Gut microbiota-immune system crosstalk: can probiotics prevent colorectal cancer?
The gut microbiota is made up of trillions of commensal and pathogenic microorganisms that interact closely with intestinal and immune cells and maintain healthy gut physiology. Altered gut microbiota composition and homeostasis have been associated with and is considered a risk factor for many diseases including metabolic disorders, cardiovascular conditions, and CRC. Emerging evidence indicates that certain gut microbiota influence oncogenesis, tumour progression and response to therapy.
Investigating the role of microbiota in immune responses
The scope of the EU-funded IMMUNO_CRC project was to understand how certain gut microbiota groups identified in CRC patients alter immune function and influence the overall clinical outcome. Previous work by the scientific team had shown that patients with CRC harbour specific subtypes of gut microbiota, which are associated with distinct mucosal gene expression profiles. IMMUNO_CRC wanted to extend these findings. They investigated the hypothesis that tumour-associated microbiota interact with host inflammatory cells, either directly or through their metabolites, and impact the outcome of carcinogenesis. Undertaken with the support of the Marie Skłodowska-Curie programme, the work involved transferring microbiota from patients into a mouse model that mirrors the biological characteristics of CRC disease. “This model allowed us to figure out how different microbiota affects the immune response, and in turn how this controls the progression of CRC,” explains research fellow Ana Santos Almeida. Scientists employed a combination of techniques to measure tumour characteristics, analyse the tumour-infiltrating immune cells and study the microbial metabolites involved in inflammation. Results showed that the size of experimental tumours in mice varied depending on the type of microbiota present. This suggested that certain microbiota species play a role in reducing tumour growth. Moreover, scientists discovered qualitative differences in the immune response of mice with different gut microbiota.
Microbiota may guide future CRC therapies
CRC is the third most prevalent form of cancer with millions of new cases worldwide every year. There is an imminent need for prognostic markers and therapeutic targets. The gut microbiota is a modifiable environmental factor that has the potential to improve the health of older individuals and patients suffering from specific disorders. This makes it an attractive target for novel live therapeutics. According to Almeida: “The IMMUNO_CRC work helped us understand more precisely how gut microbiota can influence the development of CRC in patients.” Importantly, IMMUNO_CRC suggests that the composition of microbiota in the gut dictates how fast CRC disease progresses. Although the pre-clinical evidence warrants validation in humans, it may prove critical in designing future strategies for preventing and treating cancer. Modulation of gut microbiota, potentially through diet, may reduce CRC by promoting a protective microbiome especially among the elderly. With a view to the future, Almeida emphasises that, “studies into specific bacterial taxa isolated from human biopsies and their respective metabolites, will help dissect exactly how the microbiota modulate the anti-tumour immune response.” Additionally, advances in molecular biology technologies will allow the gut microenvironment to be characterised and provide a non-invasive means for CRC diagnosis and screening.
Keywords
IMMUNO_CRC, CRC, gut microbiota, colorectal cancer, immune cells, inflammation