Microbiome and Esophageal Adenocarcinoma—Letter

The article by Peters and colleagues (1) published in Cancer Research presents exciting new evidence on the association between the oral microbiome and the two main esophageal cancers, adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). The authors examined 368 samples consisting of cases and matched controls, and report inverse associations between the abundance of Streptococcus pneumoniae and Neisseria (1), two oral commensals, and the incidence of EAC. Furthermore, they describe an association between higher EAC risk and bacterial biosynthesis of siderophores (1), molecules often associated with virulence.

The authors highlight an inverse association between bacterial biosynthesis of carotenoids and EAC risk (1). In support, Taylor and colleagues in 1994 reported a 42% reduction of esophageal cancer prevalence following nutritional intervention with β-carotene, vitamin E, and selenium (2). More recently, Ibiebele and colleagues have shown that high intake of β-carotene from both food and supplements was associated with a lower risk of dysplastic Barrett's esophagus but not nondysplastic Barrett's esophagus (3). The findings by Peters and colleagues suggest that to some extent the previously reported protective effects of carotenoid intake for Barrett's or EAC (2, 3) may be mediated by bacteria, and the authors have touched upon this in their discussion.

This is also of particular interest in the context of unhealthy diets and increased abdominal obesity, which are known to increase the risk of EAC (4). We have recently observed that bacterial biosynthesis of carotenoids was decreased in the esophagus of obese rats fed a high-fat diet when compared with rats on a control diet (5), suggesting that depletion of these pathways may play a role in obesity-associated EAC. Notably, the authors did not find any association between bacterial carotenoid biosynthesis and ESCC (1), and unlike EAC, increased body mass index is inversely associated with ESCC risk (4).

One likely mechanism of action of carotenoids in the context of reflux and Barrett's esophagus is their antioxidant activities against reactive oxygen species (ROS), considering exposure to acid can lead to ROS-mediated double strand breaks in Barrett's epithelial cells (6). Given that carotenoids are readily available in a healthy human diet as well as in supplements, the above evidence makes balanced nutritional interventions with these compounds a promising therapeutic avenue for offsetting the negative effects of poor diet on the esophagus and potentially the prevention of dysplastic Barrett's esophagus and EAC.