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

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.