Publicação
Gut microbiota metabolites positively impacts chemotherapy effects in colorectal cancer
| Resumo: | Colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths worldwide, largely due to late-stage diagnosis and limited efficacy of current therapies. 5-Fluorouracil (5-FU) is the standard chemotherapeutic agent used in CRC treatment; however, its effectiveness is often hampered by resistance, toxicity, and suboptimal outcomes in advanced-stage tumors. Recent evidence suggests that gut microbiota-derived short-chain fatty acids (SCFAs) exert anticancer effects and may hold promise as therapeutic adjuvants. In this study, we investigated the potential of a physiologically relevant mixture of SCFAs to enhance the efficacy of 5-FU against CRC. Using a combination of 2D monolayer cultures, 3D models, and the in vivo chicken chorioallantoic membrane (CAM) assay, we demonstrated that SCFAs positively affect the antitumor effects of low-dose 5-FU. SCFAs contributed to the inhibition of CRC cell growth, proliferation, survival, and migration, with an overall increase of the anti-tumour effects observed across the different models. The combined treatment led to a significant reduction in tumour size in the CAM assay, contributing for an improvement of the effects of 5-FU alone. To our knowledge, this is the first report showing that physiologically relevant SCFA combinations can be harnessed to improve the therapeutic index of 5-FU in CRC, in a context-dependent manner. These findings support the development of microbiota-targeted co-adjuvant strategies to optimize CRC chemotherapy, reduce treatment toxicity, and improve patient outcomes, which is important given the clinical interest in microbiome-chemotherapy interactions. |
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| Autores principais: | Gomes, Sara |
| Outros Autores: | Granja, Sara; Osório, Luana A.; Mackay, Ruth E.; Baltazar, Fátima; Silva, Elisabete; Preto, Ana |
| Assunto: | Ciências Naturais::Ciências Biológicas |
| Ano: | 2026 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths worldwide, largely due to late-stage diagnosis and limited efficacy of current therapies. 5-Fluorouracil (5-FU) is the standard chemotherapeutic agent used in CRC treatment; however, its effectiveness is often hampered by resistance, toxicity, and suboptimal outcomes in advanced-stage tumors. Recent evidence suggests that gut microbiota-derived short-chain fatty acids (SCFAs) exert anticancer effects and may hold promise as therapeutic adjuvants. In this study, we investigated the potential of a physiologically relevant mixture of SCFAs to enhance the efficacy of 5-FU against CRC. Using a combination of 2D monolayer cultures, 3D models, and the in vivo chicken chorioallantoic membrane (CAM) assay, we demonstrated that SCFAs positively affect the antitumor effects of low-dose 5-FU. SCFAs contributed to the inhibition of CRC cell growth, proliferation, survival, and migration, with an overall increase of the anti-tumour effects observed across the different models. The combined treatment led to a significant reduction in tumour size in the CAM assay, contributing for an improvement of the effects of 5-FU alone. To our knowledge, this is the first report showing that physiologically relevant SCFA combinations can be harnessed to improve the therapeutic index of 5-FU in CRC, in a context-dependent manner. These findings support the development of microbiota-targeted co-adjuvant strategies to optimize CRC chemotherapy, reduce treatment toxicity, and improve patient outcomes, which is important given the clinical interest in microbiome-chemotherapy interactions. |
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