The gut microbiota as modulators of the immune system and their potential in cancer therapy

Emerging evidence demonstrates the pivotal role of gut microbes in shaping our immune system. Studies have demonstrated the immunomodulatory capabilities of gut microbes in health conditions and a few diseases^1-3. In order to study the mechanistic interactions of gut microbes with the host, we have applied and further developed a metabolic labeling approach that allows fluorescent labeling, visualization and tracking of live gut microbes in real-time, in their natural localization, and in live mice⁴. We are studying the mechanistic interactions of gut microbes with the host immune system by combining immunology, microbiology, chemistry and fluorescent imaging. Recently studies have revealed intriguing potential of microbes in cancer progression and therapy^5-7. We are currently focusing on microbes that have potential effects on both cancer induction and on the efficacy of cancer immunotherapy. We see the gut microbiota as a treasure trove of potential therapeutics and believe that deciphering the principles of their interactions with the host will open new avenues for cancer treatment.

1 Geva-Zatorsky, N. et al. Mining the Human Gut Microbiota for Immunomodulatory Organisms. Cell 168, 928-943 e911, doi:10.1016/j.cell.2017.01.022 (2017).

2 Tan, T. G. et al. Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice. Proc Natl Acad Sci U S A 113, E8141-E8150, doi:10.1073/pnas.1617460113 (2016).

3 Sefik, E. et al. MUCOSAL IMMUNOLOGY. Individual intestinal symbionts induce a distinct population of RORgamma(+) regulatory T cells. Science 349, 993-997, doi:10.1126/science.aaa9420 (2015).

4 Geva-Zatorsky, N. et al. In vivo imaging and tracking of host-microbiota interactions via metabolic labeling of gut anaerobic bacteria. Nat Med 21, 1091-1100, doi:10.1038/nm.3929 (2015).

5 Geller, L. T. et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science 357, 1156-1160, doi:10.1126/science.aah5043 (2017).

6 Vetizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079-1084, doi:10.1126/science.aad1329 (2015).

7 Sivan, A. et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350, 1084-1089, doi:10.1126/science.aac4255 (2015).