Victoria Frankel

Recent Links Between The Gut Microbiome and Cancer

Oct 13, 2019

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Cancer research has come a long way in the last few decades. Although progress is often slow, taxing, and difficult to generate clinical relevance, the studies you read about today may very well be the tipping point for future therapies. Similarly, some studies have shown the gut microbiome may play a pivotal role in how cancerous conditions occur, creating a field of research that has left many scientists excited to explore.

 

Inflammation: A Gut Issue

One of the key factors that may influence our immune system, is our gut microbiome. When healthy and balanced, the gut microbiome helps to regulate the response of our immune system. However, when imbalanced – as in gut dysbiosis – an unhealthy gut microbiome may increase the exposure of inflammation.

Despite all the negative connotations typical of when we hear the words “inflammation,” it's an integral part in how we heal ourselves. Inflammation is simply our body rapidly flushing a hurt area or pathogen invasion with white blood cells to clear out harmed cells or an infection. Without it, we would die prematurely from sepsis and our wounds would never heal. It is only when inflammation becomes dysregulated and our body becomes flooded with macrophages that they begin to turn on healthy tissue. 

Macrophages are a type of white blood cell and our most savage defenders against pathogens and decaying cells(1). Their name – macrophage – literally means “large eater” and refers to their ability to devour and digest their target. Inside macrophages are an extremely acidic environment full of chemicals like hydrogen peroxide that is used to rapidly degrade and breakdown whatever it consumes(2). Macrophages are an essential component to our immune response and work hard to fight off harmful microbes. 

This is why preventing any inflammatory response can be just as or even more detrimental than allowing it to overwhelm the body in some cases. Instead, identifying ways to reduce how many immunity soldiers are produced excessively - especially when not necessary - is a prominent focus for a variety of diseases, including cancer.

But why wouldn’t we want to flood our body with these cancer-eating macrophages? Seems counterintuitive - yet scientists have shown inflammation can play a critical role in how cancer develops and progresses.


From Immune Response to Immune Offense

Our GALT – the gut-associated lymphoid system – is an important part of our digestive tract that houses upwards of 70% of our immune system(1). In cancer, the immune system plays an integral part in whether we can properly defend against cancer cell progression. Normally, when an organ or tissue in our body experiences an increase in mutations that can prove cancerous, our body rises to defend against it and eliminates those cells from growing. However, several types of mutations can actually hide cancerous cells from our immune system and allow them to continue to grow and spread. Additionally, when a cancerous tumor becomes mature enough, it can actually recruit our immune system to work for it, acting like “hypnotized” soldiers that help break down walls in our body that allow the cancer to spread. 

In cancer, when the tumor has exceeded its environment and prepares to metastasize, cancer cells begin recruiting circulating macrophages - with their impressive digesting powers - to help them break down the surrounding boundaries that is preventing the tumor to move toward other tissues(2). If we are experiencing a large amount of inflammation, the tumor has access to even more soldiers to recruit.

You can imagine, then, that how our immune system interacts with cancer is an essential area of cancer research.


Breast Cancer

Like many cancers, this becomes increasingly important for breast cancer as the 5-year survival rate for early stage breast cancer is at 99%, as long as the cancer remains in the breast(2). However, if it metastasizes – and spreads – that rate drops to a staggering 22%. 

The National Breast Cancer Foundation lists four different stages with several subtypes of breast cancer. At stages 0, 1, and 2 the cancerous tumor is restricted to the breast tissue. By stage 3, it has invaded the surrounding lymph nodes and muscle tissue. Stage 4 means the cancer has metastasized and transitioned to other organs, most frequently the bones, lungs, brain, or liver. Many scientists have sought to determine at what point does breast cancer shift from stage 3 to stage 4, only to find that it is difficult to pinpoint as it can vary drastically from case to case. As of today, there is no cure to Stage 4 breast cancer, and the average survival rate is only three years(2).

However, just recently new animal study has proposed the risk of metastasis might be influenced depending on the level of inflammation being produced by an imbalanced gut microbiome(3).

The lead scientist of this study, Dr. Melanie Rutkowski noted, "Disrupting the microbiome resulted in long-term inflammation within the tissue and the tumor environment.” She suggested that, “having an unhealthy microbiome, and the changes that occur within the tissue that are related to an unhealthy microbiome, may be early predictors of invasive or metastatic breast cancer.”

Her findings ride on the curtails of similar studies that find a link between the gut microbiome’s role in inflammation, and macrophage recruitment by cancer cells(3,4). Although only an early animal study, Rukowski’s results suggest we may be seeing future research examining how the gut microbiome may affect cancer metastasis, including ways in which we may improve gut dysbiosis in breast cancer patients.


Colorectal Cancer

While we’re on the topic of discussing cancer and the impact of gut microbiome research, it would be wrong not to touch on colorectal cancer, the third most commonly diagnosed cancer in both men and women in the United States. Colorectal cancer has been shown to have a genetic link, with a family history of the disease being one of the primary risk factors. Several genes have been linked to the development of adenomatous polyps, or benign growths found in the colon or rectum that may become precursors to colorectal cancer. However, genetic disposition toward developing colorectal cancer only accounts for 5% of cases making lifestyle, age, environment, occurrence of inflammatory bowel diseases, and many others factors main contributors to risk(5).

Similar to breast cancer, colorectal cancer has a nearly 80% survival rate over five years in the early stages of the disease(5). However, when progressing to later stages (as in Stage 4 or Stage 5), survival rates rapidly decline - making early diagnosis essential to better treatment outcomes. 

When it comes to lifestyle and dietary factors, both shown to heavily influence risk of developing colorectal cancer, gut dysbiosis can disturb the homeostasis of healthy colon cells. These cells - called colonocytes - help maintain the intestinal lining that keeps gut microbes and other particles from passing through the gaps between them and into the bloodstream. Many gut microbes have also been shown to help support the health of colonocytes in a natural symbiotic relationship. When gut microbial imbalance occurs, under the right conditions, this can lead to drastic changes to colonocyte instability that promotes leaky gut syndrome and leads to disorders like irritable bowel disease, Crohn’s, and colorectal cancer development(6). These disorders can also perpetuate a chronic inflammatory response… and we know where that might lead.


Your Gut Microbiome Takeaway

Although there is no one cause for cancer, and certainly no one-size-fits-all cure (at least yet), a considerable amount of cancer research has illuminated one thing clearly: each and every day we are getting a clearer look at how complicated cancer is: but there is hope.

We are moving further away from simplified and generalized ideas of how we should treat cancer patients and identifying ways in which they differ. By shifting our perspective to treating people at how unique their disease status is, we can find better treatments. Ultimately, what we can take away from these studies and others like them is how essential a true holistic approach is to our health. By focusing on the multifaceted role of inflammation and our gut, and exploring how interlinked the health of our gut microbiome is to the health of each of us, researchers may mark a fundamental change in how we view cancer therapies.


*The information on the Viome website is provided for informational purposes only and with the understanding that Viome is not engaged in rendering medical advice or recommendations. Viome is providing this educational information to share the exciting developments being reported in the scientific literature about the human microbiome and your health. Viome products are not intended to diagnose, treat, or prevent any disease.


 

Resources:

1.     Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013;496:445-455.

2.     https://www.cancer.net/cancer-types/breast-cancer/statistics

3.     Buchta Rosean C, Bostic RR, Ferey JCM, et al. Preexisting Commensal Dysbiosis Is a Host-Intrinsic Regulator of Tissue Inflammation and Tumor Cell Dissemination in Hormone Receptor-Positive Breast Cancer. Cancer Res. 2019;79:3662-3675.

4.     Francescone R, Hou V, Grivennikov SI. Microbiome, inflammation, and cancer. Cancer J. 2014;20:181-189.

5.     Siegel RL, Miller KD, Fedewa SA, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017;67:177-193. 

6.     Saus E, Iraola-Guzman S, Willis JR, Brunet-Vega A, Gabaldon T. Microbiome and colorectal cancer: Roles in carcinogenesis and clinical potential. Mol Aspects Med. 2019;69:93-106. 



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Recent Links Between The Gut Microbiome and Cancer

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