Reshaping of the gastrointestinal microbiome alters atherosclerotic plaque inflammation resolution in mice

Abstract Since alterations in the intestinal microbiota may induce systemic inflammation and polarization of macrophages to the M1 state, the microbiome role in atherosclerosis, an M1-driven disease, requires evaluation. We aimed to determine if antibiotic (Abx) induced alterations to the intestinal...

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Autores principales: Michael S. Garshick, Cyrus Nikain, Michael Tawil, Stephanie Pena, Tessa J. Barrett, Benjamin G. Wu, Zhan Gao, Martin J. Blaser, Edward A. Fisher
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/a8f3dfa3b18f42a5b4b2ebab1cb9df7e
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spelling oai:doaj.org-article:a8f3dfa3b18f42a5b4b2ebab1cb9df7e2021-12-02T13:40:51ZReshaping of the gastrointestinal microbiome alters atherosclerotic plaque inflammation resolution in mice10.1038/s41598-021-88479-y2045-2322https://doaj.org/article/a8f3dfa3b18f42a5b4b2ebab1cb9df7e2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88479-yhttps://doaj.org/toc/2045-2322Abstract Since alterations in the intestinal microbiota may induce systemic inflammation and polarization of macrophages to the M1 state, the microbiome role in atherosclerosis, an M1-driven disease, requires evaluation. We aimed to determine if antibiotic (Abx) induced alterations to the intestinal microbiota interferes with atherosclerotic plaque inflammation resolution after lipid-lowering in mice. Hyperlipidemic Apoe −/− mice were fed a western diet to develop aortic atherosclerosis with aortas then transplanted into normolipidemic wild-type (WT) mice to model clinically aggressive lipid management and promote atherosclerosis inflammation resolution. Gut microbial composition pre and post-transplant was altered via an enteral antibiotic or not. Post aortic transplant, after Abx treatment, while plaque size did not differ, compared to Apoe −/− mice, Abx– WT recipient mice had a 32% reduction in CD68-expressing cells (p = 0.02) vs. a non-significant 12% reduction in Abx+ WT mice. A trend toward an M1 plaque CD68-expresing cell phenotype was noted in Abx+ mice. By 16S rRNA sequence analysis, the Abx+ mice had reduced alpha diversity and increased Firmicutes/Bacteroidetes relative abundance ratio with a correlation between gut Firmicutes abundance and plaque CD68-expressing cell content (p < 0.05). These results indicate that in a murine atherosclerotic plaque inflammation resolution model, antibiotic-induced microbiome perturbation may blunt the effectiveness of lipid-lowering to reduce the content of plaque inflammatory CD68-expressing cells.Michael S. GarshickCyrus NikainMichael TawilStephanie PenaTessa J. BarrettBenjamin G. WuZhan GaoMartin J. BlaserEdward A. FisherNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Michael S. Garshick
Cyrus Nikain
Michael Tawil
Stephanie Pena
Tessa J. Barrett
Benjamin G. Wu
Zhan Gao
Martin J. Blaser
Edward A. Fisher
Reshaping of the gastrointestinal microbiome alters atherosclerotic plaque inflammation resolution in mice
description Abstract Since alterations in the intestinal microbiota may induce systemic inflammation and polarization of macrophages to the M1 state, the microbiome role in atherosclerosis, an M1-driven disease, requires evaluation. We aimed to determine if antibiotic (Abx) induced alterations to the intestinal microbiota interferes with atherosclerotic plaque inflammation resolution after lipid-lowering in mice. Hyperlipidemic Apoe −/− mice were fed a western diet to develop aortic atherosclerosis with aortas then transplanted into normolipidemic wild-type (WT) mice to model clinically aggressive lipid management and promote atherosclerosis inflammation resolution. Gut microbial composition pre and post-transplant was altered via an enteral antibiotic or not. Post aortic transplant, after Abx treatment, while plaque size did not differ, compared to Apoe −/− mice, Abx– WT recipient mice had a 32% reduction in CD68-expressing cells (p = 0.02) vs. a non-significant 12% reduction in Abx+ WT mice. A trend toward an M1 plaque CD68-expresing cell phenotype was noted in Abx+ mice. By 16S rRNA sequence analysis, the Abx+ mice had reduced alpha diversity and increased Firmicutes/Bacteroidetes relative abundance ratio with a correlation between gut Firmicutes abundance and plaque CD68-expressing cell content (p < 0.05). These results indicate that in a murine atherosclerotic plaque inflammation resolution model, antibiotic-induced microbiome perturbation may blunt the effectiveness of lipid-lowering to reduce the content of plaque inflammatory CD68-expressing cells.
format article
author Michael S. Garshick
Cyrus Nikain
Michael Tawil
Stephanie Pena
Tessa J. Barrett
Benjamin G. Wu
Zhan Gao
Martin J. Blaser
Edward A. Fisher
author_facet Michael S. Garshick
Cyrus Nikain
Michael Tawil
Stephanie Pena
Tessa J. Barrett
Benjamin G. Wu
Zhan Gao
Martin J. Blaser
Edward A. Fisher
author_sort Michael S. Garshick
title Reshaping of the gastrointestinal microbiome alters atherosclerotic plaque inflammation resolution in mice
title_short Reshaping of the gastrointestinal microbiome alters atherosclerotic plaque inflammation resolution in mice
title_full Reshaping of the gastrointestinal microbiome alters atherosclerotic plaque inflammation resolution in mice
title_fullStr Reshaping of the gastrointestinal microbiome alters atherosclerotic plaque inflammation resolution in mice
title_full_unstemmed Reshaping of the gastrointestinal microbiome alters atherosclerotic plaque inflammation resolution in mice
title_sort reshaping of the gastrointestinal microbiome alters atherosclerotic plaque inflammation resolution in mice
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/a8f3dfa3b18f42a5b4b2ebab1cb9df7e
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