Impact of Gut Microbiota on Eosinophilic Esophagitis Progression

Role of the Endocannabinoid System in Eosinophilic Esophagitis

The endocannabinoid system (ECS) plays a crucial role in maintaining gastrointestinal homeostasis and is implicated in various gastrointestinal disorders, including EoE. The ECS consists of endocannabinoids, cannabinoid receptors, and metabolic enzymes. Recent studies suggest that alterations in the ECS may contribute to the pathophysiology of EoE through mechanisms that involve inflammation and immune responses.

In patients with active EoE, a significant downregulation of monoacylglycerol lipase (MGL), an enzyme responsible for the degradation of 2-arachidonoylglycerol (2-AG), has been observed. This downregulation leads to increased levels of 2-AG, which can recruit eosinophils via cannabinoid receptor 2 (CB2). This recruitment is thought to exacerbate the inflammatory response in EoE, highlighting the importance of the ECS in this condition (Gruden et al., 2025).

Effects of Monoglyceride Lipase on Eosinophil Infiltration

MGL’s role in EoE extends beyond mere enzymatic activity; it is involved in regulating eosinophil infiltration into the esophageal epithelium. The increased availability of 2-AG due to MGL downregulation enhances eosinophil migration and activation. Inhibition of MGL in epithelial cells has been shown to promote a pro-inflammatory phenotype, further exacerbating eosinophilic infiltration. Animal models of EoE demonstrate that targeting CB2 can reduce eosinophil numbers in the esophagus, suggesting that the ECS may be a viable therapeutic target in managing EoE (Gruden et al., 2025).

Relationship Between EoE and Cannabinoid Receptor Activity

Research indicates that cannabinoid receptors, particularly CB2, play a pivotal role in immune modulation during EoE. Activation of CB2 has been associated with various immune responses, including the modulation of eosinophil activity. The ECS’s involvement in EoE suggests that cannabinoid-based therapies might offer new avenues for treatment. However, caution is warranted, as some studies suggest that cannabis use may lead to increased inflammatory features post-treatment in EoE patients, indicating a complex relationship between cannabinoid receptor activity and disease progression (Gruden et al., 2025).

Influence of Gut Microbiota on Esophageal Epithelial Function

The gut microbiota significantly influences various physiological processes, including immune response and inflammation, which are critical in the context of EoE. Dysbiosis, characterized by an imbalance in microbial communities, has been linked to the onset and progression of EoE. Studies suggest that certain microbial species can modulate immune responses, thereby affecting eosinophil recruitment and activation.

Moreover, the metabolites produced by gut microbiota, such as short-chain fatty acids (SCFAs), play essential roles in maintaining gut homeostasis and modulating inflammation. SCFAs have been shown to enhance the production of anti-inflammatory cytokines and promote epithelial barrier integrity, which may be beneficial in managing EoE (Zhang et al., 2025).

Table 1: Impact of Gut Microbiota on EoE

Therapeutic Implications for Eosinophilic Esophagitis Management

The interplay between gut microbiota, the ECS, and eosinophilic infiltration opens new avenues for therapeutic strategies in EoE management. Probiotics, prebiotics, and dietary interventions that promote a balanced gut microbiome may help mitigate EoE symptoms by enhancing epithelial integrity and reducing inflammation.

Additionally, cannabinoid-based therapies targeting the ECS could provide a novel approach to managing eosinophil activity and inflammation in EoE. However, further research is necessary to explore the long-term effects of such treatments and their potential implications for patient outcomes (Gruden et al., 2025).

FAQ

What is eosinophilic esophagitis?
Eosinophilic esophagitis (EoE) is a chronic inflammatory condition characterized by eosinophil infiltration in the esophagus, leading to symptoms such as difficulty swallowing, food impaction, and esophageal strictures.

How does the endocannabinoid system affect EoE?
The endocannabinoid system influences immune responses and inflammation in EoE. Downregulation of monoacylglycerol lipase (MGL) leads to increased levels of 2-arachidonoylglycerol (2-AG), which recruits eosinophils and exacerbates inflammation.

Can gut microbiota influence EoE?
Yes, gut microbiota can significantly affect EoE progression. Dysbiosis is linked to increased inflammation and eosinophil activity, while beneficial microbial species may help maintain gut homeostasis and reduce symptoms.

What therapeutic options are available for EoE?
Therapeutic options for EoE include dietary changes, probiotics, prebiotics, and potential cannabinoid-based therapies aimed at modulating eosinophil activity and enhancing epithelial integrity.

Are there any dietary recommendations for EoE patients?
Patients with EoE may benefit from a diet rich in fiber and low in allergens, which can promote a healthy gut microbiome and reduce inflammation.

References

1. Gruden, E., Kienzl, M., Danner, L., Kaspret, D. M., Pammer, A., Ristic, D., Kindler, O., Doyle, A. D., Wright, B. L., Taschler, U., Thomas, D., Gurke, R., Baumann-Durchschein, F., Konrad, J., Blesl, A., Schlager, H., & Bärnthaler, T. (2025). The Endocannabinoid System Drives Eosinophil Infiltration During Eosinophilic Esophagitis. Cellular and Molecular Gastroenterology and Hepatology. https://doi.org/10.1016/j.jcmgh.2025.101515

2. Zhang, Q., Liu, Y., Li, Y., Bai, G., Pang, J., Wu, M. (2025). Implications of gut microbiota-mediated epigenetic modifications in intestinal diseases. Gut Microbes

3. Yuan, J., Gao, C., Zhang, H., & Feng, L. (2025). Screening and validation of 3’-Methoxydaidzein as a therapeutic agent in ulcerative colitis based on disulfidptosis-associated molecular clusters. PLOS One. https://doi.org/10.1371/journal.pone.0324586

4. Gruden, E., Kienzl, M., Danner, L., Kaspret, D. M., Pammer, A., Ristic, D., Kindler, O., Doyle, A. D., Wright, B. L., Taschler, U., Thomas, D., Gurke, R., Baumann-Durchschein, F., Konrad, J., Blesl, A., Schlager, H., & Bärnthaler, T. (2025). The Endocannabinoid System Drives Eosinophil Infiltration During Eosinophilic Esophagitis. Cellular and Molecular Gastroenterology and Hepatology. https://doi.org/10.1016/j.jcmgh.2025.101515

5. Chen, D., Jiang, W., Wu, P., Liu, Y., Ren, H., Jin, X., Zhou, X., & Feng, L. (2025). Mechanism of fumonisin B1 on growth performance and intestinal structural integrity of juvenile grass carp (Ctenopharyngodon idella). Animal Nutrition. https://doi.org/10.1016/j.aninu.2024.11.023

6. Kargl, J., Kindler, O., Wright, B. L., Taschler, U., Thomas, D., Gurke, R., Baumann-Durchschein, F., Konrad, J., & Blesl, A. (2025). Eosinophilic Esophagitis: The Role of the Endocannabinoid System. Cellular and Molecular Gastroenterology and Hepatology. https://doi.org/10.1016/j.jcmgh.2025.101515