Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide, and its development is influenced by the gut environment. Specifically, metabolites derived from gut bacteria play a crucial role in its progression. Although the relationship between the gut microbiota and CRC has been investigated, studies on the impact of bacterial-derived metabolites are more limited.
In a new research, scientists used advanced techniques such as 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS) to analyze fecal metabolites and the gut microbiota of CRC patients and healthy individuals. Additionally, experiments were conducted in mouse models with subcutaneous and orthotopic tumors to understand how the microbe Faecalibacterium prausnitzii and the metabolite tyrosol affect tumor growth.
One of the most notable findings was that Faecalibacterium prausnitzii, a bacterium with anti-inflammatory properties, is significantly more abundant in the intestines of healthy individuals compared to CRC patients. Experiments in mice showed that this bacterium can inhibit tumor growth by reducing inflammatory responses and enhancing tumor immunity.
The study also revealed a key relationship between Faecalibacterium prausnitzii and tyrosol, a microbial-derived metabolite, which was also found in lower amounts in CRC patients. Tyrosol demonstrated potent antitumor activity in animal models and cell experiments, where it inhibited the growth of CRC cells without harming healthy intestinal epithelial cells.
In addition to inhibiting tumor growth, tyrosol significantly reduced levels of reactive oxygen species (ROS) and inflammatory cytokines in tumor cells. Molecular analysis using Western Blot showed that tyrosol blocks the activation of the NF-κB and HIF-1 signaling pathways, both of which are linked to inflammation and tumor growth.
This study provides valuable evidence that manipulating the gut microbiota and its metabolites could be an effective strategy for preventing and treating CRC. The discovery of tyrosol’s antitumor effect and its relationship with Faecalibacterium prausnitzii opens new avenues for the development of personalized treatments and microbiome-based anticancer drugs.
The findings suggest that by improving the balance of the gut microbiota, along with administering key metabolites like tyrosol, we could develop innovative and less invasive approaches to treating colorectal cancer. This could transform current prevention and treatment strategies for CRC, focusing on restoring gut health and leveraging the benefits of bacterial-derived metabolites.
Reference: Guo J, Meng F, Hu R, et alInhibition of the NF-κB/HIF-1α signaling pathway in colorectal cancer by tyrosol: a gut microbiota-derived metabolite. Journal for ImmunoTherapy of Cancer 2024;12:e008831. doi: 10.1136/jitc-2024-008831
