Obesity and cancer: a gut microbial connection.

Multiple epidemiological studies have revealed that excess bodyweight, such as in people who are overweight or obese (defined by a body mass index higher than 25 kg/m(2)), is a major risk factor for not only diabetes and cardiovascular diseases but also cancer. Effective strategies for obesity prevention are therefore needed for cancer prevention. However, because the prevalence of excess bodyweight in most developed countries has been increasing markedly over the past several decades, with no signs of abating, alternative approaches are also required to conquer obesity-associated cancer. Therefore, we sought to understand the molecular mechanisms underlying obesity-associated cancer. Although several phenomena have been proposed to explain how obesity increases cancer risk, the exact molecular mechanisms that integrate these phenomena have remained largely obscure. Recently, we have traced the association between obesity and increased cancer risk to gut microbiota communities that produce a DNA-damaging bile acid. The analyses also revealed the role of cellular senescence in cancer, which we have been studying for the past few decades. In this review, we provide an overview of our work and discuss the next steps, focusing on the potential clinical implications of these findings. ©2014 AACR.