Antibiotic-Induced Microbial Dysbiosis Worsened Outcomes in the Activity-Based Anorexia Model

Karlijn L Kooij; Nadia Andrea Andreani; Lara Keller; Stefanie Trinh; Luna van der Gun; Jamie Hak; Keith Garner; Mieneke Luijendijk; Lisa Drost; Unna Danner; Annemarie van Elburg; Astrid Dempfle; Jochen Seitz; Beate Herpertz-Dahlmann; John F Baines; Roger A H Adan

doi:10.1002/eat.24452

Antibiotic-Induced Microbial Dysbiosis Worsened Outcomes in the Activity-Based Anorexia Model

Karlijn L Kooij, Nadia Andrea Andreani, Lara Keller, Stefanie Trinh, Luna van der Gun, Jamie Hak, Keith Garner, Mieneke Luijendijk, Lisa Drost, Unna Danner, Annemarie van Elburg, Astrid Dempfle, Jochen Seitz, Beate Herpertz-Dahlmann, John F Baines, Roger A H Adan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

OBJECTIVE: Anorexia nervosa (AN) is a complex psychiatric disorder characterized by persistent dieting and reduced food intake, leading to significantly low body weight. Dysbiosis in the gut microbiome of patients with AN has been suggested to contribute to the pathogenesis. Here, we used fecal microbiota transplantation (FMT) in the activity-based anorexia (ABA) rat model to investigate the impact of AN-associated gut microbiota on disease-related outcomes.

METHOD: We validated the FMT in 12 Wistar rats by depleting the gut microbiome with antibiotics and transplanting two donors' fecal samples. We then transplanted fecal samples from four patients with AN or four healthy controls in 48 rats just before the ABA model exposure and included an antibiotic-only control group. During ABA, the rats had access to a running wheel and only 1.5 h access to chow for 7 days. We monitored body weight, body temperature, food intake, wheel revolutions, and gut microbiome biodiversity and composition.

RESULTS: The antibiotic treatment significantly depleted the rats' gut microbiome and subsequent transplantation made the rats' microbiome more similar to the donors' microbiome. The antibiotic-only group showed reduced survival, as well as lower body weight and temperature during ABA. Transplanted microbiota from patients with AN and healthy controls improved outcomes in the ABA model.

DISCUSSION: We do not find evidence that the microbiome of patients with AN differentially contributes to anorexia-like phenotypes based upon partial microbiome transplantation. However, the presence of a microbiome impacts the outcome of the ABA model.

Original language	English
Journal	International Journal of Eating Disorders
DOIs	https://doi.org/10.1002/eat.24452
Publication status	E-pub ahead of print - 2 May 2025

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). International Journal of Eating Disorders published by Wiley Periodicals LLC.

Funding

This work was supported by the ERANET\u2010NEURON 2018 (#MIGBAN FKZ: 01EW1906A\u201301EW1906B) grant and Deutsche Forschungsgemeinschaft (DFG; BA 2863/14\u20101, project number 509492174). Funding: This work was supported by the ERANET\u2010NEURON 2018 (#MIGBAN FKZ: 01EW1906A\u201001EW1906B) grant and Deutsche Forschungsgemeinschaft (DFG; BA 2863/14\u20101, project number 509492174).

Funders	Funder number
ERA_Net	MIGBAN FKZ: 01EW1906A-01EW1906B
Deutsche Forschungsgemeinschaft (DFG)	BA 2863/14-1, 509492174

Keywords

activity-based anorexia model
anorexia nervosa
fecal microbiota transplantation
microbiome depletion
microbiome dysbiosis

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10.1002/eat.24452Licence: CC BY-NC-ND

Cite this

Kooij, K. L., Andreani, N. A., Keller, L., Trinh, S., van der Gun, L., Hak, J., Garner, K., Luijendijk, M., Drost, L., Danner, U., van Elburg, A., Dempfle, A., Seitz, J., Herpertz-Dahlmann, B., Baines, J. F., & Adan, R. A. H. (2025). Antibiotic-Induced Microbial Dysbiosis Worsened Outcomes in the Activity-Based Anorexia Model. International Journal of Eating Disorders. Advance online publication. https://doi.org/10.1002/eat.24452

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title = "Antibiotic-Induced Microbial Dysbiosis Worsened Outcomes in the Activity-Based Anorexia Model",

abstract = "OBJECTIVE: Anorexia nervosa (AN) is a complex psychiatric disorder characterized by persistent dieting and reduced food intake, leading to significantly low body weight. Dysbiosis in the gut microbiome of patients with AN has been suggested to contribute to the pathogenesis. Here, we used fecal microbiota transplantation (FMT) in the activity-based anorexia (ABA) rat model to investigate the impact of AN-associated gut microbiota on disease-related outcomes.METHOD: We validated the FMT in 12 Wistar rats by depleting the gut microbiome with antibiotics and transplanting two donors' fecal samples. We then transplanted fecal samples from four patients with AN or four healthy controls in 48 rats just before the ABA model exposure and included an antibiotic-only control group. During ABA, the rats had access to a running wheel and only 1.5 h access to chow for 7 days. We monitored body weight, body temperature, food intake, wheel revolutions, and gut microbiome biodiversity and composition.RESULTS: The antibiotic treatment significantly depleted the rats' gut microbiome and subsequent transplantation made the rats' microbiome more similar to the donors' microbiome. The antibiotic-only group showed reduced survival, as well as lower body weight and temperature during ABA. Transplanted microbiota from patients with AN and healthy controls improved outcomes in the ABA model.DISCUSSION: We do not find evidence that the microbiome of patients with AN differentially contributes to anorexia-like phenotypes based upon partial microbiome transplantation. However, the presence of a microbiome impacts the outcome of the ABA model.",

keywords = "activity-based anorexia model, anorexia nervosa, fecal microbiota transplantation, microbiome depletion, microbiome dysbiosis",

author = "Kooij, {Karlijn L} and Andreani, {Nadia Andrea} and Lara Keller and Stefanie Trinh and {van der Gun}, Luna and Jamie Hak and Keith Garner and Mieneke Luijendijk and Lisa Drost and Unna Danner and {van Elburg}, Annemarie and Astrid Dempfle and Jochen Seitz and Beate Herpertz-Dahlmann and Baines, {John F} and Adan, {Roger A H}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). International Journal of Eating Disorders published by Wiley Periodicals LLC.",

year = "2025",

month = may,

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doi = "10.1002/eat.24452",

language = "English",

journal = "International Journal of Eating Disorders",

issn = "0276-3478",

publisher = "John Wiley and Sons Inc.",

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Kooij, KL, Andreani, NA, Keller, L, Trinh, S, van der Gun, L, Hak, J, Garner, K, Luijendijk, M, Drost, L, Danner, U , van Elburg, A, Dempfle, A, Seitz, J, Herpertz-Dahlmann, B, Baines, JF & Adan, RAH 2025, 'Antibiotic-Induced Microbial Dysbiosis Worsened Outcomes in the Activity-Based Anorexia Model', International Journal of Eating Disorders. https://doi.org/10.1002/eat.24452

TY - JOUR

T1 - Antibiotic-Induced Microbial Dysbiosis Worsened Outcomes in the Activity-Based Anorexia Model

AU - Kooij, Karlijn L

AU - Andreani, Nadia Andrea

AU - Keller, Lara

AU - Trinh, Stefanie

AU - van der Gun, Luna

AU - Hak, Jamie

AU - Garner, Keith

AU - Luijendijk, Mieneke

AU - Drost, Lisa

AU - Danner, Unna

AU - van Elburg, Annemarie

AU - Dempfle, Astrid

AU - Seitz, Jochen

AU - Herpertz-Dahlmann, Beate

AU - Baines, John F

AU - Adan, Roger A H

PY - 2025/5/2

Y1 - 2025/5/2

N2 - OBJECTIVE: Anorexia nervosa (AN) is a complex psychiatric disorder characterized by persistent dieting and reduced food intake, leading to significantly low body weight. Dysbiosis in the gut microbiome of patients with AN has been suggested to contribute to the pathogenesis. Here, we used fecal microbiota transplantation (FMT) in the activity-based anorexia (ABA) rat model to investigate the impact of AN-associated gut microbiota on disease-related outcomes.METHOD: We validated the FMT in 12 Wistar rats by depleting the gut microbiome with antibiotics and transplanting two donors' fecal samples. We then transplanted fecal samples from four patients with AN or four healthy controls in 48 rats just before the ABA model exposure and included an antibiotic-only control group. During ABA, the rats had access to a running wheel and only 1.5 h access to chow for 7 days. We monitored body weight, body temperature, food intake, wheel revolutions, and gut microbiome biodiversity and composition.RESULTS: The antibiotic treatment significantly depleted the rats' gut microbiome and subsequent transplantation made the rats' microbiome more similar to the donors' microbiome. The antibiotic-only group showed reduced survival, as well as lower body weight and temperature during ABA. Transplanted microbiota from patients with AN and healthy controls improved outcomes in the ABA model.DISCUSSION: We do not find evidence that the microbiome of patients with AN differentially contributes to anorexia-like phenotypes based upon partial microbiome transplantation. However, the presence of a microbiome impacts the outcome of the ABA model.

AB - OBJECTIVE: Anorexia nervosa (AN) is a complex psychiatric disorder characterized by persistent dieting and reduced food intake, leading to significantly low body weight. Dysbiosis in the gut microbiome of patients with AN has been suggested to contribute to the pathogenesis. Here, we used fecal microbiota transplantation (FMT) in the activity-based anorexia (ABA) rat model to investigate the impact of AN-associated gut microbiota on disease-related outcomes.METHOD: We validated the FMT in 12 Wistar rats by depleting the gut microbiome with antibiotics and transplanting two donors' fecal samples. We then transplanted fecal samples from four patients with AN or four healthy controls in 48 rats just before the ABA model exposure and included an antibiotic-only control group. During ABA, the rats had access to a running wheel and only 1.5 h access to chow for 7 days. We monitored body weight, body temperature, food intake, wheel revolutions, and gut microbiome biodiversity and composition.RESULTS: The antibiotic treatment significantly depleted the rats' gut microbiome and subsequent transplantation made the rats' microbiome more similar to the donors' microbiome. The antibiotic-only group showed reduced survival, as well as lower body weight and temperature during ABA. Transplanted microbiota from patients with AN and healthy controls improved outcomes in the ABA model.DISCUSSION: We do not find evidence that the microbiome of patients with AN differentially contributes to anorexia-like phenotypes based upon partial microbiome transplantation. However, the presence of a microbiome impacts the outcome of the ABA model.

KW - activity-based anorexia model

KW - anorexia nervosa

KW - fecal microbiota transplantation

KW - microbiome depletion

KW - microbiome dysbiosis

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U2 - 10.1002/eat.24452

DO - 10.1002/eat.24452

M3 - Article

C2 - 40317768

SN - 0276-3478

JO - International Journal of Eating Disorders

JF - International Journal of Eating Disorders

ER -

Antibiotic-Induced Microbial Dysbiosis Worsened Outcomes in the Activity-Based Anorexia Model

Abstract

Bibliographical note

Funding

Keywords

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