Simple SummaryEsophageal cancer has very high mortality and morbidity rates. In this study, we reviewed the current literature on the impact of microbiota on esophageal cancer and its precursor lesions. Globally, a decrease in microbiota richness and evenness in esophageal cancer is identified, which is accompanied by an increase in the abundance of Gram-negative bacteria.AbstractEsophageal cancer is a major health problem, being the seventh most incidence cancer worldwide. Due to the often-late diagnosis and lack of efficient treatments, the overall 5-year survival is as low as 10%. Therefore, understanding the etiology and the mechanisms that drive the development of this type of cancer could improve the management of patients, increasing the chance of achieving a better clinical outcome. Recently, the microbiome has been studied as a putative etiological factor for esophageal cancer. Nevertheless, the number of studies tackling this issue is low, and the heterogeneity in the study design and data analysis has hindered consistent findings. In this work, we reviewed the current literature on the evaluation of the role of microbiota in the development of esophageal cancer. We analyzed the composition of the normal microbiota and the alterations found in precursor lesions, namely Barrett’s esophagus and dysplasia, as well as in esophageal cancer. Additionally, we explored how other environmental factors can modify microbiota and contribute to the development of this neoplasia. Finally, we identify critical aspects to be improved in future studies, with the aim of refining the interpretation of the relationship between the microbiome and esophageal cancer.