Mouna Hanachi

Anorexia nervosa (AN) is the most severe and life-threatening eating disorder. Its pathophysiology remains largely unknown, and no effective treatment currently exists for severe forms of the disease. Gut microbiota (GM) dysbiosis has been consistently reported in AN; however, no study has yet considered the role of the microbiota within the full spectrum of AN symptoms. To investigate the direct involvement of the microbiota in disease symptoms, we developed a murine model of fecal microbiota transplantation (FMT), using germ-free BALB/c mice colonized with fecal samples from well-characterized AN patients and healthy controls. Physiological, organ, and behavioral parameters were systematically monitored. We found that key AN-related features (including food restriction, anxiety-like behavior, physical hyperactivity, and elevated inflammatory responses) were transmitted to germ-free mice following transplantation with AN-derived microbiota. Likewise, organ-specific alterations associated with AN, such as liver dysfunction and disruption of ovarian follicles, were also reproduced. In conclusion, we demonstrate that the transfer of AN microbiota induces behavioral, physiological, and organ-level alterations reminiscent of the human disease. These findings highlight a major role of the gut microbiota in the symptomatology and progression of AN and open new therapeutic perspectives targeting this ecosystem.

Introduction: Involuntary treatment may be a life‐saving option for extremely severe anorexia nervosa (AN) in the context of life‐threatening conditions and refusal of care. The long‐term outcomes of patients undergoing involuntary treatment for AN are poorly understood. This study aims to explore quality of life, long‐term outcomes and attitudes towards involuntary treatment in patients involuntarily treated for extremely severe AN.Methods: 23 patients involuntarily admitted for extremely severe AN (I‐AN), and 25 voluntarily admitted patients (V‐AN) were compared for body mass index (BMI), residual symptoms, quality of life, and attitudes towards treatment almost four years after discharge. In I‐AN, clinical variables were also compared between admission and follow‐up.Results: At follow‐up, weight restoration was higher in V‐AN (p = 0.01), while differences in quality of life, BMI, and mortality rates were not significant between I‐AN and V‐AN (p > 0.05). In I‐AN, BMI increased and weight‐controlling strategies decreased at follow‐up (p < 0.05). Despite negative experiences of involuntary treatment, the perception of the necessity of treatment increased from admission to follow‐up (p < 0.01) and became comparable to V‐AN (p > 0.05).Discussion: Involuntary treatment for AN does not appear to be a barrier to weight gain and clinical improvement, nor to long‐term attitudes towards treatment.

This Special Issue of Nutrients, entitled “Nutritional Management and Outcomes in Anorexia Nervosa”, aims to advance aspects of the scientific understanding of some serious or frequent somatic involvements and of the precocious nutrition management of severe forms of the disease in order to assist clinicians in the management of such patients

Introduction: Body image distortion is a core symptom of anorexia nervosa (AN), embodying dissatisfaction and overvaluation of body appearance and weight. Body image distortion is an important factor in the maintenance of weight loss behaviours such as compulsive physical exercise. Conversely, physical exercise seems to have an aggravating effect on body image in patients with AN, but the evidence is still poor. The aim of this study was to examine the relationship between body image distortion and physical exercise in AN in order to understand whether physical exercise may play a specific role in body image distortion beyond psychopathological severity. Methods: Forty patients with AN and 21 healthy controls were tested for body image distortion and different proxies of physical exercise. Univariate correlations tested the relationship between body image distortion and physical exercise in AN and control groups. Then, to experimentally assess the effect of exercise on body image distortion, participants were invited to rate their body image before and after a standardised effort test. Results: In the AN group, a correlation was found between physical activity and body image distortion (p < 0.01), which was still significant after controlling for psychopathological severity. No correlation was found in healthy controls. After a standardised effort, patients with AN had higher increases in body image distortion than healthy controls (almost 4 kg/m² vs. 0.8 kg/m²) (p < 0.01). Discussion: Physical exercise may contribute to the distortion of body image in anorexia nervosa and explain the paradoxical augmentation of unhealthy exercise despite ongoing weight loss.

Anorexia nervosa (AN) is a severe eating disorder which can lead to malnutrition and life threatening complications with high mortality rates. We designed our analysis to identify gut microbial taxa differentially abundant between AN and HC across different 16S rRNA gene datasets. We identified a reduced abundance, diversity and richness of Roseburia genus in the microbiota of patients with AN. Cares leading to partial recovery of patients with AN during hospitalization did not restore Roseburia to the levels of HC. AN dietary habit, either purgative or restrictive, did not affect Roseburia abundance. Roseburia genus and related species abundance were correlated with different health host metabolic markers. Roseburia species are key functional taxa in the human gut microbiome. Low gut Roseburia levels have been linked with other human pathologies. Our study highlights Roseburia species as a major decreased component in the gut of patients with AN.

Objective: Anorexia nervosa (AN) is associated with one of the highest mortality rates of any psychiatric disorder but limited mortality data were reported for those with extremely severe malnutrition. This study aimed to estimate standardized mortality ratio (SMR), investigate predictive factors of mortality and causes of death among a sample of patients with AN admitted to a specialized clinical nutrition unit (CNU) because of extremely severe malnutrition.Methods: Between 11/27/1997 and 01/15/2014, vital status was determined for 384 patients admitted for AN at the first time in the CNU. Sociodemographic, anamnestic, and clinical data were collected. We calculated the SMR. Univariate and multivariate Cox regression analyses were performed to identify mortality predictors.Results: Crude mortality rate was 11.5%. (44 deaths) and SMR 15.9 [CI 95% (11.6–21.4)], 5.2 years post inpatient treatment. Mortality predictors at the time of hospitalization were as follows: older age, occurrence of an in‐hospital suicide attempt, transfer to medical intensive care unit and the following somatic complications: frank anemia, dysnatremia, infectious and cardiac complications. Other predictors of mortality were: past or present history of discharge against medical advice, hematological comorbidities (not related to AN). A longer inpatient length of stay was a protective factor.Conclusion: Very severely malnourished patients with AN hospitalized in a medical unit because of extremely severe somatic issues have a medium‐term mortality rate higher than the general population and even higher than patients in tertiary specialized ED units. This study highlights predictive factors of mortality that will help clinicians in recognizing and managing patients at risk of death.

Background: Anorexia Nervosa (AN) is a complex psychiatric disorder that can lead to specific somatic complications. Heart abnormalities are frequently reported, while their frequency and associated factors in severely malnourished AN patients remain poorly defined. Objectives: This study aimed to characterize echocardiographic abnormalities in severely malnourished AN patients and to assess associated clinical, biological and related body composition features. Methods: Between January 2013 and January 2015, all severely malnourished adult patients with AN (Mental Disorders, 4th Edn.-DSM IVr) were included in a monocentric study performed in in a highly specialized AN inpatient unit. Electrocardiogram (ECG) and echocardiography were used to assess both heart rhythm and function. All inpatients underwent a Doppler echocardiography procedure after undergoing combined blood volume adjustment, micronutrients deficiencies supplementation and electrolyte disorders correction. Right Ventricular (RV) and Left Ventricular (LV) systolic and diastolic functions were collected and compared to 29 healthy normal subjects in a control group. Results: One hundred and 24 patients (119 (96%) women, 5 (4%) men) with a mean age of 30.1 ± 11 years old and an average Body Mass Index (BMI) of 12 kg/m² were included. Ninety patients (73%) had been diagnosed with AN Restrictive type (AN-R), 34 (27%) an AN Binge eating/Purging type (AN-BP). Eighteen patients (15%) disclosed an abnormal Left Ventricular Ejection Fraction (LVEF) (< 52% for male and < 54% for female). LVEF impairment was associated with AN-BP patients (p < 0.017) and hypertransaminasemia (AST and/or ALT ≥2 N) (p < 0.05). Left Ventricular mass (LV mass) and Left Ventricular End Diastolic Diameter (LVEDD) were significantly reduced in patients (p < 0.001, p < 0.001). Left and right ventricular tissue Doppler Imaging Velocities (TDI) peak were reduced in patients: Septal and Lateral LV Sm velocities peaks respectively 10 ± 2 cm/s (vs 14 ± 2 cm/s in controls, p < 0.001), 12 ± 3 cm/s (vs 16 ± 3 cm/s in controls, p < 0.001), basal RV Sm velocity peaks at 14 ± 3 cm/s (vs 19 ± 3 cm/s in controls, p < 0.001). Additionally, LV and RV diastolic velocity peaks were reduced: LV septal and lateral velocity peaks were respectively 13 ± 3 cm/s (vs 18 ± 2 cm/s p < 0.001), 12 ± 3 cm/s (vs 22 ± 4 cm/s, p < 0.001) and RV diastolic velocity peaks at 14 ± 3 cm/s (vs 21 ± 4 cm/s p < 0.001). LV diastolic velocity TDI peaks were significantly associated with hypertransaminasemia (p < 0.05) and tended to be associated with a low all body Fat-Free Mass Index (FFMI) (using Dual-energy X- ray Absorptiometry (DXA) (HOLOGICQDR 4500) (p = 0.056). Thirty-four patients (27%) had a pericardial effusion and were significantly associated with a decreased all body FFMI (p < 0.036). Conclusion: Heart abnormalities are frequent in malnourished patients with AN, particularly in AN-BP type. Both liver enzymes and body composition abnormalities tended to be associated with heart dysfunction (non-significant association). Prospective studies are needed to better characterize and describe the evolution of cardiac abnormalities during the refeeding period and subsequent weight restoration.

Introduction: Anorexia nervosa (AN) is a complex psychiatric disorder, which can lead to specific somatic complications. Undernutrition is a major diagnostic criteria of AN which can be associated with several micronutrients deficiencies. Objectives: This study aimed to determinate the prevalence of micronutrients deficiencies and to compare the differences between the two subtypes of AN (restricting type (AN-R) and binge-eating/purging type (AN-BP)). Methods: We report a large retrospective, monocentric study of patients hospitalized in a highly specialized nutrition unit between January 2011 and August 2017 for severe malnutrition treatment in the context of anorexia nervosa. Results: Three hundred and seventy-four patients (360 (96%) women, 14 (4%) men), age: 31.3 ± 12.9 years, Body Mass Index (BMI) 12.5 ± 1.7 kg/m² were included; 253 (68%) patients had AN-R subtype while, 121 (32%) had AN-BP. Zinc had the highest deficiency prevalence 64.3%, followed by vitamin D (54.2%), copper (37.1%), selenium (20.5%), vitamin B1 (15%), vitamin B12 (4.7%), and vitamin B9 (8.9%). Patients with AN-BP type had longer disease duration, were older, and had a lower left ventricular ejection fraction (LVEF) (p < 0.001, p = 0.029, p = 0.009), when compared with AN-R type, patients who instead, had significantly higher Alanine Aminotransferase (ALT) and Brain Natriuretic Peptide (BNP) levels (p < 0.001, p < 0.021). In the AN-BP subgroup, as compared to AN-R, lower selenium (p < 0.001) and vitamin B12 plasma concentration (p < 0.036) were observed, whereas lower copper plasma concentration was observed in patients with AN-R type (p < 0.022). No significant differences were observed for zinc, vitamin B9, vitamin D, and vitamin B1 concentrations between the two types of AN patients. Conclusion: Severely malnourished AN patients have many micronutrient deficiencies. Differences between AN subtypes are identified. Micronutrients status of AN patients should be monitored and supplemented to prevent deficiencies related complications and to improve nutritional status. Prospective studies are needed to explore the symptoms and consequences of each deficiency, which can aggravate the prognosis during recovery.