Uncovering causation between Intestinal bacteria and colon cancer

The gut microbiota has been recognized as important determinant in the initiation and progression of colorectal cancer. Despite recent advances in the field shedding light on the molecular mechanisms, it remains challenging to establish causal relationships between microbes and colorectal carcinogenesis in human subjects.

Researchers Floor Baas, Iris Nagtegaal and Annemarie Boleij from the Radboudumc, department of pathology in collaboration with researchers Nele Brusselaers and Lars Engstrand from the Karolinska Institutet shed light on the most prominent obstacles in establishing causality and provide potential opportunities to make advancements in this field. The Cancer Microbiome Research group, led by Boleij published the perspective “Navigating beyond associations: Opportunities to establish causal relationships between the gut microbiome and colorectal carcinogenesis” in Cell Host and Microbe on 14th of August in a special issue “Microbiome and systemic disease”.

In the perspective they discuss three important obstacles that have hampered the identification of causality in human subjects and two important opportunities that will pave the way forward. High degrees of variability, between individuals, within individuals and within bacterial species, hinder the detection of relevant microbes. Increased sampling frequency using increasingly accessible and sensitive profiling techniques should help move past this, especially as  these techniques can help to identify relevant bacterial factors. They stress the importance of  investing time and resources into high-quality longitudinal cohort studies with long follow-up and appropriate sampling strategies. Or, alternatively, to ensure that retrospective studies are performed using high-quality registries and materials. In addition, they urge researchers to take heterogeneity of colon cancer development pathways into account and report on as many variables as possible regarding disease context of the acquired samples. 

Finally, they expect that the opportunities and further developments in in vitro disease and microbial community modelling and -omics technologies will pave the way towards understanding causality between microbes and human CRC carcinogenesis. At the moment they already set up a large longitudinal prospective study to investigate the role of the microbiome and specific carcinogenic factors in early carcinogenesis and hope to make a first step towards assessing causality in humans.

Publication
Baas, F. S., et al. (2024). "Navigating beyond associations: Opportunities to establish causal relationships between the gut microbiome and colorectal carcinogenesis." Cell Host & Microbe 32(8): 1235-1247.