Gut microbiota dysbiosis augments atherosclerosis in LDLR-/- mice

Eelke Brandsma; Niels J Kloosterhuis; Daphne C Dekker; Miriam Koster; Marion Gijbels; Saskia Van Der Velden; Alain de Bruin; Menno de Winther; Marit Westerterp; Bart van de Sluis; Debby P Y Koonen; Marten H Hofker

doi:10.1016/j.atherosclerosis.2017.06.316

Gut microbiota dysbiosis augments atherosclerosis in LDLR-/- mice

Eelke Brandsma, Niels J Kloosterhuis, Daphne C Dekker, Miriam Koster, Marion Gijbels, Saskia Van Der Velden, Alain de Bruin, Menno de Winther, Marit Westerterp, Bart van de Sluis, Debby P Y Koonen, Marten H Hofker

University of Groningen, University Medical Center Groningen, Department of Pediatrics, Section Molecular Genetics, Groningen, The Netherlands.
Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.

Research output: Contribution to journal › Meeting Abstract › Other research output

Abstract

Aim: In recent years the gut microbiome has been recognized as an important participant in the etiology of obesity and -associated comorbidities. Moreover, recent studies have implicated an involvement of the gut microbiota in both cardiovascular health and disease. Although the gut microbiome has been suggested as a contributor to atherosclerosis, firm evidence to support a causal role for the gut microbiota in atherosclerosis is limited.

Methods: To investigate the effect of the gut microbiota in atherosclerosis, we performed fecal microbiota transplantation to transplant the gut microbiota of caspase1-/- mice, an established model for dysbiosis, into LDLR-/- mice (LDLR-/-[casp1-/-]). Fecal microbiota transplantation of the gut microbiota of LDLR-/- mice into LDLR-/- mice (LDLR-/-[LDLR-/-]) served as control. Mice were fed a chow or high-fat cholesterol diet (HFC, 0,21% cholesterol) for 13 weeks and fecal samples were collected to determine microbiota composition by 16S rRNA sequencing. Plaque size was analyzed in the aortic root and immune cell subsets were analyzed by flow cytometry.

Results: 16S rRNA sequencing of fecal samples confirmed the induction of dysbiosis in LDLR-/-[casp1-/-] compared to LDLR-/-[LDLR-/-] mice. Body weight, plasma triglyceride and cholesterol levels were significantly increased by HFC-feeding in LDLR-/-[casp1-/-] and LDLR-/-[LDLR-/-] mice. However, dysbiosis did not affect these parameters. In contrast, plaque size was significantly increased in HFC-fed LDLR-/-[casp1-/-] compared to HFC-fed (LDLR-/-[LDLR-/-] mice. Furthermore, dysbiosis in LDLR-/- mice was associated with a moderate increase in circulatory levels of Ly6C-high monocytes.

Conclusions: Our data shows that gut microbiota dysbiosis augments atherosclerosis, possibly by exacerbating low-grade systemic inflammation.

Original language	English
Pages (from-to)	e97
Journal	Atherosclerosis
Volume	263
DOIs	https://doi.org/10.1016/j.atherosclerosis.2017.06.316
Publication status	Published - Aug 2017
Externally published	Yes

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10.1016/j.atherosclerosis.2017.06.316

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@article{f354917cac194eac89e86bd097e5f03c,

title = "Gut microbiota dysbiosis augments atherosclerosis in LDLR-/- mice",

abstract = "Aim: In recent years the gut microbiome has been recognized as an important participant in the etiology of obesity and -associated comorbidities. Moreover, recent studies have implicated an involvement of the gut microbiota in both cardiovascular health and disease. Although the gut microbiome has been suggested as a contributor to atherosclerosis, firm evidence to support a causal role for the gut microbiota in atherosclerosis is limited.Methods: To investigate the effect of the gut microbiota in atherosclerosis, we performed fecal microbiota transplantation to transplant the gut microbiota of caspase1-/- mice, an established model for dysbiosis, into LDLR-/- mice (LDLR-/-[casp1-/-]). Fecal microbiota transplantation of the gut microbiota of LDLR-/- mice into LDLR-/- mice (LDLR-/-[LDLR-/-]) served as control. Mice were fed a chow or high-fat cholesterol diet (HFC, 0,21% cholesterol) for 13 weeks and fecal samples were collected to determine microbiota composition by 16S rRNA sequencing. Plaque size was analyzed in the aortic root and immune cell subsets were analyzed by flow cytometry.Results: 16S rRNA sequencing of fecal samples confirmed the induction of dysbiosis in LDLR-/-[casp1-/-] compared to LDLR-/-[LDLR-/-] mice. Body weight, plasma triglyceride and cholesterol levels were significantly increased by HFC-feeding in LDLR-/-[casp1-/-] and LDLR-/-[LDLR-/-] mice. However, dysbiosis did not affect these parameters. In contrast, plaque size was significantly increased in HFC-fed LDLR-/-[casp1-/-] compared to HFC-fed (LDLR-/-[LDLR-/-] mice. Furthermore, dysbiosis in LDLR-/- mice was associated with a moderate increase in circulatory levels of Ly6C-high monocytes.Conclusions: Our data shows that gut microbiota dysbiosis augments atherosclerosis, possibly by exacerbating low-grade systemic inflammation.",

author = "Eelke Brandsma and Kloosterhuis, {Niels J} and Dekker, {Daphne C} and Miriam Koster and Marion Gijbels and {Van Der Velden}, Saskia and {de Bruin}, Alain and {de Winther}, Menno and Marit Westerterp and {van de Sluis}, Bart and Koonen, {Debby P Y} and Hofker, {Marten H}",

year = "2017",

month = aug,

doi = "10.1016/j.atherosclerosis.2017.06.316",

language = "English",

volume = "263",

pages = "e97",

journal = "Atherosclerosis",

issn = "0021-9150",

publisher = "Elsevier Ireland Ltd.",

}

TY - JOUR

T1 - Gut microbiota dysbiosis augments atherosclerosis in LDLR-/- mice

AU - Brandsma, Eelke

AU - Kloosterhuis, Niels J

AU - Dekker, Daphne C

AU - Koster, Miriam

AU - Gijbels, Marion

AU - Van Der Velden, Saskia

AU - de Bruin, Alain

AU - de Winther, Menno

AU - Westerterp, Marit

AU - van de Sluis, Bart

AU - Koonen, Debby P Y

AU - Hofker, Marten H

PY - 2017/8

Y1 - 2017/8

N2 - Aim: In recent years the gut microbiome has been recognized as an important participant in the etiology of obesity and -associated comorbidities. Moreover, recent studies have implicated an involvement of the gut microbiota in both cardiovascular health and disease. Although the gut microbiome has been suggested as a contributor to atherosclerosis, firm evidence to support a causal role for the gut microbiota in atherosclerosis is limited.Methods: To investigate the effect of the gut microbiota in atherosclerosis, we performed fecal microbiota transplantation to transplant the gut microbiota of caspase1-/- mice, an established model for dysbiosis, into LDLR-/- mice (LDLR-/-[casp1-/-]). Fecal microbiota transplantation of the gut microbiota of LDLR-/- mice into LDLR-/- mice (LDLR-/-[LDLR-/-]) served as control. Mice were fed a chow or high-fat cholesterol diet (HFC, 0,21% cholesterol) for 13 weeks and fecal samples were collected to determine microbiota composition by 16S rRNA sequencing. Plaque size was analyzed in the aortic root and immune cell subsets were analyzed by flow cytometry.Results: 16S rRNA sequencing of fecal samples confirmed the induction of dysbiosis in LDLR-/-[casp1-/-] compared to LDLR-/-[LDLR-/-] mice. Body weight, plasma triglyceride and cholesterol levels were significantly increased by HFC-feeding in LDLR-/-[casp1-/-] and LDLR-/-[LDLR-/-] mice. However, dysbiosis did not affect these parameters. In contrast, plaque size was significantly increased in HFC-fed LDLR-/-[casp1-/-] compared to HFC-fed (LDLR-/-[LDLR-/-] mice. Furthermore, dysbiosis in LDLR-/- mice was associated with a moderate increase in circulatory levels of Ly6C-high monocytes.Conclusions: Our data shows that gut microbiota dysbiosis augments atherosclerosis, possibly by exacerbating low-grade systemic inflammation.

AB - Aim: In recent years the gut microbiome has been recognized as an important participant in the etiology of obesity and -associated comorbidities. Moreover, recent studies have implicated an involvement of the gut microbiota in both cardiovascular health and disease. Although the gut microbiome has been suggested as a contributor to atherosclerosis, firm evidence to support a causal role for the gut microbiota in atherosclerosis is limited.Methods: To investigate the effect of the gut microbiota in atherosclerosis, we performed fecal microbiota transplantation to transplant the gut microbiota of caspase1-/- mice, an established model for dysbiosis, into LDLR-/- mice (LDLR-/-[casp1-/-]). Fecal microbiota transplantation of the gut microbiota of LDLR-/- mice into LDLR-/- mice (LDLR-/-[LDLR-/-]) served as control. Mice were fed a chow or high-fat cholesterol diet (HFC, 0,21% cholesterol) for 13 weeks and fecal samples were collected to determine microbiota composition by 16S rRNA sequencing. Plaque size was analyzed in the aortic root and immune cell subsets were analyzed by flow cytometry.Results: 16S rRNA sequencing of fecal samples confirmed the induction of dysbiosis in LDLR-/-[casp1-/-] compared to LDLR-/-[LDLR-/-] mice. Body weight, plasma triglyceride and cholesterol levels were significantly increased by HFC-feeding in LDLR-/-[casp1-/-] and LDLR-/-[LDLR-/-] mice. However, dysbiosis did not affect these parameters. In contrast, plaque size was significantly increased in HFC-fed LDLR-/-[casp1-/-] compared to HFC-fed (LDLR-/-[LDLR-/-] mice. Furthermore, dysbiosis in LDLR-/- mice was associated with a moderate increase in circulatory levels of Ly6C-high monocytes.Conclusions: Our data shows that gut microbiota dysbiosis augments atherosclerosis, possibly by exacerbating low-grade systemic inflammation.

U2 - 10.1016/j.atherosclerosis.2017.06.316

DO - 10.1016/j.atherosclerosis.2017.06.316

M3 - Meeting Abstract

C2 - 29366290

SN - 0021-9150

VL - 263

SP - e97

JO - Atherosclerosis

JF - Atherosclerosis

ER -

Gut microbiota dysbiosis augments atherosclerosis in LDLR-/- mice

Abstract

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