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.

KEYWORDS:

• Microbiota
• anorexia nervosa
• eating disorder
• gut-brain axis
• adolescents
• longitudinal study
• weight-recovered patients
• low-weight patients
• illness duration
• long-term follow-up

Acknowledgments

The work was supported by the ERA-NET Neuron program (01EW1906A-01EW1906B) funded by the European Union; the Deutsche Forschungsgemeinschaft (DFG) under the Grant SE 2787/3-1 (“The role of the intestinal microbiome regarding prognosis and therapy in adolescent Anorexia nervosa – clinical and translational analyses”); the Deutsche Forschungsgemeinschaft (DFG) Research Unit FOR5042 under Grant DE1614/4-1 (“The microbiome as a therapeutic target in inflammatory bowel diseases”); the Deutsche Forschungsgemeinschaft (DFG) Excellence Cluster under Grant E×C2167(“Precision Medicine in Chronic 688 Inflammation PMI”).

The authors are grateful to Mrs. Katja Cloppenborg-Schmidt and Mrs. Yasmin Claußen for their excellent technical support, and to the Clinical Trial Center Aachen (CTC-A) for their support in conducting the study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

JS, JB, and BHD designed the study; BD, HS, NM, VR, and JS recruited the participants and helped gather clinical data and stool and blood samples; HS and LK oversaw sample logistics. NA analyzed the stool samples; NA, AS, and AD performed statistical analyses. NA, AS, and JS wrote the first draft of the manuscript. All coauthors revised the manuscript and agreed to its publication.

Data availability statement

Data available on request due to privacy/ethical restrictions.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2304158

Additional information

Funding

The work was supported by the ERA-NET Neuron program (01EW1906A-01EW1906B) funded by the EU; Bundesministerium für Bildung und Forschung [01EW1906A]; Deutsche Forschungsgemeinschaft [Grant SE 2787/3-1]; Deutsche Forschungsgemeinschaft [Grant DE1614/4-1]; Deutsche Forschungsgemeinschaft [Grant EXC2167].