The role of gut microbiota and metabolites in cancer chemotherapy Original paper

What was studied?

This review focused on the role of gut microbiota in modulating the efficacy and toxicity of cancer chemotherapy. The authors explored how different bacterial species and their metabolites interact with chemotherapeutic agents, potentially influencing both therapeutic outcomes and adverse effects. The review also highlighted strategies such as dietary interventions, probiotics, and fecal microbiota transplantation (FMT) that may optimize chemotherapy response.

Who was studied?

The study primarily focused on the impact of gut microbiota in cancer patients undergoing chemotherapy. The review discussed various studies involving colorectal cancer (CRC), breast cancer, and other malignancies, emphasizing how differences in microbial composition between patients could influence responses to common chemotherapeutic agents like 5-fluorouracil, irinotecan, and cisplatin. It also examined the microbiota’s role in both enhancing efficacy and mitigating side effects such as diarrhea, mucositis, and neuropathy.

Most important findings

One of the most significant findings was that gut microbiota could directly influence the efficacy of chemotherapy. For instance, Fusobacterium nucleatum, a bacterium found in CRC, was shown to promote chemoresistance by activating autophagy through a TLR4/MYD88-dependent pathway. Conversely, beneficial microbes such as Akkermansia muciniphila were linked to enhanced chemotherapy efficacy, especially in breast cancer treated with doxorubicin. Additionally, microbial metabolites like butyrate were found to enhance chemotherapy effects by inhibiting glucose metabolism through the GPR109a-AKT signaling pathway, while Ursodeoxycholic acid (UDCA) reshaped microbial composition to promote chemotherapy. Moreover, gut microbiota influenced the toxicity profile of chemotherapies, with certain strains reducing chemotherapy-induced gastrointestinal (GI) toxicity and others potentially exacerbating side effects.

Key implications

The review highlighted that targeting the gut microbiota could serve as a promising strategy for enhancing the safety and efficacy of chemotherapy. Manipulating the microbiota through interventions such as probiotics, dietary changes, and FMT could reduce chemotherapy-induced toxicity, thereby improving patient quality of life. Furthermore, gut microbiota could act as predictive biomarkers, offering a non-invasive method for forecasting chemotherapy efficacy. However, challenges remain in identifying universal microbiota profiles and metabolites that can be applied across different patient populations. The variability in microbiota composition due to host genetics, diet, and other environmental factors complicates the implementation of microbiota-targeted therapies in clinical practice. More research is needed to refine these strategies and validate their clinical effectiveness in large cohorts.