The role of microbiota in esophageal squamous cell carcinoma: A review of the literature

Hsueh-Chien Chiang; Michael Hughes; Wei-Lun Chang

doi:10.1111/1759-7714.15096

The role of microbiota in esophageal squamous cell carcinoma: A review of the literature

Thorac Cancer. 2023 Oct;14(28):2821-2829. doi: 10.1111/1759-7714.15096. Epub 2023 Sep 7.

Authors

Hsueh-Chien Chiang^{1

2}, Michael Hughes^{2

3

4}, Wei-Lun Chang^{1

2}

Affiliations

¹ Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
² Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
³ International Center for Wound Repair and Regeneration (iWRR), College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁴ Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan.

Abstract

Esophageal squamous cell carcinoma (ESCC) exhibits high incidence with poor prognosis. Alcohol drinking, cigarette smoking, and betel nut chewing are well-known risk factors. Dysbiosis, an imbalance of the microbiota residing in a local environment, is known to be associated with human diseases, especially cancer. This article reviews the current evidence of esophageal microbiota in ESCC carcinogenesis, including initiation, progression, and drug resistance. Articles involving the esophageal microbiota, diagnosis, treatment, and the progression of esophageal cancer were acquired using a comprehensive literature search in PubMed in recent 10 years. Based on 16S rRNA sequencing of human samples, cell, and animal studies, current evidence suggests dysbiosis of the esophagus promotes ESCC progression and chemotherapy resistance, leading to a poor prognosis. Smoking and drinking are associated with esophageal dysbiosis. Specific bacteria have been reported to promote carcinogenesis, involving either progression or drug resistance in ESCC, for example Porphyromonas gingivalis and Fusobacterium nucleatum. These bacteria promote ESCC cell proliferation and migration via the TLR4/NF-κB and IL-6/STAT3 pathways. F. nucleatum induces cisplatin resistance via the enrichment of immunosuppressive myeloid-derived suppressor cells (MDSCs). Correcting the dysbiosis and reducing the abundance of specific esophageal pathogens may help in suppressing cancer progression. In conclusion, esophageal dysbiosis is associated with ESCC progression and chemoresistance. Screening the oral and esophageal microbiota is a potential diagnostic tool for predicting ESCC development or drug-resistance. Repairing esophageal dysbiosis is a novel treatment for ESCC. Clinical trials with probiotics in addition to current chemotherapy are warranted to study the therapeutic effects.

Keywords: cancer therapy; diagnostic marker; dysbiosis; esophageal squamous cell carcinoma; microbiota.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinogenesis
Dysbiosis / complications
Esophageal Neoplasms* / pathology
Esophageal Squamous Cell Carcinoma* / pathology
Humans
Microbiota*
RNA, Ribosomal, 16S

Substances

RNA, Ribosomal, 16S