Webinar: Real-world Applications of Microbiome in Bladder Cancer. What Should Patients Know?

October 16, 2023

The relationship between the microbiome, probiotics, and bladder cancer is complex and not fully understood. Dr. Laura Bukavina, MD, MPH, from Case Western Reserve/University Hospitals Cleveland Medical Center, sheds some light on this complex relationship and unveils the potential impact of gut bacteria on tumor development and treatment responses.

With Dr. Laura Bukavina

Year: 2023

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Introduction to Real-world Applications of Microbiome in Bladder Cancer (Part 1)

Transcript (PDF)

Questions & Answers About the Real-world Applications of Microbiome in Bladder Cancer (Part 2)

Transcript (PDF)

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Full Transcript of Real-world applications of Microbiome in Bladder Cancer. What should patients know?

Stephanie Chisolm:

Welcome to Real World Applications of the Microbiome in Bladder Cancer. What Should Patients Know? Scientists have been looking at the relationship between the microbiome, probiotics and bladder cancer. That relationship is very complex and it’s not well understood. Today’s program is really intended to shed some light. It’s not going to give you all the answers. It might give you some good questions to bring back to your healthcare provider, that really look at the potential impact of your gut bacteria on the tumor development and your treatment responses.

We’re delighted to have urologist and scientist, Dr. Laura Bukavina from Case Western Reserve University Hospitals Cleveland Medical Center. In 2022, Dr. Bukavina received one of BCAN’s Young Investigator Awards to support her research, and today she’s going to explain that cutting-edge research that she did on the microbiome and it was showcased in BCAN’s 2023 Bladder Cancer Think Tank.

Dr. Laura Bukavina:

Hi everyone. My name is Laura Bukavina. As Stephanie has said, I am a urologic oncologist. I do a lot of work in bladder cancer research and I’m at Case Western University Hospitals. So today’s focus really is to talk a little bit about the research that we have been doing in bladder cancer, but also, I wanted to just give an overall presentation of what is microbiome. What is probiotics, prebiotics? Because I think having that level of understanding really allows you to be able to transition to microbiome and ask the appropriate questions. So we have to start at the bottom and work our way up to what microbiome is.

So as I said, we’re going to talk about the pre- and the pro- and the syn- and the post-biotics, which are a lot of confusing language, and I think everyone who looks at this is really confused. I know even a couple of years ago when I was looking into it, this was a very confusing topic overall.

Dr. Laura Bukavina:

So there are no disclosures that are relevant to this presentation. As Stephanie has said, a lot of the research that I have presented is supported by BCAN Young Investigator.

Dr. Laura Bukavina:

So in terms of historical context, the concept of probiotics and prebiotics really started a long time ago. As Hippocrates was a huge proponent of probiotics, he said on multiple occasions that, “All disease starts in the gut.” That’s one of his quotes, and, “Death sits in the bowels and bad digestion is the root of all evil.” So clearly he was a fan of microbiome and probiotics even before the term was coined.

Dr. Laura Bukavina:

And really not until about late 1800s, 1900 was the father of modern immunology, Ellie Metchnikoff coined that term of probiotics. He is considered to be the father of immunology and he’s the one that started looking at the relationship between the gut and how your immune system develops.

Dr. Laura Bukavina:

So what are prebiotics and probiotics? The simplest way to explain it is prebiotics are not alive. Those are the potential things that bacteria might digest, that help certain types of bacteria grow. Now, probiotics really do mean that it is a live organism. Typically, they’re considered to be the good type of organisms within your gut that have a host bug positive relationship.

Dr. Laura Bukavina:

Everything in-between is highlighted here. So the synbiotics are the combination of the bacteria as well as the food for the bacteria that sometimes you see manufactured and marketed. And then the postbiotics, which are in that purple right here are the byproducts of bacteria. For example, vitamin K, which is produced by bacteria, is one of the postbiotics. So this is just a wording game. A lot of the research has been focused on the probiotics, which means live bacteria. But the Nalo research really recognizes that in order for us to really move forward with microbiome, we have to almost focus on the pre and the probiotics together.

Dr. Laura Bukavina:

So prebiotics, short version is anything that is resistant to digestion. So I think the most commonly way we think about it is fiber. Some fiber is digested, some fiber is not digested. However, the things that are not digested by us, by our own enzyme will be tolerated and digested by bacteria. The most commonly are what called inulin and some of the carbohydrates. Now those are used as food by the bacteria which are further broken down into other metabolites that can affect your immune system.

Dr. Laura Bukavina:

Prebiotics are really in every vegetable possible. The most common vegetables that have a high concentration of prebiotics are your berries, your bananas, your green vegetables, your artichokes and onions. Now, the stimulation of the flora is thought to be accomplished by these prebiotics really being beneficial at increasing the growth of the good bacteria, which are your Lactobacillus. I’m pretty sure everyone has heard of Lactobacillus species being good. Your Akkermansia, which has been shown in research in humans and in mice to be beneficial to our cancer patients. And really, it selects specific bacteria because those bacteria are able to digest these prebiotics much more efficiently.

Dr. Laura Bukavina:

Research has shown that these prebiotics, which is a healthy diet, a combination of high fiber diet and not digestible carbohydrates, not only decrease the risk of multiple cancers, bladder, melanoma, colon, pancreas, I think, but also other diseases including inflammatory bowel disease and Parkinson’s disease. And then if you look at overall infection complication, children who have a high prebiotic diet have less need for antibiotics and have decreased number of total infections in their lifetime. So if you look at many of these studies in history that looked at having a good diet, balanced diet, high in vegetable content, high fiber diet decreases the risk of colon and many of these diseases, this really pinpoints to the fact that many of these are because of the prebiotic potential to increase the growth of these good bacteria.

Dr. Laura Bukavina:

Now, I wanted to dig a little bit deeper into what actually is happening within the science on the prebiotic research base. So right now as we look, there’s over 265 trials that are looking at prebiotics, probiotics, or combination of two within multiple disease states. Many of them are in cancer. The limitation of a prebiotic is that you can only eat so many leafy green vegetables and so many vegetables overall to be able to reach that five-gram recommendation of a prebiotic.

Now, dietary fiber modification, meaning that if patients or mice are given fiber in a clinical trial have been shown to correlate to response not only with development of cancer but also because it increases your response to many, many immunotherapy types. And this is one of the study that I highlighted here in melanoma. And melanoma really has been the poster child for a lot of these studies because it’s such a high morbidity disease, but also some patients have an amazing response to immunotherapy.

Now, what Dr. Vargo’s team looked at is that they noticed that mice who received a fiber rich diet in combination with probiotics, so in addition to giving supplements of healthy microbiome, really had almost an exaggerated response to immunotherapy, in compared to those mice who had a fiber poor diet. And what they’re doing now is they’re actually translating these findings to humans, to patients who are receiving immunotherapy within the clinical trial.

So I wanted to highlight this because I wanted to make sure that patients and overall public understands that microbiome modulation or supplementation with prebiotics and probiotics is never a single therapy. It is never meant to be a therapy taken alone. It is a therapy meant to be taken in combination with what we consider to be standard of care because it’s never going to be curative. However, it increases the efficacy of current therapy and it decreases the number of side effects associated with that therapy.

Dr. Laura Bukavina:

So this is a trial that I was talking about in melanoma and prebiotic, and really, they’re currently recruiting many patients and some of the early results they presented that I was able to see had incredible response to immunotherapy while patients were taking fiber supplementation. However, the limitation is that as soon as the patient are off the trial, the fiber intake drops dramatically and back to baseline. So it’s a catch 22. We know that this helps. There is a high fiber intake to better immune response. However, it’s very difficult for patients, really for anyone to have such level of dedication and to continue that high fiber intake throughout their daily life.

Dr. Laura Bukavina:

So what do we know about prebiotics and bladder cancer? We really don’t. So prebiotics research and bladder cancer is non-existent. There is some research that I’ll share with you that we have done on probiotics. However, prebiotics has not been explored and really should be the target of more research within bladder cancer in combination with probiotics.

Dr. Laura Bukavina:

As I said, prebiotics dose recommended by the Gastrointestinal Society is five grams. So just to highlight how varying amounts of this probiotic is actually listed within the supplements that we currently get, this is an example of a very popular pre and probiotic supplement on the market. And you can see here that’s highlighted by an arrow, the recommendation is five grams versus the actual content within that one capsule is 362 milligrams. That’s less than one-tenth of the recommended dose. So for one to be able to even obtain the necessary prebiotic fiber that’s recommended, you have to take 10 of these capsules, which you understand that’s highly unrealistic.

Dr. Laura Bukavina:

This is other examples. This one’s even worse. It’s a 100 milligrams and you can see this one, the prebiotic fiber is 377 milligrams. So for anyone going to the store and considering buying any probiotic or prebiotic supplementation, I wanted to highlight a couple of the things that everyone should look out for because a lot of this is unregulated and really heavily marketed towards people without really any justification for what the guidelines recommend. So one of the things you should definitely look at when you look at probiotic and prebiotic pills is the amount of prebiotic fiber that’s within these capsules.

Dr. Laura Bukavina:

So I want to move on to probiotics and talk a little bit about probiotics because that’s where a lot of the research is. So probiotics are live, these are live bacteria. Typically, they’re the good type, the good bacteria such as Lactobacillus, they typically do not cause disease. They don’t cause sepsis, they don’t cause urinary tract infections. These are bacteria that are living in tune with your body and stimulate your immune response. And they’re almost always capable of exerting some sort of beneficial effect on the host.

Dr. Laura Bukavina:

These are some of the commonly listed probiotics. Lactobacillus species really dominates this field as well as Bifidobacterium, which has been known to be prevalent in children who are breastfed and have multiple immunomodulatory, meaning stimulating the immune response, but also gut protective effects.

Dr. Laura Bukavina:

And I wanted to throw this out there, and this is really just an association, but I thought this was an interesting finding when I heard is that we hear of colon cancer fairly often in terms of the incidents and the prevalence. However, if you look at the diversity of bacteria from small bowel to large bowel, which is your colon, the microbial density within the large intestine is about 12 times higher than that of the small intestine. However, if you look at the cancer prevalence, the cancer prevalence within small intestine is almost 12 to 15 times decrease compared to colon cancer. And that really is thought to be secondary to multiple bacteria that is within the colon in addition to other factors. And also the metabolites that are produced by this high burden of bacteria.

Dr. Laura Bukavina:

And how do the bacteria really cause cancer? In addition to the immune stimulation, the bacteria do. They also have the ability to produce multiple byproducts. So those prebiotics, they’re not digested, can sometimes be digested by the bad bacteria, by these enzymes that it can later produce these toxic metabolites that cause then immune dysfunction. It can cause genetic mutations and it can cause cancer down the line.

Dr. Laura Bukavina:

This is some of the things that I talked about within bladder cancer, additional ways that your gut microbes can impact cancer immunity. Not only can they… As I talked about enzymes, can they really produce those metabolites, but also these microbes can also produce short-chain fatty acids. So short-chain fatty acids, depending on the fatty acid can actually be protective against cancer development.

Dr. Laura Bukavina:

So I wanted to dive into a little bit into the research again within melanoma and immunotherapy. So another story is combination of prebiotics and probiotics. So when we look at just supplementing someone with, for example, Lactobacillus, without supplying the necessary digestive nutrients for that bacteria, which are your prebiotics, the effect on immunotherapy response is much lower. However, if you have a mouse with cancer and you give them prebiotics and probiotics, so combination of Lactobacillus, in addition, you can see here Indole, which is the most common prebiotic, this really shifts your immune response to cancer. In this study, you can see that the mice who had melanoma when they were supplied with both Lactobacillus, which is the probiotic and the prebiotic Indole, in combination, their survival almost doubled over their duration because of this immune response.

Dr. Laura Bukavina:

So we did something similar in bladder cancer by first looking at the differences in microbiome. So we wanted to see if there’s specific bacteria that provide a signature for patients who respond to chemotherapy. A lot of you know that if you have muscle invasive bladder cancer, your treatment really starts with chemotherapy if you’re able to receive chemotherapy followed by surgery. So we wanted to see in addition to just the tumor differences, are there differences in the gut microbiome in our patients who respond to neoadjuvant chemotherapy better than others.

Dr. Laura Bukavina:

And what we did is we collected several stool samples and urine samples throughout the study to see if there are differences.

Dr. Laura Bukavina:

And we did find a difference in one bacteria that was very interesting, which is Bacteroides. Again, going back to melanoma. This previously has been shown in melanoma as well where patients with a high Bacteroides count were less likely to respond to neoadjuvant chemotherapy. In fact, the response was so strong that we found that patients who did not respond continued to have increased number of that Bacteroides throughout their therapy, while patients who are going to respond to chemotherapy actually had a significant decrease in that bacteria. So that was very interesting to us and that’s something that we continue to explore right now with other studies.

Dr. Laura Bukavina:

As I mentioned, we also collected urine as bladder. We have the ability to really collect the urine from these patients and we know that there’s a clear difference in the composition of the bacteria in patients with bladder cancer and without bladder cancer.

Dr. Laura Bukavina:

And we continue to look at response status. Again, patients who received neoadjuvant chemotherapy and had a response, had a much, much higher Lactobacillus in their urine. And this is males and females. I think we typically think of Lactobacillus to be associated with females, with vaginal flora. But really, this was within urine and actually about 60% to 70% of our patients were male.

And so Lactobacillus continued to be present in urine in many, many of our responders.

Dr. Laura Bukavina:

So based on this finding, we actually applied this to our mice and what we found is that supplementing mice with Lactobacillus specific species called Lactobacillus Rhamnosus, which is the LGG. Intravesically, so instilling this Lactobacillus during treatment, we were able to obtain a 50% complete response in these mice.

So just to interpret that, if you compare that to chemotherapy, just giving someone intravascular installation of LGG, meaning we put into the bladder the LGG and compared it to BCG and compared it to chemotherapy, gemcitabine docetaxel, the two best responses we’ve seen was actually with LGG and with chemotherapy and they were almost equivalent. BCG on the other hand did not work so well.

Dr. Laura Bukavina:

However, if you are considering going to the store and buying probiotics off the shelf, I do want to warn you that there’s a lot of difficulties in finding the right probiotic and really understanding that there’s a lot of nuances behind it. We really don’t know what the right dose of probiotic is. We know that there is a certain amount called colony forming units that has been used previously, that we have used in our studies, which is 10 to the six.

What specific antibiotics affect what microbiome? And if you are an antibiotic at the same time as your probiotic, does that affect it? If you take probiotics right now and you are already colonized with many, many harmful bacteria, it really is very difficult to change your microbiome because there’s no room for the good bacteria really to sort of colonize. So does that mean that we have to clear, sort of reset our gut before we even start to think about taking probiotics? Which is in mice studies, which is what exactly happened. You have to be able to completely clear your existing microbiome, almost like a colonoscopy prep, before you start taking probiotics.

A lot of these companies are really targeted to marketing and less so towards actual consumer testing. So their reported number on the bottle might actually be different than what is actually in the pill. A lot of them don’t have the prebiotic supplementation. So taking probiotics without really providing the food necessary for these bacteria really has limited response overall. And a lot of this is just harmful marketing over promising to many of the patients because they are just aimed for their financial incentives.

Dr. Laura Bukavina:

So there are some recommendations currently out there from many of the societies in terms of what has been very rigorously tested and is currently recommended for treatment. As you can see, a lot of these recommendations are again focused on Lactobacillus. And again, this is that Lactobacillus GG, the LGG that I talked about, in addition to the Bifidobacterium. But again, many of these recommendations are within the infectious space. None of the recommendations currently exist for any of our cancer patients.

Dr. Laura Bukavina:

So just as we did with prebiotics, I wanted to take some of the most commonly used probiotics out there and look at the composition. As I said, CFU, which stands for Colony Forming Units, is typically how we look at the content of bacteria per milliliter. So if you think of BCG as bacteria, the typical amount of BCG per milliliter is 10 to the six, and that’s the minimal amount that has been shown to be effective. Now, some of these probiotics have 50 billion CFUs and some of them have 50 billion and some of them have 10 to the two CFUs. So it’s very important to look at the CFU content in the back.

In addition, as you notice, a lot of these probiotics actually lump all of these cultures together and give you a lump sum. So if you see in the gut health probiotic blend, there’s a 400 milligram probiotic blend with 50 billion CFUs. However, it’s a combined CFU, so you’re not really getting the information on each individual bacteria. And I’ve looked through about 15 of these and I really couldn’t find one that actually gives you specific number per each bacteria. And a lot of this has to do with marketing, a lot of it has to do with just not understanding the process. But if you find one that specifically lists CFU per each bacteria, would love to see it.

Dr. Laura Bukavina:

Now, this is what someone called the best probiotic out there and it’s called synbiotic. So I wanted to dissect this synbiotic. It’s what they consider to be the pre, pro and the post-biotic supplementation. I do like that they only list two probiotic blends, which is your Lactobacillus Rhamnosus. Again, the LGG that our research focused on, in addition to the Bifidobacterium, which is great. They also listed it as compounded. So you see that they only have 11 billion CFUs. But again, this is combined. Again, let’s go look at the prebiotics. Remember we said five grams is a recommended dose. Here they have 15 milligrams is all you’re getting. And then the post-biotic, which we didn’t talk about much, but this Tributyrin, the post-biotic has never really been shown to really affect much of the outcomes within cancer outcomes. However, they also listed it here.

So as I finish up this talk, I really wanted to make sure that many of you understand that there are a lot of nuances to these supplements and when you consider buying any pre or probiotic supplement next, it’s really important to turn the bottle and question what is in the back, what is marketing and what is real and how much of this is really going to help me?

Dr. Laura Bukavina:

I looked at another one just to highlight, and this is number one seller on Amazon currently. I’m not sure why it’s just for men. I couldn’t find anything that’s men specific except Selenium in this. However, again, if you look at this probiotic blend and the prebiotic. So again, they’re lumping everything together and this one gives you 85 million CFUs, but there’s 85 different bacteria in this. In addition, if you look at their prebiotic, which they list as a fruit and veggie blend, which it doesn’t necessarily mean it’s a prebiotic. There’s only 207 milligrams within this supplement.

Dr. Laura Bukavina:

So to finish off, there is a clear and well-documented role of pre and probiotics in cancer development response. It’s a well-studied phenomenon in melanoma and we’re starting to understand it in bladder cancer. And I really look forward to exploring LGG more in bladder cancer patients, seeing how we can use this to our advantage. The use of pre- and probiotics is always in addition to current therapy. This is not meant to be a standalone therapy. However, it is meant to augment and increase the efficacy of the current therapy and decrease the side effects. And I think overall as society, we need to focus on more studies and really more trials within microbiome modulations and the use of prebiotics within the clinical trial setting. So we’re able to do vigorous signs and really be able to provide the results for our patients. And with that, I am happy to take some of these questions.

Stephanie Chisolm:

I really appreciate it, Laura. This was wonderful. So in your opinion, what percentage of urologists or even medical oncologists are tuned into this or are beginning to pay attention to the microbiome?

Dr. Laura Bukavina:

I would have to say probably very low. I think most likely patients are bringing up to oncologists as well as surgical oncologists. And I think they’re learning because patients are asking questions, but it’s not as mainstream as people think. I think over the last five years with some of the melanoma trials, that started to highlight the efficacy of this. People are paying more attention.

Stephanie Chisolm:

Sure. Well, we have some really good questions that have come in already. Some we’ll summarize. “Should bladder cancer patients try to minimize their use of antibiotics?” If you’re trying to keep a nice colony growing and you get something else, should you take antibiotics or try to minimize that use?

Dr. Laura Bukavina:

That’s a tough question because we usually give antibiotics for a reason, right? So what I can tell you is based on patients who are undergoing immunotherapy, there’s no prospective data, but if you look at data afterwards, which is called retrospective data, if you look at the patients who were receiving immunotherapy and receive antibiotics within three months of receiving their immunotherapy, those patients typically have a lower response to immunotherapy. Now, that’s not to say that the reason why they receive antibiotics potentially maybe they were in the hospital, maybe they were sicker, is the reason why they couldn’t get the immunotherapy that they needed.

However, we should minimize antibiotics to only what’s necessary and really very specific. So instead of being an antibiotic that kills everything, really asking the question, “Can I just take antibiotic that’s specific to my bacteria?” And at the same time, while you’re taking antibiotics to make sure to ask your physician if you should be taking pre and probiotics at the same time?

Stephanie Chisolm:

Right. Yeah. Okay. That’s a great question and thank you for answering it. I appreciate it. “Is there research on whether a high-fiber diet improves BCG responsiveness?”

Dr. Laura Bukavina:

There is no research on BCG and fiber diet, unfortunately.

Stephanie Chisolm:

Okay. I’ll probably say this wrong, Casei, C-A-S-E-I is not on the list of beneficial probiotics. Can you explain that one?

Dr. Laura Bukavina:

So Lactobacillus Casei is one of the beneficial probiotics. Again, I only mentioned the few that are listed, but Lactobacillus species is wide and it is one of the beneficial ones.

Stephanie Chisolm:

Okay, thank you. So it was on there.

Dr. Laura Bukavina:

Yes.

Stephanie Chisolm:

Okey doke. “Are you familiar with Visbiome and if so, do you recommend it prior to a radical cystectomy?”

Dr. Laura Bukavina:

I am familiar with Visbiome and I have a lot of patients that take it before and after cystectomy, and I can only tell you what the patients tell me, but they tell me that they feel much better and they have less infections when they have their conduits. So I am not a salesperson for Visbiome or any probiotic or prebiotic company, but at least in my experience they do use it.

Stephanie Chisolm:

Okay. You did a lot of work with Dr. Phil Abbosh when you were at Fox Chase Cancer Center, and I know he’s looked at a lot of things, the urine, there’s a question about, “Do the organisms and probiotics make it into the urine?”

Dr. Laura Bukavina:

So there’s this concept what’s called translocation, which is some bacteria are able to cross the colon and then enter into circulation without making you sick. So not as if you have bacteria and then end up in different organs. So if you think about melanoma, the studies that I talked about, those mice are given gut bacteria, probiotics, and then all of a sudden they get a better response in their melanoma. And yes, some of the concept is it’s based on their immune response. They’re able to really target their immune response, but we know that those bacteria that translocate from the gut then go to a lymph node, and then inside the lymph node they’re able to increase the response of your own immune system to cancer.

Stephanie Chisolm:

Great. Are there dangers of prebiotics?

Dr. Laura Bukavina:

When you look at prebiotics studies, the most common adverse events is bloating, gas, and diarrhea. So those are the most dangerous. In probiotics, there’s some documented case reports of people getting sepsis. Those are typically highly immunosuppressed patients, otherwise there’s very minimal side effects to pre or probiotics.

Stephanie Chisolm:

Another question, sort of two parts. “What’s the proposed mechanism that probiotics could impact bladder cancer and is it from direct contact with the bacteria on the bladder cancer cells?”

Dr. Laura Bukavina:

So both ways. So if we look at LGG, which is that Lactobacillus that I studied, there’s two ways. One is the LGG is actually able to penetrate the cancer cells and kill them directly. The other is that the bacteria is able to increase the local tumor, what we call microenvironment, by increasing the T-cells actually coming in and killing the cancer cells themselves. So both ways.

Stephanie Chisolm:

“From all the commercial brands that you’ve considered, which ones do you recommend?” You don’t have to answer this because that’s a tricky question because there could be so many, so we can go ahead and skip that.

Dr. Laura Bukavina:

Yeah.

Stephanie Chisolm:

All right, let’s skip that one. I don’t want to put you on the spot. I think you covered most… Let’s see, “Treated with BCG. Every time I get a cysto, I get an antibiotic.” Okay, somebody’s being treated with BCG. I think that’s what it is. Is it counterproductive to get an antibiotic when they’re being treated with BCG?

Dr. Laura Bukavina:

So I suspect you’re getting probably the cystoscopy antibiotic, which is that Keflex. So as long as you’re not getting, like we talked about, very broad spectrum antibiotic, it’s not counterproductive. Now, if you’re getting an antibiotic that kills a lot of gut bacteria, that could be considered counterproductive.

Stephanie Chisolm:

Great. Is there anything that you recommend that people can take to lower the possibility of getting a urinary tract infection that seems to be a common side effect from bladder cancer treatments in some way?

Dr. Laura Bukavina:

Yeah, that’s a good question. So if you look at studies in Norwegian, I think some are Norwegian countries and UTIs overall, they don’t do a lot of probiotics, but what they do is what we call natural probiotics, which is fermented foods, so fermented vegetables, fermented cheese and fermented milk. And those patients had a much lower risk of cancer and urinary tract infection. Again, this probably is because of the whole pre as well as the Lactobacillus component. So if you like fermented vegetables or pickled vegetables or fermented milk, I think that’s what you can potentially extrapolate the data from.

Stephanie Chisolm:

Okay. All right. So everybody can go out and get some fermented…

Dr. Laura Bukavina:

Pickles.

Stephanie Chisolm:

For dinner, some pickles and some kimchi or something along those lines. Okay, sauerkraut. You mentioned resetting the microbiomes similar to a colonoscopy prep. What if you have a healthy microbiome and have to have a colonoscopy? How harmful is that and how long does it take to restore your microbiome?

Dr. Laura Bukavina:

That’s a tough question because when you have a colonoscopy prep, depending on the prep, sometimes they give you this low-dose antibiotic in addition to MiraLax. MiraLax alone should not affect it because it doesn’t get rid of all of your microbiome and it will auto-populate. However, we know that every time you have any sort of prep and you take your sample of gut before and after, it’s going to be very different. It might be similar in the number of bacteria, but the total percentages are going to change. So the short answer is yes, you’re going to change it every time with colonoscopy prep, but is it going to be bad? Not necessarily.

Stephanie Chisolm:

And it looks like we have one more question. You are on top of this… There’s two more questions, on top of this in terms of getting through all of these questions. You mentioned clearing the microbiome prior to using probiotics. Is that something that somebody should try to do on their own and how would they do it? Or is it something that should only be done under the supervision of a physician?

Dr. Laura Bukavina:

Currently, that this is only done under a clinical trial setting and under supervision of a physician who’s able to monitor because there’s a risk of dehydration, there’s a risk of bowel perforation. So this shouldn’t be done at home with some MiraLax and coalesce. This should only be done within the setting of a clinical trial.

Stephanie Chisolm:

Good advice. Is there any value in rotating the type of pre and probiotics that one is taking every few months just so you get a different supply, a different set of organisms that are growing and is there value in that?

Dr. Laura Bukavina:

Unfortunately, there’s no studies looking at the value of switching pre, before and after. And if you look at a lot of these probiotics and the prebiotics, they’re essentially the same. Majority of them are focused on either Lactobacillus or Bifidobacterium. There’s very few variation. So I think switching from one to another, if I had to sort of think about it, it probably doesn’t make much difference. I think it’s the quality of your probiotic that matters more than the brand.

Stephanie Chisolm:

So again, looking at the back of the labels, you identified all of the criteria that would identify a high-quality probiotic. So it’s really on the patients to really start looking at all of those, if they’re looking at over the counter. Do doctors often recommend sort of specialty probiotics where they’re not available at say Costco or something like that, where you can pick up a big bottle of probiotics? Do they sometimes recommend something else?

Dr. Laura Bukavina:

So sometimes what I have seen in practice is that probiotics are digested too early. So when I had that slide about small intestine and your large intestine, what you really want to target is probiotics within your colon. And if you swallow a probiotic, it really gets degraded in your small intestine in your stomach, so it might not actually ever make it to your colon. So some of the new formulations actually have what’s called the double capsule, meaning they have almost like a delayed capsule response that the top of the capsule gets digested in the stomach and in the small intestine and the inside where all of the probiotics actually are makes it all the way to the colon.

And I think we are now understanding that that’s where it has to happen. And the previous formulation, really just put everything together. It gets digested in your stomach, it never makes it to your colon.

Stephanie Chisolm:

Right. And if any of them happen to make it all the way through to the colon, yay. That was a good thing. So there’s no guarantee though. Okay. Do any foods like cranberry juice, green tea help to modulate the organisms in the bladder in a beneficial way?

Dr. Laura Bukavina:

Yeah. So cranberry is one of those prebiotics that we talked about, but you have to be careful with cranberry juice because it’s usually high in sugar. So if you are getting cranberry juice from your grocery store, you’re probably going to turn the bottle around and see there’s 40 grams of sugar, and that’s probably more hurtful than helpful. The real cranberry juice without any sugar is a prebiotic and it does help.

Stephanie Chisolm:

Okay. Somebody said they’re not clear whether you’re recommending taking a pre or probiotic?

Dr. Laura Bukavina:

Both.

Stephanie Chisolm:

Both. Okay, great. And then the last question maybe, “My doctor probably using the right kind of antibiotic for my cysto, could you re-say what that right kind of antibiotic is?” I think somebody just wants to double-check.

Dr. Laura Bukavina:

Double check. So typically for cystoscopy, your doctor will use what we call a narrow spectrum antibiotic, and that means that it doesn’t kill all types of bacteria, but just aimed at the ones that are in the urine and around the skin. And that’s usually things what we call Cephalosporins or Keflex. But again, this is highly dependent in each patient’s situation. So this is Brian. Brian, if you’ve had infections before, and for example, you’ve had bacteria that are very resistant to that specific antibiotic, your doctor might be using something different.

Stephanie Chisolm:

Should you take those during a meal or before the meal? Would it make a difference?

Dr. Laura Bukavina:

You should take it before the meal or two hours after the meal because of the digestive juices and the bile that’s in your gut.

Stephanie Chisolm:

Good to know. One more question. “Is kombucha fermented and if so, is it recommended?”

Dr. Laura Bukavina:

If you look at kombucha, if you actually turn the bottle around, what you’re going to find is LGG.

Stephanie Chisolm:

Okay. So let’s see. “So take pre and pro, even though they’re so small in dosage versus what’s recommended.”

Dr. Laura Bukavina:

I think what you’re trying to say, Kelly, is that I pointed out all the problems with the prebiotic, how they’re not… But you can find ones that are higher when you might have to take a couple. In addition, don’t forget that you’re also eating vegetables, so you are getting the necessary prebiotics from your vegetables. This is a supplement, meaning you don’t need to supplement all five grams with prebiotic. You just need to understand that in addition to your healthy diet, high in vegetables, you also can supplement with prebiotics.

Stephanie Chisolm:

So there was a question about the CFUs lumping them together because they can’t be divided. You mentioned that the number of billions of CFUs alone might not actually mean that much. Is that what you were indicating there? So that’s something on the label. We think you’re trusting it and you think you’re getting the right thing, but you don’t know.

Dr. Laura Bukavina:

You don’t know because it’s lumped. So you’re getting a little bit of the good thing and a lot of the other thing that’s cheaper for them to make. So I generally don’t like the probiotics that list 80 different types of bacteria and then lump them. I prefer the ones that have one or two listed and then they give you the breakdown. The minimal, the minimal should be 10 to the six. We know this that it should be the minimal that’s necessary. If it’s more, it might not give you the better effect. However, there’s a minimal concentration that’s been studied and that’s 10 to the six.

Stephanie Chisolm:

Best to take them once or twice a day or at every meal, if you’re looking at pre and probiotics?

Dr. Laura Bukavina:

It’s dose-dependent. So if you think you’re getting the necessary prebiotics with your diet and you need to take two or three pills, it’s better to split them up, but they don’t give you the side effects of bloating and indigestion. If you’re not getting it and then you need to take more, then you might have to lump two at a time. However, it’s very difficult for anyone to start taking three pills three times a day together in addition to all the other medications that they have to take. So I wouldn’t concentrate so much on how many times you have to take it. I would concentrate on your diet and small amount of supplementation.

Stephanie Chisolm:

Okay. You didn’t talk about vitamin C, but one of the participants, urologist suggested taking 500 milligrams of vitamin C twice a day to help prevent UTIs. Is that a good thing? It’s not exactly what you were talking about.

Dr. Laura Bukavina:

Vitamin C, 500 milligrams is fine. If you do too much, vitamin C can actually cause kidney stones, so you have to be careful with that. Vitamin C improves your immune response and your immune system, which is why you have all that marketing towards vitamin C when you get sick. However, you have to be careful not taking too much of it because then you’ll end up with kidney stone.

Stephanie Chisolm:

Okay. Thank you. Well, this has been phenomenal. I learned something. I think the participants have learned something.  And thank you again for joining us, everyone