Role of the gut microbiota in the remodelling of the jejunal, colonic, hepatic and blood proteomes in a mouse model of Anorexia Nervosa
- 1University of Rouen
Abstract
Background: Anorexia nervosa (AN) is a typical form of eating disorder characterized by a severe body weight loss, a fear of gaining weight and dysmorphophobia. This disorder is associated with both psychiatric comorbidities and multi-organ dysfunctions. Increasing evidence suggests a role of the gut microbiota in the onset or maintenance of AN. Although a dysbiosis has been reported in patients with AN, the physiological consequences of this dysbiosis remain poorly documented. To gain further insight into the role of the gut microbiota in the pathophysiology of AN, we used the murine Activity-based Anorexia (ABA) model and compared the remodelling of the jejunal, colonic, hepatic and blood proteomes occurring in male mice with intact gut microbiota, as well as in gut microbiota-depleted animals. Results: We observed a significant proteome remodelling in several organs in response to the ABA model. More than 250 proteins involved in energy metabolism, catabolic processes, lipid metabolism, ghrelin regulation, and immune functions were found to show altered abundance in ABA mice compared to control mice. We observed in addition in the blood of ABA mice a significant increase in the level of circulating proteasome. By comparing mice treated or not with antibiotics, we identified 75 proteins whose regulation in ABA mice is gut-microbiota dependent. The other identified proteins were similarly affected in ABA mice with intact or depleted gut microbiota, suggesting that these factors are mainly regulated by food starvation and physical activity, and not directly by the gut microbiota. We finally confirmed that ORM2, a protein identified as significantly decreased in the plasma of ABA mice, is also decreased in the blood of patients suffering from AN. Conclusion: Our results demonstrate that the Activity-Based Anorexia model is associated with an extensive proteome remodelling in several organs and tissues. We highlight in addition that some of these targets are regulated in a gut microbiota-dependent manner, thereby reinforcing the hypothesis of a role of the gut microbiota in Anorexia Nervosa. Together, our study provides a valuable resource to better delineate the impact of undernutrition and maladaptive physical activity on the proteome of various organs and the role of the gut bacteria in the pathophysiology of Anorexia Nervosa.
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BibTeX
@misc{breton2026role,
title = {{Role of the gut microbiota in the remodelling of the jejunal, colonic, hepatic and blood proteomes in a mouse model of Anorexia Nervosa}},
author = {J. Breton and E. Timmerman and L. Houzard and M. Hure and C. Salaün and D. Van Haver and J.-L. do Rego and M. Galmiche and M. Quillard and M.-P. Tavolacci and N. Achamrah and P. Dechelotte and M. Coëffier and F. Impens and D. Ribet},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.28.762490},
url = {https://www.biorxiv.org/content/10.64898/2026.10.28.762490v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Role of the gut microbiota in the remodelling of the jejunal, colonic, hepatic and blood proteomes in a mouse model of Anorexia Nervosa
AU - J. Breton
AU - E. Timmerman
AU - L. Houzard
AU - M. Hure
AU - C. Salaün
AU - D. Van Haver
AU - J.-L. do Rego
AU - M. Galmiche
AU - M. Quillard
AU - M.-P. Tavolacci
AU - N. Achamrah
AU - P. Dechelotte
AU - M. Coëffier
AU - F. Impens
AU - D. Ribet
PY - 2026
DA - 2026/10/28
PB - bioRxiv
DO - 10.64898/2026.10.28.762490
UR - https://www.biorxiv.org/content/10.64898/2026.10.28.762490v1
AB - Background: Anorexia nervosa (AN) is a typical form of eating disorder characterized by a severe body weight loss, a fear of gaining weight and dysmorphophobia. This disorder is associated with both psychiatric comorbidities and multi-organ dysfunctions. Increasing evidence suggests a role of the gut microbiota in the onset or maintenance of AN. Although a dysbiosis has been reported in patients with AN, the physiological consequences of this dysbiosis remain poorly documented. To gain further insight into the role of the gut microbiota in the pathophysiology of AN, we used the murine Activity-based Anorexia (ABA) model and compared the remodelling of the jejunal, colonic, hepatic and blood proteomes occurring in male mice with intact gut microbiota, as well as in gut microbiota-depleted animals. Results: We observed a significant proteome remodelling in several organs in response to the ABA model. More than 250 proteins involved in energy metabolism, catabolic processes, lipid metabolism, ghrelin regulation, and immune functions were found to show altered abundance in ABA mice compared to control mice. We observed in addition in the blood of ABA mice a significant increase in the level of circulating proteasome. By comparing mice treated or not with antibiotics, we identified 75 proteins whose regulation in ABA mice is gut-microbiota dependent. The other identified proteins were similarly affected in ABA mice with intact or depleted gut microbiota, suggesting that these factors are mainly regulated by food starvation and physical activity, and not directly by the gut microbiota. We finally confirmed that ORM2, a protein identified as significantly decreased in the plasma of ABA mice, is also decreased in the blood of patients suffering from AN. Conclusion: Our results demonstrate that the Activity-Based Anorexia model is associated with an extensive proteome remodelling in several organs and tissues. We highlight in addition that some of these targets are regulated in a gut microbiota-dependent manner, thereby reinforcing the hypothesis of a role of the gut microbiota in Anorexia Nervosa. Together, our study provides a valuable resource to better delineate the impact of undernutrition and maladaptive physical activity on the proteome of various organs and the role of the gut bacteria in the pathophysiology of Anorexia Nervosa.
ER -