Strain-Specific Probiotics: Latest Evidence and Clinical Applications with Dr. Noelle Patno

What do we know about using specific probiotics for different health conditions? And is it time to move away from broad-spectrum probiotics and into condition-specific strains? With an explosion of new research on probiotics and a recent change in nomenclature, it’s easy to get confused. In this episode of New Frontiers, I lean on Dr. Noelle Patno’s extensive research knowledge to tease apart the science on probiotics. Dr. Patno holds a PhD in Molecular Metabolism and Nutrition and has designed and monitored clinical trials on microbiome and immune health. Together, we dive into the latest evidence on therapeutic uses of specific probiotic strains, including Lactobacillus rhamnosus GR-1, for women’s health and other conditions. Dr. Patno also shares excellent pearls on dosing, duration, delivery methods and antibiotic resistance. Many thanks to Noelle and the team at Metagenics for always leading the way and researching interventions. Appreciate you listening, sharing, and commenting, and always, thanks for subscribing. – DrKF

Where do condition-specific probiotic strains fit in personalized nutrition? And what is the latest evidence on probiotics for women’s health? In this episode of New Frontiers, Dr. Noelle Patno from Metagenics shares with us exciting research findings on probiotic strains for specific health conditions such as bacterial vaginosis, urinary tract infections, candidiasis, antibiotic-associated diarrhea, IBS, and IBD. Drawing on her extensive experience in pharmaceutical and medical device manufacturing, as well as microbiome research, Dr. Patno discusses the importance of probiotic strain specificity for optimal therapeutic results, mechanisms of action and the latest reclassification of probiotic naming conventions.

In this episode of New Frontiers, learn about:

Dr. Kara Fitzgerald: Welcome to New Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine, and of course, today is no exception. I am thrilled to be speaking with Dr. Noelle Patno. Now let me give you her background and we’re going to jump right into what will undoubtedly be a very useful and interesting conversation. So, Noelle received her PhD in Molecular Metabolism and Nutrition from University of Chicago, investigating bacterial stress in intestinal organoids that modeled inflammatory bowel disease. She began her career at Abbott Labs after graduating as a chemical engineer from Stanford with honors and distinction.

cHer experience in the pharmaceutical and medical device manufacturing world spanned R&D, supply chain, project management, supervision, and international technology transfer. Previously as therapeutic platform lead at Metagenics, Dr. Patno researched new ingredients, designed and monitored clinical trials and developed educational content related to digestive microbiome and immune health. She, speaks to me today as an independent contractor for Metagenics. Dr. Patno, welcome to New Frontiers.

Dr. Noelle Patno: Thank you so much. I’m grateful to be here.

Dr. Kara Fitzgerald: What a cool background. I mean, it’s just, you have a lot of experience in different vantage points in medicine and science over your career.

Dr. Noelle Patno: Yes. It’s been an interesting ride. Pharmaceuticals, biomedical devices, nutritional therapies. Probiotics.

Dr. Kara Fitzgerald: Yeah, and an interesting PhD focus. Okay. So, we’re putting our attention on probiotics and it’s pretty neat that we’re continuing our conversation, actually, we once started some years ago. You and I have talked probiotics previously, and I know that you have a really nice command of the science, so I’m going to lean into that today. I’m really, I just really want to kind of farm whatever we can from you and your extensive knowledge in the literature. What do we know about using specific probiotics for different health conditions?

Dr. Noelle Patno: Well, first of all, just not all of them have been studied for every health condition, so we need to know which of these live microorganisms have conferred a health benefit on the host in the different categories. It was really the meta-analysis in 2018, from Lynn McFarland and her co-authors that proved that probiotics are effective if, and only if, you are actually using that specific strain and that specific disease. So, just like we have vitamins that have different functionalities, vitamin A, B, et cetera, and then we have vitamin B6 being different from B12. We have Lactobacillus acidophilus NCFM different from Lactobacillus acidophilus LA14. And just to,-

Dr. Kara Fitzgerald: Let me just … Hold that thought. Just put a pin in it, because I want to hear what you have to say, but first of all, I just want to say McFarland is her, I think her and her husband, right? Their husband and wife team, and they’re just brilliant scientists for many decades in this field, back, they started doing culture and now of course they’re well into PCR and just really doing extraordinary work, and teasing out what we need to know. So, if I’m hearing you correctly, Noelle, clarify the standby approach of, let me throw a broad-spectrum probiotic at patient X, may not be the smartest way, and in fact, we need to be prescribing condition-based. Is that true?

Dr. Noelle Patno: Well, how do you know that broad spectrum probiotic is having a benefit unless it’s actually been tested and demonstrated to have benefit?

Dr. Kara Fitzgerald: Yeah.

Dr. Noelle Patno: So, there are combinations of probiotics that have shown benefits, but is that the combination that you’re taking, is the question?

Dr. Kara Fitzgerald: For a given indication, right.

Dr. Noelle Patno: For the indication, like what is it that you want that probiotic to do, is the question?

Dr. Kara Fitzgerald: Yeah. Okay. So, let’s circle back. So, I think basically you’re telling me that we need to be really paying attention to the literature on probiotics, and prescribing according to what’s been demonstrated versus just hitting all of our patients with the same sort of broad-spectrum formula.

Dr. Noelle Patno: Yes, and isn’t that what personalized medicine is partially about?

Dr. Kara Fitzgerald: Yeah. 100%, but I will say that there was a time when we didn’t have this kind of precision information.

Dr. Noelle Patno: Correct.

Dr. Kara Fitzgerald: I appreciate that once again, Metagenics is sort of at the front, and you guys are investing in researching interventions and paying attention to the literature, as you always have been. I’d like to be able to talk about that because I just appreciate how science-forward Metagenics is. Okay. So, I kind of cut you off mid-sentence. Do you remember where you were? Do you want to finish talking about using different –

Dr. Noelle Patno: Oh, no problem.

Dr. Kara Fitzgerald: Yeah.

Dr. Noelle Patno: I just wanted to give a few examples.

Dr. Kara Fitzgerald: Yeah.

Dr. Noelle Patno: One of the examples that I like to look at is in IBS, for example. So, L. plantarum MF1298 was actually studied in IBS, and shown not to have a benefit, and the IBS score actually went up in that probiotic group versus their placebo-controlled group. A different study, different study design. So, I think we need to be cautionary about that. Right? These two probiotics were not tested in the same study, but it’s a similar kind of probiotic, it’s still an L. plantarum, but 299V is the alpha-numeric strain identifier, and the 299V showed a benefit for IBS, and not just one trial, multiple trials. So it’s actually recognized by the World Gastroenterology Organization for that benefit in IBS, for abdominal pain.

Dr. Kara Fitzgerald: Okay. That’s helpful. So, not all Lactobacillus plantarum are alike, and that if you’re going, if you’re addressing IBS, you want to be strain-specific.

Dr. Noelle Patno: Yes.

Dr. Kara Fitzgerald: Or you might make it worse, actually.

Dr. Noelle Patno: Yeah. That’s one example.

Dr. Kara Fitzgerald: Yeah. Yeah.

Dr. Noelle Patno: Then if you look at E. coli, which we just always think of as a pathogen, people don’t always know that Escherichia coli Nissle 1917 is considered a probiotic.

Dr. Kara Fitzgerald: Yes.

Dr. Noelle Patno: Then the pathogenic one with the strain designator is the 0157:H7, which causes the diarrhea. So, it’s an interesting situation there where we really have to be specific about what probiotic it is.

Dr. Kara Fitzgerald: Are we able to access in this country, the probiotic E. coli?

Dr. Noelle Patno: E. coli Nissle 1917? I haven’t seen it here.

Dr. Kara Fitzgerald: Yeah. Okay. So, I know we’re aware of its benefit in the clinic, but I also know that it’s been difficult. Well, you guys need to go and get a, bring it into the US, if you can. All right. So, today we’re going to focus on women’s health and the vaginal microbiome today. So, just talk to me about that. Like give me a little bit of snapshot of the vaginal microbiome, and why we need to be tending to it.

Dr. Noelle Patno: Well, it’s really amazing that the vaginal microbiome has been associated with not just women’s health, but also the babies that they deliver. As far as women’s health, we’ll focus on that. The vaginal environment is actually associated with even her ability to conceive a child, carry that child to birth, so we’re looking at sometimes miscarriage associations with the vaginal microbiota actually. So, lower lactobacilli in the vaginal microbiota has actually been associated with risk of miscarriage later in the pregnancy.

Dr. Kara Fitzgerald: Lactobacillus in general, as a genus.

Dr. Noelle Patno: Yes, but I have to put a caution there though, because it’s, even though a lot of the literature suggests that the healthy vaginal microbiota is lactobacilli-dominant, there are, there’s more research coming out to understand the different species, and then even the different strains of those species that could be beneficial versus not as beneficial as we thought. Right? Then on top of that, there have been some differences associated with race and geography, so there have been different groups that seem to have healthy vaginal microbiota, but, or vaginal microbiota that’s associated with health, but not necessarily lactobacilli-dominant.

Dr. Kara Fitzgerald: Okay. Got it.

Dr. Noelle Patno: So, it is a little bit complicated, but the majority seems to suggest that lactobacilli-dominant vaginal microbiota is more associated with health.

Dr. Kara Fitzgerald: Okay. Okay. So, what … I mean, I know that there are probitoics, I mean, anybody in functional medicine, working with women, we see UTIs and interstitial cystitis, bacterial vaginosis. So, we see all sorts of stuff, and so we’re using probiotics, hoping for the best. Right? There are more women-specific products out there. What probiotics help? I mean, what do you know from the literature, what’s really been identified as being beneficial to the vaginal microbiome in general? Then we can talk specifically about different indications.

Dr. Noelle Patno: Yes. I think one of the greatest pieces that I saw recently, was just last year, 2021, there was a review published on Lactobacillus rhamnosus GR–1, as the most well-researched for women’s health in particular, as a probiotic. The independent group, AEProbio, with their clinical guide for probiotics has demonstrated with their criteria the highest level of evidence that they’ve seen for probiotic would be that combination of L. rhamnosus GR-1 with L. reuteri RC-14, as the combination of probiotics that has been demonstrated to help with bacterial vaginosis and vulvovaginal candidiasis. That’s what they show, and there are multiple studies that corroborate that. So, I think that that combination is really the one that stands out for bacterial vaginosis and vulvovaginal candidiasis.

Dr. Kara Fitzgerald: Let me just ask you about vaginal microbiome health in general. What you’ve just said is incredibly important, and I’m going to circle back to it in a second, because I know that everybody’s taking notes right now, and they want to know where they can get it, or they want to be using those products. By the way, folks, we will gather everything that, all the papers that Dr. Patno is mentioning, and we will put them into show notes so that you can access her references. But would you recommend these though, as maintenance probiotics, as preventative or, I mean, would you lean into diet more or like, how would you think about just maintaining a healthy flora?

Dr. Noelle Patno: Well, there are many factors that do impact the vaginal microbiota, everything from diet to smoking and hygiene. So, of course, all of those lifestyle practices are important, especially sexual practices, obviously. However, as far as talking about supplements like probiotics, if we’re thinking about a population of women who have bacterial vaginosis or a population of women who have vulvovaginal candidiasis-

Dr. Kara Fitzgerald: Which is actually really pretty high, but go ahead.

Dr. Noelle Patno: Yes. It’s kind of surprisingly high. If you want to talk about the prevalence, and we can talk about that later, but just in terms of treatment versus prevention was your question. So, these studies showed the treatment was beneficial, right? So, they took, they specifically recruited women who had bacterial vaginosis or women who had vulvovaginal candidiasis, or basically women who had lower lactobacilli, as defined by the Nugent scores that were used to measure that. Then by shifting the microbiota with the GR-1 RC-14 combination, they showed that beneficial resolution of bacterial vaginosis. So, it was a really a treatment perspective there.

Dr. Kara Fitzgerald: How did they prescribe it, in that study?

Dr. Noelle Patno: There were 2 billion CFU of the combination, GR-1 and RC-14 for bacterial vaginosis.

Dr. Kara Fitzgerald: Just given daily, administered once daily?

Dr. Noelle Patno: Given daily. Yes.

Dr. Kara Fitzgerald: Okay. And orally?

Dr. Noelle Patno: Yes. Orally

Dr. Kara Fitzgerald: Any research on intravaginal delivery?

Dr. Noelle Patno: In the past, there were multiple studies with vaginal suppositories for this combination, but the preference has become oral. It was back in 2001, showing the first oral study, a pilot study of just about 10 women, and because they were able to demonstrate the recovery of lactobacilli in the vagina, that success then sparked more clinical studies, both the probiotics by themselves, as well as probiotics in combination with antibiotics, and not just bacterial vaginosis or vulvovaginal candidiasis, but other conditions as well.

Dr. Kara Fitzgerald: Okay. I want to get to the other conditions, and when they’re used with pharma. I want to talk a little bit about that, but so I want to just get back to the oral versus vaginal delivery. The research, in your opinion, is as strong, using oral delivery versus vaginal delivery. Would you say that?

Dr. Noelle Patno: Yes, definitely.

Dr. Kara Fitzgerald: Okay.

Dr. Noelle Patno: But oral, yes.

Dr. Kara Fitzgerald: Awesome. Good. Yeah. I’m sure women would rather be taking an oral probiotic, then vaginal delivery, which can be a little bit onerous.

Dr. Noelle Patno: Yes, it can.

Dr. Kara Fitzgerald: Okay. So, then let’s circle back to treatment. In most of these cases, it’s just delivered one cap daily and then with, and without medication. Can you kind of tease that out?

Dr. Noelle Patno: Yes. So, for, I’ll talk about just two of the antibiotic studies that were done with the GR-1 RC-14 combination. In both of these studies, there’s actually a double dose. So, they took the 2 billion CFU combination of GR-1 RC-14 per capsule, twice a day, and they also took the antibiotics at the same time.

Dr. Kara Fitzgerald: Oh, they did? Okay.

Dr. Noelle Patno: They took antibiotics and probiotics the same day. In one study, the probiotics were taken at least one hour after the antibiotic, but for the other study, it didn’t really specify a time difference. In both cases, these were different types of antibiotics. There was also an in vitro study I want to point out, that these two bacteria are actually having natural antibiotic resistance to multiple types of antibiotics. Just a few of them are Metronidazole, which is a very common antibiotic used in bacterial vaginosis, and then Vancomycin and Trimethoprim, Sulfamethoxazole.

Dr. Kara Fitzgerald: Wow.

Dr. Noelle Patno: Methoxazole, so multiple antibiotics, they have that natural antibiotic resistance, and so I guess that’s why you would say there’s probably less of a concern of taking it at the same time, but for a concern, if somebody had one, at least one hour after the antibiotic was that study design. Like I said, they doubled the dose.

Dr. Kara Fitzgerald: That’s not long after, waiting just an hour.

Dr. Noelle Patno: No, it’s not.

Dr. Kara Fitzgerald: It was probably still exposed to the antibiotic.

Dr. Noelle Patno: Yes. So, the natural antibiotic assistance is important.

Dr. Kara Fitzgerald: Yeah.

Dr. Noelle Patno: Just by comparison for an in which antibiotics and probiotics were taken the same day, there was a two-hour separation of antibiotics and probiotics for the antibiotic-associated diarrhea study, that I can think of, which was a four-strain combination.

Dr. Kara Fitzgerald: And did that, and it was effective?

Dr. Noelle Patno: That was effective for sure. That reduced antibiotic-associated diarrhea. It reduced Clostridium difficile-associated diarrhea.

Dr. Kara Fitzgerald: Amazing.

Dr. Noelle Patno: It was amazing too. Yeah.

Dr. Kara Fitzgerald: What are the strains?

Dr. Noelle Patno: That combination is Lactobacillus acidophilus NCFM, Bifidobacterium lactis Bi-07, Bifidobacterium lactis Bl-04, and Lactobacillus paracasei Lpc-37.

Dr. Kara Fitzgerald: I’m so impressed with your ability. I’m watching. We’re on Zoom, so I can actually see Noelle and she’s pulling all of this off the top of her head, and I’m really impressed. This is such a good information. So, A, it worked in antibiotic- associated diarrheas, which is painfully common occurrence and B, it’s evident … They did divide. They had a bigger time difference for that particular protocol, but still, just two hours. All right. So, it’s, and also we’ll make sure folks, that we get information on that paper, so that you have it, since we’re talking about women’s health, and we’ve just sort of stepped over to antibiotic-associated diarrhea. So, we sort of went off our path here, but ,I’ll just make sure you have that information because it’s so useful. Okay. So BV, UTIs, vulvovaginal candidiasis, sometimes with medication, sometimes with antifungal sometimes without. How effective are these strains without accompanying pharma intervention?

Dr. Noelle Patno: Right. So, without antibiotics, there was a very large double-blinded, randomized controlled trial, and I will refer to some notes so I can get those numbers for you.

Dr. Kara Fitzgerald: Yeah, no –

Dr. Noelle Patno: Not everything is off the top of my head.

Dr. Kara Fitzgerald: This is BV. We’re talking BV here?

Dr. Noelle Patno: I’m talking BV. Technically, this one was what they called vaginal infection, which would include BV. They had the, like I said, the double-blind, randomized control trial, they had 544 adult women with vaginal infection. It was six weeks. This was a multicenter trial, and they had the 1 billion CFU of each strain. So, that’s, excuse me, 2 billion CFU of the combination, which is the typical dose. This was without antibiotics, like you said. 61.5% of those taking the probiotics had the normal balanced vaginal microbiota at the end of the six weeks, while only about 27% of the placebo group had normal vaginal microbiota. So, it’s a massive difference, and a pretty big success story for just the probiotics alone.

Dr. Kara Fitzgerald: Right, and just once a day.

Dr. Noelle Patno: Yes. Once a day.

Dr. Kara Fitzgerald: And only a single cap.

Dr. Noelle Patno: Yes. We just only use 2 billion CFU of the combination. Sometimes people just think you have to take tons and tons of probiotics.

Dr. Kara Fitzgerald: Yes.

Dr. Noelle Patno: Of so many different types, but look at the efficacy of this combination at 2 billion CFU.

Dr. Kara Fitzgerald: Do you, well, in your read on the literature, do you think that the outcome could have been improved with two caps or, or two caps at once or one cap twice a day, twice daily? I mean, what do you think? Can you, can you infer?

Dr. Noelle Patno: I can’t really infer, but I could hypothesize.

Dr. Kara Fitzgerald: Yeah.

Dr. Noelle Patno: I think there is sometimes an upper limit of a beneficial effect. I think, we’re talking about 61% having normal vaginal microbiota. If I think about how effective antibiotics are, I mean, they would actually be 60% or less effective. So, I don’t know if we really could go above that threshold. Maybe you could. When I think about the antibiotic and probiotic studies that were done together, that it’s higher than the 61%, if I look at-

Dr. Kara Fitzgerald: Yeah, tell me about this.

Dr. Noelle Patno: 75% were normal in the probiotic group after just four weeks of treatment, so this was a double dose of probiotics, but with the antibiotics at the same time. So it’s possible, maybe you could get up to 75%. Maybe you could even, excuse me, get up to 88%, which was the four weeks, two capsules of the probiotic with the antibiotics. So, it’s possible, but I’m not sure that we’d ever get up to 100%, but maybe that 60 to 88% range seems pretty normal.

Dr. Kara Fitzgerald: It’s already performing on par with antibiotics alone. So, the probiotic alone at 61% is on par with an antibiotic alone study. Then you can put them together and increase efficacy considerably, up to 88%. That’s so cool. I guess it just makes me think as a functional medicine and naturopathic physician, that, what if we added botanicals? What if we used CandiBactin-AR / BR concurrently, or many of the other tools at our disposal, what outcome we might see. I’m sure clinicians listening are nodding their heads saying, yes, we know we could do this, and yes, we could probably see better outcome. Well, these are, this is great. I mean, it’s just really nice to hear the power of these specific strains. Let me see, what else I want to, I want to talk to you about. Did they have any kind of side effects noted or any safety issues with these?

Dr. Noelle Patno: Well probiotics, especially of the lactobacillus genus are generally, these are generally recognized as safe, and in these studies, the probiotic arms showed actually fewer adverse events than the antibiotic, or there were, they just weren’t significantly different. Typically, with antibiotics, there are more side effects as you know.

Dr. Kara Fitzgerald: For sure.

Dr. Noelle Patno: I mean, you can have diarrhea, vomiting, nausea.

Dr. Kara Fitzgerald: Even yeast infection. Follow up with that.

Dr. Noelle Patno: It’s like those drugs that just give you the same problem back that you’re treating.

Dr. Kara Fitzgerald: Yeah. All right. Okay. So, they’re safe, not a lot of side effects reported. The duration, it seems like you’re talking, I think in the studies you’ve talked about are four weeks to six weeks. Did you mention an eight-week study also, or no?

Dr. Noelle Patno: No. The ones I mentioned were four weeks-

Dr. Kara Fitzgerald: Four to six.

Dr. Noelle Patno: … and six weeks.

Dr. Kara Fitzgerald: Okay. Go ahead.

Dr. Noelle Patno: However, like there, I will mention that the first pilot study, back in 2001, there were six women with asymptomatic bacterial vaginosis, and sort of intermediate vaginal microbiota imbalance. They resolved to their healthy vaginal score in just one week. So, that’s just a small sample size before these larger randomized trials, suggesting that there could be an earlier benefit.

Dr. Kara Fitzgerald: Then, I’ve got again, with my own clinical hat on, using some botanicals, and of course, if we change diet, if we change lifestyle. If we look at hygiene practices, and you use sort of less caustic and toxic soaps and so forth and more cotton, et cetera, I mean, it just seems like we have the potential really turning this around very effectively. What about dose and duration for BV versus UTIs versus candidiases?

Dr. Noelle Patno: Okay. So, for candidiases, that was the same dose with the, as far as the antibiotic, probiotic, complementary studies, right? So, like I said, they doubled the dose with a sort of adjuvant role with the antibiotic treatment. So, in one study for 55 women with vulvovaginal candidiasis, they were positive for candida. They were itching, burning, et cetera. They took Fluconazole in the morning, and then they had either two placebo capsules or the two probiotic capsules, and they were treated for four weeks. So, that’s kind of a similar site as designed to what I told you with the antibiotic probiotic complementarity for the bacterial vaginosis study.

The resolution was also much better for, using the probiotics, supporting the anti-fungal therapy. There was much lower presence of yeast. It was like 10% for the placebo group versus 39 percent, I mean, sorry, I reversed that.

Dr. Kara Fitzgerald: Yeah.

Dr. Noelle Patno: 10% for the probiotic group and then 39% for the placebo group. So, with the urinary tract infections, that was another question you had, this was a more complicated study, because they were looking at recurrent urinary tract infections. So, they needed to have a whole year.

Dr. Kara Fitzgerald: Wow.

Dr. Noelle Patno: In order to really measure all the urinary tract infections that could be recurrent.

Dr. Kara Fitzgerald: Yes.

Dr. Noelle Patno: That was actually, so that there was a study with the probiotics in that case, that was like I said, the 12 months they had to measure recurrence over the 12 months. In that case, I’d just like to look over to my notes for the exact numbers for you.

Dr. Kara Fitzgerald: Okay.

Dr. Noelle Patno: The primary outcome, I should mention though, this was a double-blind study again, and placebo-controlled [correction: study was just antibiotics v. probiotics; a unique study design, no additional placebo]. Again, double the dose, twice daily. They were taking the antibiotics at night, and the probiotics or placebo also at night for recurrent urinary tract infections, and their primary outcome was not actually the recurrent urinary tract infections. It was actually looking at resistance of E. coli, because with the antibiotics, is the high risk that you’re going to have all these antibiotic-resistant organisms.

Dr. Kara Fitzgerald: Yes.

Dr. Noelle Patno: So, that was actually their first outcome, and it was so much lower with the probiotic usage, as you can expect, right? At baseline, they had about the same amount of antibiotic resistance, but it decreased with the probiotic usage. Whereas, it basically skyrocketed to 100%, and-

Dr. Kara Fitzgerald: Oh, my goodness.

Dr. Noelle Patno: After 12 months with the antibiotic usage.

Dr. Kara Fitzgerald: So, chronic UTIs, antibiotics-only, increased resistance. So, basically, the UTIs are hanging around after a year of antibiotics versus the probiotic-antibiotic group, and those results were?

Dr. Noelle Patno: Well in the, I have to mention that the actual number of UTIs wasn’t that different, but it didn’t quite get to non-inferiority. So it’s, but it seems very impressive, right? At baseline, they reported average number of urinary tract infections 7.0 and 6.8, so pretty much the same for both groups.

Dr. Kara Fitzgerald: Yeah.

Dr. Noelle Patno: But at the end of 12 months, the antibiotic group had 2.9 average urinary tract infections, and then the probiotic group had 3.3. So it’s very close, but it didn’t quite get to non-inferiority.

Dr. Kara Fitzgerald: So, basically there was a reduction in UTIs, which was about the same. However, when they looked at resistant strains, they were present in the antibiotic only, whereas they were resolved. They were actually worse in the antibiotic only-

Dr. Noelle Patno: Yes.

Dr. Kara Fitzgerald: … over that year. So, basically that’s saying you will in fact get another UTI. Did they follow them beyond this study, beyond this year?

Dr. Noelle Patno: I didn’t see another publication after that, but that is really what’s most important, what’s most interesting. They did follow them three months later to see if the antibiotic resistance decreased. They did see that three months afterward that 100% antibiotic resistance, after stopping antibiotics for three months, that went down to a little over 60%.

Dr. Kara Fitzgerald: Okay.

Dr. Noelle Patno: So, it’s good to stop antibiotics, so that you won’t have as many antibiotic-resistant organisms from that perspective, but still the probiotic group was plateauing and decreasing to like 20% antibiotic-resistance, even after three months of not taking the probiotic afterwards.

Dr. Kara Fitzgerald: Wow. Okay. That’s pretty impressive. Gosh, too bad they didn’t track UTIs. You could. It would be an and/or it would be interesting to look at transitioning just to probiotics and looking at outcome, maybe long-term, beyond the year.

Dr. Noelle Patno: Yeah.

Dr. Kara Fitzgerald: And seeing if you can resolve it.

Dr. Noelle Patno: The conclusion of the authors was really that probiotics should be an acceptable alternative for women who don’t want to take antibiotics, because it’s just so close to the same efficacy as the antibiotic usage. I mean, 2.9, 3.3, it’s very close.

Dr. Kara Fitzgerald: Right.

Dr. Noelle Patno: But statistically, still not non-inferior.

Dr. Kara Fitzgerald: Yeah. It would be nice if they had just a probiotic arm within this study as well. Right? Not-

Dr. Noelle Patno: No, no, this was, this was just probiotics versus just antibiotics.

Dr. Kara Fitzgerald: Oh, okay. That’s impressive.

Dr. Noelle Patno: That’s why they were saying, it was designed to try to demonstrate non-inferiority like is-

Dr. Kara Fitzgerald: Yes.

Dr. Noelle Patno: A probiotic group, non-inferior to the antibiotic group.

Dr. Kara Fitzgerald: Okay. Geez. I misunderstood that.

Dr. Noelle Patno: Sorry about that.

Dr. Kara Fitzgerald: My apologies. Sorry. Okay. So, I thought that they were, I thought the probiotics were improving the antibiotic efficacy when given concurrent, and therefore that’s why the resistance was low. But in fact, they were just doing probiotics again, alone. Okay. So, outcome was basically the same antibiotics or probiotics except, and the resistance, the presence of resistant strains over that course of year dropped significantly within the probiotic group, and continued to stay low even after they stopped the probiotics. The incidence of UTIs in both groups was about the same. So, it would be interesting to continue to follow both groups and see what they see.

And again, of course, as a functional medicine provider, I’m thinking all of the other things that we normally do. It just strikes me that, well, in my practice, it just strikes me that we don’t need to use antibiotics, and in fact, we shouldn’t use antibiotics. I will say that the folks that come to me, the women who come to me with chronic UTIs have been inundated with antibiotics, and it’s rarely an intervention that we’re going to choose.

Dr. Noelle Patno: Yes. It can just, like you said, set you up for potentially more, if you have those, continue to have those antibiotic-resistant bacteria present.

Dr. Kara Fitzgerald: Yeah.

Dr. Noelle Patno: I think it would be great to see a study with the holistic approach that you’re talking about, because you can push so many more levers than just these single interventions with just antibiotics or probiotics or the combination, but with all of those other lifestyle changes that you mentioned.

Dr. Kara Fitzgerald: Yeah, yeah. 100%. We just need to be sort of comfortable with wrapping our arms around multimodal studies. We really, really need to do them. I mean, this, what you’re sharing today is interesting and satisfying, and I’m sure will influence how our listeners are practicing. But yeah, looking at those multimodal interventions is always, is I think is an essential step that we have to take. What about interstitial cystitis? Anything in the literature on IC, that you’ve come across?

Dr. Noelle Patno: Interstitial cystitis. Interesting. I actually haven’t reviewed that literature, so I’m not able to comment on that. I’m sorry.

Dr. Kara Fitzgerald: Okay. All right. Well maybe we can circle back if you do, because that can be a really tricky condition to treat, and it often tracks with UTI. So, yeah, I would love to, I’d love to chat with you, if and when you would be so inclined. I’d love to hear about it. So, and my suspicion, so again, just treating both of them together is likely there’s a place for these two particular strains in our IC patients. I’ll I would just have to say that would be my strong hunch, as a clinician. You’ve talked about how long until benefits can, are seen, and in some cases it can be as little as a week. You also, you talked about this last study, where they continued treatment for a full year. Is there sort of a general rule of thumb about how long we want to be thinking about prescribing before we see benefit, and how long we should continue the intervention?

Dr. Noelle Patno: I think it goes back to what you are trying to achieve. With the bacterial vaginosis and vulvovaginal candidiasis treatments, those were four months, six months in one case. Sorry, I didn’t, I don’t mean months. I mean weeks.

Dr. Kara Fitzgerald: Yeah.

Dr. Noelle Patno: Four weeks, which is one month. But it also, if the person’s receiving a benefit and resolves earlier than that, that would be different than the clinical study. That’d be great. There was another study where they showed vaginal recovery from probiotics in two weeks. So, I think there are more. There’s a little evidence to show that could, it could happen earlier than the four weeks.

Dr. Kara Fitzgerald: Yes.

Dr. Noelle Patno: Yeah. You also just have to track the patient as a clinician. What’s happening in this patient’s life? What’s happening with bacterial vaginosis, with recurrent urinary tract infections, with yeast infection. What’s going on there, in order to determine what’s the best treatment duration or dose.

Dr. Kara Fitzgerald: Okay. Okay. But it doesn’t look like we don’t need to start somebody on these and stay on them forever. Although, the chronic UTI protocol was a full year, which makes sense for anybody who’s treating people with chronic UTIs. It’s something that you kind of settle into for the long haul.

Dr. Noelle Patno: Right.

Dr. Kara Fitzgerald: Anything else that you want to add? Anything that I missed asking you? Any other pearls?

Dr. Noelle Patno: Well, if you’re interested in more of the mechanisms behind-

Dr. Kara Fitzgerald: Yeah.

Dr. Noelle Patno: … how they work.

Dr. Kara Fitzgerald: Do share.

Dr. Noelle Patno: Yes. There are multiple mechanisms of action. For example, the [L. rhamnosus] GR-1 probiotic can enhance anti-inflammatory IL-10 cytokine, as you know, and it’s also the combination showed in a preclinical model to reduce the translocation and infectivity of Salmonella across the gut barrier, and other interesting pieces of research about their properties from the mechanistic perspective.

Dr. Kara Fitzgerald: Yeah.

Dr. Noelle Patno: Are these biosurfactants that seem to be produced, and inhibiting the adhesion of gram-positive bacteria in particular, like the Staphylococcus, Group B Streptococcus, there have been studies of this combination in pregnant women.

Dr. Kara Fitzgerald: Yeah.

Dr. Noelle Patno: They’ve been deemed to be relatively safe, and one, seem to show positive benefit for the Group B Streptococcus in particular.

Dr. Kara Fitzgerald: Wow.

Dr. Noelle Patno: Biofilms sometimes is a buzzword, but these have actually been shown in vitro to pull off or disrupt those biofilms, particularly candida biofilms, which is why they were chosen to be studied in the successful clinical study that we talked about for available vulvovaginal candidiases.

Dr. Kara Fitzgerald: Interesting. Geez. That’s really cool. So these are considered safe in pregnancy as well, and could actually help. It could actually be a really potentially-

Dr. Noelle Patno: Yes.

Dr. Kara Fitzgerald: … important intervention.

Dr. Noelle Patno: I would say, look out for more studies, because I think there will be more studies in this area. Another thing that might be just sort of randomly interesting, there was a reclassification of the lactobacillus genus. I don’t know when it’s going to hit all of the labels and the documentation. When people are looking for these probiotics, they’ll probably still see them written as Lactobacillus rhamnosus GR-1, and Lactobacillus reuteri RC-14, which by the way has had name changes in the past. Some of its earlier studies were Lactobacillus fermentum, instead of reuteri RC-14. But lactobacillus, the genus has had so much diversity that they had to look at actually splitting it up, and they split it up into 25 genera recently in 2020.

Dr. Kara Fitzgerald: Geez.

Dr. Noelle Patno: That name change hasn’t really hit mainstream completely yet. But if you do see Lacticaseibacillus rhamnosus GR-1, it’s the same as what we’ve been talking about today. And Limosilactobacillus reuteri RC-14, is the same as the RC-14 we’ve been talking about today.

Dr. Kara Fitzgerald: Well, I’m glad they’re not going to change the … that’s the sub-strain that new, that-

Dr. Noelle Patno: The alpha-numeric identifier. Yes. That’s good that they’re not changing that, because that’s helpful. The other helpful thing is all of the new genus names start with L still.

Dr. Kara Fitzgerald: Okay.

Dr. Noelle Patno: So, the abbreviation L. rhamnosus is-

Dr. Kara Fitzgerald: Should be the same. Will be the same. Yeah. Okay. That’s good. Gosh. Yeah, that’s, it just gets, that’s that can potentially become just a quagmire of confusion with these new name change, but it’s just a complex, you know the microbiome is complex. So, I understand that nomenclature has to evolve as our understanding increases. So, I appreciate you teasing out some of the mechanisms. Those are really interesting. I like the anti-inflammatory effect, and of course the benefit in pregnancy. Are these guys used in gut health as well, because you did mention translocation of, I think it was a, was it a Strep strain?

Dr. Noelle Patno: Yes. And-

Dr. Kara Fitzgerald: And that was GI, I’m assuming?

Dr. Noelle Patno: Yes. So, there was a study in inflammatory bowel disease with this combination I believe. It did demonstrate a decrease in, a decrease in inflammatory cytokines and benefits from the immunomodulatory perspective.

Dr. Kara Fitzgerald: Benefits reported, as well?

Dr. Noelle Patno: I just saw a decrease in levels of inflammatory markers for that study.

Dr. Kara Fitzgerald: Was it in humans?

Dr. Noelle Patno: It was in humans. Yes.

Dr. Kara Fitzgerald: Okay. All right. So, potential place for GI health, but certainly the focus has been on the vaginal microbiome, and again, we can use it orally. We don’t have to deliver it vaginally.

Dr. Noelle Patno: Yes.

Dr. Kara Fitzgerald: An outcome is as good, and perhaps better. Well, listen, Noelle, it was really nice chatting with you. I appreciate you bringing your knowledge, and your commitment to this area, to New Frontiers. Again, we’ll harvest out all of the citations, and any other goodies that we can get from Noelle, and to post them on our show notes page. Again, Dr. Patno, thank you for joining me on New Frontiers today.

Dr. Noelle Patno: Thank you. It was a pleasure.

Noelle Patno, PhD received her PhD in Molecular Metabolism and Nutrition from the University of Chicago investigating bacterial stress in intestinal organoids that modeled inflammatory bowel disease. Dr. Patno began her career at Abbott Laboratories after graduating as a chemical engineer from Stanford University with honors and distinction. Her experience in the pharmaceutical and medical device manufacturing world spanned R&D, supply chain, project management, supervision, and international technology transfer. Previously as Therapeutic Platform Lead at Metagenics, Dr. Patno researched new ingredients, designed and monitored clinical trials, and developed educational content related to digestive, microbiome and immune health. She speaks to us today as an independent contractor for Metagenics.

Metagenics

https://www.metagenics.com/ultraflora-women-s

• Strain-Specificity and Disease-Specificity of Probiotic Efficacy: A Systematic Review and Meta-Analysis
• L. plantarum MF1298 Randomized Controlled Trial in Subjects with Irritable Bowel Syndrome
• Lacticaseibacillus rhamnosus GR-1 Past and Future Perspectives
• AEProbio clinical guide for probiotics
• Oral probiotics can resolve urogenital infections
• Probiotics reduce symptoms of antibiotic use in a hospital setting: a randomized dose response study
• Efficacy of orally applied probiotic capsules for bacterial vaginosis and other vaginal infections
• Improved treatment of vulvovaginal candidiasis with fluconazole plus probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14
• Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14
• Improved cure of bacterial vaginosis with single dose of tinidazole (2 g), Lactobacillus rhamnosus GR-1, and Lactobacillus reuteri RC-14
• Assessment of phenotypic and genotypic antibiotic susceptibility of vaginal Lactobacillus sp.
• Lactobacilli vs antibiotics to prevent urinary tract infections: a randomized, double-blind, noninferiority trial in postmenopausal women
• Anti-inflammatory effects of probiotic yogurt in inflammatory bowel disease patients
• Younger You
• DrKF Study

• DrKF FxMed Clinic: Patient consults with DrKF physicians
• DrKF FxMed Nutritional Residency Program