Longitudinal analysis of the gut microbiome in adolescent patients with anorexia nervosa: microbiome-related factors associated with clinical outcome

Abstract

There is mounting evidence regarding the role of gut microbiota in anorexia nervosa (AN). Previous studies have reported that patients with AN show dysbiosis compared to healthy controls (HCs); however, the underlying mechanisms are unclear, and data on influencing factors and longitudinal course of microbiome changes are scarce. Here, we present longitudinal data of 57 adolescent inpatients diagnosed with AN at up to nine time points (including a 1-year follow-up examination) and compare these to up to six time points in 34 HCs. 16S rRNA gene sequencing was used to investigate the microbiome composition of fecal samples, and data on food intake, weight change, hormonal recovery (leptin levels), and clinical outcomes were recorded. Differences in 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 the 1-year follow-up. Illness duration and prior weight loss were strongly associated with microbiome composition at hospital admission, whereas 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 a higher body weight at the 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 interactions 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.

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

“…There is ample evidence to suggest that the gut microbiome plays a crucial role in modulating the immune system [ 84 ]. The apparent state of gut dysbiosis in patients with AN [ 30 , 40 , 46 , 85 ] might contribute to the observed inflammatory dysregulation. Thus, we explored alterations between time points in cytokine levels and their associations with corresponding changes in bacterial taxon abundance for the core genera (those with significantly different abundances between the AN and HC groups at admission).…”

“…Recent studies have focused on elucidating the precise effects of the gut microbiota on distinct enteric target structures [ 39 , 90 ]. Andreani et al [ 46 ] examined longitudinal microbiome changes in adolescent patients with AN, finding that bacterial taxon abundances at admission were prognostic of hospital readmission. For instance, higher Sutterella abundances were associated with higher body weight in patients at the 1-year follow-up.…”

“…All stool samples from the patients and healthy controls were shipped on dry ice to collaborators at the University and Max Planck Institute in Kiel (Germany) for DNA extraction (using a DNeasy Power Soil Kit; Qiagen, Hilden, Germany) and sequencing. The resulting microbiome data, which were recently published by Andreani et al [ 46 ], also served as the basis for this study. Microbial community characteristics were analysed by investigating the V1V2 region of the 16S rRNA gene.…”

“…We focused on variation among the three time points in the abundance of the core genera (i.e., those present in ≥25% of individuals, with a relative frequency ≥1%). This method is described in more detail by Andreani et al [ 46 ].…”