The Microbiome & Cancer – The Research is PHENOMENAL

In this episode, Carla explores the ground breaking connection between the microbiome and cancer, emphasising its critical role in cancer development, progression, and treatment responses. Drawing from Hanahan and Weinberg's Hallmarks of Cancer, she highlights the ways in which microbiome research is reshaping our understanding of oncology.

Key Points:

• Microbiome’s Influence on Cancer:
• Modulating the Microbiome for Better Outcomes
• Notable Research Discussed
• Patient-Centred Approach

Carla emphasizes the incredible potential of leveraging microbiome science to improve cancer care, advocating for research-driven, individualised strategies.

Next Episode Preview: Carla dives into strategies for maintaining bone density during and after cancer treatment.

References:

• Hanahan, D. Hallmarks of cancer: new dimensions Cancer Discov. 12 ,31-36 (2022)
• Fulbright LE, Ellermann M, Arthur JC. The microbiome and the hallmarks of cancer. PLoS Pathog. 2017 Sep 21;13(9):e1006480. doi: 10.1371/journal.ppat.1006480. PMID: 28934351; PMCID: PMC5608396.
• Łaniewski P, Ilhan ZE, Herbst-Kralovetz MM. The microbiome and gynaecological cancer development, prevention and therapy. Nat Rev Urol. 2020 Apr;17(4):232-250. doi: 10.1038/s41585-020-0286-z. Epub 2020 Feb 18. PMID: 32071434; PMCID: PMC9977514.
• Andolfi C, Bloodworth JC, Papachristos A, Sweis RF. The Urinary Microbiome and Bladder Cancer: Susceptibility and Immune Responsiveness. Bladder Cancer. 2020 Sep 21;6(3):225-235. doi: 10.3233/BLC-200277. PMID: 33195783; PMCID: PMC7605348
• Dadgar N, Edlukudige Keshava V, Raj MS, Wagner PL. The Influence of the Microbiome on Immunotherapy for Gastroesophageal Cancer. Cancers (Basel). 2023 Sep 5;15(18):4426. doi: 10.3390/cancers15184426. PMID: 37760397; PMCID: PMC10526145.
• Viswanathan S, Parida S, Lingipilli BT, Krishnan R, Podipireddy DR, Muniraj N. Role of Gut Microbiota in Breast Cancer and Drug Resistance. Pathogens. 2023 Mar 16;12(3):468. doi: 10.3390/pathogens12030468. PMID: 36986390; PMCID: PMC10058520
• Bernardo G, Le Noci V, Di Modica M, Montanari E, Triulzi T, Pupa SM, Tagliabue E, Sommariva M, Sfondrini L. The Emerging Role of the Microbiota in Breast Cancer Progression. Cells. 2023 Jul 27;12(15):1945. doi: 10.3390/cells12151945. PMID: 37566024; PMCID: PMC10417285.
• Parida S., Sharma D. The Microbiome-Estrogen Connection and Breast Cancer Risk. Cells. 2019;8:1642. doi: 10.3390/cells8121642

Find PROSPER Natural Cancer CARE on Instagram @prosper.cancer.care or visit www.prospercancercare.co.

For more information or to get in touch, connect with Carla on Instagram @carlawrenn or visit www.carlawrenn.com.

Disclaimer: This podcast is intended to be informational only and represents the opinion of the participants, but not necessarily their workplace. It is not intended to be used as medical advice and does not take the place of advice from a qualified health care practitioner in a clinical setting. Please check with your healthcare practitioner before embarking upon any of the treatments or lifestyle changes discussed.

Transcript

SPEAKER_00 0:09

Welcome to Prosper Natural Cancer Care. I'm Carla Wren. We discuss naturopathic cancer care, integrative oncology and lifestyle medicine, examining complimentary medicine tradition, science, and evidence-based personalized health care for people with cancer. If you or a loved one has a cancer diagnosis, or you're a professional with an interest in complementary medicine or cancer care, you've come to the right place. Let's prosper. But before we start today, let's take a moment to define the word prosper and why it's an important word for me in the work I do. Prosper is defined as to flourish physically, grow strong and healthy, to become strong and flourishing, to cause to succeed or thrive. These words and words like choose hope are important to me as I aim to empower, educate, and encourage people in my practice and on this podcast. Please be sure to take a moment at the end of today's show to listen to the very important disclaimer. In this episode, we're going to talk about oncology and the microbiome. And this is kind of evidence-based insights that I would use to educate complementary medicine practitioners on this area. And I wanted to give you a snapshot as perhaps a carer or a patient or someone diagnosed with cancer or perhaps someone interested in this space that oncology and the microbiome are really such a fascinating area of research. So let's dive into this today and I'll try and give you a bit of a rundown of why I think cancer and the microbiome is something that really needs to be looked about. Now, you would have heard me in perhaps an earlier episode of this podcast talk about the hallmarks of cancer. And the hallmarks of cancer were really published research from Hannahan and Weinberg starting in 2000. And, you know, going for the next 22 years, up until 2022, looking at four papers that kind of constitute an organized principle of rationalizing the complexity of cancer and neoplastic disease. And so it's really looking at things like the drivers of cancer proliferative signaling, how cancer evades growth suppresses, resists cell death, why cells can develop replicative immortality, including angiogenesis and invasion and metastases. And it looks at lots of different ways tumours exhibit uh levels of complexity that change the way they grow and develop compared to normal cells, and how that all contributes to creating a tumor microenvironment. And this concept really has had a big impact on understanding how we treat cancer. And so these hallmarks have continued to develop and now include areas such as understanding the microbiome and the polymorphic microbes and how they impact the cancer microenvironment. And so understanding these areas really enables me at Prosper to allow my understanding and education to the patient to really be impactful around how we can use complementary medicines to target some of the hallmarks of cancer. And today we're going to be looking at a bit more specifically around microbiome, but areas like immune evasion and inflammation and the effects of blood glucose levels on things like angiogenesis, areas that I've covered in other podcasts. But understanding this polymorphic microbes is looking at the variability in microbes that reside within our body and have an influence on cancer phenotypes, the development and progression of cancer. And Hannahan, the researcher, builds a strong case that polymorphic microbes represent a discrete enabling characteristic that impacts the reason why we might acquire some of the hallmarks of cancer and how we can be protected against cancer, but also how cancer can be facilitated in the body. And that there's a significant amount of evidence that suggests that the microbiome can exist to have cancer protective properties, but there is also cancer promoting microbes. And we understand that they can affect the incidence and progression of cancers, not just cancers like colorectal cancer, which you really think, you know, gut-based cancers are very much connected to that gut microbiome. With the gut microbiome affecting things like the immune system, it can have such a big impact on anti-chan tumor immunity. It can also have big effects on the responses to therapy. We know this for patients with melanoma, the treatment that they undergo can very much be affected by what's happening in their microbiome. But it's not just gut-based cancers, you know, all sorts of cancers, as you'll see today, can have a real um effect on the microbiome's patterning. And that patterning can have a big impact on the progression of cancer and how people respond to inflammation, whether it be because they have an impact on genome stability or mutations or uh tumor-promoting inflammation, there is a whole uh reason why the microbiome can have a big impact uh on you know the cancer progression, diagnosis, treatment. And so certain viruses and bacteria, either in themselves or in combinations with other cofactors, can cause cancers to be affected in many of the different important cellular pathways outlined in the hallmarks of cancer. And so, what can we do about that is part of what we'll talk about today. We can easily find information on this topic with simple searches in places like PubMed. When we look up PubMed, that's a published medical trials. We can even find papers like those published in 2017 by Fulbright that talk about microbial significance and signalling and the hallmarks of cancer. So, really, uh, in this paper, Fulbright and his colleagues have looked at the intestinal microbiota and how that impacts all the hallmarks of cancer. And I'll make sure that we put this paper in the show notes so you can start to see how these different hallmarks are affected by the microbiome and maybe tap into that research. And so we know that these microbiome implications are affecting cancers like colorectal cancer. And it doesn't just have to be microbial species. We think about bacteria. We also know several viruses can be associated with human cancers, and so we know microbiome including viruses have an impact on cervical, genital, anal, and oral cancers. Epstein bar virus can have an impact on lymphomas, and hepatitis C can have an impact on uh hepatacellular carcinoma. There is lots of different cancers that have an impact or have been impacted by viruses. The microbiota can also extend to other um fungi and archaea um that modulate the hallmarks and capabilities of the body to be resilient and maybe you know impacting people with different cancer developments. And so we would call some parts of the microbiome procarcinogenic. So if we delve into some of the specifics around this, we um have to acknowledge that the gut microbiome could significantly alter the outcome of treatment, the outcome of a person's cancer experience, what they achieve with their chemotherapy and immunotherapy. Yet, frustratingly, not one seems to be addressing this in Australia, uh, let alone discussing it. And this is why I was fortunate enough to put a big presentation together this year to be able to educate my complimentary medicine community around cancer and the microbiome, and certainly like to extend that training to other fields of medicine working in the oncology space because the data is brilliant, the references are phenomenal, and the actionability and the safety of this information means it should be something that's really brought into all patients immediately. So, in the complementary medicine, particularly naturopathy, we might um we moderate the microbiome using things like prebiotics, probiotics, postbiotics, antimicrobials, antibiotics, and sometimes things like fecal microbial transplant use, but more importantly, we use diet. And so microbiome modulation can very often be a very safe intervention, quite a simple intervention. And so, while nowadays it's widely accepted that changes in normal gut microbiome cause dysbiosis and immune dysregulation, we need to understand that they play a really significant role in all cancer types. Yet no one is teaching our patients how to address this. So the microbiome in cancer is very well researched, and there is just so many different papers we can talk about. But the examination of how the microbiome impacts the body's homeostatus, uh, how it is affecting the gut, but also how it is affecting other areas of the body, um, you know, really shows us that we can utilize this for all cancers. The microbiome in cancer affects the body, the system, the tissues, and fascinatingly, there is also a microbiome in the tumor that we need to consider. So understanding the oncogenic effect of the microbiome empowers us to understand our pathogenesis, helps with early diagnosis, treatment, prevention, perhaps even life extension, I would say, and provides novel options for treatment. And there are really big benefits when we alter the dysbiosis that might be occurring in patients. We improve immune and metabolic signaling, and that can have an effect on chronic inflammation, epithelial barrier breach, changes in cellular proliferation, apoptosis, genomic instability, angiogenesis, and metabolic dysfunction. If that all goes right over your head, basically this is the microbiome making big differences to targets. We try and focus on not just in complementary medicine, integrative oncology, but also in standard oncology. The microbiome can even help us modulate estrogen metabolism, which is really important in cancers there where there is an estrogenic component, like maybe an ER-positive breast cancer. And so we can use really non-toxic interventions to support the patient to, you know, tackle this as another additional treatment option throughout their uh treatment. And despite their diagnosis, we're going to deep dive a little bit into some of the cancers, and I'll just give you a little bit of information. We know that gynecological cancers like ovarian cancers, cervical cancers, and endometrial cancers all have their own microbiome. This forms part of what's called the female microbiome axis. And microbiome species are living in the vagina, the urethra, the bladder, the bloodstream, the fallopian tubes around the ovaries. We know there is bacteria, and a whole estroboloum exists. And this is the interface between the microbiome and its effect on estrogen and other hormones. And so looking at the female reproductive tract microbiome and working with the gut and vagina axis, we can see improvements in diagnosis and also progression of different cancer types. And so when we look at this, we might see that working with microbiome in this space or diet can have a big impact. If we have dysbiotic bacteria, including some lactobacillus species, we can see an increased risk of different cancers and changes in areas like the urinary tract microbiome. And so when we have a good level of diversity in the lactobacillus within the uterus, fallopian tubes, ovary, and vaginal and cervix space, we have a healthy microbiome in that area. But if we start to see things like chlamydia, mycoplasma, you know, an increased biomass in, say, Brucella, in the fallopian tubes and ovaries, we start to see disease and increased risk of gynecological cancers, a reduced level of lactobacillus in the uterus and different amounts of biomass made up of different species, including antipodium, start to change the uterus space and increase the risk of other infections. The same applies in the vaginal and cervical area. We know that HPV has a big impact, but increasing species diversity in the wrong direction, as well as pH in the wrong direction, reduction in lactobacillus, increase in anaerobes, all change what's happening in the vaginal and cervic space. And so the paper published in 2020, The Microbiome and Gynecological Cancer Development, Prevention and Therapy, is a great paper to look at here to understand a bit more about how we can get on top of the microbiome. The paper summarizes that overall these dysbiotic microbes in the areas discussed might contribute to the etiology, disease severity, and/or treatments of gynecological cancers, which is a fascinating suggestion and something we should really be exploring more, I think. And so you can see some great articles in this paper looking at those hallmarks of cancer and the gynecological cancer microbiota and the interface between them. And so a great paper to jump on into and have a look. They do highlight some microbiome supporting strategies, including specific species like Lactobacillus crispatus, which we love to use for the vaginal microbiome. But I guess I will pause here and highlight that interventions with the microbiome can be super, super, super safe. But there are a couple of key reasons why you wouldn't use probiotics for people. So things like dietary interventions and prebiotics are usually really safe. But probiotics is not something I would recommend you willy-nilly go take during treatment for cancer because certain stages of that treatment treatment can lead to a lower white cell count or neutropenia. And in this time, patients become particularly susceptible to developing what's known as a probiotic infection. Because remember, probiotics are live bacteria or should be live bacteria. So choosing the right form of probiotics, and that is a challenge in itself. Quality probiotics, also another challenge in Australia and around the world, and knowing the safe timing can be something that can be tricky to do. So I would encourage you to discuss this with me in your next consultation. So if we move on now to thinking a little bit about urinary tract cancers, um, urinary system cancers, rather, bladder and kidney cancer, we know that there is a big microbiome shift in this area. The urinary microbiome is associated with lots of different urological diseases, including interstitial cystitis, urgency urine incontinence, neurological bladder dysfunction, and others. And that microbiome also has an impact on what can happen with the response to therapies and the outcome in cancer. So a healthy bladder has a set microbiome, and we know that in bladder cancers we see changes in that microbiome and the bladder cancer development and therapeutic responsiveness is affected by the microbiome. The paper, the urine microbiome and bladder cancer susceptibility and immune responsiveness is a great paper to look at. It was published in 2020 as well, and it highlights some of the common urine microbiomes, sorry, microbes and also some of the bladder cancer enriched microbes, and then contrasts that to the non-bladder cancer enriched microbiomes and gives us some way we can start to think about microbes and what we might need to balance for patients to better improve their immune system function and reduce inflammation to help facilitate a reduction in growth of bladder cancer and maybe considering treatment, whether or not the responsiveness might be affected by part of what's happening in that microbiome. And so really great details on tumor promoting and suppressing microbiota in bladder cancer. Next, we're going to have a think about gastroesophageal cancers. And in gastroesophageal cancers, we really see a great highlighting of increased and decreased species in the oral microbiome, gastric microbiome, gut microbiome, and tumor microbiome in esophageal cancers and gastric cancers. And the influence of these microbiome on immunotherapy responsing gastrointestinal cancers is really in an interesting paper published in 2023. And again, I'll list that in the show notes so you can have a look. And these microbiome spaces can all be tested, and many of these organisms can be assessed and measured on some really great functional testing that we do. So it's certainly something to consider. The paper gastroesophageal microbiome and its impact on cancer and hallmarks and tumor biology really highlights how things like H. pylori are encouraging the induction of vascularity to the gastroesophageal tumour from blood supply, something we want to definitely stop. How cell metabolism can be dysregulated by some lactobacillus species, how fusobacterium and H. pylori can impact immune destruction within that tumour. And so, you know, we want to really look at how we can modulate these things. And so that's important testing to get done, especially for gastroesophageal cancers. I think that microbiome testing. Breast cancer also has a huge amount of research on microbiome and breast cancer. We know that different cancer types are associated with different microbial profiles. So histological tumor subtypes like invasive ductal carcinoma was characterized to have particular species of microbes, as was invasive lobular carcinoma and advanced breast cancers, again showing a different level of microbial profile. And so, you know, we don't yet know how far this extends, but maybe these are big clues as to what we need to be doing to address those different cancer types. Really interestingly, the breast cancer and breast microbiome is really having an impact on what's happening. And one of the ways that we understand this to be progressing is through the oral pathogen phasobacterium. Fusobacterium translates by the bloodstream and builds up in the breast tumour and progressively increases in different stages of breast cancer. And so fusobacterium has been shown to promote breast tumor growth and metastatic progression, and that that tumor microenvironment changes and the colonizing of breast tumors is having an impact on you know invol uh the colonization of breast cancer. And so uh definitely assessing the microbiome in breast cancer is important. Uh, that potential microbiome is associated with improved uh outcomes. And when looking at studies, you know, there's so much information. I'm just thinking what to tell you. You know, evaluation of people with all different breast cancer diagnoses, about 50 women compared to 20 healthy tissue uh breast tissues showed a unique viral, bacterial, fungal, and parasitic signature between the different subtypes of ERPR, HER2, triple negative breast cancer, and healthy breast cancer tissue. And I just think that's so fantastic. That's for us to understand why these different diagnoses might come about. This is from the paper Role of Gut Microbiota in breast cancer and drug-resistant pathogens, um, and it's a 2023 paper. And so, again, I'll link to that in the show notes. So, dealing with different probiotics has been shown to improve outcomes, and so you know, understanding how we can use them is you know really important to act as a protection. There's a great study on Lactobacillus, case is rota, and soy iseclavones, protecting against cancers in a population-based case-controlled study in Japanese women. Um, we know that you know, using these low toxicity and highly effective microbes as a probiotic can be really um helpful to potentially affect relapse. And you know, some cancers and therapies, in particular, like immune checkpoint inhibitors, get better outcomes when the microbiome is well balanced. So lots of great data we can tap into here. A great 2023 paper called The Emerging Role of the Microbiota in Breast Cancer Progression showed that dietary fiber and the microbiome are found that evidence in breast cancer patients has shown that sodium butyrate has a promising anti-tumor effect in breast cancer cells alone or in combination with other anti-cancer treatments. They talk about transitusimab as an example for her to positive breast cancer. And so, you know, simple interventions like dietary fiber, um, which increase butyrate, having big outcomes, and also great papers around oostrobilome and how working to balance the oestrobilome, we can see changes in areas like chronic inflammation, proliferation, angiogenesis, metastasis, and invasion. Um, some of those key hallmarks we want to control. And so definitely focusing on the microbiome and its effect on immunity, the bacterial metabolites, and the estrogen level is all part of what we can think about when it comes to breast cancer. In colorectal cancer, there is a huge amount of data on colorectal cancer and the microbiome, and it is perhaps driving some of the reason why we're seeing such an increased risk of colorectal cancer. Colorectal cancer and the gut microbiome is a fascinating area of research, and I really love the 2021 paper called Gut Microbiome and its role in colorectal cancer. So I suggest you check that out if you haven't looked at it already. It really does give a great amount of information about how we can use biomarkers of the microbiome to help understand cancer better from screening to prognosis to predictive progression, prevention, and treatment. These are all areas we have evidence for now, particularly in the colorectal cancer space. So when I'm thinking about using microbiome support in patients, I assess and address the microbiome using functional testing. We then start to support the gastric mucosa and the digestive processes and think about how we can enhance nutritional state status and then maybe use probiotics. But like I said, there is some safety implications around that. So if you're interested in getting functional testing done to understand your microbiome and how it's impacting your cancer type, I strongly suggest you get in touch. There is a huge volume of information, really, really exciting information, with it being such a safe intervention. I think we need to think about how we can influence all oncology patients to have a healthy microbiome and how this can improve people with cancer's response to surgery, chemotherapy, immunotherapy, hormonal therapy, and maybe even radiotherapy in the research. And for this reason alone, it would be wonderful to start to address this, let alone all the research that's starting to show this personalized response to cancer, improving survivability and reducing progression. Um, and so understanding micro microbiota and cancer and therapy interactions, but also just how to have a healthy microbiome during cancer journey is something that I would really like to help my patients achieve. And so if you're interested, get in touch. Remember, don't just go taking probiotics willy-nilly. There are certain times we would use microbiome supporting probiotics, but other times we would use diet and other strategies like antimicrobials or antibiotics, but we need to really work around your unique diagnosis to understand that. And I do encourage you to have a look at the research I mentioned and read about the hallmarks of cancer if you haven't already. Maybe pop back and listen to that podcast. And I hope you found today's information as inspiring as I do. I look forward to the day when all patients are understanding the evidence base for this holistic intervention and the benefit of prebiotics, probiotics, on improving cancer outcomes and side effects. I didn't even talk about side effects. We talked lots about cancer specifically, but you know, so there are particular probiotics that improve mood in patients. These are known as psychobiotics, um, probiotics and help to reduce some of the gut-based and bowel-based uh side effects of treatment. And so using these safely is really something that I love to discuss. Next podcast, we're going to be talking about supporting bone density during and after oncology treatment and come up with a bit of a natural guide to how to do that. So I hope you enjoyed this uh episode. It's really one that I'm very passionate about. Um, so thanks for listening. For more information on Prosper Natural Cancer Care, visit prospercancercare.co. For more information and to get in touch, please visit Carlaren.com. Disclaimer. This podcast is intended to be informational only and represents the opinion of the participants, but not necessarily their workplace. It is not intended to be used as medical advice and does not take the place of advice from a qualified health practitioner in a clinical setting. Please check with your healthcare practitioner before embarking upon any of the treatments or lifestyle changes discussed.