Disclaimer
The webinar transcript has been modified to enhance comprehension and clarity.
Summary
In this webinar, Dr. Sarah Ellis, ND, and Dr. Holly Lucille, ND, RN, discuss two innovative ingredients for targeting dysbiosis, Pylopass™ and Immunolin®. They discuss the clinical evidence supporting the efficacy of Pylopass™, a unique strain of Lactobacillus reuteri DSM17648, and explain how it has a specific binding affinity to Helicobacter pylori and can help restore balance to a dysbiotic gut. The webinar also discusses the clinical evidence and benefits of Immunolin®, a serum-derived bovine immunoglobulin protein isolate. Immunolin® has been shown to bind to microbial components, reduce inflammation, improve gut barrier function, and decrease symptoms associated with irritable bowel syndrome.
Table of content
Foundations of the gut microbiota
Risk factors associated with gut dysbiosis
Supporting the microbiome with Fullscript
Welcome
Host Amy Regan: Welcome everyone to this special webinar event in collaboration with Microbiome Labs and Fullscript. I’m Amy Regan, and it is my pleasure to introduce Dr. Sarah Ellis, who is a naturopathic doctor and clinical science liaison at Microbiome Labs, where she trains and educates healthcare professionals on innovative approaches to improving the gut microbiome. Dr. Sarah is a naturopathic doctor with a special passion for women’s health, pediatrics, and gut health. Outside of her professional endeavors, Dr. Sarah enjoys spending time outdoors with her kids, gardening, and making herbal medicine.
We also have Dr. Holly Lucille joining us today, who is a nationally recognized licensed naturopathic doctor currently practicing in Los Angeles. A dedicated educator and expert in the field of integrative medicine, she is a consultant, author, and media figure. Dr. Lucille serves as a senior medical advisor here at Fullscript.
Dr. Lucille: We’re going to discuss the foundations of the gut microbiome. We’re going to highlight the cause and risk factors associated with gut dysbiosis. We’re going to introduce Pylopass™ and discuss its scientific and clinical data. We’ll also discuss Immunolin® and its scientific and clinical data, and then we’ll review the clinical applications of them both. At the end, we’ll also discuss how Fullscript can optimize your patient care with different protocols.
Foundations of the gut microbiota
Meet the gut microbiome
Dr. Lucille: Let’s talk about the foundations of gut microbiota. I graduated from naturopathic medical school in early 2001. We had this saying in school called “heal the hole,” which referred to the hole that starts in your mouth and ends all the way back there. Even back then, we knew that the gut is an incredible system. This essential organ is a collection of microbes and their associated genes and secreted molecules that live on or inside the human body.
We’re talking about 10 trillion microbial cells. That’s 1.3 microbiome cells to every human cell, 39 trillion bacteria in and on the human body, and 3.3 million unique microbial genes. That’s 150 times more genes than our own genome. I mean, this thing is absolutely amazing.
Microbial communities
Dr. Lucille: Let’s review the four main phyla that predominantly make up the human microbiome: firmicutes, bacteriodetes, actinobacteria, and proteobacteria. And they’re found everywhere. In our oral cavity, the vaginal canal, our gut, of course, our skin, our respiratory system. And 70% of all microbes found in the body lie in our gut microbiome.
Where does the microbiome originate?
How do we get our first inoculation of this incredible system, this organ? Well, I would say that it’s that first pass through the mom’s vaginal canal. The greatest insults to the natural assembly of the neonatal microbiome are C-section deliveries, antibiotic use, and formula feeding.
Because this is something that I think is super important, I ask every single patient if they were born via the vaginal canal or C-section. I want to know that because vaginally born babies are inoculated with microbes from the vaginal canal, whereas babies born via C-section without membrane rupture are born in a sterile environment and are primarily inoculated with skin bacteria.
The research on C-section babies indicates they have higher levels of intestinal Clostridium difficile. This is huge. If your patient was born via C-section, their microbiome might be “behind the eight ball” when it comes to this incredible organ.
Healthy gut characteristics
Dr. Lucille: Let’s briefly review the characteristics that define a healthy gut microbiome. First, increased microbial diversity. Interestingly, I’ve noticed that many of my patients are missing complete phyla when doing stool test analysis. We also want low levels of pathogens and toxins, a thick mucosal barrier, and strong and tight epithelial junctions. Those tight junctions prevent unwanted substances from crossing over into the bloodstream and activating our immune system. Finally, we want low mucosal inflammation.
Risk factors associated with gut dysbiosis
Dr. Lucille: Let’s discuss some of the risk factors associated with gut dysbiosis. We already talked about the impact of C-sections. However, antibiotic use, artificial sweeteners, excessive alcohol intake, and glyphosate exposure—which is pretty much in our rainwater at this point—are also risk factors.
Intense exercise is also involved. Why is that? It has to do with the amount of oxidative stress that intense exercise produces. Lack of sleep, saturated fats, smoking, and elevated cortisol over a period of time are also factors.
Pylopass™: How can Pylopass™ restore balance to a dysbiotic gut microbiome?
Dr. Lucille: And now I’m going to pass it off to the esteemed Dr. Ellis. Take it away.
Pylopass™
Dr. Ellis: Thank you, Dr. Lucille. Hi, everyone. I’m so glad to join you all today. Thank you for really setting the stage and the foundation for gut dysbiosis. Now that we know that we’ve discussed the different factors that can shift the health of our microbiome, let’s talk about some innovative ways that we’ve been able—and I say we, as in the scientific community,—to harness the science and technology to create some innovative options to help restore balance to the microbiome.
Specifically, we’re first going to talk about Pylopass™. Over the next few slides, we’ll discuss how Pylopass™ can help restore balance to a dysbiotic gut.
Pylopass™ is a unique and inactive strain of Lactobacillus reuteri. Through a series of tests and assays, it has been shown to have a unique and very specific binding affinity to Helicobacter pylori or H. pylori. Several screening studies have shown that L. reuteri actually has the ability to bind to the surface of H. pylori like Velcro and escort H. pylori out of the gut and out of the stomach, where it can cause a lot of damage to the gastric lining.
This is important because H. pylori is a very common gastric pathogen, and it is associated with a variety of symptoms, including indigestion, bloating, pain when eating, ulcer formation, and gastric cancer risk.
What’s interesting to note is that at least 50% of the global population carries H. pylori. So discovering a unique and innovative way to manage and eradicate H. pylori levels is definitely something of need with regard to public health.
H. pylori
Dr. Ellis: We need to talk about H. pylori before we talk about its solution.
H. pylori is a gram-negative bacterium that can burrow into the gastric lining and mucosa and adhere to the epithelial cells. This changes the gastric acid conditions and ultimately, the conditions in the stomach, which can impact our ability to digest food and kill pathogens present in the oral cavity that we swallow when we eat. It really impacts our first line of defense, particularly the gastric and gastrointestinal systems.
H. pylori makes urease, which is an enzyme, and that’s why we use the urea breath test to measure the presence of H. pylori in our patients.
H. pylori is also very intelligent. It adheres to the stomach epithelium, which allows it to evade the immune system. So, by burrowing into the mucosa, it can kind of hide and prevent the immune system from identifying it and attacking it.
H. pylori virulence factors
Dr. Ellis: We cannot talk about H. pylori without talking about its virulence factors.
It’s not enough to just identify the presence of H. pylori in someone’s gut. We also want to look at the different virulence factors that they may have. I’m just going to highlight some common virulence factors. There’s the flagella. Then we also have some secretory enzymes. H. pylori releases these enzymes to optimize the environment for its survival, meaning it decreases gastric acid and pH levels.
I also wanted to highlight some membrane proteins, particularly CAG-A. Now, CAG-A is one of the virulence factors that we really want to monitor and identify if someone is presenting with an H. pylori infection.
CAG-A can lead to an aberrant immune response. It upregulates inflammation and immune system activation. It has also been shown to upregulate cell growth while simultaneously inhibiting apoptosis. So in a way, CAG-A is setting the stage for the development of gastric cancer.
This is another reason why we want to make sure that we are effectively reducing or eradicating H. pylori to effectively reduce a patient’s risk of developing gastric cancer.
H. pylori: Conventional treatment
Dr. Ellis: Let’s discuss the conventional treatment for H. pylori. Triple therapy is the gold-standard treatment. It’s a combination of two antibiotics and a proton pump inhibitor. You can also use quadruple therapy, which adds in bismuth for a more robust approach to eradicating H. pylori.
There’s no global or regional eradication regimen that allows for 100% eradication of H. pylori. And to be honest, the research is still debating whether or not H. pylori really needs to be fully eradicated. There’s some research out there that suggests that H. pylori could be protective in certain demographics, particularly in the pediatric population. But with adults who are very symptomatic, we want to make sure that we are putting together a plan and treatment protocol that can facilitate the best eradication levels.
It’s important to note that there’s increased antibiotic resistance with H. pylori. It’s one of the fastest-growing pathogens that’s developed antibiotic resistance. And the success rate of triple therapy has actually decreased from 90% to 75%.
With multiple antibiotics and a proton pump inhibitor, patients are bound to experience side effects, which can impact their ability to comply with your treatment protocol. As many of you know, antibiotics are very important in helping to manage infections. However, they also cause quite a bit of damage to the gut microbiome.
Also, PPIs can be quite addictive or habit-forming. Once patients start PPIs, it’s very difficult to wean them off. And the increase in gastric acid production, once they stop the triple therapy, can make it hard for them to discontinue the PPI due to that rebound effect. And, of course, we know that PPIs are not without any sequelae or side effects.
Chronic use of proton pump inhibitors has been associated with osteoporosis and deficiencies in essential minerals like magnesium.
Nature teaches us how to combat pathogens
Dr. Ellis: What’s beautiful is that nature always has the answers, and nature has actually been teaching us how to combat pathogens. Researchers in Denmark wanted to look at the mechanism of action of adhesion or co-aggregation. So, how could we manipulate a natural phenomenon that occurs with bacterial species and use it as a way to modulate and reduce the presence of H. pylori?
As I mentioned, adhesion and co-aggregation are common phenomena in nature, definitely more frequently found in microbial biofilms. These co-aggregations take place when genetically distinct bacteria become attached to one another. They all secrete different adhesion molecules, like S-layer proteins, adhesions, and even endotoxins like LPS or lipopolysaccharide.
Researchers in Denmark really wanted to screen a variety of different Lactobacillus strains for this mechanism of action. In the next slides, we’re gonna walk through the ways in which the scientists actually discovered this unique Lactobacillus strain, also known as Pylopass™.
First screening level: Specific adhesion
Dr. Ellis: The first screening level, researchers inoculated a 96-well microtiter plate with a little bit of H. pylori and got it to adhere to the surface. Once it had been immobilized, it was co-incubated with fluorescent-labeled Lactobacillus strains. Then they looked at how brightly that fluorescence was shining with a fluorescence reader. The brighter the fluorescence, the more tightly bound that Lactobacillus species was to H. pylori.
Finding the one-in-a-trillion natural solution
Dr. Ellis: This whole process led us to find that one-in-a-trillion natural solution. The researchers in Denmark screened over 700 different Lactobacillus strains in the Novazymes, now NovaNessus collection. They were able to identify just one specific Lactobacillus strain that had a very strong, unique affinity to H. pylori. That strain turned out to be Lactobacillus reuteri DSM 17648. Note that Lactobacillus reuteri has been reclassified as Limosilactobacillus reuteri. However, we’ll be referring to it as Pylopass™ throughout the rest of the presentation.
As you can see here in this chart to the left (see Figure 1), compared to all of the other Lactobacillus strains, the Pylopass™ strain showed a significant increase in its ability to bind H. pylori.
Figure 1. A screening of 700 Lactobacillus strains of the Novozymes collection identified a specific Lactobacillus strain that binds to H. pylori.
The co-aggregation is fast and occurs under physiological conditions
Dr. Ellis: This is one of my favorite slides (see Figure 2) because it shows that the co-aggregation between Pylopass™ and H. pylori happens quickly and under various physiological conditions.
Figure 2. Co-aggregation of L. reuteri DSM17648 with H. pylori is macroscopically visible.
(A) H. pylori alone in artificial gastric juice (negative control); (B) H. pylori + Pylopass™ co-aggregation (Holz 2015)
Let’s start by looking at this image on the right. A, this is H. pylori alone in artificial gastric juice. B, this is H. pylori and Pylopass™. You can see some of the sediment down at the bottom of the well. This shows that Pylopass™ is bound to H. pylori and pulling it down into the bottom of that well. This co-aggregation between Pylopass™ and H. pylori occurred within seconds of being mixed in a low pH environment (pH:2 – comparable to the gastric environment), as well as a higher pH environment (pH:8).
We also saw co-aggregation in the presence of gastric salts, gastric protease activity, and mucin, as well as in two different temperature environments, room temperature and body temperature, which is 37 degrees Celsius.
Pylopass™ and its impact on the gut microbiome
Dr. Ellis: Let’s talk about Pylopass™ and its impacts on the gut microbiome. Often the next question is, if Pylopass™ binds to H. pylori, does it bind to anything else, including commensal bacteria?
Researchers found that Pylopass™ is able to bind multiple strains of H. pylori, including Helicobacter heilmannii and Helicobacter canis. However, it does not bind to other pathogens like certain Streptococcus strains, Campylobacter, different Clostridium strains, and even B. fragilis and E. coli.
We also found that Pylopass™ doesn’t disturb the commensal bacteria. Pylopass™ is a very specific, precision-pointed technology or tool to support the eradication of H. pylori.
What we saw is that Pylopass™ actually interferes with H. pylori‘s motility and keeps it from being able to burrow into that gastric mucosa. It also aggregates with H. pylori creating these clusters that can be moved out of the gastric environment.
Taking Pylopass™ with a meal helps stimulate peristaltic activity. This shakes the H. pylori out of the mucosa, allowing Pylopass™ to bind even more of the bacteria.
Pylopass™ in action!
Dr. Ellis: This is a scanning electron microscopy image that really zooms in, and we’re able to see the co-aggregation happening between the Pylopass™ in the blue and H. pylori in the red (see Figure 3). On the left, we can see that H. pylori is significantly bound to several L. reuteri cells. We know that one Pylopass™ cell can bind two to three H. pylori cells. So they’re all working overtime to really bind that H. pylori and remove it from the gastric tract.
Figure 3. Scanning electron microscopy images of co-aggregates formed by L. reuteri DSM17648 (blue) and H. pylori (red) (Holz 2015)
Pylopass™’s safety and efficacy are well documented
Dr. Ellis: Let’s review the clinical evidence for Pylopass™. Pylopass™ is been well documented. There are 11 trials that confirm its efficacy and safety both alone and in conjunction with triple therapy.
It’s been found to reduce H. pylori loads in adults as well as children. It really shines due to its ability to reduce the side effects that are associated with H. pylori overgrowth, particularly when used alone. It enhances the eradication rates of conventional triple therapy. So it’s added as a booster to triple therapy. It also reduces the side effects associated with triple therapy, like antibiotic-associated diarrhea.
New clinical trial data
Dr. Ellis: This is exciting new clinical trial data that was released almost a year ago. And it looked at 90 treatment-naive H. pylori-positive adults. These are adults who tested positive with a urea breath test. They had never done triple therapy or quadruple therapy. This was their first time trying to eradicate their H. pylori infection. The study was designed so that they would go through two weeks of triple therapy. Then one group would take Pylopass™ for four weeks while the other group would take a placebo.
The post-treatment eradication rate was assessed via a urea breath test. The GSRS or Gastrointestinal Symptom Rating Scale was also used to look at other secondary endpoints like side effects, stool habits, etc.
Pylopass™ increases H. pylori eradication rate
Dr. Ellis: This study found that Pylopass™ increased the eradication rate. When Pylopass™ was given after completing two weeks of triple therapy, the eradication rate went from 68.9 to over 90%. This study shows that, whether Pylopass™ is taken alone or in conjunction with triple therapy, it can significantly reduce the levels of H. pylori.
Pylopass™ reduces side effects associated with triple therapy
Dr. Ellis: Pylopass™ also reduced the side effects associated with triple therapy. The probiotic group showed a significant reduction in pre- and post-treatment reductions in side effects. Specifically, we looked at symptoms like indigestion, constipation, abdominal pain, and total GSRS scores.
Pylopass™ summary
Dr. Ellis: In summary:
- Pylopass™ is an inactive Lactobacillus reuteri strain. I want to emphasize that it is a dead strain of bacteria. We call it a ghost biotic. It doesn’t need to be alive because we rely on those surface proteins and molecules to bind the H. pylori like Velcro and carry it out of the GI tract.
- It has been shown to work very well as a monotherapy.
- It increases the efficacy of triple and quadruple therapy, especially when applied post-triple therapy.
- It’s also been shown to decrease symptoms of H. pylori infection, as well as reduce the side effects associated with triple therapy.
- There have been no adverse events reported, and it is suitable for long-term consumption.
Immunolin®
What is Immunolin®?
Dr. Ellis: Let’s talk about Immunolin®. Immunolin® is a serum-derived bovine immunoglobulin protein isolate, also known as SBI. Quite a mouthful, but we’ll be referring to it as SBI going forward. It’s an agglomerated cream-colored powder, and it’s 92% protein. Now this is really important because that means that most of these proteins are going to be present as immunoglobulins. IgG, IgA, and IgM are some of the main immunoglobulins within our immune system. It also contains about 10% of albumin and other proteins that are consistent with those that are found in plasma. Immunolin® has been well studied in over 45 human clinical trials focused on digestive health and immune support. It has been found to contain the highest concentration of naturally sourced immunoglobulins in the world.
Mechanism of action
Dr. Ellis: Let’s get into the mechanism of action and some of the clinical evidence. Immunoline® has been found to bind to a variety of microbial components to help reduce inflammation and improve GI function. We can see in the schematic here (see Figure 4), that many intestinal disorders often result or start because of dysbiosis. And so the immunoglobulins are able to bind those microbial components. These can be virulence factors, endotoxins like lipopolysaccharide, and other proteins. The binding of these microbial compounds really helps maintain GI-immune balance.
Figure 4. Immunolin® binds to microbial components to reduce inflammation and improve GI function.
It helps maintain the integrity of the gut barrier and can improve nutrient utilization. Again, we talked about how dysbiosis and the degradation of the microbiome can produce endotoxins like lipopolysaccharide, which leads to immune activation and the subsequent development of inflammation.
If you remember from that picture we saw at the very beginning with Dr. Lucille (see Figure 5), immune activation can actually weaken those tight junctions, cause leaky gut, and allow those materials and components to flow into circulation. So, by binding these endotoxins, we’re able to help provide balance and really calm down that inflammatory process.
Figure 5. Immune activation weakens intestinal epithelial junctions, leading to increased intestinal permeability.
I really love this schematic (see Figure 6) because it highlights many of the ways in which SBI modulates our microbiome and helps bind toxins and other bacterial components. Let’s start here at the top left. SBI is going to bind those LPS toxins from gram-negative bacteria like H. pylori. That’s going to help our immune system. Since SBI binds to bacterial components, dendritic cells cannot bind and present those antigens to other immune cells. This prevents the immune system from being activated unnecessarily. By binding these components, SBI helps calm the immune system. It also maintains GI balance by increasing the expression of the anti-inflammatory cytokine IL-10. Now, IL-10 is very important because it not only cools down the inflammation but also encourages the differentiation of T cells into regulatory T cells.
Figure 6. SBI modulates the microbiome by binding LPS toxins, calming the immune system, and promoting GI balance through increased IL-10 expression.
I consider regulatory T cells to be our immune fire extinguishers. So, if we can increase those anti-inflammatory cytokines and immune fire extinguishers, we will be able to calm down that inflammation and restore the integrity of that gut barrier. Immunoline® and SBI have also been shown to help increase the expression of tight junction proteins to help rebuild the integrity of that gut barrier.
What does Immunolin® bind to?
Dr. Ellis: So what does Immunolin® bind to? Honestly, it seems like just about everything. The list of what Immunolin® binds to just continues to grow. But I wanted to share some of the more important antigens that Immunolin® can bind to. There’s Candida albicans lysate and also H. pylori CAG-A.
Now remember when we went over the H. pylori virulence factors, we talked about CAG-A because that’s a protein that can really activate our immune system, facilitate the replication of cells, and inhibit apoptosis. So it kind of sets the stage for the development of gastric cancer. Well, what’s wonderful is that Immunolin® can bind that specific protein, H. pylori, LPS, C. diff toxins, gliadin, which is one of the main proteins that is inflammatory in wheat, as well as a host of many other pathogens.
It’s important to note that it does not adversely affect the growth of commensal, intestinal, and oral bacteria. It also doesn’t inhibit the growth and healthy activity of probiotics.
Immunolin® has been studied extensively since 2012
Dr. Ellis: Immunolin® has been studied since 2012 and has over 45 different published clinical trial manuscripts, six placebo-controlled clinical trials examining irritable bowel syndrome, particularly the diarrhea presentation, digestibility, pediatric IBS, and even HIV enteropathy.
The fact that it’s been studied with HIV patients shows its safety and efficacy and how gentle the ingredient is. It’s also been featured in several open-label pilot studies and case series.
Clinical trial results: IBS-D
Dr. Ellis: Let’s discuss some clinical trial results. As we can see on this chart (see Figure 7), we wanted to examine the decrease in the average number of days with global IBS-D-related symptoms such as loose stool, abdominal discomfort, urgency, bloating, and flatulence.
Figure 7. Results from a six-week, randomized, double-blind, placebo-controlled study (N = 66). (Wilson 2013)
We can see that Immunolin® reduces the severity of these symptoms by at least 30% across the board. What’s interesting is that not only did Immunolin® reduce the number of days that many of these symptoms are present, but particularly the one symptom that seemed to be the most influential and impactful for patients was the fact that it reduced the number of days that they experienced loose stools.
For those of you who care for patients with IBS-D, you know that having more well-formed stools really has a huge impact on their quality of life.
SBI reduces the incidence of metabolic endotoxemia (leaky gut)
Dr. Ellis: Not only does the SBI help with IBS symptoms but it’s been shown to reduce the incidence of metabolic endotoxemia or leaky gut.
Metabolic endotoxemia is what happens when that lipopolysaccharide toxin enters into circulation. When it enters systemic circulation, it can impact our metabolism like our blood sugar. In this study, we looked at subjects who had signs of metabolic endotoxemia before taking the SBI supplement. We noticed an increase in postprandial LPS five hours after the meal. We wanted to see whether or not SBI would reduce that level of endotoxemia postprandial.
What they found is that supplementing with SBI for 45 days significantly reduced, and in some cases eliminated, the postprandial LPS increase following a high-calorie and high-fat meal. Regardless of the dose, the serum bovine immunoglobulins were able to reduce the levels of lipopolysaccharide after a meal. As we know, LPS can wreak havoc in our gut and system. SBI’s ability to bind LPS and remove it from our system is quite important for gut health.
Immunogloulin® summary
Dr. Ellis: In summary, Immunolin® is a serum-derived bovine immunoglobulin protein isolate. It is clinically shown to decrease symptoms associated with irritable bowel syndrome with diarrhea, pediatric IBS, and even HIV enteropathy. There are no adverse side effects. It is suitable for long-term consumption. However, I will say that it is not suitable for those who have a beef allergy. If someone has an IgE beef allergy, Immunolin® would be contraindicated.
Supporting the microbiome with Fullscript
Dr. Lucille: Okay. I’m going to take it back over from here. Let’s go over some protocols. In case you are not familiar with Fullscript protocols, also called templates, they feature five evidence-based ingredients for a specific condition.
Check out our Reflux support protocol and Gut-mediated inflammation support protocol. OK, Amy, I’m going to give it back to you
Host Amy Regan: Well, thank you so much to everybody for joining today. What an in-depth presentation. I want to say thank you so much to Dr. Sarah Ellis and Dr. Holly Lucille.
Thank you, everyone. Take care.