High-Fructose Diet accelerates early tumorigenesis in a Mouse Model of Barrett´s Esophagus through effects on the gut microbiota

Esophageal adenocarcinoma (EAC) is mostly prevalent in industrialized countries and has been associated with obesity, commonly linked to a diet rich in fat and refined sugars containing high fructose-concentrations. In metaorganisms, dietary components are digested and metabolized by the host and its microbiota. Fructose has been shown to induce proliferation and cell growth in pancreas and colon cancer cell lines; and also induce dysbiosis in the gut microbiota. In a previous study with the L2-IL-1B mouse model, we showed that high-fat diet (HFD) accelerated EAC-progression from its precursor lesion Barrett´s esophagus (BE) through changes in the gut microbiome. Aiming to investigate whether a high-fructose diet (HFrD) also alters the gut microbiome and favors EAC carcinogenesis, we assessed the effects of HFrD on the phenotype and gut microbiota of L2-IL1B mice. Results showed a moderate acceleration in histologic disease progression, a mild effect on the systemic inflammatory response, metabolic changes in the host and a shift in the composition, metabolism and functionality of intestinal microbial communities. We conclude that HFrD alters the overall balance of the gut microbiota and induces an acceleration on EAC progression in a less pronounced manner than HFD