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Webinar #3-- The Key Microorganisms In IBS

Guy Daniels
Onegevity

Webinar #3--- Listen and learn as Guy Daniels, head of medical education at Onegevity, provides an in-depth look at the research on the microbiome and IBS. He covers the findings of the IBS study by Onegevity, and the keystone taxa involved in your IBS symptoms, including constipation and diarrhea. 


Guy Daniels:                      00:00                    Welcome to Webinar #3 in our in-depth series on the microbiome. I'm Guy Daniels-- head of medical education at Onegevity and in today's webinar we'll expose you to some great information on the microbiome's role in IBS. This is a broad topic with many directions I could have taken. So my goal was to provide you with some valuable data and also help relate to you where we're coming from. We consider more variables than presented here, but I think you'll find this quite inclusive and comprehensive.

Guy Daniels:                      00:29                    Depending on the country and paper referenced, the percent of the population suffering from IBS has a wide range for the United States. We'll take a bit of an average of several studies and call it 15%, which at 320 million people is 48 million. It is involved in about 13% of all visits to primary care practitioners and about 26% of visits to gastroenterologists. Or looked at another way, IBS is associated with 3.6 million physician visits per year, and healthcare costs are approximately 50% higher than for matched controls who did not have IBS. So what's your annual deductible? Is IBS worth fixing sooner or later for both overall health as well as financial reasons?

Guy Daniels:                      01:15                    If we look at just the diagnosis of chronic constipation, that affects about another 15% of our population. And as a nation, we spend well over $800 million per year just on laxatives alone. As you'll begin to learn about the substantial connection that gut health has to the rest of the body, you'll view these numbers as even more shocking and begin to understand why we suffer from so many conditions as a nation-- from cognitive and metabolic dysfunction to mood disorders, from autoimmune disease to cancer, and the list goes on.

Guy Daniels:                      01:47                    IBS stands for Irritable Bowel Syndrome. You'll notice the word disease is not a part of this condition which afflicts so many people. As such, it is a diagnosis given after all others, such as Crohn's and ulcerative colitis have been ruled out. In a perfect scenario, is there a genetic component? Sure, just like a number of other conditions, but that comes with a caveat or two. For example, one study showed a modest increase in risk for first degree relatives which dwindled as you went down the family tree. Twin studies show a significantly higher risk, especially if they are monozygotic or identical twins as opposed to fraternal. And another study shows that one-third of IBS patients have a family member who also suffers as opposed to only 2% for controls. But take this one with a grain of salt as family share behavioral patterns, they may eat the same way under one roof as opposed to another family and view medical care differently. If you run to antibiotics for your solution to everything, as I've seen anywhere from 30 to over 100 rounds and relatively short lives, you're going to radically change the microbiome.

Guy Daniels:                      02:56                    That's something I personally don't endorse, but others have different views. These lifestyle choices have nothing to do with genes and in fact, extensive research has identified a total of zero genes which can be accurately predictive for IBS. The point here that this is primarily lifestyle-driven, but if you do think it runs in your genes, you should pay extra close attention to this webinar. On this slide, we show some results from a meta-analysis published relatively recently encompassing data on various taxa from 13 studies. Later I'll highlight some key points from our just completed meta-analysis of 41 studies, which included these 13. A meta-analysis is just a fancy way of saying a summary of all the individual trial results previously reported and accepted for review.

Guy Daniels:                      03:44                    So what do we do to treat this vague condition, which encompasses an altered gut immune system, which includes among other things, higher expression of mast cells in close proximity to enteric nerves causing gut hypersensitivity, a dysfunctional serotonin system, elevating diarrhea and lowering constipation, possible SIBO, small intestinal bacterial overgrowth, mood disorders, malabsorption, abnormal bowel movements, bloating, pain and gas? One of the first places people turn to is food choices-- as somewhere from one third to one-half of patients can identify certain foods as triggers.

Guy Daniels:                      04:21                    As you can see from this slide, I've referenced three studies. Now, there's a lot of information between them, but I just want you to take away two key points. One, dairy products from cows and gluten-containing products are consistently shown to be the biggest offenders. Two, when it is determined that gluten and or dairy are the offender, and the subject stops consuming it, symptoms go away and when the offending food is reintroduced, the gastrointestinal symptoms return, proving that it is no longer just a suspicion or a placebo effect.

Guy Daniels:                      04:55                    And keeping on the same topic, I have two more references on this slide, two of many others I could show. A quick review of table seven to the right shows a number of dairy and gluten products listed in here as reported offenders. The point is if you do want to make dietary changes, the odds are that taking out dairy and or gluten-containing foods may likely result in some benefit. Why are these two in particular so problematic? Excluding lactose intolerance, there is really one main issue at play. These foods contain peptides and proteins which can be highly troublesome to a dysbiotic gut. You've been exposed to some of this data in our previous webinar in regards to type one diabetes and milk consumption. The concepts of gut permeability, inflammation, and the immune system will be tackled in time, but for now, we'll focus on dysbiosis because that's really at the root of everything. That needs to be addressed for overall health. There's little doubt that dietary intervention can alleviate symptoms in many patients, but that's only a part of the story. So before I move to the next slide, I want you to note that onions ranked high in this table as they did on the previous slide. Why is that?

Guy Daniels:                      06:12                    Here we have data from a review of 15 FODMAPs studies. So if you don't know, what's FODMAPs? The acronym stands for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. The goal is to reduce sugars in the gut, some of which we should be able to digest and some of which the bacteria can utilize. And it significantly reduces symptoms for about 50 to 80% of the people, at least in the short term. But we're not here to reduce symptoms. We're here to solve underlying issues. With that said, I have three major objections to this approach.

Guy Daniels:                      06:51                    One is a highly restrictive diet. If you look at the lower portion of the figure to the right in red, you'll see the foods listed to be eliminated. Not only is that a challenge for most anyone's lifestyle, but it leads to point number two. Some of these foods are among the most healthy ones we could consume. And then there's point three-- the elimination of the prebiotics contained within this list will, in the end, lead to more dysbiosis in the gut. This addresses symptoms but not the root cause. A number of studies have shown that FODMAP diets result in substantial reductions in bifidobacteria, Faecalibacterium prausnitzii, Akkermansia mucinaphila, and the Colostridium clusters IV and XIVA when compared to a habitual diet. These are all the taxa you'll learn about in time. This list is a list of superstars for health. The goal is to maximize these bacteria. You do that by feeding them the fuel they are genetically coded to utilize.

Guy Daniels:                      07:56                    These among others are the foundation for fixing dysbiosis and the GI distress that goes along with it. And the FODMAPs unintended consequence of reducing these superstar bacteria was an increase in pH in the colon. If you recall from our slides on vaginal health, this is not a good thing and well the same ph story is true in the gut. We want a lower pH. So this all highlights when the most important points I can relate to you is that when the proper prebiotics are given to a gut with dysbiosis, there will be bloating and gas. In effect, there is a war going on in the gut for fuel and for real estate. And in time, these symptoms will resolve in a healthy GI tract, which is also healthy for the rest of the body is the result. So if someone has significant dysbiosis, they need to understand that for a brief period of time they will need to cope with a possible increase in symptoms until they get over the hump.

Guy Daniels:                      08:57                    So back to the onions. Why are they a problem? Onions are a great source of Inulin, which is a prebiotic, perhaps the most steady prebiotic there is. And one you'll come to know. On Table 2 we see a review of studies using fiber for constipation. You'll notice along with others the use of inulin as I just mentioned. Other than the listed wheat bran, these fibers are some of many recommended prebiotics, which could be a part of the protocol to rectify a dysfunctional gut. The fibers, or prebiotics, is where the rubber meets the road. This will be our primary way to drive results with other products available as well. Fiber can have physical or fermentable properties as their main driver or in the case of psyllium, both. We'll come to learn about the many prebiotics in time and how their customized use can alter the microbiome. The key point here is fiber is at the center of this equation, and in essence, we are replacing it into what used to be part of the diet our microbiomes evolved with. And using it to feed the remaining good bacteria unique to your gut, which has had a toll taken on it by a lifetime of antibiotics improper diet, over the counter digestive aids such as PPIs and H2 blockers, a possible c-section delivery, and a lack of breastfeeding, none of which were part of the evolution between us and our microbiome.

Guy Daniels:                      10:27                    In addition to dietary changes, another measure someone suffering from IBS to consider is to take probiotics. These are generally available in multi-species products, mostly from the genera lactobacillus and bifidobacteria. And in fact, there have been quite a few studies done on the use of probiotics and the treatment of IBS. And with that several meta-analyses have been performed over the years. The end results being that generally, they can help in one or more symptoms, bloating, pain and or gas, and may even on occasion significantly improved diarrhea or constipation. And as the conclusion states, from this recently published paper, overall pooled conclusions of all these studies indicate that probiotics are an effective treatment for IBS. Although which individual species and strains are the most beneficial remains unclear. So how do you know which one to take? How was a product with a few billion bacteria supposed to compete in a GI tract, which harbors 10 times more bacteria than all the cells in your body combined?

Guy Daniels:                      11:32                    And if you happen to pick the appropriate bacteria to take, how are they going to survive and thrive if you don't feed them? Which brings us to an important concept of how to help the good bacteria survive and thrive. This meta-analysis looked at the use of Bifido infantis in IBS. If you recall from our section on breastfeeding, Bifido infantis is a superstar or good bacteria, for an infant. And what does its genetic machinery allow it to digest? HMOs-- human milk oligosaccharides, that huge component of breast milk exclusively designed to feed good bacteria. Bifido infantis is the best degrader of HMOs there is. It possesses the enzymatic ability to digest all 200 plus discovered HMOs to date, but as we age and we no longer breastfeed if it went fantasy as replaced by other similar bifidobacteria such as Bifido adolescentis. So it's no wonder why using Bifido infantis alone in IBS isn't successful.

Guy Daniels:                      12:33                    Our microbiome is not omnivorous like we are. They have certain sets of enzymes which are unique to breaking certain bonds, to liberate their food. If you don't feed them the fuel they need, how can they thrive? So which bugs should we be feeding? That's a simple question but complex to answer. For example, from this recently published paper from China, we see that they showed a dramatic increase in IBS versus healthy controls in both of what are considered to be generally healthy families, ruminococcaceae and lachnospiraceae. This is a common finding across all disease types, but sometimes these families can have a negative association. Because many different bacteria fall under their umbrella and just because species is closely related to another within a grouping, it doesn't mean that they are all well behaved. As our last point notes that studies are often divergent in contradictory, so we have to be able to analyze down to the species level and that's what our technology shotgun metagenomics allows us to do.

Guy Daniels:                      13:36                    Now, here's an example of something that is quite consistent: archaea methane production in constipation. Numerous studies show, essentially without a doubt at this point, that there is a significant correlation between methanobacteria and constipation. Whether it's the methane out-competing sulfate reduces for hydrogen, a direct protein effect, or something else remains to be elucidated. But if someone suffers from constipation, and their analysis shows high levels of methanobacteria, then it would be prudent to take measures to reduce them. On the flip side, if someone suffers from diarrhea or failure to thrive, then it would be wise to increase them. This slide may look intimidating, but it illustrates a few points. It contains a fair number of the bacteria found to play significant roles in health in the literature, some of which you're becoming familiar with like F Prausnitzii and Bifidobacteria, both of which were shown to be significantly reduced in IBS versus healthy control, a very typical finding.

Guy Daniels:                      14:41                    It also contains a couple of species from Ruminococcus, which have actually since been reclassified to the genus blautia. These species in question may be active opportunistic pathogens and in fact here their presence was correlated to the severity of IBS. Lastly, this study found high levels of streptococcus, the finding we often see in our results. And although two members from this genius of probiotics, you generally don't want to see high levels of this tax in the lower gut, which implies a broader level of disturbance. This genus is more common much further up the GI tract, but conditions have allowed it to migrate and or survive and thrive where it shouldn't be.

Guy Daniels:                      15:24                    Which brings us briefly to SIBO, small intestinal bacterial overgrowth. Now, this slide displays an analysis from the duodenum, which is where your food goes after it leaves the stomach. There is an incredible microbiota difference between the IBS SIBO subjects and the healthy controls. The amounts of opportunistic pathogens are vastly higher than SIBO. So like our previous slide, should some of these bugs work their way further down the gut, then they can wreak havoc on the lower GI as well. We have to think of the gut as a continuum, not just a stomach, a small intestine, or a large intestine. There were supposed to be checks and balances along the way and although the microbiome is inherently different from one location to another in the healthy gut, bacteria which thrive in one location may be problematic in another. And speaking of locations on this slide, we are comparing the bacteria between the mucosa of the sigmoid colon in the feces and IBS subjects and controls.

Guy Daniels:                      16:21                    If you recall from our first webinar, we covered this topic of mucosal versus fecal microbiome. Here as well, these researchers show that there was essentially no difference in the unprepared mucosal microbiome between the two groups. While fecal microbiome had significant differences. And this is what we do-- it convenient at-home fecal analysis which provides accurate results from appropriate analysis and customized recommendation. So let's now take a look when we probably put all this to use.

Guy Daniels:                      16:52                    In 2018 we conducted a comprehensive IBS trial, which included a questionnaire, dietary restriction, DNA and microbiome analysis, and a customized supplement regimen. Not including the healthy controls and IBD subjects, we had 68 active subjects who enrolled with either an IBS diagnosis or the symptoms. As for some background data, 36 (53%) reported 10 or more rounds of antibiotic use and their life. 30 subjects (44%) reported anxiety and or depression, which is very common in dysbiosis, but only five reported SSRI use. Only four reported H2 or PPI use and only two had the gallbladder removed. We had a number of other exclusion criteria. The point being is that this group as a whole could attribute their GI distress most likely to dysbiosis alone.

Guy Daniels:                      17:45                    In the end, we were able to analyze the microbiome and questionnaire on day zero and day 30 for 36 subjects. I'll share with you a couple of findings. On this slide, our analysis showed us that the subjects experienced significant improvement in diarrhea, constipation, and bloating after the 30 days of personalized supplement use. Other measures, although they appear to be trending in the right direction, we're not of statistical significance. And not shown here, there were significant changes in the microbiomes of these subjects driven by their personalized regimens. You can see from this slide as we have cut the data by product usage. We see that, for example, when we look at just constipation, it was impacted favorably the most by larger arabinogalactans, and also by a proprietary blend of ingredients, which includes partially hydrolyzed guar gum, glutamine, aloe, curcumin, and Boswellia.

Guy Daniels:                      18:40                    So we're able to create ongoing data points, connecting supplement use, microbiome changes in symptoms among other considerations running in the background. We have also just completed our own internal meta-analysis on all available original research articles in IBS which contained microbiome analysis. What we're looking at here are either positive or negative associations with IBS, diarrhea, or constipation. Each species may have one or more mechanisms connecting it to a particular association. These can be related to their proteins, their byproducts, or in the environment in which they thrive. So if a particular species has a negative association, it may itself not be directly pathogenic. It may just thrive in that environment, which makes it a challenge and requires multiple analyses to provide data points of value. We included a total of 41 papers, far more than any meta-analysis before us. What we found were mostly confirmations, but also a surprise or two. I'll briefly share with you the major findings now and keep in mind that we'll be dedicating entire webinars to these very important taxa.

Guy Daniels:                      19:50                    Bifidobacteria. I think we're all quite familiar with this genus. From nine different data points, eight were positive, once again, reconfirming that this genus is universally beneficial. Methanobacteria. These are actually from the domain archaea, and our results are a confirmation to us, but maybe news to you. That although often beneficial in the case of IBS, it would be best to minimize their presence and constipation and maximize them in diarrhea. Proteobacteria. From 12 data points, the 11 negative associations reconfirm our findings that these opportunistic pathogens, more specifically it's class gammaproteobacteria, should be minimized in IBS. And as you'll find in many other conditions. Faecalibacterium Prausnitzii. Yes, that's quite the name, which from now on will be referred to as simply F prausnitzii. And if you're at all familiar with the microbiome, you'll know that this species is a superstar. And from the seven data points we collected, all were positive associations. Lactobacillus. So here's the genus with which you are familiar as its species, lactobacillus acidophilus. What may be surprising to you is that of the 10 data points, six were negative associations. Now, these results are the genus level, so consider that some species may be better for constipation, while others may be better for diarrhea, while others may have little value. Also, the lactate production from this genus taken as a whole may be detrimental under certain conditions in IBS.

Guy Daniels:                      21:22                    So the point is that just providing random probiotics to IBS patients may not be the best idea. After these first three Webinars, I hope you're starting to get an understanding of what we're looking at, where we're coming from, and how comprehensive this platform is. Today, we've reviewed IBS basics, went through some dietary considerations, discussed tax specific data, and briefly covered our IBS study. From here, we'll cover a variety of other topics related to the gut microbiome, some with which you may be familiar, many of which will be new to you. These are all a part of the extreme number of data points entered into the Onegevity platform. Our next Webinar will be on IBS's more sinister cousin, IBD, which encompasses essentially Crohn's disease and ulcerative colitis. So until then.