The Effect of Microbiome-Derived Metabolites in Inflammation-Related Cancer Prevention and Treatment Original paper

What was studied?

The review explores the effects of microbiome-derived metabolites in inflammation-related cancer prevention and treatment. It focuses on how microbial metabolites such as short-chain fatty acids (SCFAs), polyamines, indoles, and bile acids influence inflammation, which plays a critical role in cancer progression. The review emphasizes the dualistic nature of these metabolites, where some contribute to cancer prevention through anti-inflammatory effects, while others, such as secondary bile acids, may exacerbate tumor progression. It also examines the molecular pathways involved, including immune regulation and epigenetic modifications, and highlights emerging therapeutic strategies targeting microbiome-derived metabolites.

Who was studied?

The review synthesizes research from preclinical and clinical studies involving various cancer types, including colorectal, liver, breast, and prostate cancers. It discusses the effects of specific microbial metabolites on inflammation and immune modulation, focusing on their potential to prevent or treat cancer. The studies cover both healthy individuals and cancer patients, evaluating the role of dietary fibers, probiotics, and microbiome-engineered therapies in influencing cancer outcomes. Additionally, the review includes evidence from experimental models and human trials that assess the impact of microbiome-derived metabolites on tumorigenesis and therapy responses.

Most important findings

Microbiome-derived metabolites, particularly SCFAs like butyrate, play a crucial role in cancer prevention by inducing apoptosis in cancer cells, enhancing immune responses, and maintaining intestinal barrier integrity. SCFAs also regulate immune cell differentiation, particularly regulatory T cells (Tregs), which suppress inflammation and contribute to an anti-tumor environment. Polyamines such as spermidine also influence inflammation and tumor growth but show a complex, dual role, where they can both promote cell proliferation and apoptosis depending on the context. Indole derivatives, produced by gut bacteria from tryptophan, modulate immune tolerance and reduce chronic inflammation. Secondary bile acids, on the other hand, exhibit a pro-inflammatory role in some cancers, promoting tumor progression. Despite promising results, challenges such as metabolite stability, bioavailability, and individual microbiome variability remain significant hurdles in applying these findings to cancer therapy.

Key implications

The review underscores the therapeutic potential of microbiome-derived metabolites in cancer prevention and treatment. It suggests that SCFAs and indoles, with their anti-inflammatory and immunomodulatory effects, could serve as powerful adjuncts to traditional cancer therapies. However, the review also highlights the complexity of using microbial metabolites in clinical practice, given their variability in effectiveness due to individual differences in microbiome composition. Personalized microbiome-based therapies that tailor interventions to an individual’s microbiome profile could enhance the precision and efficacy of cancer treatments. Future research should focus on overcoming the challenges of metabolite stability and bioavailability, along with developing new strategies for targeting inflammation-driven cancers using microbiome-derived metabolites.