Q106982900
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Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
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Genetické studie poruch příjmu potravy (AN, BN a BED), které mají multifaktoriální příčinu vzniku, vyžadují upřesnění fenotypizace jednotlivých subtypů onemocnění a studie vztahů mezi nimi a vlivy enviromentu. Současná fenotypizace neodpovídá klinicky používané klasifikaci. Proto autoři navrhují přidat k sledování a upřesnění charakteristik endofenotypů (neurofyziologické koreláty, měření bolesti, hyperaktivity a kognitivních faktorů v patologickém vnímání vlastního těla) ještě koreláty genetické. V genetické části projektu budou studovány varianty baterie genů, související se vznikem AN a BN a/nebo modifikují jejich průběh a vyústění. Zaměříme se na geny ovlivňující centrální mechanismus regulace příjmu potravy, související se stresovými faktory: receptory serotoninu, dopaminu, stresové proteiny, neurotrofní faktor; insulin-like growth factor-2; COMT a poprvé u PPP i geny pro tvorbu plynných molekul, jejichž polymorfizmy podle některých studií ovlivňují chování.; Genetic studies of eating disorders (AN, BN and BED), which have a multifactorial etiology, require a more precise phenotyping of various subtypes. Therefore, the authors propose to add refinement of characteristic endophenotypes (neurophysiological correlates, measurement of pain, overactive and cognitive factors in pathological perception of own body). The genetic part of the project will address a battery of genes related to the development of AN and BN and/or modify their course and outcome. We will focus on genes influencing the central regulation of food intake and on stress, personality and autoaggressive factors: serotonin, dopamine and cannabinoid receptors, stress proteins (Hsp 70 and 32), neurotrophic factors, insulin-like growth factor-2; arginine vasopressin 1a receptor, COMT and polymorphisms within nNOS. In families with multiple disease precipitation, new method of exome sequencing will be used to search for novel genetic determinants responsible for fenotypic expression the disease.
- MeSH
- bulimia nervosa genetika MeSH
- endofenotypy analýza MeSH
- exom MeSH
- genetická predispozice k nemoci MeSH
- mentální anorexie genetika MeSH
- metaanalýza jako téma MeSH
- nemoc vyvolaná prostředím MeSH
- poruchy příjmu potravy genetika MeSH
- záchvatovité přejídání genetika MeSH
- Konspekt
- Psychiatrie
- NLK Obory
- psychiatrie
- genetika, lékařská genetika
- environmentální vědy
- biologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
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.
- 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
Steroid profiling helps various pathologies to be rapidly diagnosed. Results from analyses investigating steroidogenic pathways may be used as a tool for uncovering pathology causations and proposals of new therapeutic approaches. The purpose of this study was to address still underutilized application of the advanced GC-MS/MS platform for the multicomponent quantification of endogenous steroids. We developed and validated a GC-MS/MS method for the quantification of 58 unconjugated steroids and 42 polar conjugates of steroids (after hydrolysis) in human blood. The present method was validated not only for blood of men and non-pregnant women but also for blood of pregnant women and for mixed umbilical cord blood. The spectrum of analytes includes common hormones operating via nuclear receptors as well as other bioactive substances like immunomodulatory and neuroactive steroids. Our present results are comparable with those from our previously published GC-MS method as well as the results of others. The present method was extended for corticoids and 17alpha-hydroxylated 5alpha/ß-reduced pregnanes, which are useful for the investigation of alternative "backdoor" pathway. When comparing the analytical characteristics of the present and previous method, the first exhibit by far higher selectivity, and generally higher sensitivity and better precision particularly for 17alpha-hydroxysteroids.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- lidé MeSH
- novorozenec MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí metody normy MeSH
- steroidy krev MeSH
- tandemová hmotnostní spektrometrie metody normy MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Intrahepatic cholestasis of pregnancy (ICP) is a frequent liver disorder, mostly occurring in the third trimester. ICP is not harmful to the mothers but threatens the fetus. The authors evaluated steroid alterations in maternal and mixed umbilical blood to elucidate their role in the ICP development. Ten women with ICP were included in the study. Steroids in the maternal blood were measured by Gas Chromatography-Mass Spectrometry (GC-MS) (n=58) and RIA (n=5) at the diagnosis of ICP, labor, day 5 postpartum, week 3 postpartum and week 6 postpartum. The results were evaluated by ANOVA consisting of the subject factor, between subject factors ICP, gestational age at the diagnosis of ICP and gestational age at labor, within-subject factor Stage and ICP × Stage interaction. The 17 controls were firstly examined in the week 36 of gestation. ICP patients showed reduced CYP17A1 activity in the C17,20 lyase step thus shifting the balance between the toxic conjugated pregnanediols and harmless sulfated 5alpha/beta-reduced-17-oxo C19 steroids. Hence, more toxic metabolites originating in maternal liver from the placental pregnanes may penetrate backward to the fetal circulation. As these alterations persist in puerperium, the circulating steroids could be potentially used for predicting the predisposition to ICP even before next pregnancy.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- genetická predispozice k nemoci genetika MeSH
- intrahepatální cholestáza krev diagnóza genetika MeSH
- jaterní testy trendy MeSH
- komplikace těhotenství krev diagnóza genetika MeSH
- lidé MeSH
- placentární oběh fyziologie MeSH
- steroidy krev MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Body image represents a multidimensional concept including body image evaluation and perception of body appearance. Disturbances of body image perception are considered to be one of the central aspects of anorexia nervosa and bulimia nervosa. There is growing evidence that body image distortion can be associated with changes in pain perception. The aim of our study was to examine the associations between body image perception, body dissatisfaction, and nociception in women with eating disorders and age-matched healthy control women. We measured body dissatisfaction and pain sensitivity in 61 patients with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition diagnoses of eating disorders (31 anorexia nervosa and 30 bulimia nervosa) and in 30 healthy women. Thermal pain threshold latencies were evaluated using an analgesia meter and body image perception and body dissatisfaction were assessed using Anamorphic Micro software (digital pictures of their own body distorted into larger-body and thinner-body images). Patients with eating disorders overestimated their body size in comparison with healthy controls, but the two groups did not differ in body dissatisfaction. In anorexia and bulimia patient groups, body dissatisfaction (calculated in pixels as desired size/true image size) correlated with pain threshold latencies (r=0.55, p=0.001), while between body image perception (determined as estimation size/true image size) and pain threshold, no correlation was found. Thus, we demonstrated that in patients with eating disorders, pain perception is significantly associated with emotional contrary to sensory (visual) processing of one's own body image. The more the patients desired to be thin, the more pain-sensitive they were. Our findings based on some shared mechanisms of body dissatisfaction and pain perception support the significance of negative emotions specific for eating disorders and contribute to better understanding of the psychosomatic characteristics of this spectrum of illnesses.
- Publikační typ
- časopisecké články MeSH
