Abstract
Esophageal adenocarcinoma (EAC) is mostly prevalent in industrialized countries and has been associated with obesity, commonly linked with a diet rich in fat and refined sugars containing high fructose concentrations. In meta-organisms, dietary components are digested and metabolized by the host and its gut microbiota. Fructose has been shown to induce proliferation and cell growth in pancreas and colon cancer cell lines and also alter the gut microbiota. In a previous study with the L2-IL-1B mouse model, we showed that a high-fat diet (HFD) accelerated EAC progression from its precursor lesion Barrett’s esophagus (BE) through changes in the gut microbiota. Aiming to investigate whether a high-fructose diet (HFrD) also alters the gut microbiota and favors EAC carcinogenesis, we assessed the effects of HFrD on the phenotype and intestinal microbial communities 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 in EAC progression in a less pronounced manner than HFD.
Highlights
The increase in many industrialized countries of obesity, metabolic syndrome, and associated comorbidities suggests that food choices have an impact on the pathogenesis of diverse diseases, cancer [1,2]
While inflammation and metaplasia scores did not differ between groups (Figure 1A–C), high-fructose diet (HFrD)-fed mice showed higher dysplasia scores (Figure 1D), a lower percentage of goblet-like cells (Figure 1E), and a lower mucus production rate (PAS staining) in the Barrett’s esophagus (BE) region (Figure 1G)
Expansion of Lgr5-positive progenitor cells in the BE region increased significantly in 6-month-old HFrD compared with CD mice (Figure 1F)
Summary
The increase in many industrialized countries of obesity, metabolic syndrome, and associated comorbidities suggests that food choices have an impact on the pathogenesis of diverse diseases, cancer [1,2]. Esophageal adenocarcinoma (EAC) is one of many cancer types associated with obesity. The incidence of EAC in most Western industrialized countries has increased at a rate exceeding that of any other cancer, with a 5-year survival rate that remains poor [3,4,5,6]. The risk factors for EAC include white race, older age, male gender, tobacco use, high waist circumference, obesity, and gastroesophageal reflux disease (GERD), but the greatest risk factor is Barrett’s esophagus (BE) [3,4]. BE appears to be the result of severe esophageal mucosa injury, followed by aberrant epithelial repair [6]
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