Clinical significance of Bacteroides fragilis as a potential prognostic factor in colorectal cancer

Yuriko Matsumiya; Mitsukuni Suenaga; Toshiaki Ishikawa; Toshifumi Kudo; Tsuyoshi Nakagawa; Kentaro Okamoto; Masanori Tokunaga; Claudia Hurtado; Yuki Yamada; Kentaro Oka; Motomichi Takahashi; Luis Francisco Lopez Kostner; Miguel Luis O'Ryan Gallardo; Hiroyuki Uetake; Yusuke Kinugasa

doi:10.1016/j.anaerobe.2023.102784

Clinical significance of Bacteroides fragilis as a potential prognostic factor in colorectal cancer

Anaerobe. 2023 Dec:84:102784. doi: 10.1016/j.anaerobe.2023.102784. Epub 2023 Oct 6.

Authors

Affiliations

¹ Department of Gastrointestinal Surgery, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan; University of Chile and TMDU Joint Degree Doctoral Program in Medical Sciences with Mention of a Medical Specialty, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. Electronic address: mtmysrg1@tmd.ac.jp.
² Department of Specialized Surgeries, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, 1-5-45 Yushima Bunkyo-ku, Tokyo, Japan; Department of Clinical Oncology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. Electronic address: suenaga.srg2@tmd.ac.jp.
³ Department of Specialized Surgeries, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, 1-5-45 Yushima Bunkyo-ku, Tokyo, Japan. Electronic address: t.ishikawa.we@juntendo.ac.jp.
⁴ Department of Specialized Surgeries, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, 1-5-45 Yushima Bunkyo-ku, Tokyo, Japan. Electronic address: t-kudo.srg1@tmd.ac.jp.
⁵ Department of Specialized Surgeries, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, 1-5-45 Yushima Bunkyo-ku, Tokyo, Japan. Electronic address: 7215srg2@tmd.ac.jp.
⁶ Department of Specialized Surgeries, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, 1-5-45 Yushima Bunkyo-ku, Tokyo, Japan. Electronic address: okasrg2@tmd.ac.jp.
⁷ Department of Gastrointestinal Surgery, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. Electronic address: tokunaga.srg1@tmd.ac.jp.
⁸ Clínica Las Condes Laboratorio de Oncología y Genética Molecular, Dirección Académica, Clínica Las Condes, Estoril 450, Las Condes, Santiago, Chile. Electronic address: churtado@clinicalascondes.cl.
⁹ Central Research Institute, Miyarisan Pharmaceutical Co., Ltd., 2-22-9, Toro-cho, Kita-ku, Saitama-shi, Saitama, Japan. Electronic address: y.yamada@miyarisan.com.
¹⁰ Central Research Institute, Miyarisan Pharmaceutical Co., Ltd., 2-22-9, Toro-cho, Kita-ku, Saitama-shi, Saitama, Japan. Electronic address: k.oka@miyarisan.com.
¹¹ Central Research Institute, Miyarisan Pharmaceutical Co., Ltd., 2-22-9, Toro-cho, Kita-ku, Saitama-shi, Saitama, Japan. Electronic address: motomichi.takahashi@miyarisan.com.
¹² Coloproctology Unit, Cancer Center, Clínica Universidad de Los Andes, Avda. Plaza 2501, Las Condes, Santiago, Chile. Electronic address: flopezk@clinicauandes.cl.
¹³ Microbiology and Mycology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Av. Libertador Bernardo O'Higgins 1058, Santiago, Chile. Electronic address: moryan@uchile.cl.
¹⁴ Department of Clinical Research, National Hospital Organization, Disaster Medical Center, 3256 Midori-cho, Tachikawa-city, Tokyo, Japan. Electronic address: h-uetake.srg2@tmd.ac.jp.
¹⁵ Department of Gastrointestinal Surgery, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. Electronic address: kinugasa.srg1@tmd.ac.jp.

PMID: 37806638
DOI: 10.1016/j.anaerobe.2023.102784

Abstract

Introduction: Bacteroides fragilis (B. fragilis) is considered to act in an anti-inflammatory manner on the intestinal tract. On the contrary, enterotoxigenic B. fragilis (ETBF), a subtype of B. fragilis, produces an enterotoxin (BFT; B. fragilis toxin), leading to asymptomatic chronic infections and colonic tumor formation. However, the impact of B. fragilis and ETBF on the clinical outcome of colorectal cancer (CRC) remains unclear. We aim to assess whether their presence affects the outcome in patients with CRC after curative resection.

Methods: We obtained 197 pairs of matched formalin-fixed paraffin-embedded samples from cancerous and adjacent non-cancerous tissues of patients with pathological stage (pstage) II and III CRC after curative resection. The presence of B. fragilis and ETBF were estimated using real-time polymerase chain reaction, and recurrence-free survival (RFS) and overall survival (OS) of the patients were analyzed.

Results: 16S rRNA for B. fragilis and bft DNA were detected in 120 (60.9%) and 12 (6.1%) of the 197 patients, respectively. B. fragilis-positive patients had better RFS than B. fragilis-negative patients, although that was not statistically significant. In subgroup analysis, better outcomes on RFS were observed in the presence of B. fragilis in pstage II and left-sided CRC. The association of B. fragilis positivity on OS was accentuated in the depth of T4 subgroup. No significant differences were observed in RFS and OS between ETBF and non-toxigenic B. fragilis.

Conclusions: Our findings suggest that the presence of B. fragilis is associated with better outcomes in patients with pstage II and III CRC after curative resection.

Keywords: Bacterial DNA; Bacteroides fragilis; Colorectal cancer; Pathogenic biology; Real-time polymerase chain reaction.

MeSH terms

Bacterial Infections* / complications
Bacteroides Infections* / diagnosis
Bacteroides fragilis / genetics
Clinical Relevance
Colorectal Neoplasms* / diagnosis
Colorectal Neoplasms* / pathology
Humans
Metalloendopeptidases / genetics
Prognosis
RNA, Ribosomal, 16S

Substances

RNA, Ribosomal, 16S
Metalloendopeptidases