Microbiome & The Holy Grail

Cancer is unfortunately the third most common cause of death in the United States today.  You would be hard pressed to find anybody who has not had someone close to them suffer with the disease.  As such, it is something of a Holy Grail in modern medical research.

But, let’s talk a little bit about the relationship between cancer and the microbiome.  Now, I already discussed the potential link between gut microbiome status and breast cancer, but some interesting recent research has taken things a bit further.  Not only do your gut bacteria play a role in the prevention and/or progression of cancer, they also appear to essential to the efficacy of common pharmaceutical therapies.

The “gold standards” of the conventional modern medicine paradigm for advanced stage cancer are chemotherapy and radiation, which present something of a double-edged sword.  These treatments, while generally effective at eliminating cancer, have a host of adverse effects, particularly toxicity in various organs [1, 2].  However, if that weren’t enough, they can also induce inflammation, increase intestinal epithelial and mucosal permeability and dysbiosis in the gut [3, 4, 5].

The next wave of cancer drugs, termed immunotherapy, work by activating, enhancing or suppressing the innate immune system to fight the cancer [6], but unfortunately, it too is subject to a variety of adverse effects [7].

However, this is where things get interesting.  Emerging research has indicated that the presence of commensal bacteria not only improves the efficacy of chemotherapy and immunotherapy drugs, but also may actually be required for them to work at all [8, 9]!

One research group was examining melanomas in mice and found that animals sourced from two different companies had different degrees of cancer progression [10].  Interestingly, once they were housed together, they displayed equivalent degrees of remission.

What changed? Well, following up on Joe’s awesome and hilarious Poop Pills video, the mice actually began eating each other’s poop!!

So basically, these mice were self-administering a very crude version of the “poop pills” or fecal transplant.

There are a couple of mechanisms thought to be at play here.  The commensal bacteria are thought to help with the production of anti-inflammatory compounds to reduce the damage, regulation of intestinal wall integrity through supporting the repair of the epithelial and mucosal layers, as well as through the activation of the innate immune system [3, 11].  So they appear to play a role in promoting homeostasis and eubiosis, to help mitigate damage and initiate attacks on the cancer cells.

Taking this into account, it helps explain many of the deleterious effects associated with common cancer therapies.  Not only do they kill the host, or “you” cells, but they also destroy a key component of your bodies carefully evolved system for maintaining homeostasis.  As we often discuss, the microflora inhabiting your gastrointestinal tract outnumber your host cells 10-1.  You are more bacteria than human!

So any treatment that impairs that process, can and likely will have negative effects to both your outcome and overall health status.

Now, to be clear, the research is still emerging and many questions remain to be answered, but the potential breakthroughs of research into the relationship between cancer and the microbiome, or “oncobiome” [12], may finally help us end our quest for the Holy Grail.

But what does that mean for you today?

Well, this helps lend further support for the regular consumption of fermented foods and directed use of probiotic supplementation, particularly for those currently undergoing cancer treatments, such as chemotherapy, radiation or immunotherapy [13].

While immensely beneficial for a number of reasons, the probiotic strains in fermented foods often do not make it through the stomach and into the gastrointestinal tract in large enough quantities to be viable, which explains the sometimes-conflicting evidence [14].

This is where the use of probiotics, such as MegaSporeBiotic really shines insomuch as they are able to bypass destruction by stomach acid and germinate and multiply where they are supposed to in the large intestine [15].

Prebiotic supplementation, which helps feed your probiotic bacteria, also appears to demonstrate similar effects regarding reversing intestinal and microflora damage [11, 16].  For more on its importance, check out my Resistant Starch article.

Turmeric, and particularly its most researched active constituent, curcumin, is also beneficial at repairing both intestinal permeability following -anti-cancer therapies [17] and in enhancing their effectiveness [18], likely based on the same mechanisms.

One more supplement to consider is glutamine, as it is yet another that has efficacy at improving intestinal wall integrity [19] and mitigating chemotherapy-induced toxicities [20].

It is absolutely incredible that the more we learn, the more we remember the things we have “forgotten.”  The emerging research mounts on a daily basis that elucidates the role of the microbiome in a wide variety of disease.  While it is only now beginning to gain acceptance, this is something Hippocrates understood over 2000 years ago, but just didn’t have the right words or context to fully explain.

So while we have been searching far and wide for our Holy Grail, perhaps the answer is already inside us.

References:

1) Maor, Y. & Malnick, S. (2013). Liver injury induced by anticancer chemotherapy & radiation therapy. Int J Hepatol. Vol. 2013:815105.

2) Magge, R.S. & DeAngelis, L.M. (2015). The double-edged sword: Neurotoxicity of chemotherapy. Blood Rev. Vol. 29(2):93-100.

3) van Vliet, M.J., Harmsen, H.J., de Bont, E.S. & Tissing, W.J. (2010). The role of intestinal microbiota in the development & severity of chemotherapy-induced mucositis. PLoS Pathog. Vol. 6(5):e1000879.

4) Thorpe, D.W., Stringer, A.M. & Gibson, R.J. (2013). Chemotherapy-induced mucositis: The role of the gastrointestinal microbiome & toll-like receptors. Exp Biol Med. Vol. 238(1):1-6.

5) Montassier, E., Gastinne, T., Vangay, P., Al-Ghalith, G.A., Bruley des Varannes, S., Massart, S., Moreau, P., Potel, G., de La Cochetière, M.F., Batard, E. & Knights, D. (2015). Chemotherapy-driven dysbiosis in the intestinal microbiome. Aliment Pharmacol Ther. Vol. 42(5):515-528.

6) Haanen, J.B. (2013). Immunotherapy of melanoma. EJC Suppl. Vol. 11(2):97-105.

7) Camacho, L.H. (2015). CTLA-4 blockade with ipilimumab: Biology, safety, efficacy, & future considerations. Cancer Med. Vol. 4(5):661-672.

8) Iida, N., Dzutsev, A,, Stewart, C.A., Smith, L., Bouladoux, N., Weingarten, R.A., Molina, D.A., Salcedo, R., Back, T., Cramer, S., Dai, R.M., Kiu, H., Cardone, M., Naik, S., Patri, A.K., Wang, E., Marincola, F.M., Frank, K.M., Belkaid, Y., Trinchieri, G. & Goldszmid, R.S. (2013). Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science.  Vol. 342(6161):967-970.

9) Vétizou, M., Pitt, J.M., Daillère, R., Lepage, P., Waldschmitt, N., Flament, C., Rusakiewicz, S., Routy, B., Roberti, M.P., Duong, C.P., Poirier-Colame, V., Roux, A., Becharef, S., Formenti, S., Golden, E., Cording, S., Eberl, G., Schlitzer, A., Ginhoux, F., Mani, S., Yamazaki, T., Jacquelot, N., Enot, D.P., Bérard, M., Nigou, J., Opolon, P., Eggermont, A., Woerther, P.L., Chachaty, E., Chaput, N., Robert, C., Mateus, C. & Kroemer, G. (2015). Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. Vol. 350(6264):1079-1084.

10) Sivan, A., Corrales, L., Hubert, N., Williams, J.B., Aquino-Michaels, K., Earley, Z.M., Benyamin, F.W., Lei, Y.M., Jabri, B., Alegre, M.L., Chang, E.B. & Gajewski, T.F. (2015). Commensal Bifidobacterium promotes antitumor immunity & facilitates anti-PD-L1 efficacy. Science. Vol. 350(6264):1084-1089.

11) Viaud, S., Daillère, R., Boneca, I.G., Lepage, P., Langella, P., Chamaillard, M., Pittet, M.J., Ghiringhelli, F., Trinchieri, G., Goldszmid, R. & Zitvogel, L. (2015). Gut microbiome & anticancer immune response: Really hot Sh*t! Cell Death Differ. Vol. 22(2):199-214.

12) Thomas, R.M. & Jobin, C. (2015). The microbiome & cancer: Is the ‘oncobiome’ mirage real? Trends Cancer. Vol. 1(1):24-35.

13) Yeung, C.Y., Chan, W.T., Jiang, C.B., Cheng, M.L., Liu, C.Y., Chang, S.W., Chiang Chiau, J.S. & Lee, H.C. (2015). Amelioration of chemotherapy-induced intestinal mucositis by orally administered probiotics in a mouse model. PLoS One. Vol. 10(9):e0138746.

14) Rao, R.K. & Samak, G. (2013). Protection & restitution of gut barrier by probiotics: Nutritional & clinical implications. Curr Nutr Food Sci. Vol. 9(2):99-107.

15) Ghelardi, E., Celandroni, F., Salvetti, S., Gueye, S.A., Lupetti, A. & Senesi, S. (2015). Survival & persistence of Bacillus clausii in the human gastrointestinal tract following oral administration as spore-based probiotic formulation. J Appl Microbiol. Vol. 119(2):552-559.

16) Wang, H., Geier, M.S. & Howarth, G.S. (2014). Prebiotics: A potential treatment strategy for the chemotherapy-damaged gut? Crit Rev Food Sci Nutr. [Epub ahead of print]

17) Yao, Q., Ye, X., Wang, L., Gu, J., Fu, T., Wang, Y., Lai, Y., Wang, Y., Wang, X., Jin, H. & Guo, Y. (2013). Protective effect of curcumin on chemotherapy-induced intestinal dysfunction. Int J Clin Exp Pathol. Vol. 6(11):2342-2349.

18) Shakibaei, M., Mobasheri, A., Lueders, C., Busch, F., Shayan, P. & Goel, A. (2013). Curcumin enhances the effect of chemotherapy against colorectal cancer cells by inhibition of NF-κB & Src protein kinase signaling pathways. PLoS One. Vol. 8(2):e57218.

19) Rapin, J.R. & Wiernsperger, N. (2010). Possible links between intestinal permeability & food processing: A potential therapeutic niche for glutamine. Clinics. Vol. 65(6):635-643.

20) Gaurav, K., Goel, R.K., Shukla, M. & Pandley, M. (2012). Glutamine: A novel approach to chemotherapy-induced toxicity. Indian J Med Paediatr Oncol. Vol. 33(1):13–20.

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