Recent research highlights the profound impact of the gut microbiome on neuropsychiatric disorders, shedding light on its potential role in shaping human behavior. In this study, we investigate the role of the gut microbiome in appetite regulation using activity-based anorexia (ABA) mouse model of anorexia nervosa (AN) - a severe eating disorder with significant health consequences. ABA was induced in conventional, antibiotic-treated, and germ-free mice. Our results show the clear influence of the gut microbiome on the expression of four orexigenic (neuropeptide Y, agouti-related peptide, melanin-concentrating hormone, and orexin) and four anorexigenic peptides (cocaine- and amphetamine-regulated transcript, corticotropin-releasing hormone, thyrotropin-releasing hormone, and pro-opiomelanocortin) in the hypothalamus. Additionally, we assessed alterations in gut barrier permeability. While variations were noted in germ-free mice based on feeding and activity, they were not directly attributable to the gut microbiome. This research emphasizes that the gut microbiome is a pivotal factor in AN's appetite regulation beyond just dietary habits or physical activity.
- Klíčová slova
- Activity-based anorexia model, Appetite regulation, Eating disorders, Gut barrier, Microbiome, Neuropeptide Y,
- MeSH
- chuť k jídlu fyziologie MeSH
- hypothalamus metabolismus MeSH
- lidé MeSH
- mentální anorexie * metabolismus MeSH
- myši MeSH
- neuropeptidy * metabolismus MeSH
- střevní mikroflóra * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- neuropeptidy * MeSH
Anorexia nervosa (AN), a pathological restriction of food intake, leads to metabolic dysregulation. We conducted a metabolomics study to reveal changes caused by AN and the effect of hospital realimentation on metabolism. Both stool and serum from patients with AN and healthy controls were analyzed by NMR and MS. Statistical analysis revealed several altered biochemical and anthropometric parameters and 50 changed metabolites, including phospholipids, acylcarnitines, amino acids, derivatives of nicotinic acid, nucleotides, and energy metabolism intermediates. Biochemical and anthropometric parameters were correlated with metabolomic data. Metabolic changes in patients with AN described in our study imply serious system disruption defects, such as the development of inflammation and oxidative stress, changed free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels, a deficit of vitamins, muscle mass breakdown, and a decrease in ketone bodies as an important source of energy for the brain and heart. Furthermore, our data indicate only a very slight improvement after treatment. However, correlations of metabolomic results with body weight, interleukin 6, tumor necrosis factor α, fT4, and TSH might entail better prognoses and treatment effectiveness in patients with better system parameter status. Data sets are deposited in MassIVE: MSV000087713, DOI: 10.25345/C57R7X.
- Klíčová slova
- anorexia nervosa, mass spectrometry, metabolomics, nuclear magnetic resonance,
- MeSH
- hormony štítné žlázy MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- mentální anorexie * metabolismus terapie MeSH
- metabolomika metody MeSH
- thyreotropin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- hormony štítné žlázy MeSH
- thyreotropin MeSH
OBJECTIVE: To present a comprehensive overview of the female adolescent population focused on physical development and reproductive healthcare. METHODS: A summary of available literature using our own experience with the treatment of patients with eating disorders. CONCLUSION: Approximately 0.5% of adolescents suffer from eating disorders (EDs) in the Czech Republic. EDs have the highest incidence during adolescence, it is a period when growth spurt, bone mineralization and reproductive organ development occur. EDs have a significant negative effect on development and can irreversibly lead to its impairment.
- Klíčová slova
- Atrophy, Bone density, Densitometry, amenorhea, anorexia nervosa, body mass index (BMI), bulimia nervosa, chronic kidney disease, oligomenorhea,
- MeSH
- dítě MeSH
- gynekologie * MeSH
- lidé MeSH
- mentální anorexie * epidemiologie terapie MeSH
- mladiství MeSH
- poruchy příjmu potravy * diagnóza epidemiologie terapie MeSH
- sanitky MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Česká republika MeSH
Brain-gut microbiota interactions are intensively studied in connection with various neurological and psychiatric diseases. While anorexia nervosa (AN) pathophysiology is not entirely clear, it is presumably linked to microbiome dysbiosis. We aimed to elucidate the gut microbiota contribution in AN disease pathophysiology. We analyzed the composition and diversity of the gut microbiome of patients with AN (bacteriome and mycobiome) from stool samples before and after renourishment, and compared them to healthy controls. Further, levels of assorted neurotransmitters and short-chain fatty acids (SCFA) were analyzed in stool samples by MS and NMR, respectively. Biochemical, anthropometric, and psychometric profiles were assessed. The bacterial alpha-diversity parameter analyses revealed only increased Chao 1 index in patients with AN before the realimentation, reflecting their interindividual variation. Subsequently, core microbiota depletion signs were observed in patients with AN. Overrepresented OTUs (operation taxonomic units) in patients with AN taxonomically belonged to Alistipes, Clostridiales, Christensenellaceae, and Ruminococcaceae. Underrepresented OTUs in patients with AN were Faecalibacterium, Agathobacter, Bacteroides, Blautia, and Lachnospira. Patients exhibited greater interindividual variation in the gut bacteriome, as well as in metagenome content compared to controls, suggesting altered bacteriome functions. Patients had decreased levels of serotonin, GABA, dopamine, butyrate, and acetate in their stool samples compared to controls. Mycobiome analysis did not reveal significant differences in alpha diversity and fungal profile composition between patients with AN and healthy controls, nor any correlation of the fungal composition with the bacterial profile. Our results show the changed profile of the gut microbiome and its metabolites in patients with severe AN. Although therapeutic partial renourishment led to increased body mass index and improved psychometric parameters, SCFA, and neurotransmitter profiles, as well as microbial community compositions, did not change substantially during the hospitalization period, which can be potentially caused by only partial weight recovery.
- Klíčová slova
- BMI, EDE-Q, Microbiome, SCFA, bacteriome, dysbiosis, gut-brain-microbiota axis, mycobiome, neurotransmitter, renourishment,
- MeSH
- Archaea klasifikace růst a vývoj MeSH
- Bacteria klasifikace růst a vývoj metabolismus MeSH
- dospělí MeSH
- feces mikrobiologie MeSH
- houby klasifikace růst a vývoj metabolismus MeSH
- index tělesné hmotnosti MeSH
- kyseliny mastné těkavé metabolismus MeSH
- lidé MeSH
- longitudinální studie MeSH
- mentální anorexie metabolismus mikrobiologie MeSH
- metagenom MeSH
- mladý dospělý MeSH
- mykobiom MeSH
- neurotransmiterové látky metabolismus MeSH
- osa mozek-střevo MeSH
- střevní mikroflóra * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- kyseliny mastné těkavé MeSH
- neurotransmiterové látky MeSH
OBJECTIVE: We aimed to evaluate the validity of a MARSIPAN-guidance-adapted Early Warning System (MARSI MEWS) and compare it to the National Early Warning Score (NEWS) and an adapted version of the Physical Risk in Eating Disorders Index (PREDIX), to ascertain whether current practice is comparable to best-practice standards. METHODS: We collated 3,937 observations from 36 inpatients from Addenbrookes Hospital over 2017-2018 and used three independent raters to create a "gold standard" of deteriorating cases. We ascertained performance metrics (Receiver Operating Characteristic Area Under the curve) for MARSI MEWS, NEWS and PREDIX; we also tested the proof of concept of a machine-learning-based early-warning-system (ML-EWS) using cross-validation and out-of-sample prediction of cases. RESULTS: The MARSI MEWS system showed higher ROC AUC (0.916) compared to NEWS (0.828) or PREDIX (0.865). ML-EWS (random forest) performed well at independent samples analysis (0.980) and multilevel analysis (0.922). CONCLUSION: MARSI MEWS seems most suitable for identifying critically deteriorating cases in anorexia nervosa inpatient population. We did not examine community practice in which the PREDIX arguably remains the best to ascertain deteriorating cases. Our results also provide a first proof of concept for the development of artificial-intelligence-based early warning systems in anorexia nervosa. Implications for inpatient clinical practice in eating disorders are discussed.
- Klíčová slova
- anorexia nervosa, deterioration, early warning system, inpatient, machine learning,
- MeSH
- časná diagnóza * MeSH
- dospělí MeSH
- hospitalizace * MeSH
- klinické zhoršení * MeSH
- lidé MeSH
- mentální anorexie terapie MeSH
- monitorování fyziologických funkcí metody MeSH
- plocha pod křivkou MeSH
- reprodukovatelnost výsledků MeSH
- ROC křivka MeSH
- systém včasného varování MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
Anorexia nervosa is a psychiatric disorder defined by an extremely low body weight, a devastating fear of weight gain, and body image disturbance, however the etiopathogenesis remains unclear. The objective of the article is to provide a comprehensive review on the potential role of gut microbiota in pathogenesis of anorexia nervosa. Recent advances in sequencing techniques used for microbial detection revealed that this disease is associated with disruption of the composition of normal gut microbiota (dysbiosis), manifested by low microbial diversity and taxonomic differences as compared to healthy individuals. Microorganisms present in the gut represent a part of the so called "microbiota-gut-brain" axis that affect the central nervous system and thus human behavior via the production of various neuroactive compounds. In addition, cells of the immune system are equipped with receptors for these neuroactive substances. Microbiota of the intestinal system also represent a very important antigenic source. These antigens can mimic some host neuropeptides and neurohormones and thus trigger the production of autoantibodies which cross-react with these compounds. The levels and affinities of these antibodies are thought to be associated with neuropsychiatric conditions including anxiety, depression, and eating and sleep disorders. The study of microbiota function in diseases could bring new insights to the pathogenetic mechanisms.
- Klíčová slova
- Dysbiosis, Intestinal microbiome, Microbiota-gut-brain axis, Neuropeptide, Probiotics, Psychoneuroimmunology,
- MeSH
- lidé MeSH
- mentální anorexie imunologie mikrobiologie MeSH
- mozek imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Anorexia nervosa (AN) is associated with various alterations including the dysfunction of the HPA axis and consequently the hypercortisolemia and deficit in sex hormones but the comprehensive evaluation of changes in circulating steroids during the hospitalization of AN patients is lacking. We investigated the effect of realimentation of women with AN during hospitalization on 45 circulating steroids, the relationships between BMI, its change during hospitalization and physical activity, on one side and initial levels and their changes for two adipokines, circulating steroids, anorexia-specific (hunger, appetite and satiety), and anorexia non-specific symptoms (anxiety, depression fatigue, sleep, and body pain) on the other side. We included 33 women with anorexia who were hospitalized for 38(35, 44) days (median with quartiles). The increase of BMI from the initial value 15.2 (13.2, 16.6) kg/m2 was 1.69 (1.37, 2.66) kg/m2. The patients with more severe anorexia showed higher activity in 7β-, and 16α-hydroxylation of androgen precursors, which declined during hospitalization. Otherwise, the 7α-hydroxylation activity is higher in AN patients with less severe malnutrition and the ratio of 5-androstene-3β,7α,17β-triol to 5-androstene-3β,7β,17β-triol increased during the realimentation. Our data allow to speculate that the intensive 7β-, and 16α- and possibly also the 7α-hydroxylation of C19 Δ5 steroids participate in the pathophysiology of anorexia by additional catabolism of substrates available for synthesis of active androgens and estrogens. However, the question remains whether the synthetic analogues of 7α/β- and 16α-hydroxy-steroids prevent the catabolism of the sex steroid precursors, or further activate the "energy wasting" mitochondrial thermogenic metabolism.
- Klíčová slova
- Anorexia nervosa, Anxiety, Depression, Refeeding, Specific symptoms and physical activity, Steroid metabolome,
- MeSH
- dospělí MeSH
- hospitalizace MeSH
- index tělesné hmotnosti MeSH
- lidé MeSH
- mentální anorexie metabolismus psychologie MeSH
- mladý dospělý MeSH
- steroidy krev metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- steroidy MeSH
Cardiovascular complications contribute to higher morbidity and mortality in patients with anorexia nervosa. We aimed to study biomarkers of cardiovascular risk in anorexic, normal-weight, and obese adolescents with focus on complex cardiovascular autonomic regulation and early arteriosclerotic damage. We examined 20 adolescent girls with anorexia nervosa, 20 obese girls, and 20 healthy normal-weight controls. Collected data: body composition analysis, 5 min recordings of R-R intervals and beat-to-beat blood pressure (BP), and arterial stiffness evaluated using cardio-ankle vascular index (CAVI). Evaluated parameters: beat-to-beat heart rate and BP variability, haemodynamic parameters (total peripheral resistance (TPR) cardiac output), CAVI, and anthropometric indices, including novel body roundness index (BRI). Adolescents with anorexia nervosa had increased CAVI associated with lower arterial constriction indexed by low-frequency band of BP variability compared with normal-weight peers (p = 0.03, p = 0.04, respectively) and obese adolescents (p < 0.01, p = 0.01, respectively). After normalization of CAVI and TPR by BRI, the relationship between CAVI and TPR was significant for all groups with the highest slope in the anorexia nervosa group (R2 = 0.724, p < 0.01). This is the first study revealing early arteriosclerotic damage in anorexic girls with increased CAVI. Complex analysis of cardiovascular autonomic regulation, and early arteriosclerotic, hemodynamic, and anthropometric changes in spectrum anorexia nervosa, normal weight, and obesity could help to understand the mechanisms of increased cardiovascular risk in malnutrition. Novelty Girls with anorexia nervosa showed signs of early arteriosclerotic damage indexed by CAVI. Insufficient sympathetic cardiovascular control was found already in adolescents with anorexia nervosa. The effect of body composition on CAVI was best predicted by novel body roundness index.
- Klíčová slova
- anorexia nervosa, anorexie mentale, arterial stiffness, arteriosclerosis, artériosclérose, blood pressure, malnutrition, obesity, obésité, pression artérielle, rigidité artérielle,
- MeSH
- dítě MeSH
- hemodynamika fyziologie MeSH
- lidé MeSH
- mentální anorexie * epidemiologie patofyziologie MeSH
- mladiství MeSH
- obezita dětí a dospívajících * epidemiologie patofyziologie MeSH
- průřezové studie MeSH
- tuhost cévní stěny fyziologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
- MeSH
- celogenomová asociační studie * MeSH
- dospělí MeSH
- duševní poruchy komplikace genetika MeSH
- fenotyp MeSH
- genetická predispozice k nemoci * MeSH
- genomika metody MeSH
- index tělesné hmotnosti MeSH
- lidé MeSH
- lokus kvantitativního znaku * MeSH
- mentální anorexie etiologie genetika patologie MeSH
- metabolické nemoci komplikace genetika MeSH
- prognóza MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by a mutation in the TYMP gene encoding thymidine phosphorylase. MNGIE causes gastrointestinal and neurological symptoms in homozygous individuals and is often misdiagnosed as anorexia nervosa, inflammatory bowel disease, or celiac disease. We present the case of a 26-year-old female with MNGIE, who was initially diagnosed with anorexia nervosa and Crohn's disease. The diagnosis of MNGIE was established by biochemical confirmation of elevated serum and urine thymidine and deoxyuridine levels after multiple examinations and several years of disease progression and ineffective treatment. Subsequent molecular genetic testing demonstrated a homozygous TYMP gene mutation. MNGIE should be considered in patients with unexplained malnutrition, intestinal dysmotility, and atypical neurological symptoms.
- MeSH
- biopsie MeSH
- Crohnova nemoc diagnóza MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- hodnocení stavu výživy MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mentální anorexie diagnóza MeSH
- mutace MeSH
- mutační analýza DNA MeSH
- nutriční stav MeSH
- oftalmoplegie vrozené MeSH
- parenterální výživa MeSH
- počítačová rentgenová tomografie MeSH
- podvýživa diagnóza etiologie patofyziologie terapie MeSH
- prediktivní hodnota testů MeSH
- střevní pseudoobstrukce komplikace diagnóza genetika terapie MeSH
- svalová dystrofie okulofaryngeální komplikace diagnóza genetika terapie MeSH
- thymidinfosforylasa genetika MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- thymidinfosforylasa MeSH
- TYMP protein, human MeSH Prohlížeč