Obese Individuals With and Without Type 2 Diabetes Show Different Gut Microbial Functional Capacity and Composition

Cell Host Microbe. 2019 Aug 14;26(2):252-264.e10. doi: 10.1016/j.chom.2019.07.004. | PubMed

Louise B Thingholm¹, Malte C Rühlemann¹, Manja Koch², Brie Fuqua³, Guido Laucke¹, Ruwen Boehm⁴, Corinna Bang¹, Eric A Franzosa⁵, Matthias Hübenthal⁶, Ali Rahnavard⁵, Fabian Frost⁷, Jason Lloyd-Price⁵, Melanie Schirmer⁵, Aldons J Lusis³, Chris D Vulpe⁸, Markus M Lerch⁷, Georg Homuth⁹, Tim Kacprowski¹⁰, Carsten O Schmidt¹¹, Ute Nöthlings¹², Tom H Karlsen¹³, Wolfgang Lieb¹⁴, Matthias Laudes¹⁵, Andre Franke¹⁶, Curtis Huttenhower⁵

1. Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany.
2. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
3. Department of Medicine, University of California, Los Angeles, CA 90095, USA.
4. Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
5. Biostatistics Department, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02115, USA.
6. Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany; Department of Dermatology, Venereology and Allergy, University Hospital, Schleswig-Holstein, 24105 Kiel, Germany.
7. Department of Medicine A, University Medicine Greifswald, 17475 Greifswald, Germany.
8. College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA.
9. Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany.
10. Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany; Research Group on Computational Systems Medicine, Chair of Experimental Bioinformatics, TUM School of Life Sciences, Weihenstephan, Technical University of Munich, Freising-Weihenstephan 85354, Germany.
11. Institute for Community Medicine SHIP-KEF, University Medicine Greifswald, Greifswald 17475, Germany.
12. Department of Nutrition and Food Sciences, Nutritional Epidemiology, Rheinische Friedrich-Wilhelms-Universität Bonn, 53115 Bonn, Germany.
13. Norwegian PSC Research Center, Department of Transplantation Medicine and Research Institute of Internal Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0315 Oslo, Norway.
14. Institute of Epidemiology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany.
15. Department of Internal Medicine I, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
16. Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany. Electronic address: a.franke@mucosa.de.

Abstract

Obesity and type 2 diabetes (T2D) are metabolic disorders that are linked to microbiome alterations. However, their co-occurrence poses challenges in disentangling microbial features unique to each condition. We analyzed gut microbiomes of lean non-diabetic (n = 633), obese non-diabetic (n = 494), and obese individuals with T2D (n = 153) from German population and metabolic disease cohorts. Microbial taxonomic and functional profiles were analyzed along with medical histories, serum metabolomics, biometrics, and dietary data. Obesity was associated with alterations in microbiome composition, individual taxa, and functions with notable changes in Akkermansia, Faecalibacterium, Oscillibacter, and Alistipes, as well as in serum metabolites that correlated with gut microbial patterns. However, microbiome associations were modest for T2D, with nominal increases in Escherichia/Shigella. Medications, including antihypertensives and antidiabetics, along with dietary supplements including iron, were significantly associated with microbiome variation. These results differentiate microbial components of these interrelated metabolic diseases and identify dietary and medication exposures to consider in future studies.

Presented By Louise B Thingholm