While mice fed a high-fat or a lean diet did not have differing rates of hepatocellular carcinoma, when mice on those diets were also exposed to a carcinogen, namely DMBA, mice on the high-fat developed liver cancer while those on the lean diet did not, Shin Yoshimoto from the Japanese Foundation for Cancer Research and colleagues report in Nature.
Further, the investigators found that the gut microbiome has a hand in this effect as the fatty diet leads to changes in the levels of deoxycholic acid present in the gut, a metabolite produced by gut microbes that leads to DNA damage. "The enterohepatic circulation of DCA provokes [senescence-associated secretory] phenotype in hepatic stellate cells, which in turn secretes various inflammatory and tumour-promoting factors in the liver, thus facilitating HCC development in mice after exposure to chemical carcinogen," they write in Nature.
Further, blocking DCA, the researchers note, "efficiently prevents HCC development in obese mice." Yoshimoto tells The Economist that he suspects that the Clostridium strain OUT-1105 is behind the effect.
"If cancer does end up being added to the growing list of problems which an upset microbiome can cause, that may stimulate research into ways of tweaking it to stop it causing disease," The Economist adds. "It will also, once again, emphasize the microbiome's role, for both good and ill, as an adjunct part of the human body."