Combination therapy with levofloxacin and the probiotic <i>Clostridium butyricum</i><scp>MIYAIRI</scp> 588 enhances immune checkpoint inhibitor efficacy
The gut microbiome influences immune checkpoint inhibitor (ICI) efficacy. In this study, we explored the effects of combined levofloxacin (LVFX) and Clostridium butyricum MIYAIRI 588 (CBM588) on ICI outcomes using a CT26 tumor model in BALB/c mice. When compared with the control, the LVFX+CBM588 combination enhanced anti-programmed cell death (PD)-1 therapy, with CD8<sup>+</sup> T cells playing a key role. Gut microbiota analysis showed reduced Lactobacillus relative abundance and increased Oscillibacter and Muribaculaceae in the LVFX+CBM588 group. A broad-spectrum antibiotic cocktail (ampicillin, neomycin, vancomycin, and metronidazole) with CBM588 diminished antitumor effects and reduced survival in mice when compared with the control, demonstrating the importance of microbiota-targeted therapeutic combinations. However, while LVFX+CBM588 improved ICI efficacy, it worsened dextran sulfate sodium (DSS)-induced colitis, suggesting immune activation contributes to inflammation. These findings emphasize the potential of customized antibiotic-probiotic combinations in cancer immunotherapy, while also stressing the necessity to manage immune-related adverse effects.
Authors
- Takuya Tsunoda (ORCID: https://orcid.org/0000-0002-6416-8211)
- Takehiko Sambe (ORCID: https://orcid.org/0000-0001-6730-7873)
- Toshiaki Tsurui (ORCID: https://orcid.org/0000-0002-6167-8953)
- Eiji Funayama
- Kiyoshi Yoshimura (ORCID: https://orcid.org/0000-0003-4816-1826)
- Atsuo Kuramasu
- Midori Shida
- Shinichi Kobayashi (ORCID: https://orcid.org/0000-0002-5600-5826)
- Yuta Baba (ORCID: https://orcid.org/0000-0002-5743-0306)
- Yasunobu Amari
- Masakazu Murayama
- Yoichiro Narikawa
- Mayumi Tsuji (ORCID: https://orcid.org/0000-0001-8005-9069)
- Junya Isobe
- Masaki Mori
- Hitoshi Toyoda
- Satoshi Wada (ORCID: https://orcid.org/0000-0001-6528-5914)
- Yuki Maruyama (ORCID: https://orcid.org/0000-0003-2695-1472)
- Yuji Kiuchi (ORCID: https://orcid.org/0000-0001-7198-3735)
- Rie Nakashima (ORCID: https://orcid.org/0000-0001-9193-1799)
- Masahiro Hosonuma (ORCID: https://orcid.org/0000-0002-5861-7543)
- Akiko Sasaki (ORCID: https://orcid.org/0000-0003-4219-554X)
- Aya Sasaki
- Kazuo Koyanagi (ORCID: https://orcid.org/0000-0002-8010-8630)
- Kohei Tajima
- Yoshitaka Yamazaki
Institutions
- SHOWA Medical University (JP)
- Tokai University (JP)
- Therapeutics Clinical Research (US)
- SHOWA Medical University Fujigaoka Hospital (JP)
- SHOWA Medical University Hospital (JP)
- Showa Pharmaceutical University (JP)
Publication Details
- Journal
- International Journal of Cancer
- Published
- 2025-06-06
- DOI
- https://doi.org/10.1002/ijc.35472
- Citations
- 5
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 4.03