Berberine treatment increases Akkermansia in the gut and improves high-fat diet-induced atherosclerosis in Apoe−/− mice
Gut microbiota plays a major role in metabolic disorders. Berberine is used to treat obesity, diabetes and atherosclerosis. The mechanism underlying the role of berberine in modulating metabolic disorders is not fully clear because berberine has poor oral bioavailability. Thus, we evaluated whether...
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| Veröffentlicht in: | Atherosclerosis 2018-01, Vol.268, p.117-126 |
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| creator | Zhu, Lin Zhang, Danying Zhu, Hong Zhu, Jimin Weng, Shuqiang Dong, Ling Liu, Taotao Hu, Yu Shen, Xizhong |
| description | Gut microbiota plays a major role in metabolic disorders. Berberine is used to treat obesity, diabetes and atherosclerosis. The mechanism underlying the role of berberine in modulating metabolic disorders is not fully clear because berberine has poor oral bioavailability. Thus, we evaluated whether the antiatherosclerotic effect of berberine is related to alterations in gut microbial structure and if so, whether specific bacterial taxa contribute to the beneficial effects of berberine.
Apoe−/− mice were fed either a normal-chow diet or a high-fat diet (HFD). Berberine was administered to mice in drinking water (0.5 g/L) for 14 weeks. Gut microbiota profiles were established by high throughput sequencing of the V3–V4 region of the bacterial 16S ribosomal RNA gene. The effects of berberine on metabolic endotoxemia, tissue inflammation and gut barrier integrity were also investigated.
Berberine treatment significantly reduced atherosclerosis in HFD-fed mice. Akkermansia spp. abundance was markedly increased in HFD-fed mice treated with berberine. Moreover, berberine decreased HFD-induced metabolic endotoxemia and lowered arterial and intestinal expression of proinflammatory cytokines and chemokines. Berberine treatment increased intestinal expression of tight junction proteins and the thickness of the colonic mucus layer, which are related to restoration of gut barrier integrity in HFD-fed mice.
Modulation of gut microbiota, specifically an increase in the abundance of Akkermansia, may contribute to the antiatherosclerotic and metabolic protective effects of berberine, which is poorly absorbed orally. Our findings therefore support the therapeutic value of gut microbiota manipulation in treating atherosclerosis.
•Berberine markedly increases Akkermansia spp. abundance in HFD-fed Apoe−/− mice.•Berberine decreases HFD-induced inflammation and restores the gut barrier integrity.•Modulation of the gut microbiota may contribute to the antiatherosclerotic effect of berberine. |
| doi_str_mv | 10.1016/j.atherosclerosis.2017.11.023 |
| format | Article |
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Apoe−/− mice were fed either a normal-chow diet or a high-fat diet (HFD). Berberine was administered to mice in drinking water (0.5 g/L) for 14 weeks. Gut microbiota profiles were established by high throughput sequencing of the V3–V4 region of the bacterial 16S ribosomal RNA gene. The effects of berberine on metabolic endotoxemia, tissue inflammation and gut barrier integrity were also investigated.
Berberine treatment significantly reduced atherosclerosis in HFD-fed mice. Akkermansia spp. abundance was markedly increased in HFD-fed mice treated with berberine. Moreover, berberine decreased HFD-induced metabolic endotoxemia and lowered arterial and intestinal expression of proinflammatory cytokines and chemokines. Berberine treatment increased intestinal expression of tight junction proteins and the thickness of the colonic mucus layer, which are related to restoration of gut barrier integrity in HFD-fed mice.
Modulation of gut microbiota, specifically an increase in the abundance of Akkermansia, may contribute to the antiatherosclerotic and metabolic protective effects of berberine, which is poorly absorbed orally. Our findings therefore support the therapeutic value of gut microbiota manipulation in treating atherosclerosis.
•Berberine markedly increases Akkermansia spp. abundance in HFD-fed Apoe−/− mice.•Berberine decreases HFD-induced inflammation and restores the gut barrier integrity.•Modulation of the gut microbiota may contribute to the antiatherosclerotic effect of berberine.</description><identifier>ISSN: 0021-9150</identifier><identifier>EISSN: 1879-1484</identifier><identifier>DOI: 10.1016/j.atherosclerosis.2017.11.023</identifier><identifier>PMID: 29202334</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Akkermansia ; Animals ; Anti-Inflammatory Agents - pharmacology ; Aorta - drug effects ; Aorta - metabolism ; Aorta - pathology ; Aortic Diseases - genetics ; Aortic Diseases - metabolism ; Aortic Diseases - microbiology ; Aortic Diseases - prevention & control ; Atherosclerosis ; Atherosclerosis - genetics ; Atherosclerosis - metabolism ; Atherosclerosis - microbiology ; Atherosclerosis - prevention & control ; Berberine ; Berberine - pharmacology ; Cytokines - metabolism ; Diet, High-Fat ; Disease Models, Animal ; Female ; Gastrointestinal Microbiome - drug effects ; Gut microbiota ; Inflammation ; Inflammation Mediators - metabolism ; Intestinal Mucosa - drug effects ; Intestinal Mucosa - metabolism ; Intestinal Mucosa - microbiology ; Mice, Inbred C57BL ; Mice, Knockout, ApoE ; Plaque, Atherosclerotic ; Tight Junction Proteins - metabolism ; Verrucomicrobia - drug effects ; Verrucomicrobia - growth & development ; Verrucomicrobia - metabolism</subject><ispartof>Atherosclerosis, 2018-01, Vol.268, p.117-126</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-44b811a4ef0b6229308921ed3988ddbbf9f8dcabd4b825f4d031781fac8d1b13</citedby><cites>FETCH-LOGICAL-c455t-44b811a4ef0b6229308921ed3988ddbbf9f8dcabd4b825f4d031781fac8d1b13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0021915017314041$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29202334$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Lin</creatorcontrib><creatorcontrib>Zhang, Danying</creatorcontrib><creatorcontrib>Zhu, Hong</creatorcontrib><creatorcontrib>Zhu, Jimin</creatorcontrib><creatorcontrib>Weng, Shuqiang</creatorcontrib><creatorcontrib>Dong, Ling</creatorcontrib><creatorcontrib>Liu, Taotao</creatorcontrib><creatorcontrib>Hu, Yu</creatorcontrib><creatorcontrib>Shen, Xizhong</creatorcontrib><title>Berberine treatment increases Akkermansia in the gut and improves high-fat diet-induced atherosclerosis in Apoe−/− mice</title><title>Atherosclerosis</title><addtitle>Atherosclerosis</addtitle><description>Gut microbiota plays a major role in metabolic disorders. Berberine is used to treat obesity, diabetes and atherosclerosis. The mechanism underlying the role of berberine in modulating metabolic disorders is not fully clear because berberine has poor oral bioavailability. Thus, we evaluated whether the antiatherosclerotic effect of berberine is related to alterations in gut microbial structure and if so, whether specific bacterial taxa contribute to the beneficial effects of berberine.
Apoe−/− mice were fed either a normal-chow diet or a high-fat diet (HFD). Berberine was administered to mice in drinking water (0.5 g/L) for 14 weeks. Gut microbiota profiles were established by high throughput sequencing of the V3–V4 region of the bacterial 16S ribosomal RNA gene. The effects of berberine on metabolic endotoxemia, tissue inflammation and gut barrier integrity were also investigated.
Berberine treatment significantly reduced atherosclerosis in HFD-fed mice. Akkermansia spp. abundance was markedly increased in HFD-fed mice treated with berberine. Moreover, berberine decreased HFD-induced metabolic endotoxemia and lowered arterial and intestinal expression of proinflammatory cytokines and chemokines. Berberine treatment increased intestinal expression of tight junction proteins and the thickness of the colonic mucus layer, which are related to restoration of gut barrier integrity in HFD-fed mice.
Modulation of gut microbiota, specifically an increase in the abundance of Akkermansia, may contribute to the antiatherosclerotic and metabolic protective effects of berberine, which is poorly absorbed orally. Our findings therefore support the therapeutic value of gut microbiota manipulation in treating atherosclerosis.
•Berberine markedly increases Akkermansia spp. abundance in HFD-fed Apoe−/− mice.•Berberine decreases HFD-induced inflammation and restores the gut barrier integrity.•Modulation of the gut microbiota may contribute to the antiatherosclerotic effect of berberine.</description><subject>Akkermansia</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Aorta - drug effects</subject><subject>Aorta - metabolism</subject><subject>Aorta - pathology</subject><subject>Aortic Diseases - genetics</subject><subject>Aortic Diseases - metabolism</subject><subject>Aortic Diseases - microbiology</subject><subject>Aortic Diseases - prevention & control</subject><subject>Atherosclerosis</subject><subject>Atherosclerosis - genetics</subject><subject>Atherosclerosis - metabolism</subject><subject>Atherosclerosis - microbiology</subject><subject>Atherosclerosis - prevention & control</subject><subject>Berberine</subject><subject>Berberine - pharmacology</subject><subject>Cytokines - metabolism</subject><subject>Diet, High-Fat</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Gastrointestinal Microbiome - drug effects</subject><subject>Gut microbiota</subject><subject>Inflammation</subject><subject>Inflammation Mediators - metabolism</subject><subject>Intestinal Mucosa - drug effects</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestinal Mucosa - microbiology</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout, ApoE</subject><subject>Plaque, Atherosclerotic</subject><subject>Tight Junction Proteins - metabolism</subject><subject>Verrucomicrobia - drug effects</subject><subject>Verrucomicrobia - growth & development</subject><subject>Verrucomicrobia - metabolism</subject><issn>0021-9150</issn><issn>1879-1484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkM9O3DAQh62Kqmy3fQXkCxKXBI_jbOwDhwW1tBJSL9wtx56wXjbJYjtIqC_Qcx-RJ8HRQg-cevAfWd_4N_MRcgqsBAar821p0gbDGO1u3n0sOYOmBCgZrz6QBchGFSCkOCILxjgUCmp2TD7HuGWMiQbkJ3LMFc90JRbk9yWGFoMfkKaAJvU4JOoHm-8RI13f32PozRC9ya80J9O7KVEzOOr7fRgfM7Pxd5uiM4k6j6nwg5ssOvquy7l6vR_x-c_f87xo7y1-IR87s4v49fVcktvv326vfhQ3v65_Xq1vCivqOhVCtBLACOxYu-JcVUwqDugqJaVzbdupTjprWpc5XnfCsQoaCZ2x0kEL1ZKcHb7N_T5MGJPufbS425kBxylqUE2VRalVndGLA2pz0zFgp_fB9yY8aWB61q-3-t1getavAfQsdElOXqOmtkf3r_rNdwauDwDmeR89Bh2txyEL8wFt0m70_xn1AmmSpKY</recordid><startdate>201801</startdate><enddate>201801</enddate><creator>Zhu, Lin</creator><creator>Zhang, Danying</creator><creator>Zhu, Hong</creator><creator>Zhu, Jimin</creator><creator>Weng, Shuqiang</creator><creator>Dong, Ling</creator><creator>Liu, Taotao</creator><creator>Hu, Yu</creator><creator>Shen, Xizhong</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201801</creationdate><title>Berberine treatment increases Akkermansia in the gut and improves high-fat diet-induced atherosclerosis in Apoe−/− mice</title><author>Zhu, Lin ; Zhang, Danying ; Zhu, Hong ; Zhu, Jimin ; Weng, Shuqiang ; Dong, Ling ; Liu, Taotao ; Hu, Yu ; Shen, Xizhong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-44b811a4ef0b6229308921ed3988ddbbf9f8dcabd4b825f4d031781fac8d1b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Akkermansia</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Aorta - drug effects</topic><topic>Aorta - metabolism</topic><topic>Aorta - pathology</topic><topic>Aortic Diseases - genetics</topic><topic>Aortic Diseases - metabolism</topic><topic>Aortic Diseases - microbiology</topic><topic>Aortic Diseases - prevention & control</topic><topic>Atherosclerosis</topic><topic>Atherosclerosis - genetics</topic><topic>Atherosclerosis - metabolism</topic><topic>Atherosclerosis - microbiology</topic><topic>Atherosclerosis - prevention & control</topic><topic>Berberine</topic><topic>Berberine - pharmacology</topic><topic>Cytokines - metabolism</topic><topic>Diet, High-Fat</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Gastrointestinal Microbiome - drug effects</topic><topic>Gut microbiota</topic><topic>Inflammation</topic><topic>Inflammation Mediators - metabolism</topic><topic>Intestinal Mucosa - drug effects</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Intestinal Mucosa - microbiology</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout, ApoE</topic><topic>Plaque, Atherosclerotic</topic><topic>Tight Junction Proteins - metabolism</topic><topic>Verrucomicrobia - drug effects</topic><topic>Verrucomicrobia - growth & development</topic><topic>Verrucomicrobia - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhu, Lin</creatorcontrib><creatorcontrib>Zhang, Danying</creatorcontrib><creatorcontrib>Zhu, Hong</creatorcontrib><creatorcontrib>Zhu, Jimin</creatorcontrib><creatorcontrib>Weng, Shuqiang</creatorcontrib><creatorcontrib>Dong, Ling</creatorcontrib><creatorcontrib>Liu, Taotao</creatorcontrib><creatorcontrib>Hu, Yu</creatorcontrib><creatorcontrib>Shen, Xizhong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Atherosclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Lin</au><au>Zhang, Danying</au><au>Zhu, Hong</au><au>Zhu, Jimin</au><au>Weng, Shuqiang</au><au>Dong, Ling</au><au>Liu, Taotao</au><au>Hu, Yu</au><au>Shen, Xizhong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Berberine treatment increases Akkermansia in the gut and improves high-fat diet-induced atherosclerosis in Apoe−/− mice</atitle><jtitle>Atherosclerosis</jtitle><addtitle>Atherosclerosis</addtitle><date>2018-01</date><risdate>2018</risdate><volume>268</volume><spage>117</spage><epage>126</epage><pages>117-126</pages><issn>0021-9150</issn><eissn>1879-1484</eissn><abstract>Gut microbiota plays a major role in metabolic disorders. Berberine is used to treat obesity, diabetes and atherosclerosis. The mechanism underlying the role of berberine in modulating metabolic disorders is not fully clear because berberine has poor oral bioavailability. Thus, we evaluated whether the antiatherosclerotic effect of berberine is related to alterations in gut microbial structure and if so, whether specific bacterial taxa contribute to the beneficial effects of berberine.
Apoe−/− mice were fed either a normal-chow diet or a high-fat diet (HFD). Berberine was administered to mice in drinking water (0.5 g/L) for 14 weeks. Gut microbiota profiles were established by high throughput sequencing of the V3–V4 region of the bacterial 16S ribosomal RNA gene. The effects of berberine on metabolic endotoxemia, tissue inflammation and gut barrier integrity were also investigated.
Berberine treatment significantly reduced atherosclerosis in HFD-fed mice. Akkermansia spp. abundance was markedly increased in HFD-fed mice treated with berberine. Moreover, berberine decreased HFD-induced metabolic endotoxemia and lowered arterial and intestinal expression of proinflammatory cytokines and chemokines. Berberine treatment increased intestinal expression of tight junction proteins and the thickness of the colonic mucus layer, which are related to restoration of gut barrier integrity in HFD-fed mice.
Modulation of gut microbiota, specifically an increase in the abundance of Akkermansia, may contribute to the antiatherosclerotic and metabolic protective effects of berberine, which is poorly absorbed orally. Our findings therefore support the therapeutic value of gut microbiota manipulation in treating atherosclerosis.
•Berberine markedly increases Akkermansia spp. abundance in HFD-fed Apoe−/− mice.•Berberine decreases HFD-induced inflammation and restores the gut barrier integrity.•Modulation of the gut microbiota may contribute to the antiatherosclerotic effect of berberine.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>29202334</pmid><doi>10.1016/j.atherosclerosis.2017.11.023</doi><tpages>10</tpages></addata></record> |
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| subjects | Akkermansia Animals Anti-Inflammatory Agents - pharmacology Aorta - drug effects Aorta - metabolism Aorta - pathology Aortic Diseases - genetics Aortic Diseases - metabolism Aortic Diseases - microbiology Aortic Diseases - prevention & control Atherosclerosis Atherosclerosis - genetics Atherosclerosis - metabolism Atherosclerosis - microbiology Atherosclerosis - prevention & control Berberine Berberine - pharmacology Cytokines - metabolism Diet, High-Fat Disease Models, Animal Female Gastrointestinal Microbiome - drug effects Gut microbiota Inflammation Inflammation Mediators - metabolism Intestinal Mucosa - drug effects Intestinal Mucosa - metabolism Intestinal Mucosa - microbiology Mice, Inbred C57BL Mice, Knockout, ApoE Plaque, Atherosclerotic Tight Junction Proteins - metabolism Verrucomicrobia - drug effects Verrucomicrobia - growth & development Verrucomicrobia - metabolism |
| title | Berberine treatment increases Akkermansia in the gut and improves high-fat diet-induced atherosclerosis in Apoe−/− mice |
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