Choline and butyrate beneficially modulate the gut microbiome without affecting atherosclerosis in APOE*3-Leiden.CETP mice

Atherosclerosis, vol. 362, pp. 47–55

Abstract

BACKGROUND AND AIMS: mice, related to its conversion by gut bacteria into trimethylamine (TMA) that is converted by the liver into the proinflammatory metabolite trimethylamine-N-oxide (TMAO). Since butyrate beneficially modulates the gut microbiota and has anti-inflammatory and antiatherogenic properties, the aim of the present study was to investigate whether butyrate can alleviate choline-induced atherosclerosis. To this end, we used APOE*3-Leiden.CETP mice, a well-established atherosclerosis-prone model with human-like lipoprotein metabolism. METHODS: Female APOE*3-Leiden.CETP mice were fed an atherogenic diet alone or supplemented with choline, butyrate or their combination for 16 weeks. RESULTS: Interestingly, choline protected against fat mass gain, increased the abundance of anti-inflammatory gut microbes, and increased the expression of gut microbial genes involved in TMA and TMAO degradation. Butyrate similarly attenuated fat mass gain and beneficially modulated the gut microbiome, as shown by increased abundance of anti-inflammatory and short chain fatty acid-producing microbes, and inhibited expression of gut microbial genes involved in lipopolysaccharide synthesis. Both choline and butyrate upregulated hepatic expression of flavin-containing monooxygenases, and their combination resulted in highest circulating TMAO levels. Nonetheless, choline, butyrate and their combination did not influence atherosclerosis development, and TMAO levels were not associated with atherosclerotic lesion size. CONCLUSIONS: mice as related to changes in the gut microbiota, both dietary constituents did not affect atherosclerosis development while beneficially modulating the gut microbiome in APOE*3-Leiden.CETP mice.

Authors 8

1. Cong Liu Aachen Department of Medicine Division of Endocrinology, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands

   Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands

2. Li Zhuang Aachen Department of Medicine Division of Endocrinology, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands

   Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands

3. Zikuan Song Aachen Department of Medicine Division of Endocrinology, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands

   Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands

4. Hua Shao

   First Affiliated Hospital of Xi'an Jiaotong University · Xi'an Jiaotong University

   Affiliation as printed

   Med-X Institute, Center for Immunological and Metabolic Diseases, Department of Endocrinology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, China

5. Milena Schönke Aachen Department of Medicine Division of Endocrinology, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands

   Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands

6. Mariëtte R. Boon Aachen Department of Medicine Division of Endocrinology, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands

   Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands

7. Patrick C.N. Rensen Aachen Department of Medicine Division of Endocrinology, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University Medical Center · First Affiliated Hospital of Xi'an Jiaotong University · Xi'an Jiaotong University

   Affiliation as printed

   Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands; Med-X Institute, Center for Immunological and Metabolic Diseases, Department of Endocrinology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, China

   Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands

   Med-X Institute, Center for Immunological and Metabolic Diseases, Department of Endocrinology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, China

8. Yanan Wang corresponding Aachen Department of Medicine Division of Endocrinology, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University · Leiden University Medical Center · First Affiliated Hospital of Xi'an Jiaotong University · Xi'an Jiaotong University

   Affiliation as printed

   Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands; Med-X Institute, Center for Immunological and Metabolic Diseases, Department of Endocrinology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, China. Electronic address: yanan.wang@xjtu.edu.cn

   Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands

   Med-X Institute, Center for Immunological and Metabolic Diseases, Department of Endocrinology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, China