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

被引:71
作者
Fan, Yong [1 ]
Stoving, Rene Klinkby [2 ,3 ,4 ]
Ibraim, Samar Berreira [5 ]
Hyotylainen, Tuulia [6 ]
Thirion, Florence [5 ]
Arora, Tulika [1 ]
Lyu, Liwei [1 ,7 ,8 ]
Stankevic, Evelina [1 ]
Hansen, Tue Haldor [1 ]
Dechelotte, Pierre [9 ,10 ]
Sinioja, Tim [6 ]
Ragnarsdottir, Oddny [6 ]
Pons, Nicolas [5 ]
Galleron, Nathalie [5 ]
Quinquis, Benoit [5 ]
Levenez, Florence [5 ]
Roume, Hugo [5 ]
Falony, Gwen [11 ,12 ,13 ,14 ,15 ]
Vieira-Silva, Sara [11 ,12 ,13 ,14 ,15 ]
Raes, Jeroen [11 ,12 ]
Clausen, Loa [16 ,17 ]
Telleus, Gry Kjaersdam [18 ,19 ]
Backhed, Fredrik [1 ,20 ,21 ]
Oresic, Matej [22 ,23 ,24 ]
Ehrlich, S. Dusko [5 ,25 ]
Pedersen, Oluf [1 ,7 ,8 ]
机构
[1] Univ Copenhagen, Novo Nord Fdn Ctr Basic Metab Res, Fac Hlth & Med Sci, Copenhagen, Denmark
[2] Odense Univ Hosp, Ctr Eating Disorders, Odense, Denmark
[3] Univ Southern Denmark, Mental Hlth Serv Reg Southern Denmark, Res Unit Med Endocrinol, Open Patient Data Explorat Network OPEN, Odense, Denmark
[4] Univ Southern Denmark, Clin Inst, Odense, Denmark
[5] Univ Paris Saclay, INRAE, MGP, Jouy En Josas, France
[6] Orebro Univ, Sch Sci & Technol, Orebro, Sweden
[7] Univ Copenhagen, Dept Med, Copenhagen, Denmark
[8] Herlev Gentofte Univ Hosp, Copenhagen, Denmark
[9] Rouen Univ, INSERM U1073, Res Unit, Rouen, France
[10] Rouen Univ, TargEDys, Rouen, France
[11] Katholieke Univ Leuven, Rega Inst, Lab Mol Bacteriol, Dept Microbiol & Immunol, Leuven, Belgium
[12] Ctr Microbiol VIB, Leuven, Belgium
[13] Johannes Gutenberg Univ Mainz, Inst Med Microbiol & Hyg, Mainz, Germany
[14] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Res Ctr Immunotherapy FZI, Mainz, Germany
[15] Inst Mol Biol IMB, Mainz, Germany
[16] Aarhus Univ Hosp, Dept Child & Adolescent Psychiat, Aarhus, Denmark
[17] Aarhus Univ, Fac Hlth, Dept Clin Med, Aarhus, Denmark
[18] Aalborg Univ Hosp, Unit Psychiat Res, Aalborg, Denmark
[19] Aalborg Univ, Fac Social Sci & Humanities, Dept Commun & Psychol, Aalborg, Denmark
[20] Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med,Wallenberg Lab, Gothenburg, Sweden
[21] Sahlgrens Univ Hosp, Dept Clin Physiol, Gothenburg, Region Vastra G, Sweden
[22] Orebro Univ, Sch Med Sci, Orebro, Sweden
[23] Univ Turku, Turku Biosci Ctr, Turku, Finland
[24] Abo Akad Univ, Turku, Finland
[25] UCL, Dept Clin & Movement Neurosci, London, England
关键词
EATING-DISORDERS; BEHAVIOR; MORTALITY; DISEASE; PROTEIN; HYPOTHALAMUS; PREVALENCE; DEPRESSION; ALIGNMENT; ANXIETY;
D O I
10.1038/s41564-023-01355-5
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:787 / +
页数:29
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