Epigenetic alterations in patients with anorexia nervosa-a systematic review.

Anorexia nervosa (AN) is a complex metabolic and psychological disorder that is influenced by both heritable genetic components and environmental factors. Exposure to various environmental influences can lead to epigenetically induced changes in gene expression. Epigenetic research in AN is still in its infancy, and studies to date are limited in determining clear, valid links to disease onset and progression are limited. Therefore, the aim of this systematic review was to compile and critically evaluate the available results of epigenetic studies specifically in AN and to provide recommendations for future studies. In accordance with the PRISMA guidelines, a systematic literature search was performed in three different databases (PubMed, Embase, and Web of Science) through May 2023. Twenty-three original papers or conference abstracts on epigenetic studies in AN were collected. Epigenome-wide association studies (EWASs), which analyze DNA methylation across the genome in patients with AN and identify potential disease-relevant changes in promoter/regulatory regions of genes, are the most promising for future research. To date, five EWASs on AN have been published, suggesting a potential reversibility of malnutrition-induced epigenetic changes once patients recover. Hence, determining differential DNA methylation levels could serve as a biomarker for disease status or early diagnosis and might be involved in disease progression or chronification. For future research, EWASs with a larger sample size, longitudinal study design and uniform methods should be performed to contribute to the understanding of the pathophysiology of AN, the development of individual interventions and a better prognosis for affected patients.

Long-Term Dynamics of Serum α-MSH and α-MSH-Binding Immunoglobulins with a Link to Gut Microbiota Composition in Patients with Anorexia Nervosa.

INTRODUCTION: Immunoglobulins (Ig) reactive with α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, are present in humans and were previously associated with eating disorders. In this longitudinal study involving patients with anorexia nervosa (AN), we determined whether α-MSH in serum is bound to IgG and analyzed long-term dynamics of both α-MSH peptide and α-MSH-reactive Ig in relation to changes in BMI and gut microbiota composition. METHODS: The study included 64 adolescents with a restrictive form of AN, whose serum samples were collected at hospital admission, discharge, and during a 1-year follow-up visit and 41 healthy controls, all females. RESULTS: We found that in both study groups, approximately 40% of serum α-MSH was reversibly bound to IgG and that levels of α-MSH-reactive IgG but not of α-MSH peptide in patients with AN were low at hospital admission but recovered 1 year later. Total IgG levels were also low at admission. Moreover, BMI-standard deviation score correlated positively with α-MSH IgG in both groups studied but negatively with α-MSH peptide only in controls. Significant correlations between the abundance of specific bacterial taxa in the gut microbiota and α-MSH peptide and IgG levels were found in both study groups, but they were more frequent in controls. CONCLUSION: We conclude that IgG in the blood plays a role as an α-MSH-binding protein, whose characteristics are associated with BMI in both patients with AN and controls. Furthermore, the study suggests that low production of α-MSH-reactive IgG during the starvation phase in patients with AN may be related to altered gut microbiota composition.

Considering Sufficient Weight Loss as a Prerequisite for Development of Anorexia Nervosa and Atypical Anorexia Nervosa.

BACKGROUND: Because premorbid BMI strongly predicts the amount of weight loss in anorexia nervosa (AN)/atypical AN, we hypothesize that weight loss triggers both disorders by inducing the endocrine adaptation to starvation. METHOD: We propose research to capture the onset of AN/atypical AN following intentional, otherwise behaviorally motivated, or unintentional weight loss in relationship to premorbid weight. RESULTS: We propose retrospective and prospective studies to examine the temporal development of symptoms in AN/atypical AN. Given a greater frequency of weight loss behaviors in individuals with high BMIs, patients with intentionally driven weight loss should demonstrate a higher mean weight loss and greater premorbid weight and shape concerns. Practice guidelines necessitate weight gain for AN recovery, yet how weight gain induces improvements is unspecified and warrants systematic elucidation. Finally, we highlight implications for the current conceptualization of genetic and environmental contributors of AN/atypical AN in twin and molecular genetic studies. CONCLUSION: We propose separating the starvation-induced mechanisms relevant for AN/atypical AN development from the reasons/mechanisms inherent to weight loss.

MiRNA research-The potential for understanding the multiple facets of anorexia nervosa.

Anorexia nervosa (AN) has a multifaceted and complex pathology, yet major gaps remain in our understanding of factors involved in AN pathology. MicroRNAs (miRNAs) play a regulatory role in translating genes into proteins and help understand and treat diseases. An extensive literature review on miRNAs with AN and comorbidities has uncovered a significant lack in miRNA research. To demonstrate the importance of understanding miRNA deregulation, we surveyed the literature on depression and obesity providing examples of relevant miRNAs. For AN, no miRNA sequencing or array studies have been found, unlike other psychiatric disorders. For depression and obesity, screenings and mechanistic studies were conducted, leading to clinical studies to improve understanding of their regulatory influences. MiRNAs are promising targets for studying AN due to their role as signaling molecules, involvement in psychiatric-metabolic axes, and potential as biomarkers. These characteristics offer valuable insights into the disease's etiology and potential new treatment options. The first miRNA-based treatment for rare metabolic disorders has been approved by the FDA and it is expected that these advancements will increase in the next decade. MiRNA research in AN is essential to examine its role in the development, manifestation, and progression of the disease. PUBLIC SIGNIFICANCE: The current understanding of the development and treatment of AN is insufficient. miRNAs are short regulatory sequences that influence the translation of genes into proteins. They are the subject of research in various diseases, including both metabolic and psychiatric disorders. Studying miRNAs in AN may elucidate their causal and regulatory role, uncover potential biomarkers, and allow for future targeted treatments.

Fecal microbiota transplantation of patients with anorexia nervosa did not alter flexible behavior in rats.

OBJECTIVE: Patients with anorexia nervosa (AN) are often anxious, display inflexible behavior and disrupted reward processing. Emerging evidence suggests that gut dysbiosis in patients contributes to the disease phenotype and progression. METHODS: In a preclinical study, we explored whether AN-derived microbiota impacts cognitive flexibility, anxiety, and dopamine signaling using fecal microbiota transplantation (FMT) in tyrosine hydroxylase-cre rats. We performed probabilistic reversal learning task (PRLT) at the baseline, after antibiotic treatment, and following FMT from patients with AN and controls. We assessed flexible behavior, task engagement, and ventral tegmental area (VTA) dopamine signaling during and in the absence of reward. Furthermore, anxiety-like behavior was evaluated with open field (OF) and elevated plus maze (EPM) tests. RESULTS: Neither antibiotic-induced dysbiosis nor AN FMT led to significant alterations in the number of reversals or lever press strategies after reinforced or nonreinforced lever presses (win and lose-stay) in the PRLT. However, the number of initiated trials decreased after antibiotic treatment while remaining unchanged after FMT. No significant differences were observed in VTA dopamine activity, anxiety measures in the OF and EPM tests. Microbiome analysis revealed limited overlap between the microbiota of the donors and recipients. DISCUSSION: No evidence was found that the microbiota of patients compared to controls, nor a depleted microbiome impacts cognitive flexibility. Nonetheless, antibiotic-induced dysbiosis resulted in reduced task engagement during the PRLT. The relatively low efficiency of the FMT is a limitation of our study and highlights the need for improved protocols to draw robust conclusions in future studies. PUBLIC SIGNIFICANCE: While our study did not reveal direct impacts of AN-associated gut microbiota on cognitive flexibility or anxiety behaviors in our preclinical model, we observed a decrease in task engagement after antibiotic-induced dysbiosis, underscoring that the presence of a gut microbiome matters. Our findings underscore the need for further refinement in FMT protocols to better elucidate the complex interplay between gut microbiota and behaviors characteristic of anorexia nervosa.

Premorbid body weight predicts weight loss in both anorexia nervosa and atypical anorexia nervosa: Further support for a single underlying disorder.

OBJECTIVE: For adolescents, DSM-5 differentiates anorexia nervosa (AN) and atypical AN with the 5th BMI-centile-for-age. We hypothesized that the diagnostic weight cut-off yields (i) lower weight loss in atypical AN and (ii) discrepant premorbid BMI distributions between the two disorders. Prior studies demonstrate that premorbid BMI predicts admission BMI and weight loss in patients with AN. We explore these relationships in atypical AN. METHOD: Based on admission BMI-centile < or ≥5th, participants included 411 female adolescent inpatients with AN and 49 with atypical AN from our registry study. Regression analysis and t-tests statistically addressed our hypotheses and exploratory correlation analyses compared interrelationships between weight loss, admission BMI, and premorbid BMI in both disorders. RESULTS: Weight loss in atypical AN was 5.6 kg lower than in AN upon adjustment for admission age, admission height, premorbid weight and duration of illness. Premorbid BMI-standard deviation scores differed by almost one between both disorders. Premorbid BMI and weight loss were strongly correlated in both AN and atypical AN. DISCUSSION: Whereas the weight cut-off induces discrepancies in premorbid weight and adjusted weight loss, AN and atypical AN overall share strong weight-specific interrelationships that merit etiological consideration. Epidemiological and genetic associations between AN and low body weight may reflect a skewed premorbid BMI distribution. In combination with prior findings for similar psychological and medical characteristics in AN and atypical AN, our findings support a homogenous illness conceptualization. We propose that diagnostic subcategorization based on premorbid BMI, rather than admission BMI, may improve clinical validity. PUBLIC SIGNIFICANCE: Because body weights of patients with AN must drop below the 5th BMI-centile per DSM-5, they will inherently require greater weight loss than their counterparts with atypical AN of the same sex, age, height and premorbid weight. Indeed, patients with atypical AN had a 5.6 kg lower weight loss after controlling for these variables. In comparison to the reference population, we found a lower and higher mean premorbid weight in patients with AN and atypical AN, respectively. Considering previous psychological and medical comparisons showing little differences between AN and atypical AN, we view a single disorder as the most parsimonious explanation. Etiological models need to particularly account for the strong relationship between weight loss and premorbid body weight.

The impact of the COVID-19 pandemic on administrative eating disorder prevalence in the outpatient sector and on severity of anorexia nervosa.

The COVID-19 pandemic appears to have had a considerable impact on the mental health of children and adolescents, particularly regarding eating disorders. However, it remains unclear whether the pandemic affected only the frequency or also the severity of eating disorders. We examined potential pandemic-related changes in the administrative prevalence of eating disorders in the outpatient sector compared with other mental disorders using German statutory health insurance data for the age group 10 to 16 years. We also examined disorder severity of anorexia nervosa using data from the multicenter German Registry of Children and Adolescents with Anorexia Nervosa in the same age group. Our results showed a marked increase in the administrative prevalence of eating disorders (based on documented diagnoses) in the outpatient sector among girls but not among boys. A similar pattern was found for internalizing disorders, whereas the administrative prevalences of externalizing disorders decreased. Regarding the severity of anorexia nervosa among inpatients, we found no pandemic-related changes in body mass index standard deviation score at admission, body weight loss before admission, psychiatric comorbidities and psychopharmacological medication. Given the administrative prevalence increase in the outpatient sector, the lack of impact of the pandemic on the inpatient sector may also be partly due to a shift in healthcare utilization towards outpatient services during the pandemic. Thus, the higher number of children and adolescents requiring specialized and timely outpatient care may be a major concern under pandemic conditions.

Intra-individual cortical networks in Anorexia Nervosa: Evidence from a longitudinal dataset.

OBJECTIVE: This work investigates cortical thickness (CT) and gyrification patterns in Anorexia Nervosa (AN) before and after short-term weight restoration using graph theory tools. METHODS: 38 female adolescents with AN underwent structural magnetic resonance imaging scans at baseline and after - on average - 3.5 months following short-term weight restoration while 53 age-matched healthy controls (HCs) were scanned once. Graph measures were compared between groups and longitudinally within the AN group. Associations with clinical measures such as age of onset, duration of illness, BMI standard deviation score (BMI-SDS), and longitudinal weight changes were tested via stepwise regression. RESULTS: Cortical thickness graphs of patients with acute AN displayed lower modularity and small-world index (SWI) than HCs. Modularity recovered after weight gain. Reduced global efficiency and SWI were observed in patients at baseline compared to HCs based on gyrification networks. Significant associations between local clustering of CT at admission and BMI-SDS, and clustering/global efficiency of gyrification and duration of illness emerged. CONCLUSIONS: Our results indicate a shift towards less organised CT networks in patients with acute AN. After weight recovery, the disarrangement seems to be partially reduced. However, longer-term follow-ups are needed to determine whether cortical organizational patterns fully return to normal.

[New aspects in etiology and treatment of adolescent anorexia nervosa-a postulated bio-psycho-social model and the impact of the COVID-19 pandemic]. / Neue Aspekte in der Ätiologie und Therapie der jugendlichen Anorexia nervosa ­ ein postuliertes biopsychosoziales Modell und die Auswirkungen der COVID-19-Pandemie.

Anorexia nervosa is one of the most frequent chronic disorders of adolescence associated with a high mortality. During the COVID-19-pandemic, the number of hospitalized children and adolescents with anorexia nervosa significantly increased. This article outlines new research findings to decode the etiology of this serious disorder, especially a genetic disposition and changes of metabolism. Against the background of increasing rates during the COVID-19 pandemic, the importance of the gene-environment interaction is discussed, and new treatment forms are described. Besides the development of new biological treatment strategies, there is also some important progress in psychotherapeutic interventions. Carers should always be integrated when treating children and adolescents with anorexia nervosa, which is especially emphasized in the new "home treatment" setting. The new concept of anorexia nervosa as a metabo-psychiatric disorder gives us hope for new research ideas and treatment strategies in this often-debilitating disorder of childhood and adolescence.

Gut Microbiota and Brain Alterations after Refeeding in a Translational Anorexia Nervosa Rat Model.

The gut microbiota composition is causally involved in the regulation of body weight. Through the gut-brain axis, microbiota play a role in psychiatric disorders including anorexia nervosa (AN). Previously, we showed microbiome changes to be associated with brain volume and astrocyte reductions after chronic starvation in an AN animal model. Here, we analyzed whether these alterations are reversible after refeeding. The activity-based anorexia (ABA) model is a well-established animal model that mimics several symptoms of AN. Fecal samples and the brain were analyzed. Like previous results, significant alterations in the microbiome were observed after starvation. After refeeding, including the normalization of food intake and body weight, α- and ß-diversity, as well as the relative abundance of specific genera, were largely normalized in starved rats. Brain parameters appeared to normalize alongside microbial restitution with some aberrations in the white matter. We confirmed our previous findings of microbial dysbiosis during starvation and showed a high degree of reversibility. Thus, microbiome alterations in the ABA model appear to be mostly starvation-related. These findings support the usefulness of the ABA model in investigating starvation-induced effects on the microbiota-gut-brain axis to help comprehend the pathomechanisms of AN and potentially develop microbiome-targeted treatments for patients.

Sex-dependent clinical presentation, body image, and endocrine status in long-term remitted anorexia nervosa.

OBJECTIVE: Although anorexia nervosa (AN) in males has recently gained attention, knowledge of its psychological and physiological outcomes is still scarce. We explore sex-specific characteristics of long-term remitted AN with respect to residual eating disorder (ED) psychopathology, body image, and endocrinology. METHOD: We recruited 33 patients with AN in remission for at least 18 months (24 women, 9 men) and 36 matched healthy controls (HCs). Eating disorder psychopathology and body image ideals were assessed via clinical interviews, questionnaires, and an interactive 3D body morphing tool. Plasma levels of leptin, free triiodothyronine, cortisol, and sex hormones were quantified. Univariate models controlled for age and weight were used to test for the effects of diagnosis and sex. RESULTS: Both patient groups showed residual ED psychopathology but normal weight and hormone levels relative to HCs. Male remitted patients demonstrated significantly stronger muscularity-focused body image ideals, evident in interviews, self-reports, and behavioural data, than both female patients and HCs. CONCLUSIONS: Sex-specific body image characteristics in patients with remitted AN point towards the need to adjust test instruments and diagnostic criteria to male-specific psychopathology. In the future, sufficiently powered studies should evaluate the risk of men with AN developing muscle dysmorphia in the long term.

[Fecal Microbiota Transplants in the Context of (Child and Adolescent) Psychiatric Disorders]. / Fäkale Mikrobiotatransplantationen im Zusammenhang mit (kinder- und jugend-)psychiatrischen Erkrankungen.

Fecal Microbiota Transplants in the Context of (Child and Adolescent) Psychiatric Disorders Abstract: There has recently been a significant increase in interest in gut microbiota and its interaction with the brain (gut-brain axis). Not only are the findings of microbiome research interesting for basic scientists, they also offer relevant insights for clinical practice. A causal relationship between gut microbiome and various somatic diseases such as diabetes mellitus, inflammatory bowel diseases, and obesity as well as psychiatric diseases such as major depression, anxiety disorders, and eating disorders seems plausible. To study the causal relationship of intestinal bacteria with individual phenotypes, researchers apply so-called stool transplantations (fecal microbiota transplantations) in the preclinical context. For this purpose, they transfer microbiota samples from patients into laboratory animals to observe possible changes in phenotype. In the clinical context, fecal microbiota transplantation is already being used with therapeutic intentions for selected diseases, for example, recurrent infections with Clostridioides difficile or inflammatory bowel diseases; they have already become part of the official clinical guidelines for C. difficile. For many other diseases, however, including mental illnesses, the potential of using fecal transplantations for therapeutic purposes is still being explored. Previous findings suggest that the intestinal microbiome, particularly fecal microbiota transplantations, represent a promising starting point for new therapeutic approaches.

Neural mechanisms underlying social recognition and theory of mind in adolescent patients with bulimia nervosa and transdiagnostic comparison with anorexia nervosa.

INTRODUCTION: Theory of mind (ToM) is important for social interactions and typical development and has been found to be impaired in patients with anorexia nervosa (AN) and bulimia nervosa (BN). Hypoactivation in frontotemporal brain regions seems to be the underlying neural mechanism in AN while whole-brain analyses in BN are lacking. METHODS: We used the well-validated social recognition task fMRI paradigm to assess ToM in a total of 72 female adolescents (16 BN, 18 AN and 38 matched healthy controls [HC]). RESULTS: Compared to HCBN , patients with BN showed hyperactivity during ToM-activity in the right frontal pole, middle temporal gyrus and left temporal pole and differed fundamentally from hypoactivation in these regions observed in patients with AN before and after short-term weight rehabilitation. Interaction and overlap analyses confirmed that similar regions were affected in opposite directions in both diseases. Hyperactivations in BN in the right middle temporal gyrus and right frontal pole were associated with clinical BN-severity markers binging and purging frequency. DISCUSSION: The hyperactivation in BN suggest different underlying neural mechanisms for ToM compared to AN. Hyperactivity might correspond to a different but also ineffective cognitive style in patients with BN when approaching social interactions. These important transdiagnostic differences are relevant for future brain-targeted therapeutic approaches.

The effects of probiotics administration on the gut microbiome in adolescents with anorexia nervosa-A study protocol for a longitudinal, double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Knowledge on gut-brain interaction might help to develop new therapies for patients with anorexia nervosa (AN), as severe starvation-induced changes of the microbiome (MI) do not normalise with weight gain. We examine the effects of probiotics supplementation on the gut MI in patients with AN. METHOD: This is a study protocol for a two-centre double-blind randomized-controlled trial comparing the clinical efficacy of multistrain probiotic administration in addition to treatment-as-usual compared to placebo in 60 patients with AN (13-19 years). Moreover, 60 sex- and age-matched healthy controls are included in order to record development-related changes. Assessments are conducted at baseline, discharge, 6 and 12 months after baseline. Assessments include measures of body mass index, psychopathology (including eating-disorder-related psychopathology, depression and anxiety), neuropsychological measures, serum and stool analyses. We hypothesise that probiotic administration will have positive effects on the gut microbiota and the treatment of AN by improvement of weight gain, gastrointestinal complaints and psychopathology, and reduction of inflammatory processes compared to placebo. CONCLUSIONS: If probiotics could help to normalise the MI composition, reduce inflammation and gastrointestinal discomfort and increase body weight, its administration would be a readily applicable additional component of multi-modal AN treatment.

[Parents as Co-Therapists in Home Treatment for Adolescents with Anorexia Nervosa - Factors and Mechanisms]. / Eltern als Ko-Therapeuten im home treatment bei adoleszenter Anorexia nervosa ­Wirkfaktoren und Mechanismen.

Caring for a child with anorexia nervosa (AN) puts a strain on many parents. At the same time, actively involving the parents in treatment to increase their skills tomanage the disorder is important, as it seems to improve the child's prognosis. Home treatment requires the parents to be particularly involved. The aim of this study was to assess parental burden and caregiving skills and the association of these factors with the child's AN pathology in the course of a multidisciplinary home treatment (HoT). After 4 to 8 weeks of inpatient treatment, 22 adolescent patients with AN received home treatment with intensive involvement of their parents as co-therapists. Caregiving burden and caregiving behavior and the symptom severity of the child's AN were assessed using standardized questionnaires on admission to the hospital, at discharge from the HoT, and 1 year after admission (Eating Disorder Inventory-2 (EDI-II), Beck Depression Inventory-2 (BDI-II), Accommodation and Enabling Scale for Eating Disorders (AESED), Eating Disorders Symptom Impact Scale (EDSIS)). Parental burden was reduced and the parents' ability to manage their child's AN improved after the step-down treatment frominpatient treatment to home treatment and was also associated with lower eating disorder-specific psychopathology of the patients. HoT as a treatment setting does not seem to burden the parents as co-therapists and is associated with an improvement in skills in dealing with the child's AN.

BDNF levels in adolescent patients with anorexia nervosa increase continuously to supranormal levels 2.5 years after first hospitalization.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) influences brain plasticity and feeding behaviour, and it has been linked to anorexia nervosa in numerous studies. Findings in mostly adult patients point to reduced serum BDNF levels in the acute stage of anorexia nervosa and rising levels with weight recovery. However, it is unclear whether this increase leads to normalization or supranormal levels, a difference that is potentially important for the etiology of anorexia nervosa and relapse. METHODS: We measured serum BDNF at admission (n = 149), discharge (n = 130), 1-year follow-up (n = 116) and 2.5-year follow-up (n = 76) in adolescent female patients with anorexia nervosa hospitalized for the first time, and in healthy controls (n = 79). We analyzed associations with body mass index, eating disorder psychopathology and comorbidities. RESULTS: Serum BDNF was only nominally lower at admission in patients with anorexia nervosa compared to healthy controls, but it increased continuously and reached supranormal levels at 2.5-year follow-up. BDNF was inversely associated with eating disorder psychopathology at discharge and positively associated with previous weight gain at 1-year follow-up. LIMITATIONS: We compensated for attrition and batch effects using statistical measures. CONCLUSION: In this largest longitudinal study to date, we found only nonsignificant reductions in BDNF in the acute stage of anorexia nervosa, possibly because of a shorter illness duration in adolescent patients. Supranormal levels of BDNF at 2.5-year follow-up could represent a pre-existing trait or a consequence of the illness. Because of the anorexigenic effect of BDNF, it might play an important predisposing role for relapse and should be explored further in studies that test causality.

Gut microbiota alteration in adolescent anorexia nervosa does not normalize with short-term weight restoration.

OBJECTIVE: Gut microbiota are linked to metabolic function, body weight regulation, and brain and behavioral changes. Alteration of gut microbiota is repeatedly demonstrated in adults with anorexia nervosa (AN) and transplantation of stool from adult patients with AN reduces weight gain, food consumption and food efficiency in germ-free mice. No similar data are available for adolescents, who might differ from adults due to their shorter duration of illness. METHOD: Nineteen female adolescent patients with AN at admission and after short-term weight recovery were included in a longitudinal study and compared to 20 healthy controls (HC). DNA was extracted from stool samples and subjected to 16S rRNA gene sequencing and analysis. Group comparisons, indicator genera and simper analysis were applied. Taxon abundances at admission was used to predict inpatient treatment duration. RESULTS: Alpha diversity is increased in patients with AN after short-term weight recovery, while beta diversity shows clear group differences with HC before and after weight gain. A reduction in Romboutsia and taxa belonging to Enterobacteriaceae at both timepoints and an increase in taxa belonging to Lachnospiraceae at discharge are most indicative of patients. Lachnospiraceae abundance at admission helped to predict shorter inpatient treatment duration. DISCUSSION: This pilot study provides first evidence of gut microbiota alterations in adolescent patients with AN that do not normalize with weight gain. If verified in larger studies, the predictive power of taxa belonging to Lachnospiraceae for clinical outcome could complement known predictors at admission, inform clinicians and serve as a target for nutritional interventions.

[The Gut Microbiome and Its Clinical Implications in Anorexia Nervosa]. / Das Darmmikrobiom und seine klinischen Implikationen im Kontext der Anorexia nervosa.

The Gut Microbiome and Its Clinical Implications in Anorexia Nervosa Abstract. The diverse interactions of the gut microbiome with the metabolism, the immune system, and the brain of the host are increasingly becoming to the forefront of relevant research. Studies suggest a connection between an altered intestinal microbiome and somatic diseases, such as colitis ulcerosa, Crohn's disease, and diabetes, as well as mental illnesses such as anxiety and depression. Patients with anorexia nervosa (AN) also show significant changes in their gut microbiome which seem to be associated, among other things, with a different energy uptake from food, immunological and inflammatory processes, genetic predisposition, hormonal changes, and possibly increased intestinal permeability. In rats, stool transplantation from patients with AN resulted in decreased appetite and weight as well as anxious and compulsive behavior. In this review, we summarize the possible mechanisms of interaction between the microbiome and the host, and present initial findings on the microbiome in AN. Research on nutritional interventions, for example, with prebiotics and probiotics or nutritional supplements such as omega-3 fatty acids, which aim to positively influence the intestinal microbiome, could lead to additional treatment options in the therapy of patients with AN.

Vehicle-to-Pedestrian Communication for Vulnerable Road Users: Survey, Design Considerations, and Challenges.

In the last few years, increasing attention has been provided to research Vehicle-to-Pedestrian (V2P) communication systems. These V2P systems serve different purposes (safety or convenience) and cater to different Vulnerable Road User (VRU) groups. Also, these V2P systems employ different communication technologies, and use different mechanisms to interact with the users. An effective V2P system also needs to consider varying characteristics of different VRUs. These various elements may be considered as design parameters of the V2P system. In this paper, we discuss such elements and propose a design framework for the V2P system based on them. We also provide an extensive survey of existing V2P efforts for safety and convenience applications and their design considerations. We perform a case study that compares the different approaches of V2P safety system for different VRU groups under different pre-crash scenarios. Finally, we discuss a few technological challenges in integration of VRUs into V2X systems.