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

Inulin consumption and dihydrogen (H) administration both exert antitumor effects on preclinical models as well as in clinical trials. As H is one of the major byproducts of inulin fermentation by bacterial species of the gut microbiota (GM), we hypothesized that H could mediate the antitumor effects of inulin. To provide evidence in favor of this hypothesis, we first determined the pattern of H-exposure to which mice are subjected after inulin administration and developed an inhaled hydrogen therapy (HT) protocol replicating this pattern. We then compared the effects on circulating immunity of a two-week daily inulin gavage with those of the corresponding HT. We also compared the effects of inulin supplementation to those of the corresponding HT on implanted melanoma growth and infiltration by T lymphocytes. Inulin and HT 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 H resulting from inulin fermentation by the GM diffuses across the intestinal barrier and stimulates the immunosurveillance responsible for the antitumor effect.