Conviction

It is our conviction that more benign approaches can be developed to treat cancers and other illnesses by modulating the nutrition / microbiome / metabolite / immune system axis. New technologies have the potential to measure the impact of these approaches. Our conviction has evolved from:
Rigorous analysis of existing
peer-reviewed research from
credible high-impact journals.
Observations of a gap between
current clinical practice and
many promising novel approaches.
Observations made from impact
of lifestyle changes when
dealing with the disease of Eva Rees.
Label
Conviction Image

Scientific rationale

for the nutrition / microbiome / metabolite / immune system axis

  • Humans have evolved to live in symbiosis with microbes – bacteria, archea, viruses, fungi and protozoa.

  • More than 99% of these microbes are bacteria (ca: 100 trillion) living within the human gut (the “gut microbiome”).

  • 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.

  • 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.

  • The resulting metabolites (collectively called the “gut metabolome”) can have potent effects on human physiology, including the brain, metabolism and immune cell function.

  • 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.

  • 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.

  • 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

Our goal is to work with partners, establishing scientific proof of principle and ultimately clinical proof of principle that novel benign approaches to cancer are safe and efficacious and may also complement current therapies. Our aim is for partners to publish this evidence when these foundation supported projects are completed.

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.

http://doi.org/10.1038/ni.3754

Cell Metabolism (2017). Korem, T., Zeevi, D., Zmora, N., Weissbrod, O., Bar, N., Lotan-Pompan, M., et al.

http://doi.org/10.1016/j.cmet.2017.05.002

Personalized Medicine (2017). Toribio-Mateas, M. A., & Spector, T. D.

http://doi.org/10.2217/pme-2016-0017

Cell (2017). Scott, T. A., Quintaneiro, L. M., Norvaisas, P., Lui, P. P., Wilson, M. P., Leung, K.-Y., et al.

http://doi.org/10.1016/j.cell.2017.03.040

Gut (2017). Vandeputte, D., Falony, G., Vieira-Silva, S., Wang, J., Sailer, M., Theis, S., et al.

http://doi.org/10.1136/gutjnl-2016-313271

Cell (2015). Zeevi, D., Korem, T., Zmora, N., Israeli, D., Rothschild, D., Weinberger, A., et al.

http://doi.org/10.1016/j.cell.2015.11.001

Nature (2015). O’Keefe, S., Li, J. V., Lahti, L., Ou, J., & Carbonero, F.

http://doi.org/10.1038/ncomms7342

Current Opinion in Gastroenterology (2014). Kinross, J., Li, J. V., Muirhead, L. J., & Nicholson, J.

http://doi.org/10.1097/MOG.0000000000000036

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.

http://doi.org/10.1038/nature12820

Science (2013). Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., et al.

http://doi.org/10.1126/science.1241165

Nature Reviews Cancer (2013). Kaoutari, El, A., Armougom, F., Gordon, J. I., Raoult, D., & Henrissat, B.

http://doi.org/10.1038/nrmicro3050

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.

http://doi.org/10.1038/nature23874

Science (2017). Cervantes-Barragan, L., Chai, J. N., Tianero, M. D., Di Luccia, B., Ahern, P. P., Merriman, J., et al.

http://doi.org/10.1126/science.aah5825

Nature (2017). Panigrahi, P., Parida, S., Nanda, N. C., Satpathy, R., Pradhan, L., Chandel, D. S., et al.

http://doi.org/10.1038/nature23480

Nature Immunology (2017). Blander, J. M., Longman, R. S., Iliev, I. D., Sonnenberg, G. F., & Artis, D.

http://doi.org/10.1038/ni.3780

Cell (2017). Geva-Zatorsky, N., Sefik, E., Kua, L., Pasman, L., Tan, T. G., Ortiz-Lopez, A., et al.

http://doi.org/10.1016/j.cell.2017.01.022

Current Opinion in Microbiology (2017). Levy, M., Blacher, E., & Elinav, E.

http://doi.org/10.1016/j.mib.2016.10.003

Nature (2015). Naik, S., Bouladoux, N., Linehan, J. L., Han, S.-J., Harrison, O. J., Wilhelm, C., et al.

http://doi.org/10.1038/nature14052

Proceedings of the National Academy of Sciences (2014). Chang, P. V., Hao, L., Offermanns, S., & Medzhitov, R.

http://doi.org/10.1073/pnas.1322269111

Cell (2014). An, D., Oh, S. F., Olszak, T., Neves, J. F., Avci, F. Y., Erturk-Hasdemir, D., et al.

http://doi.org/10.1016/j.cell.2013.11.042

Nature (2013). Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., et al. (2013).

http://doi.org/10.1038/nature12726

Science (2013). Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., et al.

http://doi.org/10.1126/science.1241165

3 .Immune system / Cancer

Nature (2017). Jacquelot, N., Roberti, M. P., Enot, D. P., Rusakiewicz, S., Ternès, N., Jegou, S., et al.

http://doi.org/10.1038/s41467-017-00608-2

Science Translational Medicine (2017). Fankhauser, M., Broggi, M. A. S., Potin, L., Bordry, N., Jeanbart, L., Lund, A. W., et al.

http://doi.org/10.1126/scitranslmed.aal4712

Nature (2017). Mezzadra, R., Sun, C., Jae, L. T., Gomez-Eerland, R., de Vries, E., Wu, W., et al.

http://doi.org/10.1038/nature23669

Nature (2017). Ott, P. A., Hu, Z., Keskin, D. B., Shukla, S. A., Sun, J., Bozym, D. J., et al. (2017).

http://doi.org/10.1038/nature22991

Nature Communications (2017). Enamorado, M., Iborra, S., Priego, E., Cueto, F. J., Quintana, J. A., nez-Cano, S. M. I., et al.

http://doi.org/10.1038/ncomms16073

Trends in Immunology (2016). Gardner, A., & Ruffell, B.

http://doi.org/10.1016/j.it.2016.09.006

Nature Reviews Immunology (2016). Speiser, D. E., Ho, P.-C., & Verdeil, G.

http://doi.org/10.1038/nri.2016.80

Cell (2016). Hugo, W., Zaretsky, J. M., Sun, L., Song, C., Moreno, B. H., Hu-Lieskovan, S., et al.

http://doi.org/10.1016/j.cell.2016.02.065

Science Translational Medicine (2016). Mlecnik, B., Bindea, G., Kirilovsky, A., Angell, H. K., Obenauf, A. C., Tosolini, M., et al.

http://doi.org/10.1126/scitranslmed.aad6352

Trends in Immunology (2016). Kumar, V., Patel, S., Tcyganov, E., & Gabrilovich, D. I.

http://doi.org/10.1016/j.it.2016.01.004

Nature Reviews Cancer (2016). Morvan, M. G., & Lanier, L. L.  

http://doi.org/10.1038/nrc.2015.5

Cancer Discovery (2016). Lund, A. W., Medler, T. R., Leachman, S. A., & Coussens, L. M.

http://doi.org/10.1158/2159-8290.CD-15-0023

Nature Reviews Cancer (2016). Restifo, N. P., Smyth, M. J., & Snyder, A.

http://doi.org/10.1038/nrc.2016.2

New England Journal of Medicine (2015). Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., et al.

http://doi.org/10.1056/NEJMoa1504030

New England Journal of Medicine (2015). Postow, M. A., Chesney, J., Pavlick, A. C., Robert, C., Grossmann, K., McDermott, D., et al.

http://doi.org/10.1056/NEJMoa1414428

Science (2015). Schumacher, T. N., & Schreiber, R. D. (2015).

http://doi.org/10.1126/science.aaa4971

Cancer Cell (2015). Schumacher, T. N., Kesmir, C., & van Buuren, M. M.

http://doi.org/10.1016/j.ccell.2014.12.004

4 .Microbiome / Cancer

Science (2017). Routy, B., Le Chatelier, E., Derosa, L., Duong, C. P. M., Alou, M. T., Daillère, R., et al. (2017).

http://doi.org/10.1126/science.aan3706

Science (2017). Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., et al.

http://doi.org/10.1126/science.aan4236

PLoS Pathogens (2017). Fulbright, L. E., Ellermann, M., & Arthur, J. C. (2017).

http://doi.org/10.1371/journal.ppat.1006480

Science (2017). Geller, L. T., Barzily-Rokni, M., Danino, T., Jonas, O. H., Shental, N., Nejman, D., et al.

http://doi.org/10.1126/science.aah5043

Nature Reviews Microbiology (2017).  Zitvogel, L., Daillère, R., Roberti, M. P., Routy, B., & Kroemer, G.

http://doi.org/10.1038/nrmicro.2017.44

Semin Immunol (2017). Bashiardes, S., Tuganbaev, T., Federici, S., & Elinav, E.

http://doi.org/10.1016/j.smim.2017.04.001

Nature Reviews Cancer (2017). Roy, S., & Trinchieri, G.

http://doi.org/10.1038/nrc.2017.13

Nature Reviews Cancer (2017). Tsilimigras, M. C. B., Fodor, A., & Jobin, C.

http://doi.org/10.1038/nmicrobiol.2017.8

Immunity (2016). Daillère, R., Vétizou, M., Waldschmitt, N., Yamazaki, T., Isnard, C., Poirier-Colame, V., et al.

http://doi.org/10.1016/j.immuni.2016.09.009

Cancer Res (2016). Pitt, J. M., Vétizou, M., Waldschmitt, N., Kroemer, G., Chamaillard, M., Boneca, I. G., & Zitvogel, L.

http://doi.org/10.1158/0008-5472.CAN-16-0448

Immunity (2016). Pitt, J. M., Vétizou, M., Daillère, R., Roberti, M. P., Yamazaki, T., Routy, B., et al.

http://doi.org/10.1016/j.immuni.2016.06.001

Nature Communications (2016), Dubin, K., Callahan, M. K., Ren, B., Khanin, R., Viale, A., Ling, L., et al.

http://doi.org/10.1038/ncomms10391

Science (2015). Sivan, A., Corrales, L., Hubert, N., Williams, J. B., Aquino-Michaels, K., Earley, Z. M., et al.

http://doi.org/10.1126/science.aac4255

Science (2015). Vétizou, M., Pitt, J. M., Daillère, R., Lepage, P., Waldschmitt, N., Flament, C., et al.

http://doi.org/10.1126/science.aad1329

Nature (2015). O’Keefe, S., Li, J. V., Lahti, L., Ou, J., & Carbonero, F.

http://doi.org/10.1038/ncomms7342

Science (2013). Iida, N., Dzutsev, A., Stewart, C. A., Smith, L., Bouladoux, N., Weingarten, R. A., et al.

http://doi.org/10.1126/science.1240527