Cancer Microbiome

Reprogramming Gut Microbiome to Prevent and Treat Cancer

Investigator

Saori Furuta, Ph.D.

Each person contains about 40 trillion commensal microbes —collectively termed the microbiome—reaching the number as much as host cells (30 trillion)1.  These microbes are the most abundant in the gut, weighing up to one kilogram per person2.  They are not merely passive passengers, but essential components for body’s fundamental functions, including immunity and metabolism3,4.  Guts provide the largest contact surface for microbes and immune cells, allowing the latter to fight against pathogens, but also to establish tolerance towards harmless symbionts5-7

Interactions between gut microbes and host immune cells play pivotal roles in prevention and treatment responses of various diseases, especially, cancer.  This feat is largely attributed to their reciprocal regulation through microbial products, such as PAMPs (pathogen-associated molecular patterns) and MAMPs (microbe-associated molecular patterns), and immune cell products, such as anti-microbial peptides8,9.  Nevertheless, microbe-immune cell interactions are greatly influenced by host metabolism, diet, diseases, and drug treatment, potentially leading to a condition termed dysbiosis—an imbalance in the composition of the microflora10-12.  Thus, certain patients could be benefited by dietary interventions or transplantation of fecal microbiota from healthy donors7,13.

Our current research focuses on two major aims: 1) to ameliorate microbial dysbiosis of cancer patients through metabolic/dietary interventions or microbial transfer; and 2) to identify MAMPs that could improve anti-cancer immunity of patients and be potentially utilized in clinics.  

References

  1. Sender, R., Fuchs, S. & Milo, R. Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans. Cell 164, 337-340, doi:10.1016/j.cell.2016.01.013 (2016).
  2. Goodrich, J. K., Davenport, E. R., Clark, A. G. & Ley, R. E. The Relationship Between the Human Genome and Microbiome Comes into View. Annu Rev Genet 51, 413-433, doi:10.1146/annurev-genet-110711-155532 (2017).
  3. Smith, K., McCoy, K. D. & Macpherson, A. J. Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin Immunol 19, 59-69, doi:10.1016/j.smim.2006.10.002 (2007).
  4. Zheng, D., Liwinski, T. & Elinav, E. Interaction between microbiota and immunity in health and disease. Cell Research 30, 492-506, doi:10.1038/s41422-020-0332-7 (2020).
  5. Turner, J. R. Intestinal mucosal barrier function in health and disease. Nature Reviews Immunology 9, 799-809, doi:10.1038/nri2653 (2009).
  6. Mowat, A. M. To respond or not to respond - a personal perspective of intestinal tolerance. Nat Rev Immunol 18, 405-415, doi:10.1038/s41577-018-0002-x (2018).
  7. Beamer, M. A. et al. Novel 3D Flipwell system that models gut mucosal microenvironment for studying interactions between gut microbiota, epithelia and immunity. Sci Rep 13, 870, doi:10.1038/s41598-023-28233-8 (2023).
  8. Schroeder, B. O. Fight them or feed them: how the intestinal mucus layer manages the gut microbiota. Gastroenterol Rep (Oxf) 7, 3-12, doi:10.1093/gastro/goy052 (2019).
  9. Khosravi, A. et al. Gut microbiota promote hematopoiesis to control bacterial infection. Cell Host Microbe 15, 374-381, doi:10.1016/j.chom.2014.02.006 (2014).
  10. Yoo, J. Y., Groer, M., Dutra, S. V. O., Sarkar, A. & McSkimming, D. I. Gut Microbiota and Immune System Interactions. Microorganisms 8,doi:10.3390/microorganisms8101587 (2020).
  11. Goldsmith, J. R. & Sartor, R. B. The role of diet on intestinal microbiota metabolism: downstream impacts on host immune function and health, and therapeutic implications. J Gastroenterol 49, 785-798, doi:10.1007/s00535-014-0953-z (2014).
  12. Xuan, C. et al. Microbial dysbiosis is associated with human breast cancer. PLoS One 9, e83744, doi:10.1371/journal.pone.0083744 (2014).
  13. Chen, D., Wu, J., Jin, D., Wang, B. & Cao, H. Fecal microbiota transplantation in cancer management: Current status and perspectives. International journal of cancer 145, 2021-2031, doi:10.1002/ijc.32003 (2019).
MetroHealth Logo