title: Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome.
abstract: The human gut microbiome is known to be associated with various human disorders, but a major challenge is to go beyond association studies and elucidate causalities. Mathematical modeling of the human gut microbiome at a genome scale is a useful tool to decipher microbe-microbe, diet-microbe and microbe-host interactions. Here, we describe the CASINO (Community And Systems-level INteractive Optimization) toolbox, a comprehensive computational platform for analysis of microbial communities through metabolic modeling. We first validated the toolbox by simulating and testing the performance of single bacteria and whole communities in vitro. Focusing on metabolic interactions between the diet, gut microbiota, and host metabolism, we demonstrated the predictive power of the toolbox in a diet-intervention study of 45 obese and overweight individuals and validated our predictions by fecal and blood metabolomics data. Thus, modeling could quantitatively describe altered fecal and serum amino acid levels in response to diet intervention.
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, Kemivägen 10, 41296 Gothenburg, Sweden.
authors.forename: Saeed
authors.initials: S
authors.lastname: Shoaie
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, Kemivägen 10, 41296 Gothenburg, Sweden.
authors.forename: Pouyan
authors.initials: P
authors.lastname: Ghaffari
authors.affiliation: The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden.
authors.forename: Petia
authors.initials: P
authors.lastname: Kovatcheva-Datchary
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, Kemivägen 10, 41296 Gothenburg, Sweden.
authors.forename: Adil
authors.initials: A
authors.lastname: Mardinoglu
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, Kemivägen 10, 41296 Gothenburg, Sweden.
authors.forename: Partho
authors.initials: P
authors.lastname: Sen
authors.affiliation: Institut National de la Recherche 'Agronomique (INRA), Nutrition Humaine, Plateforme Exploration du Métabolisme, 63000 Clermont-Ferrand, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Pujos-Guillot
authors.affiliation: Institut National de la Recherche 'Agronomique (INRA), UMR1319 Micalis and USR1367 MetaGenoPolis, 78352 Jouy-en-Josas, France.
authors.forename: Tomas
authors.initials: T
authors.lastname: de Wouters
authors.affiliation: Institut National de la Recherche 'Agronomique (INRA), UMR1319 Micalis and USR1367 MetaGenoPolis, 78352 Jouy-en-Josas, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Juste
authors.affiliation: Institute of Cardiometabolism and Nutrition (ICAN), Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, 75013 Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1166, NutriOmics Team 6, 75013 Paris, France.
authors.forename: Salwa
authors.initials: S
authors.lastname: Rizkalla
authors.affiliation: Section of Biomolecular Medicine, Department of Surgery and Cancer, Division of Computational and Systems Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, South Kensington, London SW7 2AZ, UK.
authors.forename: Julien
authors.initials: J
authors.lastname: Chilloux
authors.affiliation: Section of Biomolecular Medicine, Department of Surgery and Cancer, Division of Computational and Systems Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, South Kensington, London SW7 2AZ, UK.
authors.forename: Lesley
authors.initials: L
authors.lastname: Hoyles
authors.affiliation: Section of Biomolecular Medicine, Department of Surgery and Cancer, Division of Computational and Systems Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, South Kensington, London SW7 2AZ, UK.
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.affiliation: Institut National de la Recherche 'Agronomique (INRA), UMR1319 Micalis and USR1367 MetaGenoPolis, 78352 Jouy-en-Josas, France.
authors.forename: Joel
authors.initials: J
authors.lastname: Dore
authors.affiliation: Section of Biomolecular Medicine, Department of Surgery and Cancer, Division of Computational and Systems Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, South Kensington, London SW7 2AZ, UK.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Dumas
authors.affiliation: Institute of Cardiometabolism and Nutrition (ICAN), Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, 75013 Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1166, NutriOmics Team 6, 75013 Paris, France; Sorbonne Universités, UPMC University Paris 06, UMR S-1166, Team 6, 75013 Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Clement
authors.affiliation: The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Bäckhed
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, Kemivägen 10, 41296 Gothenburg, Sweden. Electronic address: nielsenj@chalmers.se.
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
mesh_terms: D001419:Bacteria / Q000378:metabolism*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology*; D008297:Male; D064307:Microbiota / Q000502:physiology*; D008954:Models, Biological