Conviction

peer-reviewed research from
credible high-impact journals.

current clinical practice and
many promising novel approaches.

of lifestyle changes when
dealing with the disease of Eva Rees.

Scientific rationale
for the nutrition / microbiome / metabolite / immune system axis
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Humans have evolved to live in symbiosis with microbes – bacteria, archea, viruses, fungi and protozoa.
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More than 99% of these microbes are bacteria (ca: 100 trillion) living within the human gut (the “gut microbiome”).
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Ten times as many bacteria inhabit a human body as there are cells in that body, and the vast majority of these bacteria are helpful and sometimes necessary for human survival.
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Numerous nutrients are metabolized by the gut microbiome which in turn determines the extent these nutrients and/or their metabolites are taken up by the host.
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The resulting metabolites (collectively called the “gut metabolome”) can have potent effects on human physiology, including the brain, metabolism and immune cell function.
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Efficient immune cell function is needed to kill or keep cancer cells at bay. Regulation of immune cells with immunotherapy (e.g. checkpoint blockade) has emerged as one of the most promising approaches to anti-cancer therapy.
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Given the interplay between the microbiome and the immune system, and in turn the immune system and cancer, there is an increasing body of scientific evidence showing that a poorly functioning gut microbiome negatively impacts immune cells and in turn allows cancer development.
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In contrast a healthy microbiome has been shown to increase the efficacy of cancer immunotherapy (only 20-30% of patients usually respond to current treatments) and reduce the side effects of immunotherapy drugs.
Evidence
So far from our research and discussions with experts, we have identified some key peer-reviewed publications and sources which underpin our rationale that more benign approaches can be developed to treat cancers and other illnesses by modulating the nutrition/microbiome/metabolite/immune system axis. It is interesting to observe that there is quite a range of published research on different elements of this axis (see below). Our goal at Seerave is to join the dots between these different elements and the diverse research efforts.
Please note that we do not necessarily endorse any of the peer-reviewed publications.
1 .Nutrition / Microbiome
Nature Immunology (2017). Zitvogel, L., Pietrocola, F., & Kroemer, G.
Cell Metabolism (2017). Korem, T., Zeevi, D., Zmora, N., Weissbrod, O., Bar, N., Lotan-Pompan, M., et al.
Personalized Medicine (2017). Toribio-Mateas, M. A., & Spector, T. D.
Cell (2017). Scott, T. A., Quintaneiro, L. M., Norvaisas, P., Lui, P. P., Wilson, M. P., Leung, K.-Y., et al.
Gut (2017). Vandeputte, D., Falony, G., Vieira-Silva, S., Wang, J., Sailer, M., Theis, S., et al.
Journal of the Royal Society of Medicine (2016). Pallister, T., & Spector, T. D.
Nature (2016). Sonnenburg, J. L., & Bäckhed, F.
Cell (2016). Koh, A., De Vadder, F., Kovatcheva-Datchary, P., & Bäckhed, F.
Cell Host and Microbe (2016). Zmora, N., Zeevi, D., Korem, T., Segal, E., & Elinav, E.
Cell (2015). Zeevi, D., Korem, T., Zmora, N., Israeli, D., Rothschild, D., Weinberger, A., et al.
Nature (2015). O’Keefe, S., Li, J. V., Lahti, L., Ou, J., & Carbonero, F.
Current Opinion in Gastroenterology (2014). Kinross, J., Li, J. V., Muirhead, L. J., & Nicholson, J.
Nature (2013). David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., et al. (2013)., 1–18.
Science (2013). Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., et al.
Nature Reviews Cancer (2013). Kaoutari, El, A., Armougom, F., Gordon, J. I., Raoult, D., & Henrissat, B.
2 .Microbiome / Metabolites / Immune system
Nature (2017). Cohen, L. J., Esterhazy, D., Kim, S.-H., Lemetre, C., Aguilar, R. R., Gordon, E. A., et al.
Science (2017). Cervantes-Barragan, L., Chai, J. N., Tianero, M. D., Di Luccia, B., Ahern, P. P., Merriman, J., et al.
Nature (2017). Panigrahi, P., Parida, S., Nanda, N. C., Satpathy, R., Pradhan, L., Chandel, D. S., et al.
Nature Immunology (2017). Blander, J. M., Longman, R. S., Iliev, I. D., Sonnenberg, G. F., & Artis, D.
Immunity (2017). Belkaid, Y., & Harrison, O. J.
Cell Host and Microbe (2017). Ivanov, I. I.
Cell (2017). Yissachar, N., Zhou, Y., Ung, L., Lai, N. Y., Mohan, J. F., Ehrlicher, A., et al.
Cell (2017). Geva-Zatorsky, N., Sefik, E., Kua, L., Pasman, L., Tan, T. G., Ortiz-Lopez, A., et al.
Current Opinion in Microbiology (2017). Levy, M., Blacher, E., & Elinav, E.
Trends in Immunology (2016). Margolis, K. G., Gershon, M. D., & Bogunovic, M.
Science (2016). Gensollen, T., Iyer, S. S., Kasper, D. L., & Blumberg, R. S.
Nature (2015). Naik, S., Bouladoux, N., Linehan, J. L., Han, S.-J., Harrison, O. J., Wilhelm, C., et al.
Proceedings of the National Academy of Sciences (2014). Chang, P. V., Hao, L., Offermanns, S., & Medzhitov, R.
Cell (2014). An, D., Oh, S. F., Olszak, T., Neves, J. F., Avci, F. Y., Erturk-Hasdemir, D., et al.
Nature (2013). Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., et al. (2013).
Science (2013). Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., et al.
Nature Immunology (2013). Belkaid, Y., & Naik, S.
Cell (2005). Mazmanian, S. K., Liu, C. H., Tzianabos, A. O., & Kasper, D. L. (2005).
3 .Immune system / Cancer
Nature (2017). Jacquelot, N., Roberti, M. P., Enot, D. P., Rusakiewicz, S., Ternès, N., Jegou, S., et al.
Science Translational Medicine (2017). Fankhauser, M., Broggi, M. A. S., Potin, L., Bordry, N., Jeanbart, L., Lund, A. W., et al.
Nature (2017). Mezzadra, R., Sun, C., Jae, L. T., Gomez-Eerland, R., de Vries, E., Wu, W., et al.
Nature (2017). Ott, P. A., Hu, Z., Keskin, D. B., Shukla, S. A., Sun, J., Bozym, D. J., et al. (2017).
Nature Communications (2017). Enamorado, M., Iborra, S., Priego, E., Cueto, F. J., Quintana, J. A., nez-Cano, S. M. I., et al.
Nature Reviews Immunology (2017). Nagarsheth, N., Wicha, M. S., & Zou, W.
Trends in Immunology (2016). Gardner, A., & Ruffell, B.
Nature Reviews Immunology (2016). Speiser, D. E., Ho, P.-C., & Verdeil, G.
Cell (2016). Hugo, W., Zaretsky, J. M., Sun, L., Song, C., Moreno, B. H., Hu-Lieskovan, S., et al.
Science Translational Medicine (2016). Mlecnik, B., Bindea, G., Kirilovsky, A., Angell, H. K., Obenauf, A. C., Tosolini, M., et al.
Trends in Immunology (2016). Kumar, V., Patel, S., Tcyganov, E., & Gabrilovich, D. I.
Nature Reviews Cancer (2016). Morvan, M. G., & Lanier, L. L.
Cancer Discovery (2016). Lund, A. W., Medler, T. R., Leachman, S. A., & Coussens, L. M.
Current Opinion in Immunology (2016). Munn, D. H., & Bronte, V.
Nature Reviews Cancer (2016). Restifo, N. P., Smyth, M. J., & Snyder, A.
Cancer Discovery (2015). Ribas, A.
Seminars in Oncology (2015). Gajewski, T. F. (2015)
New England Journal of Medicine (2015). Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., et al.
New England Journal of Medicine (2015). Postow, M. A., Chesney, J., Pavlick, A. C., Robert, C., Grossmann, K., McDermott, D., et al.
Nature (2015). Spranger, S., Bao, R., & Gajewski, T. F
Science (2015). Schumacher, T. N., & Schreiber, R. D. (2015).
Cancer Cell (2015). Schumacher, T. N., Kesmir, C., & van Buuren, M. M.
Frontiers in Physiology (2011). Greer, J. B., & O’Keefe, S. J.
4 .Microbiome / Cancer
Science (2017). Routy, B., Le Chatelier, E., Derosa, L., Duong, C. P. M., Alou, M. T., Daillère, R., et al. (2017).
Science (2017). Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., et al.
Neoplasia (2017). Frankel, A. E., Coughlin, L. A., Kim, J., Froehlich, T. W., Xie, Y., Frenkel, E. P., & Koh, A. Y.
PLoS Pathogens (2017). Fulbright, L. E., Ellermann, M., & Arthur, J. C. (2017).
Science (2017). Geller, L. T., Barzily-Rokni, M., Danino, T., Jonas, O. H., Shental, N., Nejman, D., et al.
Cell (2017). Yu, T., Guo, F., Yu, Y., Sun, T., Ma, D., Han, J., et al.
Nature Reviews Microbiology (2017). Zitvogel, L., Daillère, R., Roberti, M. P., Routy, B., & Kroemer, G.
Semin Immunol (2017). Bashiardes, S., Tuganbaev, T., Federici, S., & Elinav, E.
Nature Reviews Cancer (2017). Roy, S., & Trinchieri, G.
Nature Reviews Cancer (2017). Tsilimigras, M. C. B., Fodor, A., & Jobin, C.
Immunity (2016). Daillère, R., Vétizou, M., Waldschmitt, N., Yamazaki, T., Isnard, C., Poirier-Colame, V., et al.
Cancer Res (2016). Pitt, J. M., Vétizou, M., Waldschmitt, N., Kroemer, G., Chamaillard, M., Boneca, I. G., & Zitvogel, L.
Immunity (2016). Pitt, J. M., Vétizou, M., Daillère, R., Roberti, M. P., Yamazaki, T., Routy, B., et al.
Nature Communications (2016), Dubin, K., Callahan, M. K., Ren, B., Khanin, R., Viale, A., Ling, L., et al.
Science (2015). Sivan, A., Corrales, L., Hubert, N., Williams, J. B., Aquino-Michaels, K., Earley, Z. M., et al.
Science (2015). Vétizou, M., Pitt, J. M., Daillère, R., Lepage, P., Waldschmitt, N., Flament, C., et al.
Nature (2015). O’Keefe, S., Li, J. V., Lahti, L., Ou, J., & Carbonero, F.
Science (2013). Iida, N., Dzutsev, A., Stewart, C. A., Smith, L., Bouladoux, N., Weingarten, R. A., et al.
Frontiers in Physiology (2011). Greer, J. B., & O’Keefe, S. J.