High-fat diet impact on intestinal cholesterol conversion by the microbiota and serum cholesterol levels

Alena M Bubeck; Paul Urbain; Cathrine Horn; Anna S Jung; Lisa Ferrari; Hannah K Ruple; Daniel Podlesny; Stefanie Zorn; Johnny Laupsa-Borge; Caroline Jensen; Inge Lindseth; Gülen Arslan Lied; Jutta Dierkes; Gunnar Mellgren; Hartmut Bertz; Silke Matysik; Sabrina Krautbauer; Gerhard Liebisch; Hans-Frieder Schoett; Simon N Dankel; W Florian Fricke

doi:10.1016/j.isci.2023.107697

High-fat diet impact on intestinal cholesterol conversion by the microbiota and serum cholesterol levels

iScience. 2023 Aug 21;26(9):107697. doi: 10.1016/j.isci.2023.107697. eCollection 2023 Sep 15.

Authors

Alena M Bubeck¹, Paul Urbain², Cathrine Horn^{3

4}, Anna S Jung¹, Lisa Ferrari¹, Hannah K Ruple¹, Daniel Podlesny¹, Stefanie Zorn², Johnny Laupsa-Borge³, Caroline Jensen^{3

4}, Inge Lindseth⁵, Gülen Arslan Lied⁴, Jutta Dierkes⁴, Gunnar Mellgren^{3

4}, Hartmut Bertz^{2

6}, Silke Matysik⁷, Sabrina Krautbauer⁷, Gerhard Liebisch⁷, Hans-Frieder Schoett⁸, Simon N Dankel^{3

4}, W Florian Fricke^{1

9}

Affiliations

¹ Department of Microbiome Research and Applied Bioinformatics, Institute of Nutritional Sciences, University of Hohenheim, Stuttgart, Germany.
² Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
³ Mohn Nutrition Research Laboratory, Centre for Nutrition, Department of Clinical Science, University of Bergen, Bergen, Norway.
⁴ Mohn Nutrition Research Laboratory, Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
⁵ Balderklinikken, Oslo, Norway.
⁶ Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁷ Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany.
⁸ Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore, Singapore.
⁹ Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.

Abstract

Cholesterol-to-coprostanol conversion by the intestinal microbiota has been suggested to reduce intestinal and serum cholesterol availability, but the relationship between intestinal cholesterol conversion and the gut microbiota, dietary habits, and serum lipids has not been characterized in detail. We measured conserved proportions of cholesterol high and low-converter types in individuals with and without obesity from two distinct, independent low-carbohydrate high-fat (LCHF) dietary intervention studies. Across both cohorts, cholesterol conversion increased in previous low-converters after LCHF diet and was positively correlated with the fecal relative abundance of Eubacterium coprostanoligenes. Lean cholesterol high-converters had increased serum triacylglycerides and decreased HDL-C levels before LCHF diet and responded to the intervention with increased LDL-C, independently of fat, cholesterol, and saturated fatty acid intake. Our findings identify the cholesterol high-converter type as a microbiome marker, which in metabolically healthy lean individuals is associated with increased LDL-C in response to LCHF.

Keywords: Genomics; Health sciences; Human metabolism; Microbiology.