PHGG supplementation modulates gut microbiome metabolites and breast cancer progression

Short-chain fatty acids (SCFAs) are linked to improved anti-tumor immune responses and reduced breast cancer risk. Isoflavones in soybean-based (SB) high fiber diets may block fiber's advantages by triggering immunosuppression. We investigated the effect of SB diet, combined with partially hydrolyzed guar gum (PHGG) supplementation, on triple negative E0771 mammary tumor growth in mice fed AIN93G control or SB diet. Some SB-fed mice received PHGG or maltodextrin (MDX) control in drinking water. We found that SB diet increased tumor burden, and both MDX and PHGG revered the increase. Fecal microbiota transplants (FMTs) were prepared from the AIN93G, SB, SB+PHGG, and SB+MDX fed mice, and transferred to antibiotic-treated hosts fed AIN93G diet. Tumor burden was similar in hosts receiving FMT from AIN93G, SB, or SB+MDX donors, suggesting that SB diet did not increase mammary tumorigenesis through changes in the gut microbiome but perhaps directly by affecting immune cells in the tumor microenvironment. Mice receiving FMT from SB+PHGG fed donors exhibited significantly reduced tumor burden. To further investigate whether cellulose in AIN93G diet affected PHGG's ability to reduce mammary tumorigenesis, compared with MDX, we fed mice cellulose-free AIN93G diet. In this setting, PHGG reduced tumorigenesis compared with MDX. However, PHGG increased fecal SCFAs both in cellulose containing and cellulose-free AIN93G diet fed mice. Further, PHGG-supplemented mice exhibited significantly increased FFAR3 expression in CD4+ T cells in the spleen. Our findings indicate that PHGG reduces mammary tumorigenesis in mice fed fiber-deficient diet, and the effect is likely mediated through the gut microbiome.