Bifidobacterium Genus in Colorectal Carcinoma Tissue in relation to Tumor Characteristics and Patient Survival
Authors: Borowsky Jennifer , Kosumi Keisuke , Hamada Tsuyoshi , Koh Hideo , Bullman Susan , Twombly Tyler S. , Masugi Yohei , Liu Li , da Silva Annacarolina , Chen Yang , Du Chunxia , Gu Mancang , Li Chenxi , Li Wanwan , Liu Hongli , Shi Yan , Song Mingyang , Nosho Katsuhiko , Nowak Jonathan A. , Nishihara Reiko , Baba Hideo , Zhang Xuehong , Wu Kana , Huttenhower Curtis , Garrett Wendy S. , Meyerson Matthew , Lennerz Jochen K. , Giannakis Marios , Chan Andrew T. , Meyerhardt Jeffrey A. , Fuchs Charles S. , Ogino Shuji 
Published: June 2021

Evidence suggests that members of the Bifidobacterium genus may not only inhibit colorectal carcinogenesis, but also enhance the anti‐tumor immune response and efficacy of immunotherapy. We hypothesized that the amount of bifidobacteria in colorectal carcinoma tissue might be associated with distinctive clinical features, higher immune response to colorectal cancer, and favorable clinical outcome.Using 1,313 rectal and colon carcinoma cases in the Nurses' Health Study and Health Professionals Follow‐up Study, we measured the amount of Bifidobacterium DNA in carcinoma tissue by a quantitative polymerase chain reaction assay. Multivariable logistic and Cox proportional hazards regression models were used to adjust for potential confounders, including microsatellite instability status, CpG island methylator phenotype, long interspersed nucleotide element‐1 methylation, KRAS, BRAF and PIK3CA mutations.Intratumor bifidobacteria were detected in 393 (30%) cases. The amount of bifidobacteria was associated with the extent of signet ring cells (P = 0.002, with adjusted α of 0.002). Compared with signet ring cell‐absent cases, multivariable odds ratios for the amount of bifidobacteria were 1.45 (95% confidence interval 0.98–2.14) for cases with 1–50% signet ring cell components and 2.21 (95% confidence interval 1.05–4.69) for cases with ≥51% signet ring cell components (Ptrend = 0.011). The amount of bifidobacteria was not significantly associated with any T cell densities, histological lymphocytic reaction patterns, or colorectal cancer survival.The amount of detectable Bifidobacterium DNA in colorectal cancer tissue is associated with the extent of signet ring cells.Support or Funding InformationThis work was supported by U.S. National Institutes of Health (NIH) grants (P01 CA87969 to M.J. Stampfer; UM1 CA186107 to M.J. Stampfer; P01 CA55075 to W.C. Willett; UM1 CA167552 to W.C. Willett; U01 CA167552 to W.C. Willett and L.A. Mucci; P50 CA127003 to C.S.F.; R01 CA118553 to C.S.F.; R01 CA169141 to C.S.F.; R01 CA137178 to A.T.C.; K24 DK098311 to A.T.C.; R35 CA197735 to S.O.; R01 CA151993 to S.O.; K07 CA190673 to R.N.; and K07 CA188126 to X.Z.); by Nodal Award from the Dana‐Farber Harvard Cancer Center (to S.O.); and by grants from the Project P Fund, The Friends of the Dana‐Farber Cancer Institute, Bennett Family Fund, and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance, and by Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant (to C.S.F. and M.Gi.). J.B. was supported by the Australia Awards‐Endeavour Scholarships and Fellowships Program. K.K. was supported by grants from Overseas Research Fellowship (JP2017‐775) from Japan Society for the Promotion of Science. T.H. was supported by a fellowship grant from the Mitsukoshi Health and Welfare Foundation.T.H. was supported by a fellowship grant from the Mitsukoshi Health and Welfare Foundation. L.L. was supported by a scholarship grant from Chinese Scholarship Council and a fellowship grant from Huazhong University of Science and Technology. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.