The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice

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The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice

Fan, Y. (författare): Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark

Stoving, R. K. (författare): Center for Eating Disorders, Odense University Hospital, and Research Unit for Medical Endocrinology, Mental Health Services in the Region of Southern Denmark, Open Patient data Explorative Network (OPEN) and Clinical Institute, University of Southern Denmark, Odense, Denmark

Ibraim, S. B. (författare): Université Paris-Saclay, INRAE, MGP, Jouy-en-Josas, France

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Hyötyläinen, Tuulia, 1971- (författare): Örebro universitet,Institutionen för naturvetenskap och teknik

Thirion, F. (författare): Université Paris-Saclay, INRAE, MGP, Jouy-en-Josas, France

Arora, T. (författare): Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark

Lyu, L. (författare): Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark; Department of Medicine, University of Copenhagen and Herlev-Gentofte University Hospital, Copenhagen, Denmark

Stankevic, E. (författare): Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark,Université Paris-Saclay, INRAE, MGP, Jouy-en-Josas, France; Department of Clinical and Movement Neurosciences, University College London, London, UK

Hansen, T. H. (författare): Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark

Dechelotte, P. (författare): INSERM U1073 Research Unit and TargEDys, Rouen University, Rouen, France

Sinioja, Tim, 1983- (författare): Örebro universitet,Institutionen för naturvetenskap och teknik

Ragnarsdottir, O. (författare): School of Science and Technology, Örebro University, Örebro, Sweden

Pons, N. (författare): Université Paris-Saclay, INRAE, MGP, Jouy-en-Josas, France

Galleron, N. (författare): Université Paris-Saclay, INRAE, MGP, Jouy-en-Josas, France

Quinquis, B. (författare): Université Paris-Saclay, INRAE, MGP, Jouy-en-Josas, France

Levenez, F. (författare): Université Paris-Saclay, INRAE, MGP, Jouy-en-Josas, France

Roume, H. (författare): Université Paris-Saclay, INRAE, MGP, Jouy-en-Josas, France

Falony, G. (författare): Laboratory of Molecular bacteriology, Department of Microbiology and Immunology, Rega Institute Ku Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven, Belgium; Institute of Medical Microbiology and Hygiene and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Institute of Molecular Biology (IMB), Mainz, Germany

Vieira-Silva, S. (författare): Laboratory of Molecular bacteriology, Department of Microbiology and Immunology, Rega Institute Ku Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven, Belgium; Institute of Medical Microbiology and Hygiene and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Institute of Molecular Biology (IMB), Mainz, Germany

Raes, J. (författare): Laboratory of Molecular bacteriology, Department of Microbiology and Immunology, Rega Institute Ku Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven, Belgium

Clausen, L. (författare): Department of Child and Adolescent Psychiatry, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark

Telleus, G. K. (författare): Unit for Psychiatric Research, Aalborg University Hospital, Aalborg, Denmark; Department of Communication and Psychology, The Faculty of Social Sciences and Humanities, Aalborg University, Aalborg, Denmark

Bäckhed, Fredrik, 1973 (författare): Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark; The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Clinical Physiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden

Oresic, Matej, 1967- (författare): Örebro universitet,Institutionen för medicinska vetenskaper,Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland

Ehrlich, S. D. (författare)

Pedersen, O. (författare): Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark; Department of Medicine, University of Copenhagen and Herlev-Gentofte University Hospital, Copenhagen, Denmark

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Nature Publishing Group, 2023
2023
Engelska.
Ingår i: Nature Microbiology. - : Nature Publishing Group. - 2058-5276. ; 8, s. 787-802

Relaterad länk:: https://doi.org/10.1...; visa fler...; https://gup.ub.gu.se...; https://doi.org/10.1...; https://urn.kb.se/re...; visa färre...

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Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral-bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our 'omics' and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis. Faecal metagenomics and serum metabolomics reveal compositional and functional alterations in the gut microbiota of women with anorexia nervosa, and faecal transplants could transfer an anorexia-associated phenotype to germ-free mice.

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The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice

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