiwei Li Ting Wang Libo Yang Ru Yan Hao Wang Shaobin Jia
author_facet	Ning Yan Lijuan Wang Yiwei Li Ting Wang Libo Yang Ru Yan Hao Wang Shaobin Jia
author_sort	Ning Yan
title	Metformin intervention ameliorates AS in ApoE-/- mice through restoring gut dysbiosis and anti-inflammation.
title_short	Metformin intervention ameliorates AS in ApoE-/- mice through restoring gut dysbiosis and anti-inflammation.
title_full	Metformin intervention ameliorates AS in ApoE-/- mice through restoring gut dysbiosis and anti-inflammation.
title_fullStr	Metformin intervention ameliorates AS in ApoE-/- mice through restoring gut dysbiosis and anti-inflammation.
title_full_unstemmed	Metformin intervention ameliorates AS in ApoE-/- mice through restoring gut dysbiosis and anti-inflammation.
title_sort	metformin intervention ameliorates as in apoe-/- mice through restoring gut dysbiosis and anti-inflammation.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/e7a17c8b3b494220966b3aacb9fc9c7f
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Metformin intervention ameliorates AS in ApoE-/- mice through restoring gut dysbiosis and anti-inflammation.

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