Publication

A Pro-Inflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis

Brandsma, E., Kloosterhuis, N. J., Koster, M. H., Dekker, D., Gijbels, M., van der Velden, S., Rios Morales, M., van Faassen, M. J., Loreti, M., de Bruin, A., Fu, J., Kuipers, F., Bakker, B. M., Westerterp, M., de Winther, M. P., Hofker, M. H., van de Sluis, B. & Koonen, D. P., 4-Jan-2019, In : Circulation research. 124, p. 94-100 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Brandsma, E., Kloosterhuis, N. J., Koster, M. H., Dekker, D., Gijbels, M., van der Velden, S., ... Koonen, D. P. (2019). A Pro-Inflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis. Circulation research, 124, 94-100. https://doi.org/10.1161/CIRCRESAHA.118.313234

Author

Brandsma, Eelke ; Kloosterhuis, Niels J ; Koster, Mirjam H ; Dekker, Daphne ; Gijbels, Marion ; van der Velden, Saskia ; Rios Morales, Melany ; van Faassen, Martijn Jr ; Loreti, Marco ; de Bruin, Alain ; Fu, Jingyuan ; Kuipers, Folkert ; Bakker, Barbara M ; Westerterp, Marit ; de Winther, Menno Pj ; Hofker, Marten H ; van de Sluis, Bart ; Koonen, Debby Py. / A Pro-Inflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis. In: Circulation research. 2019 ; Vol. 124. pp. 94-100.

Harvard

Brandsma, E, Kloosterhuis, NJ, Koster, MH, Dekker, D, Gijbels, M, van der Velden, S, Rios Morales, M, van Faassen, MJ, Loreti, M, de Bruin, A, Fu, J, Kuipers, F, Bakker, BM, Westerterp, M, de Winther, MP, Hofker, MH, van de Sluis, B & Koonen, DP 2019, 'A Pro-Inflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis', Circulation research, vol. 124, pp. 94-100. https://doi.org/10.1161/CIRCRESAHA.118.313234

Standard

A Pro-Inflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis. / Brandsma, Eelke; Kloosterhuis, Niels J; Koster, Mirjam H; Dekker, Daphne; Gijbels, Marion; van der Velden, Saskia; Rios Morales, Melany; van Faassen, Martijn Jr; Loreti, Marco; de Bruin, Alain; Fu, Jingyuan; Kuipers, Folkert; Bakker, Barbara M; Westerterp, Marit; de Winther, Menno Pj; Hofker, Marten H; van de Sluis, Bart; Koonen, Debby Py.

In: Circulation research, Vol. 124, 04.01.2019, p. 94-100.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Brandsma E, Kloosterhuis NJ, Koster MH, Dekker D, Gijbels M, van der Velden S et al. A Pro-Inflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis. Circulation research. 2019 Jan 4;124:94-100. https://doi.org/10.1161/CIRCRESAHA.118.313234


BibTeX

@article{977807e7c0c14a50ac7903c2af5182db,
title = "A Pro-Inflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis",
abstract = "RATIONALE: Several studies have suggested a role for the gut microbiota in inflammation and atherogenesis. A causal relation relationship between gut microbiota, inflammation and atherosclerosis has not been explored previously.OBJECTIVE: Here, we investigated whether a pro-inflammatory microbiota from Caspase1-/- ( Casp1-/-) mice accelerates atherogenesis in Ldlr-/- mice.METHODS AND RESULTS: We treated female Ldlr-/- mice with antibiotics and subsequently transplanted them with fecal microbiota from Casp1-/- mice based on a co-housing approach. Autologous transplantation of fecal microbiota of Ldlr-/- mice served as control. Mice were co-housed for 8 or 13 weeks and fed chow or a high-fat cholesterol-rich (HFC) diet. Fecal samples were collected, and factors related to inflammation, metabolism, intestinal health and atherosclerotic phenotypes were measured. Unweighted Unifrac distances of 16S rDNA sequences confirmed the introduction of the Casp1-/- and Ldlr-/- microbiota into Ldlr-/- mice (referred to as Ldlr-/-( Casp1-/-) or Ldlr-/-( Ldlr-/-) mice). Analysis of atherosclerotic lesion size in the aortic root demonstrated a significant 29{\%} increase in plaque size in 13-week HFC-fed Ldlr-/-( Casp1-/-) mice compared to Ldlr-/-( Ldlr-/-) mice. We found increased numbers of circulating monocytes and neutrophils and elevated pro-inflammatory cytokine levels in plasma in HFC-fed Ldlr-/-( Casp1-/-) compared to Ldlr-/-( Ldlr-/-) mice. Neutrophil accumulation in the aortic root of Ldlr-/-( Casp1-/-) mice was enhanced compared to Ldlr-/-( Ldlr-/-) mice. 16S-rDNA-encoding sequence analysis in feces identified a significant reduction in the short-chain fatty acid (SCFA)-producing taxonomies Akkermansia, Christensenellaceae, Clostridium and Odoribacter in Ldlr-/-( Casp1-/-) mice. Consistent with these findings, cumulative concentrations of the anti-inflammatory SCFAs proprionate, acetate and butyrate in the cecum were significantly reduced in 13-week HFC-fed Ldlr-/-( Casp1-/-) compared to Ldlr-/-( Ldlr-/-) mice.CONCLUSIONS: Introduction of the pro-inflammatory Casp1-/- microbiota into Ldlr-/- mice enhances systemic inflammation and accelerates atherogenesis.",
author = "Eelke Brandsma and Kloosterhuis, {Niels J} and Koster, {Mirjam H} and Daphne Dekker and Marion Gijbels and {van der Velden}, Saskia and {Rios Morales}, Melany and {van Faassen}, {Martijn Jr} and Marco Loreti and {de Bruin}, Alain and Jingyuan Fu and Folkert Kuipers and Bakker, {Barbara M} and Marit Westerterp and {de Winther}, {Menno Pj} and Hofker, {Marten H} and {van de Sluis}, Bart and Koonen, {Debby Py}",
year = "2019",
month = "1",
day = "4",
doi = "10.1161/CIRCRESAHA.118.313234",
language = "English",
volume = "124",
pages = "94--100",
journal = "Circulation research",
issn = "0009-7330",
publisher = "LIPPINCOTT WILLIAMS & WILKINS",

}

RIS

TY - JOUR

T1 - A Pro-Inflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis

AU - Brandsma, Eelke

AU - Kloosterhuis, Niels J

AU - Koster, Mirjam H

AU - Dekker, Daphne

AU - Gijbels, Marion

AU - van der Velden, Saskia

AU - Rios Morales, Melany

AU - van Faassen, Martijn Jr

AU - Loreti, Marco

AU - de Bruin, Alain

AU - Fu, Jingyuan

AU - Kuipers, Folkert

AU - Bakker, Barbara M

AU - Westerterp, Marit

AU - de Winther, Menno Pj

AU - Hofker, Marten H

AU - van de Sluis, Bart

AU - Koonen, Debby Py

PY - 2019/1/4

Y1 - 2019/1/4

N2 - RATIONALE: Several studies have suggested a role for the gut microbiota in inflammation and atherogenesis. A causal relation relationship between gut microbiota, inflammation and atherosclerosis has not been explored previously.OBJECTIVE: Here, we investigated whether a pro-inflammatory microbiota from Caspase1-/- ( Casp1-/-) mice accelerates atherogenesis in Ldlr-/- mice.METHODS AND RESULTS: We treated female Ldlr-/- mice with antibiotics and subsequently transplanted them with fecal microbiota from Casp1-/- mice based on a co-housing approach. Autologous transplantation of fecal microbiota of Ldlr-/- mice served as control. Mice were co-housed for 8 or 13 weeks and fed chow or a high-fat cholesterol-rich (HFC) diet. Fecal samples were collected, and factors related to inflammation, metabolism, intestinal health and atherosclerotic phenotypes were measured. Unweighted Unifrac distances of 16S rDNA sequences confirmed the introduction of the Casp1-/- and Ldlr-/- microbiota into Ldlr-/- mice (referred to as Ldlr-/-( Casp1-/-) or Ldlr-/-( Ldlr-/-) mice). Analysis of atherosclerotic lesion size in the aortic root demonstrated a significant 29% increase in plaque size in 13-week HFC-fed Ldlr-/-( Casp1-/-) mice compared to Ldlr-/-( Ldlr-/-) mice. We found increased numbers of circulating monocytes and neutrophils and elevated pro-inflammatory cytokine levels in plasma in HFC-fed Ldlr-/-( Casp1-/-) compared to Ldlr-/-( Ldlr-/-) mice. Neutrophil accumulation in the aortic root of Ldlr-/-( Casp1-/-) mice was enhanced compared to Ldlr-/-( Ldlr-/-) mice. 16S-rDNA-encoding sequence analysis in feces identified a significant reduction in the short-chain fatty acid (SCFA)-producing taxonomies Akkermansia, Christensenellaceae, Clostridium and Odoribacter in Ldlr-/-( Casp1-/-) mice. Consistent with these findings, cumulative concentrations of the anti-inflammatory SCFAs proprionate, acetate and butyrate in the cecum were significantly reduced in 13-week HFC-fed Ldlr-/-( Casp1-/-) compared to Ldlr-/-( Ldlr-/-) mice.CONCLUSIONS: Introduction of the pro-inflammatory Casp1-/- microbiota into Ldlr-/- mice enhances systemic inflammation and accelerates atherogenesis.

AB - RATIONALE: Several studies have suggested a role for the gut microbiota in inflammation and atherogenesis. A causal relation relationship between gut microbiota, inflammation and atherosclerosis has not been explored previously.OBJECTIVE: Here, we investigated whether a pro-inflammatory microbiota from Caspase1-/- ( Casp1-/-) mice accelerates atherogenesis in Ldlr-/- mice.METHODS AND RESULTS: We treated female Ldlr-/- mice with antibiotics and subsequently transplanted them with fecal microbiota from Casp1-/- mice based on a co-housing approach. Autologous transplantation of fecal microbiota of Ldlr-/- mice served as control. Mice were co-housed for 8 or 13 weeks and fed chow or a high-fat cholesterol-rich (HFC) diet. Fecal samples were collected, and factors related to inflammation, metabolism, intestinal health and atherosclerotic phenotypes were measured. Unweighted Unifrac distances of 16S rDNA sequences confirmed the introduction of the Casp1-/- and Ldlr-/- microbiota into Ldlr-/- mice (referred to as Ldlr-/-( Casp1-/-) or Ldlr-/-( Ldlr-/-) mice). Analysis of atherosclerotic lesion size in the aortic root demonstrated a significant 29% increase in plaque size in 13-week HFC-fed Ldlr-/-( Casp1-/-) mice compared to Ldlr-/-( Ldlr-/-) mice. We found increased numbers of circulating monocytes and neutrophils and elevated pro-inflammatory cytokine levels in plasma in HFC-fed Ldlr-/-( Casp1-/-) compared to Ldlr-/-( Ldlr-/-) mice. Neutrophil accumulation in the aortic root of Ldlr-/-( Casp1-/-) mice was enhanced compared to Ldlr-/-( Ldlr-/-) mice. 16S-rDNA-encoding sequence analysis in feces identified a significant reduction in the short-chain fatty acid (SCFA)-producing taxonomies Akkermansia, Christensenellaceae, Clostridium and Odoribacter in Ldlr-/-( Casp1-/-) mice. Consistent with these findings, cumulative concentrations of the anti-inflammatory SCFAs proprionate, acetate and butyrate in the cecum were significantly reduced in 13-week HFC-fed Ldlr-/-( Casp1-/-) compared to Ldlr-/-( Ldlr-/-) mice.CONCLUSIONS: Introduction of the pro-inflammatory Casp1-/- microbiota into Ldlr-/- mice enhances systemic inflammation and accelerates atherogenesis.

U2 - 10.1161/CIRCRESAHA.118.313234

DO - 10.1161/CIRCRESAHA.118.313234

M3 - Article

VL - 124

SP - 94

EP - 100

JO - Circulation research

JF - Circulation research

SN - 0009-7330

ER -

ID: 72776225