Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Sep;57(9):1868-1881.
doi: 10.1002/eat.24231. Epub 2024 Jun 27.

Fecal microbiota transplantation of patients with anorexia nervosa did not alter flexible behavior in rats

Karlijn L Kooij  1   2 , Nadia Andrea Andreani  3   4 , Luna L van der Gun  1 , Lara Keller  5 , Stefanie Trinh  6 , Benny van der Vijgh  2 , Mieneke Luijendijk  1 , Astrid Dempfle  7 , Beate Herpertz-Dahlmann  6 , Jochen Seitz  6   8 , Annemarie van Elburg  2   9 , Unna N Danner  2 , John Baines  3   4 , Roger A H Adan  1   2   10
Affiliations

Fecal microbiota transplantation of patients with anorexia nervosa did not alter flexible behavior in rats

Karlijn L Kooij et al. Int J Eat Disord. 2024 Sep.

Abstract

Objective: Patients with anorexia nervosa (AN) are often anxious, display inflexible behavior and disrupted reward processing. Emerging evidence suggests that gut dysbiosis in patients contributes to the disease phenotype and progression.

Methods: In a preclinical study, we explored whether AN-derived microbiota impacts cognitive flexibility, anxiety, and dopamine signaling using fecal microbiota transplantation (FMT) in tyrosine hydroxylase-cre rats. We performed probabilistic reversal learning task (PRLT) at the baseline, after antibiotic treatment, and following FMT from patients with AN and controls. We assessed flexible behavior, task engagement, and ventral tegmental area (VTA) dopamine signaling during and in the absence of reward. Furthermore, anxiety-like behavior was evaluated with open field (OF) and elevated plus maze (EPM) tests.

Results: Neither antibiotic-induced dysbiosis nor AN FMT led to significant alterations in the number of reversals or lever press strategies after reinforced or nonreinforced lever presses (win and lose-stay) in the PRLT. However, the number of initiated trials decreased after antibiotic treatment while remaining unchanged after FMT. No significant differences were observed in VTA dopamine activity, anxiety measures in the OF and EPM tests. Microbiome analysis revealed limited overlap between the microbiota of the donors and recipients.

Discussion: No evidence was found that the microbiota of patients compared to controls, nor a depleted microbiome impacts cognitive flexibility. Nonetheless, antibiotic-induced dysbiosis resulted in reduced task engagement during the PRLT. The relatively low efficiency of the FMT is a limitation of our study and highlights the need for improved protocols to draw robust conclusions in future studies.

Public significance: While our study did not reveal direct impacts of AN-associated gut microbiota on cognitive flexibility or anxiety behaviors in our preclinical model, we observed a decrease in task engagement after antibiotic-induced dysbiosis, underscoring that the presence of a gut microbiome matters. Our findings underscore the need for further refinement in FMT protocols to better elucidate the complex interplay between gut microbiota and behaviors characteristic of anorexia nervosa.

Keywords: anorexia nervosa; dopamine signaling; fecal microbiota transplantation; gut‐brain axis; reversal learning.

PubMed Disclaimer

References

REFERENCES

    1. Aarts, E., Ederveen, T. H. A., Naaijen, J., Zwiers, M. P., Boekhorst, J., Timmerman, H. M., Smeekens, S. P., Netea, M. G., Buitelaar, J. K., Franke, B., van Hijum, S. A. F. T., & Arias Vasquez, A. (2017). Gut microbiome in ADHD and its relation to neural reward anticipation. PLoS One, 12(9), 1–17.
    1. Allen, P. J., Jimerson, D. C., Kanarek, R. B., & Kocsis, B. (2017). Impaired reversal learning in an animal model of anorexia nervosa. Physiology and Behavior, 179, 313–318.
    1. American Psychiatric Association (Ed.). (2013). Diagnostic and statistical manual of mental disorders (5th ed.). American Psychiatric Association. https://doi.org/10.1176/appi.books.9780890425596
    1. Andreani, N. A., Sharma, A., Dahmen, B., Specht, H. E., Mannig, N., Ruan, V., Keller, L., Baines, J. F., Herpertz‐Dahlmann, B., Dempfle, A., & Seitz, J. (2024). Longitudinal analysis of the gut microbiome in adolescent patients with anorexia nervosa: Microbiome‐related factors associated with clinical outcome. Gut Microbes, 16(1), 2304158.
    1. Arnoriaga‐Rodríguez, M., Mayneris‐Perxachs, J., Contreras‐Rodríguez, O., Burokas, A., Ortega‐Sanchez, J. A., Blasco, G., Coll, C., Biarnés, C., Castells‐Nobau, A., Puig, J., Garre‐Olmo, J., Ramos, R., Pedraza, S., Brugada, R., Vilanova, J. C., Serena, J., Barretina, J., Gich, J., Pérez‐Brocal, V., … Fernández‐Real, J. M. (2021). Obesity‐associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one‐carbon and aromatic amino acids metabolic pathways. Gut Microbiota, 70(12), 2283–2296.

LinkOut - more resources