Does Blastocystis Hominis Need to be Treated?

Episode Intro :

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DrMichaelRuscio:

Hey, everyone. Welcome back to Dr. Ruscio Radio. This is Dr. Ruscio. Let’s go into Blastocystis hominis (blasto). This is an intestinal organism – a protozoa – that has a debatable impact on a human, their individual microbiome, and symptoms. The backstory here is that in naturopathic, integrative and alternative medicine, a lot was assigned to the importance of parasites and that’s partially true. In fact, I am a shining case study of someone who showed up to a few doctor’s offices with non-digestive symptoms – brain fog, fatigue, insomnia, depression – and actually ended up having an intestinal parasite (Entamoeba histolytica – a very pathogenic organism) as the underlying cause. It was defined and identified by the gold standard (or at least what was the gold standard) of antigen recognition (or seeing it under a microscope.) This is something that I would say is partially near and dear to my heart.

DrMR:

However, as I went through my training in my early years – when I did every educational course and seminar on anything in integrative and functional medicine, but especially gut health care – I started to see a very non-nuanced perspective being presented regarding these organisms. Every organism was pathogenic. Even the ones that weren’t traditionally recognized as being pathogenic, but were cousins to pathogenic organisms, were also pathogenic. Anytime there was any finding on a stool test, the perspective was, “Well, go in guns a-blazing with antimicrobial therapy, whether that be herbal or antibiotic.” The point I want to make at the beginning – I think it’s a really important lead we don’t want to bury – is there is a growing body of evidence showing this is the incorrect paradigm and may actually potentially do more harm than it could good.

Blastocystis hominis

DrMR:

Blastocystis hominis is such a good example because it is this gray area organism. Hopefully you’ve heard my perspective on this – amongst others – which is that the thinking has evolved. Blastocystis hominis probably should not be classified as a true pathogen. It may cause symptoms in some, but not in all. This is really important to keep in mind because what I would like to prevent someone from doing is thinking, “Oh, I had this come back positive on my labs… labs, labs, labs, labs labs, and I’ve got to hit this hard.” While there is some signal – and we’ll go into all the details here in a moment – that treatment can be helpful, there’s also data showing no association between blasto and symptoms… and other data showing no association between treatment and improvement. Why that’s important is there’s this dividing line forming in functional medicine. The two sides are treat the labs, and the other side is treat the individual.

DrMR:

The camp I embody, which is treating the individual, accenting your care, partially guiding your care with labs, but understanding that labs are not the end all be all. Just to reiterate this one more time – I think it can never be said enough – when you actually fact check many of the labs in functional medicine, what you find is (just to give you a rough approximation) that over half are not accurate and not validated. So, even though it’s very appealing on the surface, “Ooh, this lab marker… I’m not feeling well… I’m looking for answers… here’s something… Blastocystis hominis (as an example) is coming back positive… this must be why I’m having non-responsive fatigue, non-responsive insomnia, non-responsive brain fog…” What’s really unfortunate is that’s a highly spurious finding or way of thinking, meaning it’s appealing on its face, but it’s not actually true.

The Over-Reliance on Lab Testing

DrMR:

What this can do is lead someone down this wild goose chase of continually treating labs and not seeing response. So, let’s go into the details here on blasto. Again, the high level interpretation here would be – there is some association, although it’s not very high, between blasto and symptoms… and some association between treatment and improvement. What that would mean is finding blasto on a lab would be a finding I would consider somewhat inconsequential, and it would be one of the last things I would worry about. In fact, it would probably have little to no bearing on how we navigated the gut health algorithm because addressing low level imbalances like this is already codified into the algorithm. Just one other remark I’d like to make – As the clinic is growing, there are a couple things I’m learning. Sorry if this is a bit off the topic, but I think this is really important for both patients and providers to understand. One of the things we’re finding that we are challenged by and confronted with at the clinic is some of the educated patients we work with sometimes feel the care is not personalized.

DrMR:

Now, I think I’ve mentioned before that I’ve been taking steps to create educational materials, to help people understand the immense amount of data analysis and heavy lifting that we’re doing on the backend. I think part of the reason why we’re confronting this educational hurdle is because people can come from a paradigm that’s so lab heavy. People may feel good about having labs done. Then, personalized care – meaning the lab results – are being treated. However, and this is the key point – If those labs are not valid, you might as well just throw your money at the wall or burn it because care that looks personalized, but is based upon fallacious lab markers is not going to help you. It’s kind of like junk food. It tastes good, but it’s actually not good for you. So, I want to weave that into this conversation because blasto was one of these examples that someone may say, “Well, why aren’t we treating the blasto?”

DrMR:

As I’ll share with you in a moment here, one study even found that Flagyl (or metronidazole – quite a strong antibiotic) was less successful in treating blasto than Saccharomyces boulardii, which is exactly how we codify (or organize) those treatments in our hierarchy. Probiotic therapies – namely triple therapy – comes before herbal antimicrobials, which comes before antibiotics. Healthcare educators need to do a better job in getting patients to understand that even though this promise of highly personalized care (based upon labs) sounds good, and seems to be highly marketable, in many cases, it’s actually not what’s best for the individual. The underlying validity of those labs is questionable. Now, blasto is something where there’s some evidence, right? Again, I would say this would be a very minimally impactful finding.

DrMR:

The summary here regarding the association to blasto and symptoms (most namely the symptoms that have been looked at as IBS) are studies are mixed as to whether Blastocystis hominis is associated with IBS. If there is an association, it’s modest at best. Blasto may be more associated with a diarrheal type of IBS, than the constipative type. It’s also possible that blasto may be considered more of a dysbiotic finding than really a pathogenic finding.

Response to Treatment

DrMR:

Regarding response to treatment, there’s one point of context here. When a various treatment is administered Flagyl in one study and Rifaximin in another, it’s hard to say the only impact is the blasto. Are we maybe addressing SIBO? Anther dysbiosis? So, it’s possible that we’re seeing a non-specific impact that also improves the health of the individual. That’s one of these challenges with many of these antibiotics – or even probiotics or herbal antimicrobials. They’re not incredibly narrow in scope. They’re not going to just impact this one organism.

DrMR:

So, if someone uses a treatment of various antimicrobial type and they see improvement, it’s a little bit more challenging to fully associate that to eradication of blasto. Some studies have looked at this, but I just want to give that context, in terms of one of the challenges with trying to associate treatment to improvement and how that maps onto eradication. One other point of context, and this might be going a little bit deep, but much of the testing has used the more traditional stool testing. One could argue, “Well, wouldn’t these results be different and shouldn’t we update this narrative based upon using the PCR testing?” I actually don’t think that’s the case because the stool tests are going to show you the more overt cases. This is contestable, but the stool testing is usually only going to be positive when someone’s fairly positive – fairly high degree.

DrMR:

One might be able to argue that we’re going to be seeing the worst of the worst cases and therefore the signal here should be strong. Again, contestable, and I’d be open to amending any conclusion on additional data looking at PCR testing or DNA testing. There is one study we’ll talk about in a moment that does use DNA, but the majority do not. Just as further context, most contemporary stool testing is moving away from the more traditional stool tests that either use culture, antigen or microscope recognition toward this DNA-based methodology or this PCR technique.

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DrMR:

Regarding response to treatment, clinical response to Blastocystis hominis eradication is sometimes associated with eradication, but not always. Another point here – One study comparing Flagyl (aka metronidazole) to Saccharomyces boulardii found better resolution of symptoms using the probiotics. Another study found a 77% clearance rate using oil of oregano. It’s important to underscore both of these because sometimes patients think more is better… stronger is better… pharmaceutical is better, and there are certainly maybe a time or a place. However, especially as this one study with the Saccharomyces boulardii supports — knocking around the intestinal bacteria and microbiota harder isn’t always better. In fact, I would argue the more subtle approach is probably the best way to go. You build your way up to these stronger interventions. Two things happen there.

DrMR:

1 – You can select out for the need for the stronger ones if you see resolution with an earlier, milder therapeutic and 2- As you maneuver through these various interventions, you’re going to see improvements in one’s gut health and ostensibly, you’re going to see better response. Let’s say, you get someone sleeping, get someone on probiotics, get them on a diet that seems to be the right fit for their gut. Now there’s less inflammation, less leaky gut, tissues are healing and the immune system in the gut is likely stronger. So, now you’re in a more leveraged position for other subsequent therapies. This is what’s known as a bottoms up approach. There are two approaches in conventional medicine – top down… bottom up. Bottom up is starting with one therapy and stacking additional therapies on top. Top down is doing everything and trying to whittle your way down. So, the bottom up approach, I think, is much more justifiable in most realms of GI.

DrMR:

Treatment of Blastocystis hominis – regardless of eradication success – is modestly associated with improved outcomes, especially in those with diarrhea. The true prevalence of blasto might be blurred since most studies are using microscopy, which is lower in sensitivity as compared to the PCR. One other note here – Dientamoeba fragilis (a cousin that is proclaimed to hang out with Entamoeba histolytica) is often proclaimed to be a parasite. I always cringe when someone comes in with a stool test that’s totally unremarked/totally clean other than this Dientamoeba fragilis and they say, “Well, I’ve got a parasite and I’ve been trying to get rid of this defrag.” Knowing from the many reviews I’ve done, this doesn’t pop up as a pathogen. It’s a red herring that unfortunately can lead someone down a chase of the wrong organism or in the wrong direction. This is just one more data point that came up on defrag. The prevalence of Blastocystis hominis is 5% in industrialized countries and 30% – 60% in non-westernized countries. So, it’s not highly prevalent. There is a notable preference there, but it’s not something that you’re going to see a lot of. Now, what I’d like to do is go into a quick snapshot overview of the main evidence points or studies that reinforce those conclusions.

Main Evidence Points & Studies: Blastocystis hominis

DrMR:

One study was a systematic review and meta-analysis (probably the best data point we were able to find) looking at 5,900 patients. There was no association with Dientamoeba fragilis, but there was an association to IBS symptoms and having Blastocystis hominis. There is an association. This was reported as an odds ratio of 2.19. So, not very high – a moderate association, but an association. In another study, the prevalence of blasto was 33%, and in healthy controls, it was 12%. There’s about a doubling of the prevalence when you go from healthy controls – 12% of healthy people are walking around with blasto. I need to be careful with that wording. This might be a normal resident for them as non-problematic, whereas in 33% of IBS patients, it’s present.

DrMR:

So again, some signal there. There was another study looking at the prevalence of blasto in 616 Italian individuals and 16% had blasto. What was interesting here — Of those with blasto, a quarter of them also had another organism like Giardia or cryptosporidium. That muddles the finding a little bit, but again, some association there. An Egyptian study of 120 individuals found that 45% of those with IBS had blasto and 10% of healthy controls had blasto. Another study in 100 healthy controls and 100 IBS patients, found 26% of those with IBS had blasto and 9% of controls had blasto. Yet, in another study of 100 people, it was found that 15% had blasto and 16% of the healthy controls had blasto. So, an overlapping kind of prevalence there. Looking further, another study of about 500 adolescents in Indonesia found that 30% of IBS individuals had blasto. So again, we are seeing an association. One more study that looked at about 100 hundred Egyptian individuals found that blasto had a prevalence of about 16% in those with irritable bowel syndrome. If all we were trying to do was convince you about how pathogenic or harmful blasto was, we would put a period there in the conversation. However, as you’re probably accustomed to, we look for data both reinforcing and contradicting any hypothesis. So, let’s go into the data that found no correlation between blasto and IBS.

DrMR:

In a Danish cohort of roughly 100 patients with IBS, 100 patients with functional GI disorders and about 200 healthy controls looking at Blastocystis hominis, 18% of those with Blastocystis hominis had IBS, but 27% of healthy controls had Blastocystis hominis. So, we’re seeing a higher prevalence of blasto in this study in the healthy control group. In another study, looking at 37 IBS patients in Chile, there was no association found between blasto and IBS. Continuing to another smaller study that looked at 36 IBS patients and 36 healthy controls, there was no difference between the prevalence of blasto in the IBS group (19% had blasto) as compared to blasto healthy controls (36% had blasto). Another study looked at 122 IBS patients and 122 healthy controls in Iran found no difference in Blastocystis hominis individuals who had IBS versus controls who had IBS: 19% to 17%. So, take a group of people who all have blasto – 19% had IBS and 17% were perfectly healthy. So, this is all making the argument that when an individual is not feeling well and they have blasto, we shouldn’t jump too quickly to treat that with strong antimicrobial therapy, right? There are these data points reinforcing the other side of the story, which is being more bridled, and thinking about other ways to improve that person’s health; not just hammering on the nail of antimicrobial therapy. In another narrative review, they looked at a few different studies. One here I just want to point out is where they found a higher prevalence of blasto in the healthy controls than there was in the IBS patients.

DrMR:

If that’s a little bit detailed, I apologize, but essentially what I’m trying to point out is there are a number of studies showing association, and there are a number of studies showing no association. I think this sometimes is challenging for patients, although I really have to give patients credit. It does seem over the past couple of years – and I’d like to think it’s at least in part to the discussions we’ve been having on the podcast – patients are coming in with a more nuanced view, and they’re not thinking so dichotomously… so black and white… regarding findings on the stool test. This is information that both patients and doctors need to be armed with. The most important application is a person who is not feeling well and looking for answers.

DrMR:

It’s quite critical to not just treat lab markers. There are other things that can be done that don’t have lab markers to substantiate their use – probiotics, as an example. To my knowledge, there is not one (or perhaps there is one and I’ve missed it), but having had read studies on probiotics until my eyes have bled, I know of no good data that shows a stool finding will predict what probiotics someone will benefit from. There is no evidence for showing when to use elemental diets. There’s no lab marker. We know people with IBS, a lot of people with IBD (because there are many studies there) and one study in SIBO shows people can improve, but there is no lab marker that tells you, “You should use an elemental diet.” There’s no lab marker for immunoglobulins. So, it’s really important to keep this in mind.

DrMR:

So, going over to treatment data. In about 100 patients who had Nitazoxanide – which is an antibiotic that can treat protozoa – what was documented here was a clinical response in 86% of the treatment group and about 40% of the placebo group. So, definitely something there. In another study looking at roughly 600 Italians, there was a breakdown to either Flagyl or placebo, and an elimination of symptoms was seen in 88% of the Flagyl group and only in 14% of the placebo group. That correlated fairly closely with eradication. In the Flagyl group, 88% saw a resolution of their symptoms, and there was also an 80% reduction rate. Now, interestingly in the placebo group, 14% saw a resolution of their symptoms, but there was only a 3% eradication rate. So, it speaks to the power of placebo. Interestingly, at six months, they followed up again. In the Flagyl group (or metronidazole, the antibiotic), 75% were still asymptomatic, but only 48% maintained eradication. This belies part of my rationale for the hypothesis, for the statement, that the antibiotics may be doing things other than eradicating the blasto.

DrMR:

This is one of the posits I propose in ‘Healthy Gut, Healthy You,’ which is the antimicrobial as a general class of treatment may nudge the microbiota. Especially if you have healthy inputs present – proper diet, proper lifestyle probiotics, what have you – that’s going to encourage a resetting to a healthy equilibrium. Perhaps that’s what is happening here, where you’re still seeing almost 80% of the individuals having no symptoms, but there was a drop off of about half of the individuals from having “cleared blasto” to now finding it. It may not just be the eradication of the blasto that we’re after. This may be doing things that we still can’t fully quantify. There’s a thousand some odd bacteria in the gut. There are, I believe, 200 some odd fungi. There is a number of protozoa and also viruses, which likely are influenced by these other populations.

DrMR:

At the end of treatment, 14% of the placebo group saw a reduction or a resolution of their symptoms. Six months later that went up to 33% of people, pre post 3% in the placebo group had eradication and now 14% had eradication at a six month follow up in the placebo group. The more we look at data like this, the more challenging it is to make really definitive proclamations. This is another reason why I say that one should be careful with any kind of healthcare provider or educator who seems to be very confident and very convinced. In many cases, we just don’t have data that supports that level of confidence, as I’m hoping this one study in particular supports and showcases. Another study looked at chronic abdominal pain in children – 138 patients with Blastocystis hominis and functional abdominal pain.

DrMR:

73% received antimicrobial treatment, which I believe was herbal. 69% saw an improvement in symptoms. Whereas, 37% did not receive any treatment. Of those who did not receive treatment, 35% improved their symptoms. So, another reason why we shouldn’t be too quick to act because more than 1/3 of these patients improved with no therapy. Now, yes, more patients did respond who had therapy, but this may be another justification point for why we intervene minimally – let’s say probiotics initially for a child with abdominal pain and then re-evaluating and considering the escalation to antimicrobial therapy. This is why the real hierarchial – or algorithmic thinking – has so much more merit, even though sometimes patients may feel that a lab value is being ignored or the treatment isn’t being personalized. I think this is what the next generation of functional medicine providers have to contend with from a messaging perspective. The labs are not the primary driver of the decisions we make.

Paradigm Shift: Therapeutics

DrMR:

We want to use this large body of evidence that tells us who responds to what therapy when, and a lot of that is not guided by labs. This is where we need to have a bit of a paradigm shift. Continuing on to this other study that’s quite exciting and really supports the way that we organize therapeutics… this is looking at 48 children with blasto who also had symptoms. Saccharomyces boulardii was given in one group… Flagyl (aka metronidozole) in another… and no treatment in a third. After 10 days of treatment, in 77% of those who took Saccharomyces boulardii, there was a resolution of symptoms. In 67% of the Flagyl group, there was a resolution of symptoms. In 40% of the no treatment group, there was a resolution of symptoms. What’s equally interesting here is there was also a higher eradication rate using the Saccharomyces boulardii: 80% as compared to 72% in the Flagyl group. So, more evidence for these minimally invasive therapies that can be quite effective.

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DrMR:

Another study – a systematic review of the efficacy of metronidazole (aka Flagyl) on blasto – found that 80% had a clinical response, but only 49% had eradication. So, more evidence that shows there’s not this direct correlation between eradication and symptom response. Another study found a 77% eradication rate when using oil of oregano. 7 of these 8 patients also had improved symptoms, but there’s also data showing no correlation between treatment and IBS. This is a bit harder to pull because it’s a smaller study, but I think also worth mentioning. 10 patients with IBS and blasto received 14 days of triple antibiotic therapy, and they did stool tests at baseline 15 days and at four weeks. After 14 days, there was a 60% eradication rate, but there was not a corresponding improvement in symptoms. While there was symptomatic improvement demonstrated, it didn’t correlate with eradication. The signal here – zooming way out – seems to be stronger for symptomatic response to treatment, but it does break down a little bit when you’re trying to correlate treatment to eradication.

Episode Wrap-Up

DrMR:

The three main signals are the association between IBS and blasto; response to treatment with antimicrobials or probiotics; correlation between eradication and symptomatic improvement. The strongest signal is that any treatment – any antimicrobial or probiotic treatment – seems to improve symptoms. Per my rough eyeballing of the trend, if you will, the second strongest association is likely to the association and the third strongest association may be between eradication and improvement of symptoms. I think this should really tell us that blasto can be a problem, but it would be an overreach to call it a parasite, and it would definitely be an overreach to say it’s a problem for all people. It would also be a vast overreach to say it needs to be eradicated in all people.

DrMR:

Do people benefit from treatment? Yes. Is that specific? No. Does treatment response correlate with eradication? No. I think there’s more data showing it does not correlate than it does. Remember, part of what might be happening is other things changing in the GI that underlie where that symptomatic improvement is coming from. Also, there is some fairly impressive data that shows equivalence or better outcomes using probiotics or herbal therapies – that Chinese blend or oil of oregano. This all perfectly correlates with the way that we algorithmically apply these therapeutics in the clinic. I hope that’s reassuring because if we’re doing things right in the clinic, when we go through a review, what we’re doing in the clinic should be reinforced by that review. If we’re ever not doing things right in the clinic, myself (and no one at the clinic) are too proud to not immediately update what we’re doing to correspond to whatever the data are showing.

DrMR:

Hopefully that was helpful in terms of explaining some of the nuance regarding Blastocystis hominis. I very much hope this allows to update from the paradigm that blasto was a parasite and always needs to be treated. Even further, some will say that if you have blasto, we should test everyone in the family. If anyone has it, the whole family needs to go on antibiotics or antimicrobials. I think that’s really an overreach. We want to thread that needle of being progressive, using these labs to help people, but not being reckless or overstating the case, which can harm people. Now, one other coming review I want to just make you aware of is regarding micronutrient testing. I’ve been talking about this for a while. We finally had the time to go through a review of this evidence and it is something that we’ll go through in a future podcast.

DrMR:

I just want to kind of foreshadow by saying – thankfully again – what the review of the evidence found, correlates with how we are practicing in the clinic. That was also reassuring to me in terms of making a good choice before we had the luxury of going through the full, robust review. More to follow on that. Hopefully this discussion on blasto was helpful. I want to briefly tie that back to one of the case studies we talked about a few weeks ago. One of Robert Abbott’s patients was very insistent on treating blasto with antimicrobials and antibiotics. It’s always cases like that where people come in convinced and educated into thinking that blasto is not what it really is that motivate me to hopefully do a good job in these discussions so that patients and providers alike have a better understanding of, “Okay, this is flagged positive on the lab. What does that mean?” I know, especially when you’re not feeling well, a lab finding can be scary. So, there you have the overview of blasto, what that means, how we should be thinking about that and the responsible balance to navigate with how you approach this. I hope that helps, and I will talk to you guys next time. Thanks.

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