Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice.
The importance of the gut microbiota (GM) in disease development has recently received increased attention, and numerous approaches have been made to better understand this important interplay. For example, metabolites derived from the GM have been shown to promote atherosclerosis, the underlying ca...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4723129?pdf=render |
| _version_ | 1818475366253068288 |
|---|---|
| author | Ida Rune Bidda Rolin Christian Larsen Dennis Sandris Nielsen Jenny E Kanter Karin E Bornfeldt Jens Lykkesfeldt Karsten Buschard Rikke Kaae Kirk Berit Christoffersen Johannes Josef Fels Knud Josefsen Pernille Kihl Axel Kornerup Hansen |
| author_facet | Ida Rune Bidda Rolin Christian Larsen Dennis Sandris Nielsen Jenny E Kanter Karin E Bornfeldt Jens Lykkesfeldt Karsten Buschard Rikke Kaae Kirk Berit Christoffersen Johannes Josef Fels Knud Josefsen Pernille Kihl Axel Kornerup Hansen |
| author_sort | Ida Rune |
| collection | DOAJ |
| description | The importance of the gut microbiota (GM) in disease development has recently received increased attention, and numerous approaches have been made to better understand this important interplay. For example, metabolites derived from the GM have been shown to promote atherosclerosis, the underlying cause of cardiovascular disease (CVD), and to increase CVD risk factors. Popular interest in the role of the intestine in a variety of disease states has now resulted in a significant proportion of individuals without coeliac disease switching to gluten-free diets. The effect of gluten-free diets on atherosclerosis and cardiovascular risk factors is largely unknown. We therefore investigated the effect of a gluten-free high-fat cholesterol-rich diet, as compared to the same diet in which the gluten peptide gliadin had been added back, on atherosclerosis and several cardiovascular risk factors in apolipoprotein E-deficient (Apoe-/-) mice. The gluten-free diet transiently altered GM composition in these mice, as compared to the gliadin-supplemented diet, but did not alter body weights, glucose tolerance, insulin levels, plasma lipids, or atherosclerosis. In parallel, other Apoe-/- mice fed the same diets were treated with ampicillin, a broad-spectrum antibiotic known to affect GM composition. Ampicillin-treatment had a marked and sustained effect on GM composition, as expected. Furthermore, although ampicillin-treated mice were slightly heavier than controls, ampicillin-treatment transiently improved glucose tolerance both in the absence or presence of gliadin, reduced plasma LDL and VLDL cholesterol levels, and reduced aortic atherosclerotic lesion area. These results demonstrate that a gluten-free diet does not seem to have beneficial effects on atherosclerosis or several CVD risk factors in this mouse model, but that sustained alteration of GM composition with a broad-spectrum antibiotic has beneficial effects on CVD risk factors and atherosclerosis. These findings support the concept that altering the microbiota might provide novel treatment strategies for CVD. |
| first_indexed | 2024-12-10T09:11:38Z |
| format | Article |
| id | doaj.art-7e260d4bc6914d3d9feefa4dad2a5b9d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T09:11:38Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7e260d4bc6914d3d9feefa4dad2a5b9d2022-12-22T01:54:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014643910.1371/journal.pone.0146439Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice.Ida RuneBidda RolinChristian LarsenDennis Sandris NielsenJenny E KanterKarin E BornfeldtJens LykkesfeldtKarsten BuschardRikke Kaae KirkBerit ChristoffersenJohannes Josef FelsKnud JosefsenPernille KihlAxel Kornerup HansenThe importance of the gut microbiota (GM) in disease development has recently received increased attention, and numerous approaches have been made to better understand this important interplay. For example, metabolites derived from the GM have been shown to promote atherosclerosis, the underlying cause of cardiovascular disease (CVD), and to increase CVD risk factors. Popular interest in the role of the intestine in a variety of disease states has now resulted in a significant proportion of individuals without coeliac disease switching to gluten-free diets. The effect of gluten-free diets on atherosclerosis and cardiovascular risk factors is largely unknown. We therefore investigated the effect of a gluten-free high-fat cholesterol-rich diet, as compared to the same diet in which the gluten peptide gliadin had been added back, on atherosclerosis and several cardiovascular risk factors in apolipoprotein E-deficient (Apoe-/-) mice. The gluten-free diet transiently altered GM composition in these mice, as compared to the gliadin-supplemented diet, but did not alter body weights, glucose tolerance, insulin levels, plasma lipids, or atherosclerosis. In parallel, other Apoe-/- mice fed the same diets were treated with ampicillin, a broad-spectrum antibiotic known to affect GM composition. Ampicillin-treatment had a marked and sustained effect on GM composition, as expected. Furthermore, although ampicillin-treated mice were slightly heavier than controls, ampicillin-treatment transiently improved glucose tolerance both in the absence or presence of gliadin, reduced plasma LDL and VLDL cholesterol levels, and reduced aortic atherosclerotic lesion area. These results demonstrate that a gluten-free diet does not seem to have beneficial effects on atherosclerosis or several CVD risk factors in this mouse model, but that sustained alteration of GM composition with a broad-spectrum antibiotic has beneficial effects on CVD risk factors and atherosclerosis. These findings support the concept that altering the microbiota might provide novel treatment strategies for CVD.http://europepmc.org/articles/PMC4723129?pdf=render |
| spellingShingle | Ida Rune Bidda Rolin Christian Larsen Dennis Sandris Nielsen Jenny E Kanter Karin E Bornfeldt Jens Lykkesfeldt Karsten Buschard Rikke Kaae Kirk Berit Christoffersen Johannes Josef Fels Knud Josefsen Pernille Kihl Axel Kornerup Hansen Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice. PLoS ONE |
| title | Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice. |
| title_full | Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice. |
| title_fullStr | Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice. |
| title_full_unstemmed | Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice. |
| title_short | Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice. |
| title_sort | modulating the gut microbiota improves glucose tolerance lipoprotein profile and atherosclerotic plaque development in apoe deficient mice |
| url | http://europepmc.org/articles/PMC4723129?pdf=render |
| work_keys_str_mv | AT idarune modulatingthegutmicrobiotaimprovesglucosetolerancelipoproteinprofileandatheroscleroticplaquedevelopmentinapoedeficientmice AT biddarolin modulatingthegutmicrobiotaimprovesglucosetolerancelipoproteinprofileandatheroscleroticplaquedevelopmentinapoedeficientmice AT christianlarsen modulatingthegutmicrobiotaimprovesglucosetolerancelipoproteinprofileandatheroscleroticplaquedevelopmentinapoedeficientmice AT dennissandrisnielsen modulatingthegutmicrobiotaimprovesglucosetolerancelipoproteinprofileandatheroscleroticplaquedevelopmentinapoedeficientmice AT jennyekanter modulatingthegutmicrobiotaimprovesglucosetolerancelipoproteinprofileandatheroscleroticplaquedevelopmentinapoedeficientmice AT karinebornfeldt modulatingthegutmicrobiotaimprovesglucosetolerancelipoproteinprofileandatheroscleroticplaquedevelopmentinapoedeficientmice AT jenslykkesfeldt modulatingthegutmicrobiotaimprovesglucosetolerancelipoproteinprofileandatheroscleroticplaquedevelopmentinapoedeficientmice AT karstenbuschard modulatingthegutmicrobiotaimprovesglucosetolerancelipoproteinprofileandatheroscleroticplaquedevelopmentinapoedeficientmice AT rikkekaaekirk modulatingthegutmicrobiotaimprovesglucosetolerancelipoproteinprofileandatheroscleroticplaquedevelopmentinapoedeficientmice AT beritchristoffersen modulatingthegutmicrobiotaimprovesglucosetolerancelipoproteinprofileandatheroscleroticplaquedevelopmentinapoedeficientmice AT johannesjoseffels modulatingthegutmicrobiotaimprovesglucosetolerancelipoproteinprofileandatheroscleroticplaquedevelopmentinapoedeficientmice AT knudjosefsen modulatingthegutmicrobiotaimprovesglucosetolerancelipoproteinprofileandatheroscleroticplaquedevelopmentinapoedeficientmice AT pernillekihl modulatingthegutmicrobiotaimprovesglucosetolerancelipoproteinprofileandatheroscleroticplaquedevelopmentinapoedeficientmice AT axelkorneruphansen modulatingthegutmicrobiotaimprovesglucosetolerancelipoproteinprofileandatheroscleroticplaquedevelopmentinapoedeficientmice |