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Alteration of Esophageal Microbiome by Antibiotic Treatment Does Not Affect Incidence of Rat Esophageal Adenocarcinoma

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Abstract

Background

Recent studies suggest that chronic inflammation-associated cancer is relevant to microbiome. Esophageal adenocarcinoma arises from an inflammatory condition called Barrett’s esophagus, which is caused by gastroesophageal reflux. We hypothesized that esophageal microbiome plays a role in carcinogenesis of esophageal adenocarcinoma.

Aim

We investigated whether alteration of microbiome using antibiotics affects the development of esophageal adenocarcinoma in a rat model.

Methods

Seven-week-old male Wistar rats which had undergone esophagojejunostomy were divided into control (n = 21) and antibiotic groups (n = 22) at 21 weeks after surgery. Control animals were given drinking water, while the other group was given penicillin G and streptomycin in drinking water until rats were killed at 40 weeks after operation. Incidence rates of Barrett’s esophagus and adenocarcinoma in each group were evaluated by histological analysis. DNA was extracted from a portion of the distal esophagus, and the microbiome was investigated using terminal restriction fragment length polymorphism (T-RFLP) analysis.

Results

All rats in both groups developed Barrett’s esophagus. Incidence of esophageal adenocarcinoma was similar between both groups with a trend to reduced incidence in the antibiotics group (89 % in the control group, 71 % in the antibiotics group, P = 0.365). T-RFLP analysis showed that esophageal microbiome was different between two groups such as the proportion of Lactobacillales was lower in the antibiotics group and Clostridium cluster XIVa and XVIII was higher in the antibiotics group.

Conclusions

Alteration of microbiome does not affect the incidence of esophageal adenocarcinoma. Microbiome may not contribute to the development of esophageal adenocarcinoma.

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Funding

This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology in Japan (No. 15K08957).

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Authors and Affiliations

  1. Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-7 Asahimachi, Abenoku, Osaka, 545-8585, Japan

    Akinari Sawada, Yasuhiro Fujiwara, Yasuaki Nagami, Fumio Tanaka, Hirokazu Yamagami, Tetsuya Tanigawa, Masatsugu Shiba, Kazunari Tominaga, Toshio Watanabe & Tetsuo Arakawa

  2. SAMURAI GI Research Center, Osaka City University Graduate School of Medicine, 1-4-7 Asahimachi, Abenoku, Osaka, 545-8585, Japan

    Yasuhiro Fujiwara, Tetsuya Tanigawa, Kazunari Tominaga, Toshio Watanabe & Tetsuo Arakawa

  3. Department of Premier Preventive Medicine, Osaka City University Graduate School of Medicine, 1-4-7 Asahimachi, Abenoku, Osaka, 545-8585, Japan

    Fumio Tanaka

  4. Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-7 Asahimachi, Abenoku, Osaka, 545-8585, Japan

    Min Gi & Hideki Wanibuchi

Authors
  1. Akinari Sawada
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  2. Yasuhiro Fujiwara
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  3. Yasuaki Nagami
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  7. Masatsugu Shiba
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  10. Min Gi
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  11. Hideki Wanibuchi
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  12. Tetsuo Arakawa
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Corresponding author

Correspondence to Yasuhiro Fujiwara.

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Conflict of interest

Dr. Arakawa received lecture fees from Otsuka and Eisai and research grants from Otsuka, Eisai, Astellas, Abbott Japan, Takeda, Dainippon Sumitomo, and Daiichi Sankyo. Dr. Fujiwara received lecture fees from Takeda and research grants from Ono. The remaining authors have no conflicts to disclose.

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Sawada, A., Fujiwara, Y., Nagami, Y. et al. Alteration of Esophageal Microbiome by Antibiotic Treatment Does Not Affect Incidence of Rat Esophageal Adenocarcinoma. Dig Dis Sci 61, 3161–3168 (2016). https://doi.org/10.1007/s10620-016-4263-6

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  • DOI: https://doi.org/10.1007/s10620-016-4263-6

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