Microbiome and potential targets for chemoprevention of esophageal adenocarcinoma

Abstract

Esophageal cancer is one of the deadliest cancers, with a dismal prognosis. It is increasingly recognized that esophageal cancer is a heterogeneous disease. It can be subdivided into two distinct groups: squamous cell carcinoma and adenocarcinoma, based on histological appearance. In the Western world, the incidence of squamous cell carcinoma was considerably higher than esophageal adenocarcinoma (EA) until the 1990s when, due to a dramatic increase, the incidence of EA surpassed that of squamous cell carcinoma. EA typically follows a well-established stepwise evolution from chronic inflammation due to reflux esophagitis (RE) that progresses to metaplasia (Barrett’s esophagus- BE) to dysplasia, which often culminates in EA. The pathophysiology of EA is complex and involves diverse factors, including gastroesophageal reflux, gastric acid secretion, dysfunction of the antireflux barrier, gastric emptying disturbances, and abnormalities in esophageal defense mechanisms. The current understanding of the etiology of EA is mainly derived from epidemiological studies of risk factors such as cigarette smoking, obesity, gastroesophageal reflux disorders (GERD), and low fruit and vegetable consumption. Numerous studies have been done but the factors that drive the dynamic increase in the incidence of EA remain elusive. The advent of widespread antibiotic use occurred in the 1950s, preceding the surge of EA. Based on this temporal sequence, it has been hypothesized that antibiotics alter the microbiome to which the esophagus is exposed in patients who have GERD and that chronic exposure to this abnormal microbiome (i.e., changes in species diversity or abundance) accounts for the increase in EA. If changes in the proposed factors alter the stepwise progression (RE-BE-dysplasia- EA), they may represent potential targets for chemoprevention. New discoveries will help improve our understanding of the biology and pathogenesis of these cancers, and aid in finding novel therapeutic targets.

The esophageal microbiota in health and disease

“…As previously mentioned, GERD‐related esophagitis and Barrett's metaplasia are the major conditions associated with chronic reflux of acidic material from the stomach into the lower part of the esophagus. Under these circumstances, a modification of the esophageal microbiota is expected to occur owing to the altered environment, and it has been hypothesized that the modification of the microbiota could contribute to disease persistence and/or progression . The relevant literature available on this subject is summarized in Table and discussed below.…”

“…The microbiota composition in esophageal cancers has been investigated since the early 1980s, and during the last three decades it has been studied using diverse culture‐dependent and culture‐independent approaches (Table ). The interest in such studies arises from the recognition that gastrointestinal tract dysbiosis may play a role in disease initiation and perpetuation . The mechanisms accounting for dysbiosis‐mediated carcinogenesis could involve both the induction of a cancer‐promoting inflammatory response (mainly mediated by innate immunity) and the production of procarcinogenic compounds by the bacterial taxa enriched in dysbiosis .…”

“…The esophageal mucosa is one of the sites colonized by HM, and consequently there is an interest in understanding a possible role of HM alterations in esophageal diseases. Some articles have recently reviewed various aspects of this topic . Here, we provide an updated review of current knowledge on the esophageal microbiota in health and in different esophageal diseases and discuss the major challenges encountered in investigation of this topic.…”

Green Tea and Its Extracts in Cancer Prevention and Treatment

“…The upper gastrointestinal tract is most likely to show a specific response; this has been proven for viruses like human papilloma viruses [220] or hot and spicy food [221][222][223], cooking with wood and coal also are likely etiological agents [224,225]. In addition, genetic factors [226,227] contribute to the individual cancer risk, antibiotic treatment of H. pylori gastritis has caused a shift from squamous cell carcinoma to adenocarcinoma in esophageal cancers [218].…”

“…Among esophageal cancers, location (proximal and distal carcinoma) and histological subtype (adenocarcinoma and squamous cell carcinoma) can be separated [215][216][217][218][219], with differing etiology and prognosis. The upper gastrointestinal tract is most likely to show a specific response; this has been proven for viruses like human papilloma viruses [220] or hot and spicy food [221][222][223], cooking with wood and coal also are likely etiological agents [224,225].…”