From the gut to disease: Microbiota-derived short chain fatty acids and their precursors lactate and succinate in atherosclerosis and cancer
Lídia Cedó, Ana Madeira, Pau Caro
Abstract
Atherosclerosis and cancer are two of the most prevalent chronic diseases worldwide, representing leading causes of morbidity and mortality. These conditions share overlapping risk factors and pathophysiological mechanisms, including persistent inflammation, oxidative stress, immune dysregulation, aberrant apoptosis, uncontrolled proliferation, and angiogenesis. In recent years, the gut microbiota and its metabolites have emerged as key players in these processes. Beyond serving as markers of dysbiosis, microbial-derived compounds actively influence host physiology by modulating immune responses, inflammatory pathways, and metabolic homeostasis. This review explores the shared pathological links between atherosclerosis and cancer through the lens of microbial-derived metabolites, with a particular focus on short-chain fatty acids and their precursors, lactate and succinate. We discuss the mechanisms by which these metabolites influence disease progression -including G protein-coupled receptor activation and epigenetic modulation-, and therapeutic strategies aimed at modulating these metabolites.