Erythropoietin supplementation induces dysbiosis of the gut microbiota and impacts mucosal immunity in a non-diseased mouse model

A number of drug treatments are known to alter the dialogue between the gut microbiota and the immune system components in the digestive mucosa. Alterations in intestinal homeostasis are now well known to affect peripheral immune responses and favor the occurrence of a number of pathologies such as...

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Main Authors: Guillaume Sarrabayrouse, Corentin Joulain, Stéphanie Bessoles, Andrada S. Chiron, Amine M. Abina, Salima Hacein-Bey-Abina
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1465410/full
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author Guillaume Sarrabayrouse
Corentin Joulain
Stéphanie Bessoles
Andrada S. Chiron
Andrada S. Chiron
Amine M. Abina
Salima Hacein-Bey-Abina
Salima Hacein-Bey-Abina
author_facet Guillaume Sarrabayrouse
Corentin Joulain
Stéphanie Bessoles
Andrada S. Chiron
Andrada S. Chiron
Amine M. Abina
Salima Hacein-Bey-Abina
Salima Hacein-Bey-Abina
author_sort Guillaume Sarrabayrouse
collection DOAJ
description A number of drug treatments are known to alter the dialogue between the gut microbiota and the immune system components in the digestive mucosa. Alterations in intestinal homeostasis are now well known to affect peripheral immune responses and favor the occurrence of a number of pathologies such as allergies and cancers. Erythropoietin’s known pleiotropic effects might explain the adverse events sometimes observed in anemic patients treated by erythropoiesis-stimulating agents (ESA). However, the impact of this therapeutic cytokine on the homeostasis of the intestinal tract has not previously been investigated in detail. By studying a mouse model of erythropoietin (EPO) supplementation for 28 days, we observed EPO-induced dysbiosis of the fecal microbiota characterized by a greater bacterial load, lower bacterial diversity and taxonomic changes. With regard to the mucosal immune system, an analysis of leukocyte populations in the small intestine and colon treatment revealed low proportions of ileal CD4 lymphocyte subpopulations (Treg, Tr17 and Th17 cells), IgA-secreting plasma cells, and a major macrophage subpopulation, involved in the control of lymphocyte responses. Our results provide for the first time a descriptive analysis of intestinal EPO’s regulatory properties and raise questions about the involvement of EPO-induced alterations in the microbiota and the gut immune effectors in the control of intestinal and peripheral immune responses.
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spelling doaj-art-00de9809f35b40cc84da62b34e31860a2025-01-23T06:56:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14654101465410Erythropoietin supplementation induces dysbiosis of the gut microbiota and impacts mucosal immunity in a non-diseased mouse modelGuillaume Sarrabayrouse0Corentin Joulain1Stéphanie Bessoles2Andrada S. Chiron3Andrada S. Chiron4Amine M. Abina5Salima Hacein-Bey-Abina6Salima Hacein-Bey-Abina7Unité des technologies Chimiques et Biologiques pour la Santé, Université Paris Cité, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), UTCBS, Paris, FranceUnité des technologies Chimiques et Biologiques pour la Santé, Université Paris Cité, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), UTCBS, Paris, FranceUnité des technologies Chimiques et Biologiques pour la Santé, Université Paris Cité, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), UTCBS, Paris, FranceUnité des technologies Chimiques et Biologiques pour la Santé, Université Paris Cité, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), UTCBS, Paris, FranceClinical Immunology Laboratory, Groupe Hospitalier Universitaire Paris-Saclay, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le-Kremlin-Bicêtre, FranceUnité des technologies Chimiques et Biologiques pour la Santé, Université Paris Cité, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), UTCBS, Paris, FranceUnité des technologies Chimiques et Biologiques pour la Santé, Université Paris Cité, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), UTCBS, Paris, FranceClinical Immunology Laboratory, Groupe Hospitalier Universitaire Paris-Saclay, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le-Kremlin-Bicêtre, FranceA number of drug treatments are known to alter the dialogue between the gut microbiota and the immune system components in the digestive mucosa. Alterations in intestinal homeostasis are now well known to affect peripheral immune responses and favor the occurrence of a number of pathologies such as allergies and cancers. Erythropoietin’s known pleiotropic effects might explain the adverse events sometimes observed in anemic patients treated by erythropoiesis-stimulating agents (ESA). However, the impact of this therapeutic cytokine on the homeostasis of the intestinal tract has not previously been investigated in detail. By studying a mouse model of erythropoietin (EPO) supplementation for 28 days, we observed EPO-induced dysbiosis of the fecal microbiota characterized by a greater bacterial load, lower bacterial diversity and taxonomic changes. With regard to the mucosal immune system, an analysis of leukocyte populations in the small intestine and colon treatment revealed low proportions of ileal CD4 lymphocyte subpopulations (Treg, Tr17 and Th17 cells), IgA-secreting plasma cells, and a major macrophage subpopulation, involved in the control of lymphocyte responses. Our results provide for the first time a descriptive analysis of intestinal EPO’s regulatory properties and raise questions about the involvement of EPO-induced alterations in the microbiota and the gut immune effectors in the control of intestinal and peripheral immune responses.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1465410/fullEPO - erythropoietinmucosal immunitymicrobiotamice model experimentsdysbiosis
spellingShingle Guillaume Sarrabayrouse
Corentin Joulain
Stéphanie Bessoles
Andrada S. Chiron
Andrada S. Chiron
Amine M. Abina
Salima Hacein-Bey-Abina
Salima Hacein-Bey-Abina
Erythropoietin supplementation induces dysbiosis of the gut microbiota and impacts mucosal immunity in a non-diseased mouse model
Frontiers in Immunology
EPO - erythropoietin
mucosal immunity
microbiota
mice model experiments
dysbiosis
title Erythropoietin supplementation induces dysbiosis of the gut microbiota and impacts mucosal immunity in a non-diseased mouse model
title_full Erythropoietin supplementation induces dysbiosis of the gut microbiota and impacts mucosal immunity in a non-diseased mouse model
title_fullStr Erythropoietin supplementation induces dysbiosis of the gut microbiota and impacts mucosal immunity in a non-diseased mouse model
title_full_unstemmed Erythropoietin supplementation induces dysbiosis of the gut microbiota and impacts mucosal immunity in a non-diseased mouse model
title_short Erythropoietin supplementation induces dysbiosis of the gut microbiota and impacts mucosal immunity in a non-diseased mouse model
title_sort erythropoietin supplementation induces dysbiosis of the gut microbiota and impacts mucosal immunity in a non diseased mouse model
topic EPO - erythropoietin
mucosal immunity
microbiota
mice model experiments
dysbiosis
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1465410/full
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