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 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.

Study details

Article type

Original Research

Disease / injury model

Melanoma (B16-OVA mouse model)

Duration

14 days

Dose-dependent effect

No

Outcome

Positive

Findings

Both inulin supplementation and inhaled molecular hydrogen therapy (H2T) in mice led to similar increases in circulating CD4+ and CD8+ T cells, and both treatments significantly inhibited melanoma tumor growth. The results suggest that H2 produced by gut microbiota fermentation of inulin mediates the antitumor effect by stimulating immunosurveillance.