Bifidobacterium bifidum strains synergize with immune checkpoint inhibitors to reduce tumour burden in mice

Se Hoon Lee, Sung Yup Cho, Youngmin Yoon, Changho Park, Jinyoung Sohn, Jin Ju Jeong, Bu Nam Jeon, Mongjoo Jang, Choa An, Suro Lee, Yun Yeon Kim, Gihyeon Kim, Sujeong Kim, Yunjae Kim, Gwang Bin Lee, Eun Ju Lee, Sang Gyun Kim, Hong Sook Kim, Yeongmin Kim, Hyun KimHyun Suk Yang, Sarang Kim, Seonggon Kim, Hayung Chung, Myeong Hee Moon, Myung Hee Nam, Jee Young Kwon, Sungho Won, Joon Suk Park, George M. Weinstock, Charles Lee, Kyoung Wan Yoon, Hansoo Park

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)


The gut microbiome can influence the development of tumours and the efficacy of cancer therapeutics1–5; however, the multi-omics characteristics of antitumour bacterial strains have not been fully elucidated. In this study, we integrated metagenomics, genomics and transcriptomics of bacteria, and analyses of mouse intestinal transcriptome and serum metabolome data to reveal an additional mechanism by which bacteria determine the efficacy of cancer therapeutics. In gut microbiome analyses of 96 samples from patients with non-small-cell lung cancer, Bifidobacterium bifidum was abundant in patients responsive to therapy. However, when we treated syngeneic mouse tumours with commercial strains of B. bifidum to establish relevance for potential therapeutic uses, only specific B. bifidum strains reduced tumour burden synergistically with PD-1 blockade or oxaliplatin treatment by eliciting an antitumour host immune response. In mice, these strains induced tuning of the immunological background by potentiating the production of interferon-γ, probably through the enhanced biosynthesis of immune-stimulating molecules and metabolites.

Original languageEnglish
Pages (from-to)277-288
Number of pages12
JournalNature microbiology
Issue number3
Publication statusPublished - 2021 Mar

Bibliographical note

Funding Information:
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF), funded by the Ministry of Science & ICT (NRF-2017M3A9F3046536 to H.P.); a GIST Research Institute (GRI) grant, funded by the GIST in 2020; Genome and Company (grant number GNC GR 17-01 to H.P.). This work was also supported by grants from National Cancer Centre, Korea (NCC-1911267 to H.P); the Post-Genome Technology Development Program (10067758, Business model development driven by clinico-genomic database for precision immuno-oncology to S.-H.L.) funded by the Ministry of Trade, Industry and Energy (MOTIE, Korea). S.-Y.C. is supported by the Bio & Medical Technology Development Program of the NRF, funded by the Ministry of Science & ICT (NRF-2018M3A9F3056902). This research was also supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number HI17C1076 to K.W.Y). This work was supported by the NRF grant funded by the Korea government (MSIT) (number 2017R1C1B2011196 to K.W.Y). M.H.M. is supported by grant NRF-2018R1A2A1A05019794 from the NRF of Korea. B.-N.J. is supported by the Basic Science Research Program through the NRF of Korea, funded by the Ministry of Education, Science and Technology (MEST) (2018R1C1B6005768). The International Research & Development Program of the NRF of Korea, funded by the Ministry of Science, ICT & Future Planning (grant no. 2015K1A4A3047851) also funded C.L. The Ewha Womans University Professorship is supported in part by the Ewha Womans University research grant of 2017-2019. This study is also supported in part by operational funds from The First Affiliated Hospital of Xi’an Jiaotong University.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology


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