Molecular hydrogen as a potential mediator of the antitumor effect of inulin consumption

Abstract Inulin consumption and dihydrogen (H2) administration both exert antitumor effects on preclinical models as well as in clinical trials. As H2 is one of the major byproducts of inulin fermentation by bacterial species of the gut microbiota (GM), we hypothesized that H2 could mediate the anti...

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Main Authors: Victor Pascal-Moussellard, Jean-Pierre Alcaraz, Stéphane Tanguy, Cordélia Salomez-Ihl, Philippe Cinquin, François Boucher, Emilie Boucher
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-96346-3
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author Victor Pascal-Moussellard
Jean-Pierre Alcaraz
Stéphane Tanguy
Cordélia Salomez-Ihl
Philippe Cinquin
François Boucher
Emilie Boucher
author_facet Victor Pascal-Moussellard
Jean-Pierre Alcaraz
Stéphane Tanguy
Cordélia Salomez-Ihl
Philippe Cinquin
François Boucher
Emilie Boucher
author_sort Victor Pascal-Moussellard
collection DOAJ
description Abstract Inulin consumption and dihydrogen (H2) administration both exert antitumor effects on preclinical models as well as in clinical trials. As H2 is one of the major byproducts of inulin fermentation by bacterial species of the gut microbiota (GM), we hypothesized that H2 could mediate the antitumor effects of inulin. To provide evidence in favor of this hypothesis, we first determined the pattern of H2-exposure to which mice are subjected after inulin administration and developed an inhaled hydrogen therapy (H2T) protocol replicating this pattern. We then compared the effects on circulating immunity of a two-week daily inulin gavage with those of the corresponding H2T. We also compared the effects of inulin supplementation to those of the corresponding H2T on implanted melanoma growth and infiltration by T lymphocytes. Inulin and H2T induced a similar increase in circulating CD4+ and CD8+ T cells. In addition, both treatments similarly inhibited melanoma tumor growth. These results support a mechanism by which the H2 resulting from inulin fermentation by the GM diffuses across the intestinal barrier and stimulates the immunosurveillance responsible for the antitumor effect.
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spelling doaj-art-9b36fb30b7a646a5808c00669bde8b972025-08-20T03:07:41ZengNature PortfolioScientific Reports2045-23222025-04-0115111110.1038/s41598-025-96346-3Molecular hydrogen as a potential mediator of the antitumor effect of inulin consumptionVictor Pascal-Moussellard0Jean-Pierre Alcaraz1Stéphane Tanguy2Cordélia Salomez-Ihl3Philippe Cinquin4François Boucher5Emilie Boucher6Univ. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMCUniv. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMCUniv. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMCUniv. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMCUniv. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMCUniv. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMCUniv. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMCAbstract Inulin consumption and dihydrogen (H2) administration both exert antitumor effects on preclinical models as well as in clinical trials. As H2 is one of the major byproducts of inulin fermentation by bacterial species of the gut microbiota (GM), we hypothesized that H2 could mediate the antitumor effects of inulin. To provide evidence in favor of this hypothesis, we first determined the pattern of H2-exposure to which mice are subjected after inulin administration and developed an inhaled hydrogen therapy (H2T) protocol replicating this pattern. We then compared the effects on circulating immunity of a two-week daily inulin gavage with those of the corresponding H2T. We also compared the effects of inulin supplementation to those of the corresponding H2T on implanted melanoma growth and infiltration by T lymphocytes. Inulin and H2T induced a similar increase in circulating CD4+ and CD8+ T cells. In addition, both treatments similarly inhibited melanoma tumor growth. These results support a mechanism by which the H2 resulting from inulin fermentation by the GM diffuses across the intestinal barrier and stimulates the immunosurveillance responsible for the antitumor effect.https://doi.org/10.1038/s41598-025-96346-3InulinMolecular hydrogenMelanomaImmunosurveillance
spellingShingle Victor Pascal-Moussellard
Jean-Pierre Alcaraz
Stéphane Tanguy
Cordélia Salomez-Ihl
Philippe Cinquin
François Boucher
Emilie Boucher
Molecular hydrogen as a potential mediator of the antitumor effect of inulin consumption
Scientific Reports
Inulin
Molecular hydrogen
Melanoma
Immunosurveillance
title Molecular hydrogen as a potential mediator of the antitumor effect of inulin consumption
title_full Molecular hydrogen as a potential mediator of the antitumor effect of inulin consumption
title_fullStr Molecular hydrogen as a potential mediator of the antitumor effect of inulin consumption
title_full_unstemmed Molecular hydrogen as a potential mediator of the antitumor effect of inulin consumption
title_short Molecular hydrogen as a potential mediator of the antitumor effect of inulin consumption
title_sort molecular hydrogen as a potential mediator of the antitumor effect of inulin consumption
topic Inulin
Molecular hydrogen
Melanoma
Immunosurveillance
url https://doi.org/10.1038/s41598-025-96346-3
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