Esophageal adenocarcinoma (EA), the type of cancer linked to heartburn due to gastroesophageal reflux diseases (GERD), has increased six fold in the past 30 years, which can not be explained by the usual environmental or host factors. EA is the end result of a sequence of GERD-related diseases, preceded by reflux esophagitis (RE) and Barrett's esophagus (BE). Our preliminary study in elderly male veterans found two types of microbiotas in the esophagus. Patients who carry the type II microbiota are >15 fold likely to have esophagitis and BE than those harboring the type I microbiota. In a small scale study, we also found that 3 of 3 cases of EA harbored the type II biota. The findings have opened a new approach to understanding the recent surge in the incidence of EA. Our long-term goal is to identify the cause of GERD sequence. The hypothesis to be tested is that changes in the foregut microbiome are associated with EA and its precursors, RE and BE in GERD sequence. We will examine whether the finding in elderly male subjects also applies to younger as well as female subjects. We will conduct a case control study to demonstrate the microbiome- disease association in every stage of GERD sequence as well as analyze the trend in changes in the microbiome along disease progression toward EA, by two specific aims.
Aim 1 is to conduct a comprehensive population survey of the foregut microbiome and demonstrate its association with GERD sequence. Furthermore, spatial relationship between the esophageal microbiota and upstream (mouth) and downstream (stomach) foregut microbiotas as well as temporal stability of the microbiome-disease association will also be examined.
Aim 2 is to define the distal esophageal metagenome and demonstrate its association with GERD sequence. Detailed analyses will include pathway-disease and gene-disease associations. Archaea, fungi and viruses, if identified, also will be correlated with the diseases. A significant association between the foregut microbiome and GERD sequence, if demonstrated, will be the first step for eventually testing whether an abnormal microbiome is required for the development of the sequence of phenotypic changes toward EA. If EA and its precursors represent a microecological disease, treating the cause of GERD might become possible, for example, by normalizing the microbiota through use of antibiotics, probiotics, or prebiotics. Causative therapy of GERD could prevent its progression and reverse the current trend of increasing incidence of EA.
Esophageal adenocarcinoma, the type of cancer linked to heartburn due to gastroesophageal reflux diseases (GERD), has jumped six folds in the past 30 years, which can not be explained by the usual environmental or host factors. We intend to characterize the change in the esophageal microbiome (the native bacterial population of the esophagus), in patients at various stages in GERD. If GERD represents a microbiome-related disease, it could be possible to design new antibiotic or probiotic treatment strategies to prevent GERD and reverse the current trend of increasing rate of esophageal adenocarcinoma.
|Guma, Sergei; Maglantay, Remegio; Lau, Ryan et al. (2016) Papillary urothelial carcinoma with squamous differentiation in association with human papilloma virus: case report and literature review. Am J Clin Exp Urol 4:12-6|
|Neto, Antonio Galvao; Whitaker, April; Pei, Zhiheng (2016) Microbiome and potential targets for chemoprevention of esophageal adenocarcinoma. Semin Oncol 43:86-96|
|Yang, Liying; Poles, Michael A; Fisch, Gene S et al. (2016) HIV-induced immunosuppression is associated with colonization of the proximal gut by environmental bacteria. AIDS 30:19-29|
|Hickman, Richard A; Bradshaw, Azore-Dee; Cassai, Nicholas et al. (2016) A rare case of anal carcinosarcoma with human papilloma virus infection in both biphasic tumor elements: An immunohistochemical, molecular and ultrastructural study. Papillomavirus Res 2:164-166|
|Shin, Hakdong; Pei, Zhiheng; Martinez 2nd, Keith A et al. (2016) Erratum to: The first microbial environment of infants born by C-section: the operating room microbes. Microbiome 4:4|
|Ren, Wuze; Ma, Yingfei; Yang, Liying et al. (2015) Fast disease progression in simian HIV-infected female macaque is accompanied by a robust local inflammatory innate immune and microbial response. AIDS 29:F1-8|
|Shin, Hakdong; Pei, Zhiheng; Martinez 2nd, Keith A et al. (2015) The first microbial environment of infants born by C-section: the operating room microbes. Microbiome 3:59|
|Neto, Antonio Galvao; Bradshaw, Azore-Dee; Pei, Zhiheng (2015) Microbiome, a new dimension in cancer research. Ann Transl Med 3:229|
|Dominianni, Christine; Sinha, Rashmi; Goedert, James J et al. (2015) Sex, body mass index, and dietary fiber intake influence the human gut microbiome. PLoS One 10:e0124599|
|Xu, Weisheng; Yang, Liying; Lee, Peng et al. (2014) Mini-review: perspective of the microbiome in the pathogenesis of urothelial carcinoma. Am J Clin Exp Urol 2:57-61|
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