The Amount of Bifidobacterium Genus in Colorectal Carcinoma Tissue in Relation to Tumor Characteristics and Clinical Outcome

Keisuke Kosumi, Tsuyoshi Hamada, Hideo Koh, Jennifer Borowsky, Susan Bullman, Tyler S. Twombly, Daniel Nevo, Yohei Masugi, Li Liu, Annacarolina da Silva, Yang Chen, Chunxia Du, Mancang Gu, Chenxi Li, Wanwan Li, Hongli Liu, Yan Shi, Kosuke Mima, Mingyang Song, Katsuhiko NoshoJonathan A. Nowak, Reiko Nishihara, Hideo Baba, Xuehong Zhang, Kana Wu, Molin Wang, Curtis Huttenhower, Wendy S. Garrett, Matthew L. Meyerson, Jochen K. Lennerz, Marios Giannakis, Andrew T. Chan, Jeffrey A. Meyerhardt, Charles S. Fuchs, Shuji Ogino

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


Evidence indicates a complex link between microbiota, tumor characteristics, and host immunity in the tumor microenvironment. In experimental studies, bifidobacteria appear to modulate intestinal epithelial cell differentiation. Accumulating evidence suggests that bifidobacteria may enhance the antitumor immunity and efficacy of immunotherapy. We hypothesized that the amount of bifidobacteria in colorectal carcinoma tissue might be associated with tumor differentiation and higher immune response to colorectal cancer. Using a molecular pathologic epidemiology database of 1313 rectal and colon cancers, we measured the amount of Bifidobacterium DNA in carcinoma tissue by a quantitative PCR assay. The multivariable regression model was used to adjust for potential confounders, including microsatellite instability status, CpG island methylator phenotype, long-interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Intratumor bifidobacteria were detected in 393 cases (30%). The amount of bifidobacteria was associated with the extent of signet ring cells (P = 0.002). Compared with Bifidobacterium-negative cases, multivariable odd ratios for the extent of signet ring cells were 1.29 (95% CI, 0.74–2.24) for Bifidobacterium-low cases and 1.87 (95% CI, 1.16–3.02) for Bifidobacterium-high cases (Ptrend = 0.01). The association between intratumor bifidobacteria and signet ring cells suggests a possible role of bifidobacteria in determining distinct tumor characteristics or as an indicator of dysfunctional mucosal barrier in colorectal cancer.

Original languageEnglish
Pages (from-to)2839-2852
Number of pages14
JournalAmerican Journal of Pathology
Issue number12
Publication statusPublished - 2018 Dec
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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