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.
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.


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

Frontiers in Immunology (2020). Arroyo Hornero, R., Hamad, I., Côrte-Real, B., & Kleinewietfeld, M.

Gastroenterology (2020). Le Roy, C. I., Wells, P. M., Si, J., Raes, J., Bell, J. T., & Spector, T. D.

Cell (2020). Liou, C. S., Sirk, S. J., Diaz, C. A. C., Klein, A. P., Fischer, C. R., Higginbottom, S. K., et al.

Science (2020). Kimura, I., Miyamoto, J., Ohue-Kitano, R., Watanabe, K., Yamada, T., Onuki, M., et al.

Nature (2020). Zhao, S., Jang, C., Liu, J., Uehara, K., Gilbert, M., Izzo, L., et al.

Scientific Reports (2020). Thompson, R. S., Vargas, F., Dorrestein, P. C., Chichlowski, M., Berg, B. M., & Fleshner, M.

Cell (2020). Nemet, I., Saha, P. P., Gupta, N., Zhu, W., Romano, K. A., Skye, S. M., et al.

Cell Host and Microbe (2020). Deehan, E. C., Yang, C., Perez-Muñoz, M. E., Nguyen, N. K., Cheng, C. C., Triador, L., et al.

mSystems (2020). Taylor, B. C., Lejzerowicz, F., Poirel, M., Shaffer, J. P., Jiang, L., Aksenov, A., et al.

Cell (2020). Ang, Q. Y., Alexander, M., Newman, J. C., Tian, Y., Cai, J., Upadhyay, V., et al.

Gut Microbes (2020). Boling, L., Cuevas, D. A., Grasis, J. A., Kang, H. S., Knowles, B., Levi, K., et al. (2020).

Cell (2019). Patnode, M. L., Beller, Z. W., Han, N. D., Cheng, J., Peters, S. L., Terrapon, N., et al.

Science (2019). Stein-Thoeringer, C. K., Nichols, K. B., Lazrak, A., Docampo, M. D., Slingerland, A. E., Slingerland, J. B., et al.

Nature Reviews Microbiology (2019). Kolodziejczyk, A. A., Zheng, D., & Elinav, E.

Scientific Reports (2019). Holder, M. K., Peters, N. V., Whylings, J., Fields, C. T., Gewirtz, A. T., Chassaing, B., & de Vries, G. J.

Oncoimmunology (2019). Lévesque, S., Pol, J. G., Ferrere, G., Galluzzi, L., Zitvogel, L., & Kroemer, G.

Oncoimmunology (2019). Lévesque, S., Le Naour, J., Pietrocola, F., Paillet, J., Kremer, M., Castoldi, F., et al. (2019).

The Journal of Nutrition (2018). Holscher, H. D., Guetterman, H. M., Swanson, K. S., An, R., Matthan, N. R., Lichtenstein, A. H., et al.


Science (2018). Zhao, L., Zhang, F., Ding, X., Wu, G., Lam, Y. Y., Wang, X., et al.


Nature Microbiology (2018). Tramontano, M., Andrejev, S., Pruteanu, M., Klünemann, M., Kuhn, M., Galardini, M., et al.

Nature Microbiology (2018). Hryckowian, A. J., Treuren, W., Smits, S. A., Davis, N. M., Gardner, J. O., Bouley, D. M., & Sonnenburg, J. L.

Nature Biomedical Engineering (2018). Ho, C. L., Tan, H. Q., Chua, K. J., Kang, A., Lim, K. H., Ling, K. L., et al.

Cell Host and Microbe (2018). Zou, J., Chassaing, B., Singh, V., Pellizzon, M., Ricci, M., Fythe, M. D., et al.

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.

mBio (2017). Maier, T. V., Lucio, M., Lee, L. H., VerBerkmoes, N. C., Brislawn, C. J., Bernhardt, J., et al.

Gastroenterology (2017). Llewellyn, S. R., Britton, G. J., Contijoch, E. J., Vennaro, O. H., Mortha, A., Colombel, J.-F., et al.

Nature (2017). Wilck, N., Matus, M. G., Kearney, S. M., Olesen, S. W., Forslund, K., Bartolomaeus, H., et al.

Bioscience, Biotechnology, and Biochemistry (2017). Kawabata, K., Baba, N., Sakano, T., Hamano, Y., Taira, S., Tamura, A., et al.

Journal of Translational Medicine (2017). Singh, R. K., Chang, H.-W., Di Yan, Lee, K. M., Ucmak, D., Wong, K., et al.

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 Reviews Microbiology (2020). Krautkramer, K. A., Fan, J., & Bäckhed, F.


Cell Host and Microbe (2020). Sinha, S. R., Haileselassie, Y., Nguyen, L. P., Tropini, C., Wang, M., Becker, L. S., et al.

Nat Immunol (2020). James, K. R., Gomes, T., Elmentaite, R., Kumar, N., Gulliver, E. L., King, H. W., et al.

Nature Communications (2019). Vojinovic, D., Radjabzadeh, D., Kurilshikov, A., Amin, N., Wijmenga, C., Franke, L., et al.

Curr Opin Pharmacol (2019). Gheorghe, C. E., Martin, J. A., Manriquez, F. V., Dinan, T. G., Cryan, J. F., & Clarke, G.

Cell (2019). Sberro, H., Fremin, B. J., Zlitni, S., Edfors, F., Greenfield, N., Snyder, M. P., et al.

Cell (2019). Hagan, T., Cortese, M., Rouphael, N., Boudreau, C., Linde, C., Maddur, M. S., et al.

Cell (2019). Chen, H., Nwe, P.-K., Yang, Y., Rosen, C. E., Bielecka, A. A., Kuchroo, M., et al.

Nat Rev Immunol (2019). Tilg, H., Zmora, N., Adolph, T. E., & Elinav, E.

Science (2019). Petersen, C., Bell, R., Klag, K. A., Lee, S.-H., Soto, R., Ghazaryan, A., et al.

Nature Biotechnology (2019). Wilmanski, T., Rappaport, N., Earls, J. C., Magis, A. T., Manor, O., Lovejoy, J., et al.

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.

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.

Nature (2017). Dodd, D., Spitzer, M. H., Van Treuren, W., Merrill, B. D., Hryckowian, A. J., Higginbottom, S. K., et al.

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

Cell (2015). Brodin, P., Jojic, V., Gao, T., Bhattacharya, S., Angel, C. J. L., Furman, D., et al. (2015).

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.

3 . Immune system / Cancer

Nature (2020). Cabrita, R., Lauss, M., Sanna, A., Donia, M., Larsen, M. S., Mitra, S., et al. (2020)., 1–20.

Nature (2020). Helmink, B. A., Reddy, S. M., Gao, J., Zhang, S., Basar, R., Thakur, R., et al.

Nature (2020). Petitprez, F., s, A. X. L. R. X., Keung, E. Z., Chen, T. W.-W., Sun, C.-M., Calderaro, J., et al.

Nature Communications (2019). Kong, Y., Rose, C. M., Cass, A. A., Williams, A. G., Darwish, M., Lianoglou, S., et al.

Nature (2019). Alspach, E., Lussier, D. M., Miceli, A. P., Kizhvatov, I., DuPage, M., Luoma, A. M., et al. (2019). 574(7780), 696–701.

Cell Research (2019). Jacquelot, N., Yamazaki, T., Roberti, M. P., Duong, C. P. M., Andrews, M. C., Verlingue, L., et al.


Nat Rev Immunol (2019). Blank, C. U., Haining, W. N., Held, W., Hogan, P. G., Kallies, A., Lugli, E., et al.

Nature Communications (2019). Xiao, Z., Dai, Z., & Locasale, J. W. (2019). 1–12.

Cell (2019). Miao, Y., Yang, H., Levorse, J., Yuan, S., Polak, L., Sribour, M., et al.

Cell (2019). Li, H., van der Leun, A. M., Yofe, I., Lubling, Y., Gelbard-Solodkin, D., van Akkooi, A. C. J., et al.

Nature Genetics (2019). Samstein, R. M., Lee, C.-H., Shoushtari, A. N., Hellmann, M. D., Shen, R., Janjigian, Y. Y., et al.

Nature Medicine (2019). Scheper, W., Kelderman, S., Fanchi, L. F., Linnemann, C., Bendle, G., de Rooij, M. A. J., et al.

Kearney, C. J., Vervoort, S. J., Hogg, S. J., Ramsbottom, K. M., Freeman, A. J., Lalaoui, N., et al. (2018).

Lancet Oncology (2018). MD, F. C., MD, L. P., PhD, V. B., De Pas MD, T., BSc, M. M., MD, P. G. V., et al.

Nature Medicine (2018). Binnewies, M., Roberts, E. W., Kersten, K., Chan, V., Fearon, D. F., Merad, M., et al.

Immunity (2018). Thorsson, V., Gibbs, D. L., Brown, S. D., Wolf, D., Bortone, D. S., Yang, T.-H. O., et al.

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.

European Journal of Cancer (2017). Ugurel, S., Röhmel, J., Ascierto, P. A., Flaherty, K. T., Grob, J. J., Hauschild, A., et al.

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.

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

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.

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

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

4 . Microbiome / Cancer

Science (2020). Baruch, E. N., Youngster, I., Ben-Betzalel, G., Ortenberg, R., Lahat, A., Katz, L., et al.

Nature (2020). Kadosh, E., Snir-Alkalay, I., Venkatachalam, A., May, S., Lasry, A., Elyada, E., et al.

European Urology (2020). Salgia, N. J., Bergerot, P. G., Maia, M. C., Dizman, N., Hsu, J., Gillece, J. D., et al.

Science (2020). Mager, L. F., Burkhard, R., Pett, N., Cooke, N. C. A., Brown, K., Ramay, H., et al.

Science (2020). Fluckiger, A., Daillère, R., Sassi, M., Sixt, B. S., Liu, P., Loos, F., et al.

Nature Medicine (2020). Roberti, M. P., Yonekura, S., Duong, C. P. M., Picard, M., Ferrere, G., Tidjani Alou, M., et al.

Science (2020). Nejman, D., Livyatan, I., Fuks, G., Gavert, N., Zwang, Y., Geller, L. T., et al.

Nature Communications (2020). Coutzac, C., Jouniaux, J.-M., Paci, A., Schmidt, J., Mallardo, D., Seck, A., et al.

Nature (2020). Poore, G. D., Kopylova, E., Zhu, Q., Carpenter, C., Fraraccio, S., Wandro, S., et al.

Nature Microbiology (2020). Zagato, E., Pozzi, C., Bertocchi, A., Schioppa, T., Saccheri, F., Guglietta, S., et al.

Nature Reviews Cancer (2019). Elinav, E., Garrett, W. S., Trinchieri, G., & Wargo, J.

Cell (2019). Riquelme, E., Zhang, Y., Zhang, L., Montiel, M., Zoltan, M., Dong, W., et al.

Nature Communications (2019). Li, Y., Tinoco, R., Elmén, L., Segota, I., Xian, Y., Fujita, Y., et al. (2019)., 1–16.

Cell (2019) Jin, C., Lagoudas, G. K., Zhao, C., Bullman, S., Bhutkar, A., Hu, B., et al.

Nature (2019). Tanoue, T., Morita, S., Plichta, D. R., Skelly, A. N., Suda, W., Sugiura, Y., et al.


Journal of Hematology & Oncology (2018). Yi, M., Yu, S., Qin, S., Liu, Q., Xu, H., Zhao, W., et al.

Uribe-Herranz, M., Bittinger, K., Rafail, S., Guedan, S., Pierini, S., Tanes, C., et al.

Science (2018). Dejea, C. M., Fathi, P., Craig, J. M., Boleij, A., Taddese, R., Geis, A. L., et al.

Science (2018). Matson, V., Fessler, J., Bao, R., Chongsuwat, T., Zha, Y., Alegre, M.-L., et al.

Cancer Cell (2018). Gopalakrishnan, V., Helmink, B. A., Spencer, C. N., Reuben, A., & Wargo, J. A.

Nature Communications (2018). Calcinotto, A., Brevi, A., Chesi, M., Ferrarese, R., Perez, L. G., Grioni, M., et al.

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.

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.

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.

Bullman, S., Pedamallu, C. S., Sicinska, E., Clancy, T. E., Zhang, X., Cai, D., et al.

Peters, B. A., Wu, J., Pei, Z., Yang, L., Purdue, M. P., Freedman, N. D., et al.

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.

Cancer Cell (2015). Rutkowski, M. R., Stephen, T. L., Svoronos, N., Allegrezza, M. J., Tesone, A. J., Perales-Puchalt, A., et al.

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