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Nervenheilkunde 2020; 39(01/02): 67-73
DOI: 10.1055/a-1037-2119
Schwerpunkt
© Georg Thieme Verlag KG Stuttgart · New York

Rolle des Mikrobioms und der Darm-Gehirn-Interaktion bei Anorexia nervosa

Role of the microbiome and the gut-brain interaction in anorexia nervosa
Stefanie Trinh∗
1   Institut für Neuroanatomie, RWTH Aachen
,
Beate Herpertz-Dahlmann∗
2   Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Universitätsklinikum Aachen
,
Jochen Seitz
2   Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Universitätsklinikum Aachen
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
12. Februar 2020 (online)

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ZUSAMMENFASSUNG

Das menschliche Darm-Mikrobiom ist am Stoffwechsel, der Gewichtsregulierung, der Entwicklung des Immunsystems sowie an der Interaktion zwischen Darm und Gehirn des Wirtes beteiligt. Patientinnen mit Anorexia nervosa (AN) zeigen deutliche Mikrobiomveränderungen, zum Beispiel eine reduzierte Bakterienvielfalt. AN-bezogene Veränderungen im Mikrobiom können die Darmpermeabilität, Entzündungsprozesse und die Bildung von Autoantikörpern fördern. Eine reduzierte Bakterienvielfalt in AN scheint mit Depressions-, Angst- und Essstörungssymptomen zusammenzuhängen. Auf das Mikrobiom ausgerichtete Therapien wie Ernährungsinterventionen oder Prä- und Probiotika könnten zusätzliche Behandlungsperspektiven bieten.

ABSTRACT

The human gut microbiome is involved in host metabolism, weight regulation, development of the immune system and gut-brain interaction. Patients with Anorexia nervosa (AN) show significant aberrations in their microbiome, for example reduced bacterial diversity. AN-related aberrations could result in increased gut permeability, inflammation and autoantibody synthesis. Reduced bacterial diversity in AN appears to be associated with anxious, depressive, and eating disorder symptoms. Therapies targeting the microbiome, for example dietary interventions or pre- and probiotics could provide additional treatment possibilities.

Schlüsselwörter

Mikrobiom - Anorexia nervosa - Gewichtsregulierung - Entzündung - Darm-Gehirn-Achse

Key words

Microbiome - anorexia nervosa - body weight regulation - inflammation - gut-brain-axis
 

  • Literatur

  • 1 Herpertz-Dahlmann B. Adolescent eating disorders: update on definitions, symptomatology, epidemiology, and comorbidity. Child and adolescent psychiatric clinics of North America 2015; 24 (01) 177-96
    CrossrefPubMedGoogle Scholar
  • 2 Javaras KN, Runfola CD, Thornton LM. et al Sex- and age-specific incidence of healthcare-register-recorded eating disorders in the complete swedish, 1979–2001 birth cohort. The International journal of eating disorders 2015; 48 (08) 1070-81
    CrossrefPubMedGoogle Scholar
  • 3 Smink FR, van Hoeken D, Donker GA. et al Three decades of eating disorders in Dutch primary care: decreasing incidence of bulimia nervosa but not of anorexia nervosa. Psychological medicine 2016; 46 (06) 1189-96
    CrossrefPubMedGoogle Scholar
  • 4 Holland J, Hall N, Yeates DG. et al Trends in hospital admission rates for anorexia nervosa in Oxford 1968–2011 and England 1990–2011 database studies. Journal of the Royal Society of Medicine 2016; 109 (02) 59-66
    CrossrefPubMedGoogle Scholar
  • 5 Steinhausen HC, Jensen CM. Time trends in lifetime incidence rates of first-time diagnosed anorexia nervosa and bulimia nervosa across 16 years in a Danish nationwide psychiatric registry study. The International journal of eating disorders 2015; 48 (07) 845-50
    CrossrefPubMedGoogle Scholar
  • 6 Treasure J, Stein D, Maguire S. Has the time come for a staging model to map the course of eating disorders from high risk to severe enduring illness? An examination of the evidence. Early intervention in psychiatry 2015; 9 (03) 173-84
    CrossrefPubMedGoogle Scholar
  • 7 Hoang U, Goldacre M, James A. Mortality following hospital discharge with a diagnosis of eating disorder: national record linkage study, England, 2001–2009. The International journal of eating disorders 2014; 47 (05) 507-15
    CrossrefPubMedGoogle Scholar
  • 8 Schmidt U, Adan R, Bohm I. et al Eating disorders: the big issue. The lancet Psychiatry 2016; 3 (04) 313-5
    CrossrefPubMedGoogle Scholar
  • 9 Sender R, Fuchs S. Revised Estimates for the Number of Human and Bacteria Cells in the Body. Plos Biol 2016; 14 (08) e1002533
    CrossrefPubMedGoogle Scholar
  • 10 Almeida A, Mitchell AL, Boland M. et al A new genomic blueprint of the human gut microbiota. Nature 2019; 568 7753 499-504
    CrossrefPubMedGoogle Scholar
  • 11 Clavel T, Lagkouvardos I, Hiergeist A. Microbiome sequencing: challenges and opportunities for molecular medicine. Expert review of molecular diagnostics 2016; 16 (07) 795-805
    CrossrefPubMedGoogle Scholar
  • 12 Neuman H, Debelius JW, Knight R. et al Microbial endocrinology: the interplay between the microbiota and the endocrine system. FEMS microbiology reviews 2015; 39 (04) 509-21
    CrossrefPubMedGoogle Scholar
  • 13 Kelly JR, Kennedy PJ, Cryan JF. et al Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Frontiers in cellular neuroscience 2015; 9: 392
    PubMedGoogle Scholar
  • 14 Carr J, Kleiman SC, Bulik CM. et al Can attention to the intestinal microbiota improve understanding and treatment of anorexia nervosa?. Expert review of gastroenterology & hepatology 2016; 10 (05) 565-9
    CrossrefPubMedGoogle Scholar
  • 15 Herpertz-Dahlmann B, Seitz J. et al Food matters: how the microbiome and gut-brain interaction might impact the development and course of anorexia nervosa. European child & adolescent psychiatry 2017; 26 (09) 1031-41
    CrossrefPubMedGoogle Scholar
  • 16 Mack I, Cuntz U, Gramer C. et al Weight gain in anorexia nervosa does not ameliorate the faecal microbiota, branched chain fatty acid profiles, and gastrointestinal complaints. Scientific reports 2016; 6: 26752
    CrossrefPubMedGoogle Scholar
  • 17 Morkl S, Lackner S, Muller W. et al Gut microbiota and body composition in anorexia nervosa inpatients in comparison to athletes, overweight, obese, and normal weight controls. The International journal of eating disorders 2017; 50 (12) 1421-31
    CrossrefPubMedGoogle Scholar
  • 18 Ridaura VK, Faith JJ, Rey FE. et al Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 2013; 341 6150 1241214
    CrossrefPubMedGoogle Scholar
  • 19 Tremaroli V, Karlsson F, Werling M. et al Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation. Cell metabolism 2015; 22 (02) 228-38
    CrossrefPubMedGoogle Scholar
  • 20 Kleiman SC, Watson HJ, Bulik-Sullivan EC. et al The Intestinal Microbiota in Acute Anorexia Nervosa and During Renourishment: Relationship to Depression, Anxiety, and Eating Disorder Psychopathology. Psychosomatic medicine 2015; 77 (09) 969-81
    CrossrefPubMedGoogle Scholar
  • 21 Million M, Angelakis E, Maraninchi M. et al Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacterium animalis, Methanobrevibacter smithii and Escherichia coli. International journal of obesity (2005) 2013; 37 (11) 1460-6
    CrossrefPubMedGoogle Scholar
  • 22 Smith MI, Yatsunenko T, Manary MJ. et al Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science (New York, NY) 2013; 339 6119 548-54
    CrossrefPubMedGoogle Scholar
  • 23 Trehan I, Goldbach HS, LaGrone LN. et al Antibiotics as part of the management of severe acute malnutrition. The New England journal of medicine 2013; 368 (05) 425-35
    CrossrefPubMedGoogle Scholar
  • 24 Depommier C, Everard A, Druart C. et al Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med 2019; 25 (07) 1096-103
    CrossrefPubMedGoogle Scholar
  • 25 Marzola E, Nasser JA, Hashim SA. et al Nutritional rehabilitation in anorexia nervosa: review of the literature and implications for treatment. BMC psychiatry 2013; 13: 290
    CrossrefPubMedGoogle Scholar
  • 26 Wostman B. Germfree and gnotobiotic animal models. Morphology and physiology, endocrinology and biochemistry. Crc Press Inc 1996: 43-71
    PubMedGoogle Scholar
  • 27 Wikoff WR, Anfora AT, Liu J. et al Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proceedings of the National Academy of Sciences of the United States of America 2009; 106 (10) 3698-703
    CrossrefPubMedGoogle Scholar
  • 28 Asano Y, Hiramoto T, Nishino R. et al Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. American journal of physiology Gastrointestinal and liver physiolog 2012; 303 (11) G1288-95
    Google Scholar
  • 29 Roshchina V. Evolutionary considerations of neurotransmitters in microbial, plant, and animal cells. Microbial endocrinology: interkingdom 2010
    PubMedGoogle Scholar
  • 30 Flores R, Shi J, Fuhrman B. et al Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study. Journal of translational medicine 2012; 10: 253
    CrossrefPubMedGoogle Scholar
  • 31 Queipo-Ortuno MI, Seoane LM, Murri M. et al Gut microbiota composition in male rat models under different nutritional status and physical activity and its association with serum leptin and ghrelin levels. PloS one 2013; 8 (05) e65465
    CrossrefPubMedGoogle Scholar
  • 32 Seitz J, Trinh S, Herpertz-Dahlmann B. The Microbiome and Eating Disorders. The Psychiatric clinics of North America 2019; 42 (01) 93-103
    CrossrefPubMedGoogle Scholar
  • 33 Grenham S, Clarke G, Cryan JF. et al Brain-gut-microbe communication in health and disease. Frontiers in physiology 2011; 2: 94
    PubMedGoogle Scholar
  • 34 Messaoudi M, Lalonde R, Violle N. et al Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. The British journal of nutrition 2011; 105 (05) 755-64
    CrossrefPubMedGoogle Scholar
  • 35 Schorr M, Miller KK. The endocrine manifestations of anorexia nervosa: mechanisms and management. Nature reviews Endocrinology 2017; 13 (03) 174-86
    CrossrefPubMedGoogle Scholar
  • 36 Petra AI, Panagiotidou S, Stewart JM. et al Spectrum of mast cell activation disorders. Expert review of clinical immunology 2014; 10 (06) 729-39
    CrossrefPubMedGoogle Scholar
  • 37 Vanuytsel T, van Wanrooy S, Vanheel H. et al Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut 2014; 63 (08) 1293-9
    CrossrefPubMedGoogle Scholar
  • 38 Morkl S, Lackner S, Meinitzer A. et al [Pilot study: Gut microbiome and intestinal barrier in anorexia nervosa]. Fortschritte der Neurologie-Psychiatrie 2019; 87 (01) 39-45
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 39 Fasano A, Not T, Wang W. et al Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet 2000; 355 9214 1518-9
    CrossrefPubMedGoogle Scholar
  • 40 Monteleone P, Carratu R, Carteni M. et al Intestinal permeability is decreased in anorexia nervosa. Molecular psychiatry 2004; 9 (01) 76-80
    CrossrefPubMedGoogle Scholar
  • 41 Jesus P, Ouelaa W, Francois M. et al Alteration of intestinal barrier function during activity-based anorexia in mice. Clinical nutrition 2014; 33 (06) 1046-53
    CrossrefPubMedGoogle Scholar
  • 42 Bambury A, Sandhu K, Cryan JF. et al Finding the needle in the haystack: systematic identification of psychobiotics. Br J Pharmacol 2018; 175 (24) 4430-8
    CrossrefPubMedGoogle Scholar
  • 43 Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biological psychiatry 2013; 74 (10) 720-6
    CrossrefPubMedGoogle Scholar
  • 44 Kelly JR, Minuto C, Cryan JF. et al Cross Talk: The Microbiota and Neurodevelopmental Disorders. Frontiers in neuroscience 2017; 11: 490
    CrossrefPubMedGoogle Scholar
  • 45 Dalton B, Bartholdy S, Robinson L. et al A meta-analysis of cytokine concentrations in eating disorders. Journal of psychiatric research 2018; 103: 252-64
    CrossrefPubMedGoogle Scholar
  • 46 Solmi M, Veronese N, Favaro A. et al Inflammatory cytokines and anorexia nervosa: A meta-analysis of cross-sectional and longitudinal studies. Psychoneuroendocrinology 2015; 51: 237-52
    CrossrefPubMedGoogle Scholar
  • 47 Dai C, Zheng CQ, Meng FJ. et al VSL#3 probiotics exerts the anti-inflammatory activity via PI3k/Akt and NF-kappaB pathway in rat model of DSS-induced colitis. Molecular and cellular biochemistry 2013; 374 1–2 1-11
    CrossrefPubMedGoogle Scholar
  • 48 Raevuori A, Haukka J, Vaarala O. et al The increased risk for autoimmune diseases in patients with eating disorders. PloS on 2014; 9 (08) e104845
    Google Scholar
  • 49 Fetissov SO. Role of the gut microbiota in host appetite control: bacterial growth to animal feeding behaviour. Nature reviews Endocrinology 2017; 13 (01) 11-25
    CrossrefPubMedGoogle Scholar
  • 50 Tennoune N, Chan P, Breton J. et al Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide alpha-MSH, at the origin of eating disorders. Translational psychiatry 2014; 4: e458
    CrossrefPubMedGoogle Scholar
  • 51 Santoro A, Ostan R, Candela M. et al Gut microbiota changes in the extreme decades of human life: a focus on centenarians. Cellular and molecular life sciences : CMLS 2018; 75 (01) 129-48
    CrossrefPubMedGoogle Scholar
  • 52 Luczynski P, McVey Neufeld KA. et al Growing up in a Bubble: Using Germ-Free Animals to Assess the Influence of the Gut Microbiota on Brain and Behavior. The international journal of neuropsychopharmacology 2016; 19: 8
    Google Scholar
  • 53 Sherwin E, Rea K, Dinan TG. et al A gut (microbiome) feeling about the brain. Current opinion in gastroenterology 2016; 32 (02) 96-102
    CrossrefPubMedGoogle Scholar
  • 54 Zwipp J, Hass J, Schober I. et al Serum brain-derived neurotrophic factor and cognitive functioning in underweight, weight-recovered and partially weight-recovered females with anorexia nervosa. Progress in neuro-psychopharmacology & biological psychiatry 2014; 54: 163-9
    CrossrefPubMedGoogle Scholar
  • 55 Haleem DJ. Improving therapeutics in anorexia nervosa with tryptophan. Life sciences 2017; 178: 87-93
    CrossrefPubMedGoogle Scholar
  • 56 Hata T, Asano Y, Yoshihara K. et al Regulation of gut luminal serotonin by commensal microbiota in mice. Plos One 2017; 12 (07) e0180745
    CrossrefPubMedGoogle Scholar
  • 57 Gershon MD. Review article: roles played by 5-hydroxytryptamine in the physiology of the bowel. Alimentary pharmacology & therapeutics 1999; 13 (Suppl. 02) 15-30
    CrossrefPubMedGoogle Scholar
  • 58 Mohle L, Mattei D, Heimesaat MM. et al Ly6C(hi) Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis. Cell reports 2016; 15 (09) 1945-56
    CrossrefPubMedGoogle Scholar
  • 59 Seitz J, Herpertz-Dahlmann B. et al Brain morphological changes in adolescent and adult patients with anorexia nervosa. Journal of neural transmission 2016; 123 (08) 949-59
    CrossrefPubMedGoogle Scholar
  • 60 Seitz J, Walter M, Mainz V. et al Brain volume reduction predicts weight development in adolescent patients with anorexia nervosa. Journal of psychiatric research 2015; 68: 228-37
    CrossrefPubMedGoogle Scholar
  • 61 Frintrop L, Liesbrock J, Paulukat L. et al Reduced astrocyte density underlying brain volume reduction in activity-based anorexia rats. The world journal of biological psychiatry 2017: 1-11
    PubMedGoogle Scholar
  • 62 Paulukat L, Frintrop L, Liesbrock J. et al Memory impairment is associated with the loss of regular oestrous cycle and plasma oestradiol levels in an activity-based anorexia animal model. The world journal of biological psychiatry 2016; 17 (04) 274-84
    CrossrefPubMedGoogle Scholar
  • 63 Armougom F, Henry M, Vialettes B. et al Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients. PloS one 2009; 4 (09) e7125
    CrossrefPubMedGoogle Scholar
  • 64 Borgo F, Riva A, Benetti A. et al Microbiota in anorexia nervosa: The triangle between bacterial species, metabolites and psychological tests. Plos One 2017; 12 (06) e0179739
    CrossrefPubMedGoogle Scholar
  • 65 Hanachi M, Manichanh C, Schoenenberger A. et al Altered host-gut microbes symbiosis in severely malnourished anorexia nervosa (AN) patients undergoing enteral nutrition: An explicative factor of functional intestinal disorders?. Clinical nutrition 2018; 38 (05) 2304-2310
    PubMedGoogle Scholar
  • 66 Morita C, Tsuji H, Hata T. et al Gut Dysbiosis in Patients with Anorexia Nervosa. PloS one 2015; 10 (12) e0145274
    CrossrefPubMedGoogle Scholar
  • 67 Kleiman SC, Glenny EM, Bulik-Sullivan EC. et al Daily Changes in Composition and Diversity of the Intestinal Microbiota in Patients with Anorexia Nervosa: A Series of Three Cases. European eating disorders review : the journal of the Eating Disorders Association 2017; 25 (05) 423-7
    CrossrefPubMedGoogle Scholar
  • 68 Mack I, Penders J, Cook J. et al Is the Impact of Starvation on the Gut Microbiota Specific or Unspecific to Anorexia Nervosa? A Narrative Review Based on a Systematic Literature Search. Current neuropharmacology 2018; 16 (08) 1131-49
    CrossrefPubMedGoogle Scholar
  • 69 Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology 2014; 146 (06) 1489-99
    CrossrefPubMedGoogle Scholar
  • 70 Geirnaert A, Calatayud M, Grootaert C. et al Butyrate-producing bacteria supplemented in vitro to Crohn’s disease patient microbiota increased butyrate production and enhanced intestinal epithelial barrier integrity. Sci Rep 2017; 7 (01) 11450
    CrossrefPubMedGoogle Scholar
  • 71 Vieira AT, Fukumori C, Ferreira CM. New insights into therapeutic strategies for gut microbiota modulation in inflammatory diseases. Clinical & translational immunology 2016; 5 (06) e87
    CrossrefPubMedGoogle Scholar
  • 72 Holzer P, Farzi A. Neuropeptides and the microbiota-gut-brain axis. Advances in experimental medicine and biology 2014; 817: 195-219
    PubMedGoogle Scholar
  • 73 David LA, Maurice CF, Carmody RN. et al Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014; 505 7484 559-63
    Google Scholar
  • 74 Bagga D, Aigner CS, Reichert JL. et al Influence of 4-week multi-strain probiotic administration on resting-state functional connectivity in healthy volunteers. Eur J Nutr 2019; 58 (05) 1821-7
    CrossrefPubMedGoogle Scholar
  • 75 Bagga D, Reichert JL. Probiotics drive gut microbiome triggering emotional brain signatures. Gut Microbes 2018; 9 (06) 486-96
    PubMedGoogle Scholar
  • 76 Pirbaglou M, Katz J, de Souza RJ. et al Probiotic supplementation can positively affect anxiety and depressive symptoms: a systematic review of randomized controlled trials. Nutrition research 2016; 36 (09) 889-98
    CrossrefPubMedGoogle Scholar
  • 77 de Clercq NC, Frissen MN, Davids M. et al Weight Gain after Fecal Microbiota Transplantation in a Patient with Recurrent Underweight following Clinical Recovery from Anorexia Nervosa. Psychotherapy and psychosomatics 2019; 88 (01) 58-60
    CrossrefPubMedGoogle Scholar
  • 78 Mauler B, Dubben S, Pawelzik M. et al Hypercaloric diets differing in fat composition have similar effects on serum leptin and weight gain in female subjects with anorexia nervosa. Nutrition research 2009; 29 (01) 1-7
    CrossrefPubMedGoogle Scholar
  • 79 Maier L, Pruteanu M, Kuhn M. et al Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 2018; 555 7698 623-8
    Google Scholar