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Probiotics enhances anti‐tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer

Chemotherapy drugs, such as gemcitabine and cisplatin (GC), are frequently administered to patients with advanced urothelial carcinoma, however the influence of the gut microbiota on their action is unclear. Thus, we investigated the effects of GC on the gut microbiome and determined whether oral su...

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Autores principales: Miyake, Makito, Oda, Yuki, Owari, Takuya, Iida, Kota, Ohnishi, Sayuri, Fujii, Tomomi, Nishimura, Nobutaka, Miyamoto, Tatsuki, Shimizu, Takuto, Ohnishi, Kenta, Hori, Shunta, Morizawa, Yosuke, Gotoh, Daisuke, Nakai, Yasushi, Torimoto, Kazumasa, Tanaka, Nobumichi, Fujimoto, Kiyohide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986082/
https://www.ncbi.nlm.nih.gov/pubmed/36398663
http://dx.doi.org/10.1111/cas.15666
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author Miyake, Makito
Oda, Yuki
Owari, Takuya
Iida, Kota
Ohnishi, Sayuri
Fujii, Tomomi
Nishimura, Nobutaka
Miyamoto, Tatsuki
Shimizu, Takuto
Ohnishi, Kenta
Hori, Shunta
Morizawa, Yosuke
Gotoh, Daisuke
Nakai, Yasushi
Torimoto, Kazumasa
Tanaka, Nobumichi
Fujimoto, Kiyohide
author_facet Miyake, Makito
Oda, Yuki
Owari, Takuya
Iida, Kota
Ohnishi, Sayuri
Fujii, Tomomi
Nishimura, Nobutaka
Miyamoto, Tatsuki
Shimizu, Takuto
Ohnishi, Kenta
Hori, Shunta
Morizawa, Yosuke
Gotoh, Daisuke
Nakai, Yasushi
Torimoto, Kazumasa
Tanaka, Nobumichi
Fujimoto, Kiyohide
author_sort Miyake, Makito
collection PubMed
description Chemotherapy drugs, such as gemcitabine and cisplatin (GC), are frequently administered to patients with advanced urothelial carcinoma, however the influence of the gut microbiota on their action is unclear. Thus, we investigated the effects of GC on the gut microbiome and determined whether oral supplementation with a probiotics mixture of Lactobacillus casei Shirota and Bifidobacterium breve enhanced the anti‐tumor immune response. After subcutaneous inoculation with MBT2 murine bladder cancer cells, syngenic C3H mice were randomly allocated into eight groups. The gut microbiome cluster pattern was altered in both the GC and oral probiotics groups (p = 0.025). Both tumor‐bearing conditions (no treatment) and GC chemotherapy influenced Pseudoclostridium, Robinsoniella, Merdimonas, and Phocea in the gut. Furthermore, comparison of the GC‐treated and GC + probiotics groups revealed an association of four methyltransferase family enzymes and two short‐change fatty acid‐related enzymes with oral probiotics use. A significant difference in tumor volume was observed between the GC and GC + probiotics groups at week 2 of treatment. Additionally, decreased recruitment of cancer‐associated fibroblasts and regulatory T cells, and activation of CD8(+) T cells and dendritic cells were observed in the tumor microenvironment. Our findings reveal the positive effects of a probiotics mixture of Lactobacillus and Bifidobacterium in enhancing anti‐tumor effects through the gut–tumor immune response axis. Future clinical trials are needed to evaluate the full benefits of this novel supplement with oral probiotics in patients with advanced urothelial carcinoma.
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spelling pubmed-99860822023-03-07 Probiotics enhances anti‐tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer Miyake, Makito Oda, Yuki Owari, Takuya Iida, Kota Ohnishi, Sayuri Fujii, Tomomi Nishimura, Nobutaka Miyamoto, Tatsuki Shimizu, Takuto Ohnishi, Kenta Hori, Shunta Morizawa, Yosuke Gotoh, Daisuke Nakai, Yasushi Torimoto, Kazumasa Tanaka, Nobumichi Fujimoto, Kiyohide Cancer Sci ORIGINAL ARTICLES Chemotherapy drugs, such as gemcitabine and cisplatin (GC), are frequently administered to patients with advanced urothelial carcinoma, however the influence of the gut microbiota on their action is unclear. Thus, we investigated the effects of GC on the gut microbiome and determined whether oral supplementation with a probiotics mixture of Lactobacillus casei Shirota and Bifidobacterium breve enhanced the anti‐tumor immune response. After subcutaneous inoculation with MBT2 murine bladder cancer cells, syngenic C3H mice were randomly allocated into eight groups. The gut microbiome cluster pattern was altered in both the GC and oral probiotics groups (p = 0.025). Both tumor‐bearing conditions (no treatment) and GC chemotherapy influenced Pseudoclostridium, Robinsoniella, Merdimonas, and Phocea in the gut. Furthermore, comparison of the GC‐treated and GC + probiotics groups revealed an association of four methyltransferase family enzymes and two short‐change fatty acid‐related enzymes with oral probiotics use. A significant difference in tumor volume was observed between the GC and GC + probiotics groups at week 2 of treatment. Additionally, decreased recruitment of cancer‐associated fibroblasts and regulatory T cells, and activation of CD8(+) T cells and dendritic cells were observed in the tumor microenvironment. Our findings reveal the positive effects of a probiotics mixture of Lactobacillus and Bifidobacterium in enhancing anti‐tumor effects through the gut–tumor immune response axis. Future clinical trials are needed to evaluate the full benefits of this novel supplement with oral probiotics in patients with advanced urothelial carcinoma. John Wiley and Sons Inc. 2022-11-30 /pmc/articles/PMC9986082/ /pubmed/36398663 http://dx.doi.org/10.1111/cas.15666 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle ORIGINAL ARTICLES
Miyake, Makito
Oda, Yuki
Owari, Takuya
Iida, Kota
Ohnishi, Sayuri
Fujii, Tomomi
Nishimura, Nobutaka
Miyamoto, Tatsuki
Shimizu, Takuto
Ohnishi, Kenta
Hori, Shunta
Morizawa, Yosuke
Gotoh, Daisuke
Nakai, Yasushi
Torimoto, Kazumasa
Tanaka, Nobumichi
Fujimoto, Kiyohide
Probiotics enhances anti‐tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer
title Probiotics enhances anti‐tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer
title_full Probiotics enhances anti‐tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer
title_fullStr Probiotics enhances anti‐tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer
title_full_unstemmed Probiotics enhances anti‐tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer
title_short Probiotics enhances anti‐tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer
title_sort probiotics enhances anti‐tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer
topic ORIGINAL ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986082/
https://www.ncbi.nlm.nih.gov/pubmed/36398663
http://dx.doi.org/10.1111/cas.15666
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