A Step Toward Discovering the New World of Esophageal Microbiota.

Due to the development of next-generation sequencing techniques, microbiota in healthy or diseased gastrointestinal mucosa have been thoroughly investigated.[1,2] The impact of the new sequencing technique is synonymous with developing a new navigation tool in the age of exploration. We have known about normally existing bacterial taxa in the esophagus consisting of Streptococcus, Haemophilus, Neisseria, Prevotella, and Veillonella.[2] The composition of esophageal microbiota differs depending on disease states, such as gastroesophageal reflux disease (GERD), Barrett’s esophagus, esophageal adenocarcinoma, esophageal squamous cell carcinoma, and eosinophilic esophagitis. For example, in patients with GERD or Barrett’s esophagus, the abundance of Streptococcus decreases whereas that of Haemophilus, Neisseria, Prevotella, and Veillonella increases.[3,4] In esophageal adenocarcinoma, the abundance of Streptococcus decreases while that of Lactobacillus, Enterobacteriaceae, and Akkermansia increases.[5,6] Although the reason for the change has not been clearly elucidated, there are 2 potential sources of the esophageal microbiota: one is the swallowed oropharyngeal microbiota, and the other is intragastric microbiota refluxed from the stomach. A previous study found that Streptococci, bacteria abundantly found in the esophagus of healthy and individuals with GERD or esophageal adenocarcinomas, are commonly observed in the oropharynx.[7] Streptococcus in the esophagus may be originated from the oropharynx and outside the body. Other bacteria such as Veillonella, which typically increases in esophageal mucosa exposed to refluxed gastric acid, may have been refluxed from intragastric microbiota. However, there is still a possibility that microbiota in diseased esophageal mucosa originates from the oral cavity. For instance, Prevotella, Fusobacteria phylum, Neisseria, and Corynebacterium, may be increased in patients with esophageal squamous cell carcinoma or eosinophilic esophagitis, despite the lack of reflux.[2]

Esophageal microbiota is a new world that is yet to be discovered. The reason for the changes in esophageal microbiota is still not fully understood. As such, the study on esophageal microbiota in patients with esophageal achalasia, published in this issue of the Journal of Neurogastroenterology and Motility, is very interesting.[8] In this study, Jung et al[8] analyzed microbiota in the esophageal mucosa and retention fluid from 29 patients with esophageal achalasia. Pathophysiologically, esophageal achalasia is the opposite of GERD. Esophageal microbiota in patients with esophageal achalasia may be affected by saliva and diet rather than refluxed gastric contents. Therefore, we can assess the impact of the external environment on esophageal microbiota by analyzing the esophageal microbiota in patients with achalasia. Although Jung et al[8] did not include healthy individuals, the relative abundance of Streptococcus in participants was low (< 40%), similar to patients with GERD. Interestingly, the composition of esophageal microbiota in the mucosa and retention fluid differed. For example, Lactobacillus and Enterobacteriaceae, generally associated with esophageal adenocarcinoma, were found more abundantly in esophageal mucosa than retention fluid. These bacterial taxa may be targets for future research on esophageal carcinogenesis. Similarly, Veillonella, which is known to be associated with GERD, was more abundant in the retention fluid than in the esophageal mucosa. Given that gastric acid reflux is minimal in patients with esophageal achalasia, the increased abundance of Veillonella may be due to poor clearance of esophageal fluid. In GERD, Veillonella may be present due to swallowing the content and poor esophageal clearance rather than refluxed gastric acid. More importantly, Jung et al[8] demonstrated that esophageal microbiota did not differ between pre- and post-peroral endoscopic myotomies. If reflux was the main reason for esophageal dysbiosis, the microbiota composition should differ between the pre- and post-myotomy in patients with esophageal achalasia since the procedure increases acid reflux.[9]

As the authors already stated, the study by Jung et al[8] is limited due to insufficient sample size and lack of healthy controls. Nevertheless, this study is the first to describe the esophageal microbiota compositions in patients with esophageal achalasia. It provides a better understanding of the esophageal microbiota and provides hope to achieve a greater understanding of the esophageal microbiota in the near future.