IntroductionAnorexia nervosa (AN) is an often chronic and debilitating psychiatric disease whose etiology is not completely understood. Recently, a potential role of inflammation has emerged in other psychiatric diseases, such as depression, PTSD and schizophrenia. The first results in adults with AN seemed to confirm a low-grade proinflammatory state until recent studies presented more differential findings. Studying adolescents with a shorter illness duration and fewer confounding factors might help elucidate the role of inflammation in the underlying pathophysiology of AN; however, the few available studies in adolescents remain ambiguous, and no longitudinal data are available in this age range.MethodsWe examined the proinflammatory cytokines Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1β, IL-6, IL-15, and the cytokine-receptor IL-6 Receptor alpha (IL-6 Rα) in the serum of twenty-two hospitalized female adolescent patients with AN longitudinally at admission and discharge and compared their results to nineteen healthy controls (HC). We also collected clinical data and stool samples that were analyzed with 16S rRNA amplicon sequencing to explore potential influencing factors of cytokine changes.ResultsTNF-α serum levels were significantly elevated in patients with AN at admission, while IL-1β and IL-6 levels were lower at admission and discharge than in HC. After treatment, we also found significantly elevated levels of IL-6 Rα compared to HC, while IL-15 did not show significant changes. Exploratory analyses revealed positive associations of cytokine and genus-level changes between admission and discharge for IL-1β (Bacteroides) and IL-15 (Romboutsia), and negative associations for IL-15 (Anaerostipes) and TNF-α (uncultured Lachnospiraceae).ConclusionWe confirmed a previous finding of elevated levels of TNF-α also in adolescents with AN; however, the reduced IL-1β and IL-6 levels differed from the mostly increased levels found in adults. A mixed pro- and anti-inflammatory state appears to be present in adolescents, potentially due to their shorter illness duration. The gut microbiota, with its regulatory function on cytokine production, might play a role in mediating these inflammatory processes in AN and could offer targets for new therapeutic approaches.

There is mounting evidence about the role of gut microbiota in anorexia nervosa (AN). Previous studies reported patients with AN to show dysbiosis compared to healthy controls (HCs), however, underlying mechanisms are unclear and data on influencing factors and the longitudinal course of microbiome changes are scarce. Here we present longitudinal data of 57 adolescent inpatients diagnosed with AN at up to nine timepoints (including 1-year follow-up examination) and compare these to up to six timepoints in 34 HCs. 16S rRNA gene sequencing was used to investigate the microbiome composition of fecal samples, while data on food intake, weight change, hormonal recovery (leptin levels) and clinical outcome were recorded. Differences in the microbiome composition compared to HCs were greatest during acute starvation and in the low-weight group, while diminishing with weight gain and especially weight recovery at 1-year follow-up. Illness duration and prior weight loss were strongly associated with microbiome composition at hospital admission, while microbial changes during treatment were associated with kilocalories consumed, weight gain and hormonal recovery. The microbiome at admission was prognostic for hospital readmission and a higher abundance of Sutterella was associated with higher body weight at 1-year follow-up. Identifying these clinically important factors further underlines the potential relevance of gut microbial changes and may help elucidate the underlying pathophysiology of gut-brain interaction in AN. The characterization of prognostically relevant taxa could be useful to stratify patients at admission and to potentially identify candidate taxa for future supplementation studies aimed at improving AN-treatment.