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Rebamipide Alters the Esophageal Microbiome and Reduces the Incidence of Barrett’s Esophagus in a Rat Model

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Abstract

Background

Barrett’s esophagus (BE) is characterized by a distinct Th2-predominant cytokine profile. However, antigens that shift the immune response toward the Th2 profile are unknown.

Aim

We examined the effects of rebamipide on the esophageal microbiome and BE development in a rat model.

Methods

BE was induced by esophagojejunostomy in 8-week-old male Wistar rats. Rats were divided into control and rebamipide-treated group receiving either a normal or a 0.225 % rebamipide-containing diet, respectively, and killed 8, 16, 24, and 32 weeks after the operation. PCR-amplified 16S rDNAs extracted from esophageal samples were examined by terminal-restriction fragment length polymorphism (T-RFLP) analysis to assess microbiome composition. The dynamics of four bacterial genera (Lactobacillus, Clostridium, Streptococcus, and Enterococcus) were analyzed by real-time PCR.

Results

The incidences of BE in the control and rebamipide group at 24 and 32 weeks were 80 and 100, and 20 and 33 %, respectively. T-RFLP analysis of normal esophagus revealed that the proportion of Clostridium was 8.3 %, while that of Lactobacillales was 71.8 %. The proportions of Clostridium increased and that of Lactobacillales decreased at 8 weeks in both groups. Such changes were consistently observed in the control but not in the rebamipide group. Clostridium and Lactobacillus expression was lower and higher, respectively, in the rebamipide group than in the control group.

Conclusions

Rebamipide reduced BE development and altered the esophageal microbiome composition, which might play a role in BE development.

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Acknowledgments

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 (Nos. 24590925, 23590924).

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. The remaining authors have no conflict to disclose.

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Authors and Affiliations

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

    Yukie Kohata, Kenichi Nakahara, Tetsuya Tanigawa, Hirokazu Yamagami, Masatsugu Shiba, Toshio Watanabe, Kazunari Tominaga, Yasuhiro Fujiwara & Tetsuo Arakawa

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  1. Yukie Kohata
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  2. Kenichi Nakahara
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  3. Tetsuya Tanigawa
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  4. Hirokazu Yamagami
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  5. Masatsugu Shiba
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  6. Toshio Watanabe
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  7. Kazunari Tominaga
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  8. Yasuhiro Fujiwara
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  9. Tetsuo Arakawa
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Correspondence to Yasuhiro Fujiwara.

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Kohata, Y., Nakahara, K., Tanigawa, T. et al. Rebamipide Alters the Esophageal Microbiome and Reduces the Incidence of Barrett’s Esophagus in a Rat Model. Dig Dis Sci 60, 2654–2661 (2015). https://doi.org/10.1007/s10620-015-3662-4

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  • DOI: https://doi.org/10.1007/s10620-015-3662-4

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