Distinct microbiome dysbiosis and epigenetic anomaly in esophageal adenocarcinoma and its underlying Barrett’s esophagus
Abstract Interaction between host genotoxic changes and mucosa-associated microbiome (MAM) dysbiosis may have a role in various digestive cancers. We investigated MAM in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) progression sequence and its association with host genotoxic changes....
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BMC
2024-12-01
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| Series: | Clinical Epigenetics |
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| Online Access: | https://doi.org/10.1186/s13148-024-01801-z |
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| author | Takuya Shijimaya Tomomitsu Tahara Jumpei Yamazaki Sanshiro Kobayashi Yasushi Matsumoto Naohiro Nakamura Yu Takahashi Takashi Tomiyama Toshiro Fukui Tomoyuki Shibata Makoto Naganuma |
| author_facet | Takuya Shijimaya Tomomitsu Tahara Jumpei Yamazaki Sanshiro Kobayashi Yasushi Matsumoto Naohiro Nakamura Yu Takahashi Takashi Tomiyama Toshiro Fukui Tomoyuki Shibata Makoto Naganuma |
| author_sort | Takuya Shijimaya |
| collection | DOAJ |
| description | Abstract Interaction between host genotoxic changes and mucosa-associated microbiome (MAM) dysbiosis may have a role in various digestive cancers. We investigated MAM in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) progression sequence and its association with host genotoxic changes. 16S rRNA gene sequencing was performed in three different groups of biopsies from nonneoplastic BE from patients without cancer (N, normal group; n = 47) and with EAC (ADJ, adjacent group; n = 27). Endoscopic biopsies were also obtained from EAC tissues (T, tumor group; n = 22). Results were correlated with TP53 mutation, telomere length and DNA methylation of candidate genes (N33, DPYS, SLC16A12, miR124A3 and miR34bc). Genome-wide DNA methylation examined by reduced representation bisulfite sequencing (RRBS) was available for 32 samples (n = 12 for N, n = 12 for ADJ and n = 22 for T groups). Lower microbial alpha diversity measures were observed in ADJ/T groups relative to N group and associated with higher mean Z score DNA methylation of candidate genes. Specific genera (n = 16) with significant change between ADJ/T groups relative to N group occurred mostly in ADJ group (13/16) and half of them (8/16) were associated with DNA methylation status. Integrated MAM and genome-wide methylation analysis demonstrated that hyper-methylated sites, associated with lower alpha diversity measures dominantly occurred within near the transcription start site, codifying genes were involved in metabolic processes. Our result shows that microbial dysbiosis in EAC mostly occurs in adjacent BE and such dysbiosis was associated with DNA methylation status, offering support for a pathogenic role of interaction between host genotoxic changes and MAM in this tumor type. |
| format | Article |
| id | doaj-art-02d604e4b8614a01a3ff1d5fb0a4007f |
| institution | Kabale University |
| issn | 1868-7083 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj-art-02d604e4b8614a01a3ff1d5fb0a4007f2024-12-22T12:33:32ZengBMCClinical Epigenetics1868-70832024-12-0116111110.1186/s13148-024-01801-zDistinct microbiome dysbiosis and epigenetic anomaly in esophageal adenocarcinoma and its underlying Barrett’s esophagusTakuya Shijimaya0Tomomitsu Tahara1Jumpei Yamazaki2Sanshiro Kobayashi3Yasushi Matsumoto4Naohiro Nakamura5Yu Takahashi6Takashi Tomiyama7Toshiro Fukui8Tomoyuki Shibata9Makoto Naganuma10Third Department of Internal Medicine, Kansai Medical UniversityThird Department of Internal Medicine, Kansai Medical UniversityTranslational Research Unit, Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido UniversityThird Department of Internal Medicine, Kansai Medical UniversityThird Department of Internal Medicine, Kansai Medical UniversityThird Department of Internal Medicine, Kansai Medical UniversityThird Department of Internal Medicine, Kansai Medical UniversityThird Department of Internal Medicine, Kansai Medical UniversityThird Department of Internal Medicine, Kansai Medical UniversityDepartment of Gastroenterology, Fujita Health University School of MedicineThird Department of Internal Medicine, Kansai Medical UniversityAbstract Interaction between host genotoxic changes and mucosa-associated microbiome (MAM) dysbiosis may have a role in various digestive cancers. We investigated MAM in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) progression sequence and its association with host genotoxic changes. 16S rRNA gene sequencing was performed in three different groups of biopsies from nonneoplastic BE from patients without cancer (N, normal group; n = 47) and with EAC (ADJ, adjacent group; n = 27). Endoscopic biopsies were also obtained from EAC tissues (T, tumor group; n = 22). Results were correlated with TP53 mutation, telomere length and DNA methylation of candidate genes (N33, DPYS, SLC16A12, miR124A3 and miR34bc). Genome-wide DNA methylation examined by reduced representation bisulfite sequencing (RRBS) was available for 32 samples (n = 12 for N, n = 12 for ADJ and n = 22 for T groups). Lower microbial alpha diversity measures were observed in ADJ/T groups relative to N group and associated with higher mean Z score DNA methylation of candidate genes. Specific genera (n = 16) with significant change between ADJ/T groups relative to N group occurred mostly in ADJ group (13/16) and half of them (8/16) were associated with DNA methylation status. Integrated MAM and genome-wide methylation analysis demonstrated that hyper-methylated sites, associated with lower alpha diversity measures dominantly occurred within near the transcription start site, codifying genes were involved in metabolic processes. Our result shows that microbial dysbiosis in EAC mostly occurs in adjacent BE and such dysbiosis was associated with DNA methylation status, offering support for a pathogenic role of interaction between host genotoxic changes and MAM in this tumor type.https://doi.org/10.1186/s13148-024-01801-zBarrett’s esophagusEsophageal adenocarcinomaMucosa-associated microbiomeDNA methylationRRBSTelomere shortening |
| spellingShingle | Takuya Shijimaya Tomomitsu Tahara Jumpei Yamazaki Sanshiro Kobayashi Yasushi Matsumoto Naohiro Nakamura Yu Takahashi Takashi Tomiyama Toshiro Fukui Tomoyuki Shibata Makoto Naganuma Distinct microbiome dysbiosis and epigenetic anomaly in esophageal adenocarcinoma and its underlying Barrett’s esophagus Clinical Epigenetics Barrett’s esophagus Esophageal adenocarcinoma Mucosa-associated microbiome DNA methylation RRBS Telomere shortening |
| title | Distinct microbiome dysbiosis and epigenetic anomaly in esophageal adenocarcinoma and its underlying Barrett’s esophagus |
| title_full | Distinct microbiome dysbiosis and epigenetic anomaly in esophageal adenocarcinoma and its underlying Barrett’s esophagus |
| title_fullStr | Distinct microbiome dysbiosis and epigenetic anomaly in esophageal adenocarcinoma and its underlying Barrett’s esophagus |
| title_full_unstemmed | Distinct microbiome dysbiosis and epigenetic anomaly in esophageal adenocarcinoma and its underlying Barrett’s esophagus |
| title_short | Distinct microbiome dysbiosis and epigenetic anomaly in esophageal adenocarcinoma and its underlying Barrett’s esophagus |
| title_sort | distinct microbiome dysbiosis and epigenetic anomaly in esophageal adenocarcinoma and its underlying barrett s esophagus |
| topic | Barrett’s esophagus Esophageal adenocarcinoma Mucosa-associated microbiome DNA methylation RRBS Telomere shortening |
| url | https://doi.org/10.1186/s13148-024-01801-z |
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