When relationships turn sour – cancer and the holobiont

Cancer Research UK suggests that understanding the complex interplay of ageing, physiology, and the microbiome is crucial to comprehending colorectal cancer risk. While cancer was once thought to be primarily a genetic disease driven by the accumulation of mutations, researchers now view it more as a systems-level breakdown. This perspective aligns with the process of ageing, which also accumulates biological noise.

The holobiont – a term encompassing a host and its microbial communities – plays a significant role in disease risk, particularly in the intestine, where colorectal cancer (CRC) is common. Even with oncogenic mutations, many individuals do not develop malignancy. Instead, additional biological factors, including holobiont interactions and external environmental influences, determine whether a tumour emerges.

Age is a key orchestrator of holobiont biology, causing mitochondrial defects in the colonic epithelium and shifts in microbial function. The idea that age-associated mitochondrial and microbial dysfunction actively participate in tumour initiation is gaining experimental support. Mitochondrial dysfunction can accelerate tumour development in APC-deficient intestines, and certain gut bacteria produce genotoxins and metabolites that damage host DNA and promote inflammation.

This emerging view of cancer as an emergent property of a destabilised system with age suggests that managing the microbiome, metabolism, and other holobiont components may prove pivotal in cancer prevention. However, considerable challenges remain, including the complexity, personalization, and environmental interdependencies of the microbiome.