Differences in the intratumour microbiome of patients with colorectal cancer in Europe and Japan compared to the US.

Abstract Summary

Following advances in understanding the role of the microbiome in carcinogenesis, we find that inter-country differences exist in the intratumoral microbiome of patients with colorectal cancer in the USA compared to those from Europe and Japan.

Background

The microbiome appears critical to human health. Following advances in understanding the gut microbiome in carcinogenesis, the presence of bacteria within tumours has generated significant attention1. The intratumour microbiome can be linked with both positive and negative effects on cancer development2 and immune response3,4. Understanding sources of variation to manage this dichotomy could inform personalised treatment. Mucosal barrier penetration is a mechanism for environmental microbe translocation present in colorectal cancer (CRC)5. We hypotheses this may vary between countries given the difference in gut microbiome. We studied the intratumour microbiome in CRC patients across Europe, the USA and Japan.

Methods

We leveraged BioCorteX’s industry leading knowledge graph and integrated proprietary technology engines. Utilising a data driven mechanistic approach, 1,549 colorectal tumour microbiome samples from 5 different countries (France, Spain, Switzerland, the USA and Japan) were analysed in BioCorteX’s Carbon MirrorTM platform v20230504_112227. Microbiome analyses were performed, including alpha diversity, beta diversity, compositional abundance profile and permutational analysis of variance (PERMANOVA). No significant batch effects were observed.

Results

We found significant population-level differences in alpha diversity, which was lowest in the USA compared to Japan. The intratumoral microbiome of samples from the USA significantly differed from that of other countries in beta diversity and PERMANOVA analyses (p < 0.001). Fusobacteriota were present in the composition of all intratumour microbiome groups, but notably abundant in Spain (34.6%).

Conclusion

The intratumour microbiome exists as an important source of variation across cancer populations. There are links with pathogenic bacteria posited to drive tumorigenesis in pre-clinical models of CRC, such as Fusobacteriota7, abundant in Spanish and Swiss patient groups. Future studies should explore the functional importance of these differences, and seek to translate these findings into actionable insights for cancer treatment.

References

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