Cytokine and Microbiome Changes in Adolescents with Anorexia Nervosa at Admission, Discharge, and One-Year Follow-Up.

Anorexia nervosa (AN) is a severe eating disorder that predominantly affects females and typically manifests during adolescence. There is increasing evidence that serum cytokine levels are altered in individuals with AN. Previous research has largely focused on adult patients, assuming a low-grade pro-inflammatory state. The serum levels of the cytokine tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6 and IL-15, which are pro-inflammatory, were examined in 63 female adolescents with AN and 41 age-matched healthy controls (HC). We included three time points (admission, discharge, and 1-year follow-up) and investigated the clinical data to assess whether the gut microbiota was associated with cytokine alterations. Relative to the HC group, serum levels of IL-1ß and IL-6 were significantly lower during the acute phase (admission) of AN. IL-1ß expression was normalised to control levels after weight recovery. TNF-α levels were not significantly different between the AN and HC groups. IL-15 levels were significantly elevated in patients with AN at all time points. We found associations between cytokines and bodyweight, illness duration, depressive symptoms, and the microbiome. In contrast to most findings for adults, we observed lower levels of the pro-inflammatory cytokines IL-1ß and IL-6 in adolescent patients, whereas the level of IL-15 was consistently increased. Thus, the presence of inflammatory dysregulation suggests a varied rather than uniform pro-inflammatory state.

Gut microbiota and body composition in anorexia nervosa inpatients in comparison to athletes, overweight, obese, and normal weight controls.

OBJECTIVES: Anorexia nervosa (AN) is a heterogeneous eating disorder associated with alterations of body structure and the gut microbiome. We aimed to investigate the gut microbiota composition of a large female cohort including different BMI groups and activity levels along with body composition parameters. METHOD: 106 female participants were included in this cross-sectional study: AN patients (n = 18), athletes (n = 20), normal weight (n = 26), overweight (n = 22), and obese women (n = 20). DNA was extracted from stool samples and subjected to 16S rRNA gene analysis. The software Quantitative Insights Into Microbial Ecology (QIIME) was used to analyze data. Additionally, we performed anthropometric assessments, ultrasound measurements of subcutaneous adipose tissue thickness, bioimpedance analysis, administered depression inventories, and ascertained laboratory parameters and dietary intakes. RESULTS: Alpha diversity was particularly lower in AN patients and obese participants compared to other groups, while athletes showed highest alpha diversity. Several categories significantly associated with community structure were identified: body fat parameters, serum lipids, CRP, depression scales and smoking. Comparative analysis revealed Coriobacteriaceae as the only enriched phylotype in AN compared to other entities (LDA score >3.5). DISCUSSION: This study provides further evidence of intestinal dysbiosis in AN and sheds light on characteristics of the gut microbiome in different BMI and physical activity groups. These insights point to new modulation possibilities of the gut microbiota which could improve the standard therapy of AN.

Intestinal microbiota - a key to understanding the pathophysiology of anorexia nervosa? / Mikrobiota jelitowa ­ klucz do zrozumienia patofizjologii jadlowstretu psychicznego?

Anorexia nervosa (AN) is a psychiatric disorder related to very serious consequences for physical and mental health of patients. Due to a complex clinical picture, which consists of anumber of somatic and mental symptoms, AN remains a serious problem of modern medicine and encourages the search for possible causes of the illness and new, more effective therapies. The recent reports emphasize the role of the intestinal microbiota in regulation of body weight. In this light, the hypothesis that in AN patients there is a significant imbalance of the intestinal microbiota, which contributes to the pathogenesis of the illness, seems interesting. The results of the latest research suggest that abnormal composition of the intestinal microbiota may be an important factor supporting cachexia of AN patients. Detailed analyzes of the composition of the microbiota characteristic for anorexia nervosa could be useful in developing new methods for monitoring and treatment of this illness. This paper aims to present the current state of the art about the role of the intestinal microbiota in the pathogenesis, course and treatment of AN.

Elevated plasma concentrations of bacterial ClpB protein in patients with eating disorders.

OBJECTIVE: Caseinolytic protease B (ClpB) produced by Enterobacteria, such as Escherichia coli, has been identified as a conformational mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic and anxiogenic neuropeptide. In mice, ClpB induces α-MSH cross-reactive antibodies and activates anorexigenic brain neurons. In patients with eating disorders (ED), anti-ClpB and anti-α-MSH antibodies correlate with psychopathological traits. However, it is not known if ClpB is present in human plasma including ED patients. METHODS: Plasma concentrations of ClpB were measured using a recently developed ClpB immunoassay in female patients with anorexia nervosa, bulimia nervosa, and binge-eating disorder and compared with healthy participants, all characterized by the Eating Disorder Inventory-2 (EDI-2) scale. RESULTS: We found that ClpB was readably detectable in plasma of healthy participants and ED patients and that its concentrations were elevated in ED patients, without significant differences in patient's subgroups. Plasma ClpB concentrations correlated with the EDI-2 scores, with α-MSH as well as with plasma levels of anti-ClpB and anti-α-MSH antibodies. DISCUSSION: These data revealed that bacterial ClpB is naturally present in human plasma and that its concentrations can be elevated in ED patients and associated with ED-related psychopathological traits. These results support a link between bacterial ClpB and the ED pathophysiology. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:805-808).