The complete guide to soil-based probiotics

 BY LUCY MAILING, MD/PHD STUDENT

Soil-based probiotics have been touted for their ability to improve digestion, stimulate the immune system, and help maintain a healthy gut microbiota. On the other hand, some people believe that SBOs should be avoided at all costs, due to their spore-forming nature and ability to compete with resident gut microbes. So, should you be taking soil-based probiotics? If so, which formula or brand is best? Read on to find out.

Until recently, I recommended Prescript Assist as the best soil-based probiotic. While some of the microbes in the old probiotic formula were not well-studied, Prescript Assist had been used in several clinical trials with excellent results and no reported adverse events.1,2 It was also well tolerated, even by those with SIBO, severe gut dysbiosis, or other gut pathologies.

In late 2017, the manufacturer made major changes to the ingredients of Prescript Assist, so it is no longer using the formulation that was studied in clinical trials. While the original formula contained 29 different strains, the new formula contains 28 strains, only 9 of which are from the original formula. There’s very limited evidence for most of the strains included in the new formula.

I’ve been asked by many people what my new recommended alternative to Prescript Assist is, so I decided to do some digging. This guide is a result of 50+ hours of independent research on soil-based organisms and the products commercially available today.

First, though, I’ll review what soil-based organisms are, the controversy, and the evidence for the most commonly used strains.

What are soil-based organisms?

The term soil-based organism (SBO) encompasses over 100 different species of microbes naturally found in soil. Some of these have been isolated and adapted for use as probiotics. Most SBO used in soil-based probiotics are spore-forming. This means that when they replicate, they form a small spore that is protected by a hard coating, making them resistant to heat, acid, and most antibiotics. This also means that they are more likely to survive the upper gastrointestinal tract and reach the large intestine compared to other commonly used probiotic strains.

The controversy and the evidence

There is currently a lot of debate within health circles about the safety of SBOs. Advocates claim that they are probiotics that normalize bowel function, aid in digestion, beneficially stimulate the immune system, and help re-seed the gut microbiota. They also praise SBOs for their ability to resist stomach acid and the lack of need for refrigeration.

On the other hand, opponents of SBOs argue that because of their spore-forming nature, they proliferate rapidly, and may compete with our resident gut microbes, rather than helping to bring the gut microbiota back to normalcy. In some individuals, opportunistic SBOs could overgrow, with the potential to become pathogenic.

My take: Several individual SBO strains have been shown to be beneficial, with no adverse effects, in dozens of randomized, placebo-controlled, human clinical trials. However, other strains have very limited or no clinical evidence and may be able to cause infection in people with a compromised immune system.

Rather than labeling all SBOs as good or bad, I think we need a more nuanced discussion – one that considers the evidence for each particular strain, microbe, and formula. That’s what I’ll try to provide in the next few sections. If you just want to see my recommendations, feel free to skip down to the “Conclusions” section at the end.

Common soil-based species used in probiotics:

Before I do an analysis of the soil-based probiotic formulations on the market, it’s important to understand which species are most commonly used.

I searched PubMed and Google Scholar for every available human clinical trial on the seven most commonly used soil-based microbes:

Bacillus coagulans

Bacillus subtilis

Bacillus clausii

Bacillus indicus

Bacillus licheniformis

Enterococcus faecium

Clostridium butyricum

Before I share my findings below, it’s important to note that microbes are denoted by their genus, species, and strain. The list above provides the genus and species but does not tell you anything about the strain. Strain is incredibly important since two strains of the same species can have very different characteristics.3 Unfortunately, most probiotic formulations do not provide information about which strains they contain.

To see my full analysis of the available clinical trial literature for each strain, click here to download my Excel spreadsheet. For just the key findings, read on:

Bacillus coagulans

Bacillus coagulans is a gram-positive bacterium that produces L-lactic acid and, as a result, was formerly misclassified as Lactobacillus sporogenes. It exhibits many characteristics typical of the Lactobacillaceae family, but unlike most lactic acid bacteria, B. coagulans can form spores.

There are three strains of B. coagulans that have been heavily studied:

GBI-30, 6086 (“Ganeden BC30”): with over 8 human randomized, placebo-controlled trials, this is one of the most well-studied Bacillus strains. GBI-30, 6086 has been shown to improve IBS,4–6 immune function,7,8 and beneficially modulate the gut microbiota.9,10 In cell culture experiments, this strain has been shown to stimulate production of anti-inflammatory cytokines and regenerative markers.11

Unique IS-2 (“ProDURA”): three human clinical trials have found this strain to be efficacious for bacterial vaginosis12 and children with IBS.13,14 Cell culture studies have also found that it inhibits the proliferation of cancer cells.15

MTCC 5856 (“LactoSpore”): two randomized controlled trials showed that MTCC 5856 significantly reduced bloating, abdominal pain, and depressive symptoms in IBS patients.16,17

Verdict: These three strains of Bacillus coagulans appear to be safe, well-tolerated, and may be especially beneficial for those with IBS.

Bacillus subtilis

Bacillus subtilis is recognized as a normal inhabitant of the human gut.18 Even before the introduction of antibiotics, cultures of B. subtilis were popularly used worldwide as an immune stimulant to aid in the treatment of urinary tract and gastrointestinal disease.19,20

B. subtilis produces an enzyme that can degrade oxalate, which may be particularly helpful for people with hyperoxaluria,21 and may also produce small amounts of Vitamin K-2. B. subtilis is found naturally in natto, a traditional Japanese food made from fermented soybeans.

Only four strains of B. subtilis have been studied in humans:

DE111: two placebo-controlled RCTs of Division 1 athletes during off-season training found that B. subtilis DE111 was well tolerated. Female athletes saw greater reductions in body fat percentage; male athletes saw reduced blood TNFalpha, a marker of inflammation. There were no effects on physical performance.22,23 Another study found that DE111 improved bowel irregularity in otherwise healthy adults.24

CU1 (“LifeinU”): one placebo-controlled RCT found that ten-day supplementation with B. subtilis CU1 was well tolerated and improved immune function (fecal and salivary sIgA) in elderly adults.25 It does not exhibit any antibiotic resistance and was shown to be absent of toxigenic activity in vitro.26

R0179: one study found B. subtilis R0179 to be well tolerated in healthy adults at a dose of 1 or 10 billion CFU per day, and confirmed that it survived passage through the GI tract.27

IP 5832: one Croatian study found that B. subtilis IP 5832 given during parenteral rehydration therapy for acute nontyphoid Salmonella gastroenteritis reduced patient-weeks of carrier state and resulted in fewer positive stool cultures at week four.28

Several studies for which I could not find strain information also showed benefits from B. subtilis: One Chinese study found that B. subtilis plus lactulose was more effective at treating functional constipation than lactulose alone.29 Several other studies found that B. subtilis + Enterococcus faecium reduced IBS-related abdominal pain30,31 and improved bowel preparation for colonoscopy.32

Verdict: Commonly studied strains of B. subtilis appear to be safe, well-tolerated, and with no adverse effects. Some strains appear to be particularly beneficial for improving immune function and bowel regularity.

Bacillus clausii

Bacillus clausii has been studied extensively and used for many years as the Italian pharmaceutical preparation Enterogermina for the treatment of a wide range of gastrointestinal diseases. B. clausii has been shown to have antimicrobial activity against Staphylococcus aureus and Clostridium difficile.

Enterogermina is the only formulation of B. clausii that has been studied in controlled human clinical trials and is made up of four different strains (OC, NR, SIN, and T). These strains have been shown to be acid and bile resistant,33 and can be recovered in stool for up to 12 days after a single administration.34

Enterogermina has found to be particularly beneficial for those with allergies, reducing nasal congestion and the need for anti-histamines.35–37 It has also been shown to reduce side effects during antibiotic treatment for H. pylori.38

One study of 40 SIBO patients found that taking Enterogermina for 1 month resulted in a normalization of glucose breath test result in 47 percent of patients!39 This is astounding and comparable to the rate observed with many antibiotics commonly used for SIBO treatment. Only one patient reported a side effect of constipation.

Verdict: Very well-studied and well-tolerated, with clear efficacy documented in several randomized, placebo-controlled trials. May be particularly beneficial for those with allergies or SIBO. Since beginning this analysis, I have also tried Enterogermina myself and noticed improved tolerance to foods.

Enterogermina can be purchased from international online pharmacies as either capsules or liquid vials. Shipment should not be an issue since B. clausii is extremely heat-stable and does not require refrigeration.

Bacillus indicus:

Bacillus indicus has been touted for its ability to potently stimulate the immune system and produce high levels of carotenoids, vitamins, and quinols.

However, after an exhaustive search of the literature, I could find no scientific studies of Bacillus indicus in humans (with the exception of one study that used a preparation of 5 Bacillus strains – see “MegaSporeBiotic” section below).

Verdict: Currently lacking scientific evidence. This does not necessarily mean that B. indicus is not beneficial – it just means we have little to no evidence to speak to its safety and efficacy in humans.

Bacillus licheniformis

Bacillus licheniformis is commonly used in the fermentation history. Of all soil-based species used in probiotics, B. licheniformis is perhaps the most controversial. According to some reports, B. licheniformis may be an opportunistic pathogen and can cause infection in immunocompromised hosts. However, other reports have concluded that the virulence of B. licheniformis is very low: “In order to achieve an infection, either the number of microorganisms must be very high or the immune status of the host low.”40

The same EPA report further notes: “While there have been cases of acute, self-limited gastroenteritis associated with the isolation of large numbers of this species, a toxic or direct effect on intestinal epithelia has not been demonstrated. It is difficult to ascertain whether the species in these reported cases, which are quite limited in number, actively participated in the infection or were isolated in conjunction with an unidentified pathogen.”40

A literature search only revealed only three human studies of Bacillus licheniformis – two from Russia and one from China – none of which were placebo-controlled. I could not determine which strain was used in any of these studies, and the results were largely unimpressive.

Nonetheless, B. licheniformis is found in many fermented foods traditionally consumed in Korean culture. Certain strains found in these foods have been found to enhance the longevity of worms by upregulating serotonin signaling.41

Verdict: While traditional fermented foods containing B. licheniformis are almost undoubtedly safe, I believe there is currently insufficient evidence to support high-dose supplementation of isolated B. licheniformis. I think it’s best to err on the side of caution and avoid probiotics that contain this species, especially if they can provide no strain information and/or do not regularly test the genetic identity of their strains.

Enterococcus faecium

Enterococcus faecium is a normal resident of the human gut, metabolizing carbohydrates and producing lactic acid as a byproduct. Some strains of E. faecium can be found in traditional fermented foods, such as dadih, an Indonesian fermented buffalo milk.42

However, it can also be pathogenic, causing diseases like neonatal meningitis and endocarditis. Many strains of this bacterium have developed multi-drug antibiotic resistance and virulence factors that allow it to aggregate and form biofilms. In the United States, 80-90 percent of medical device-associated infections can be attributed to antibiotic-resistant E. faecium.43 Thus, there are concerns about its use as a probiotic.

Many different strains have been studied:

M-74: This strain has the most “randomized” clinical trials associated with it, but every single one gave the probiotic in conjunction with 50 micrograms of selenium.44–47 Many probiotics point to these studies to suggest that E. faecium can “reduce cholesterol”, but the lack of a selenium control group means that it’s entirely plausible that the selenium alone was reducing cholesterol levels.

L3: one Russian randomized controlled trial found that this strain of E. faecium reduced the frequency of infectious complications in premature infants on antibiotic therapy, reduced persistence of C. difficile, and increased abundance of Bifidobacterium and Lactobacillus spp.48

IS 27526: one Indonesian randomized, placebo-controlled study found that this strain of E. faecium increased salivary sIgA and weight gain in underweight preschool children.42

WB 2000: one Japanese study found that a combination of E. faecium with fish oil, lactoferrin, and several vitamins and minerals improved clinical symptoms of dry eye.49 However, the effects of probiotic cannot be separated because it was not adequately controlled.

SF68: one Italian randomized crossover study found that cirrhosis patients taking this strain of E. faecium had a greater reduction in blood ammonia than those taking lactulose.50 There was no control group taking neither E. faecium or lactulose.

CRL 183: one study performed in Brazil found that a combination of isoflavone-supplemented soy fermented with E. faecium and Lactobacillus helveticus was better than soy alone at improving total cholesterol, but again, we cannot separate out the effects of E. faecium from L. helveticus and the isoflavone supplementation.51

As mentioned above, several studies found that B. subtilis + E. faecium reduced IBS-related abdominal pain30,31 and improved bowel preparation for colonoscopy,32 but I could not determine which strains were used in these studies.

To make matters more complicated, Streptococcus faecium was reclassified to Enterococcus faecium several years ago. However, Enterococcus faecalis (previously known as Streptococcus faecalis) is an entirely separate organism. Unfortunately, I believe this delineation has been smudged in studies of these organisms.

Verdict: Very few well-designed RCTs have demonstrated the efficacy of E. faecium, and all seem to use different strains. E. faecium also has the potential to acquire multi-drug antibiotic resistance and cause infection. Until more studies can be performed, I would exercise caution with high doses of isolated E. faecium.

Clostridium butyricum

Clostridium butyricum is a natural resident of the human GI tract. It is one of the many important microbes in the gut that ferments dietary fiber and produces the beneficial short-chain-fatty acid butyrate. Butyrate is an important source of energy for colon epithelial cells, helps maintain the gut barrier, has anti-inflammatory effects, and protects against colon cancer.

MIYAIRI 588: This strain of C. butyricum has been used as a probiotic in Asia since as early as 1963. It does not carry any genes encoding any known toxins or virulence factors.

Two randomized controlled trials showed that this strain alone reduces side effects for abdominal symptoms and diarrhea incidence in patients undergoing H. pylori eradication therapy.52,53 Another randomized, placebo-controlled trial in ulcerative colitis patients found that fewer subjects in the group receiving MIYAIRI 588 developed pouchitis, though the effects were not statistically significant, and the placebo given was lactose, which can exacerbate colitis in many people.54

TO-A: this strain of C. butyricum, in combination with E. faecium and B. subtilis, has been heavily used and somewhat well studied as a probiotic in Asia. The combined product is called BIO-THREE and has been shown in randomized controlled trials to reduce postoperative infections in patients undergoing surgery55 and shorten hospital stay for children with acute diarrhea.56

In cell culture studies, C. butyricum TO-A has been shown to reduce expression of TLR4, a gene involved in the inflammatory immune response. One randomized trial of ulcerative colitis patients found lower relapse rates in the group receiving BIO-THREE, but the difference was not statistically significant.57 No changes were observed in SCFA levels with probiotic supplementation.

Several studies for which I could not find any strain information found that C. butyricum reduced the incidence of sepsis and diarrhea in premature infants,58 and improved antigen-specific immunotherapy.59 In animal studies, C. butyricum has been shown to improve intestinal homeostasis and attenuate colitis.60

Verdict: I really like the idea of being able to supplement with isolated C. butyricum. It’s a normal inhabitant of the gut, appears to be safe and well-tolerated in randomized trials, and could help increase butyrate levels in a way that is unlikely to induce toxicity.

Unfortunately, isolated forms of either of the strains listed above are not currently available in the United States, and I haven’t been able to find any international sources that I trust. The only alternative is to use the three-probiotic formulation BIO-THREE, which I’ll discuss more in the next section.

Product analysis

Note: I have no affiliation with any of these companies or products. This is the objective analysis that I used to determine which products I wanted to use for myself and with my clients.

Like all supplements, probiotics are not regulated by any governing agency (FDA, FTC, etc.), so it’s important to do your homework regarding their claims, sourcing, etc. Many companies that sell probiotics use species and strains that lack clinical evidence, make unsubstantiated statements, and cite highly questionable “research”.

In this section, I break down the ingredients, quality, claims, and evidence of the top eight most popular SBO products on the market.

While you might argue that a company’s marketing is less important than its ingredients or strains, I think it’s a key component. If they can’t provide evidence-based claims on their website or even sound remotely scientific, I don’t trust them to be manufacturing a high-quality product that I’m going to take on a daily basis and recommend to my readers and clients.

Probiotic-3 (Advanced Orthomolecular Research)

Soil-based species: Bacillus subtilis TO-A, E. faecium T-100, and C. butyricum TO-A, (also known as BIO-THREE)

Colony-forming units: 19.2 million CFU

Other ingredients: contains lactose, polyvinyl alcohol, and potato starch (may be an issue for many with gut symptoms

What they claim on their website:

“Probiotic-3 is a probiotic formula that has been used clinically for more than 50 years in Japan and across Asia.”

  • Reduces the growth of pathogenic bacteria while promoting the growth of beneficial bacteria
  • Normalizes the inflammatory response, promotes detoxification and supports immunity

They reference several studies of BIO-THREE.61–63

Verdict: Inclusion of E. faecium is questionable, but the formula has shown benefits in several randomized clinical trials. Not recommended for those sensitive to lactose, alcohol, or potato starch.

MegaSporeBiotic (Microbiome Labs)

Soil-based species: B. coagulans SC-208, B. subtilis HU58, B. clausii SC-109, B. indicus HU36, and B. licheniformis

Colony-forming units: 4 billion CFU

What they claim on their website: “MegaSporeBiotic™ is the first 100% spore-based, broad-spectrum probiotic clinically shown to improve leaky gut by 60% in just 30 days. This unique all-spore formula effectively RECONDITIONS the gut by increasing microbial diversity and encouraging the growth of key health-promoting, commensal gut bacteria. MegaSporeBiotic™ boasts a 5-year shelf-life, does not require refrigeration, and maintains efficacy during antibiotic therapy.”

What their single research study actually found: In a “randomized”, placebo-controlled trial, 30 days of supplementation with MegaSporeBiotic reduced endotoxin (a measure of bacterial translocation into the blood) by 42 percent after a high-fat cheese pizza meal, compared to a 36 percent increase in endotoxin in the group receiving placebo. However, the subjects included in the “randomized” trial were really a hand-picked group of endotoxin hyper-responders.64 So yes, MegaSporeBiotic may reduce leaky gut by 60 percent if you are a dietary endotoxin hyper-responder and you happen to eat cheese pizza regularly.

Furthermore, there is NO evidence that this particular formulation increases microbial diversity, promotes health-promoting, commensal gut bacteria, or maintains efficacy during antibiotics.

Verdict: Inclusion of B. licheniformis and B. indicus is questionable, as few studies have been performed on the safety and efficacy of these strains. One clinical trial showed some benefit in hyper-responders, but the findings are heavily exaggerated on their website.

Just Thrive (Microbiome Labs)

Soil-based species: B. coagulans, B. subtilis HU58, B. clausii, B. indicus HU36

Colony-forming units: 3 billion CFU

What they claim on their website:

 “With Just Thrive™ […] the body becomes a super-antioxidant factory right in the digestive system at the site where these important nutrients are most needed and absorbed.”

“Just Thrive® is the only product on the shelf to contain the patented Bacillus Indicus HU36®, a strain that produces high levels of antioxidants.”

What the evidence says:

There is absolutely no evidence to suggest that your gut becomes a “super-antioxidant factory”. In fact, any antioxidants produced by this probiotic are likely negligible if you consume a nutrient-dense diet rich in fruits and vegetables.

Moreover, Just Thrive is not the only product on the shelf to contain Bacillus indicus HU36, since MegaSporeBiotic also contains this strain.

Verdict: Contains B. indicus, which has little clinical evidence. Their website makes some pretty glorified claims that are clearly not backed by any real evidence. Supposedly they have about 10 clinical trials underway, so I’ll be happy to reevaluate Just Thrive when I see the data.

Primal Probiotics (Primal Blueprint):

Soil-based microbes: B. coagulans, B. subtilis, B. clausii (no strain information; quality assurance team said it was proprietary information)

Other probiotics: B. bifidus, L. plantarum, S. boulardii

Colony-forming units: 5 billion CFU soil-based, 5 billion CFU other probiotics

Other ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide, and 50 mg potato starch. Potato starch may be an issue for some people with gut issues. Resistant starch deserves an article on its own, but for now, I’ll say that I do not recommend supplementing with raw potato starch if you have gut dysbiosis, intestinal permeability, or autoimmunity.

What they claim on their website:

Like every probiotic, they make some lofty claims, such as:

A simple daily dose of Primal Probiotics can help rebalance and restore gut health and improve immune function*”.

However, they are careful to note that:

“* There is no guarantee of specific results and results can vary from person to person.”

Verdict: A good mix of species with high CFU count but no strain information. No supporting clinical evidence for this formula, and not suitable for those who can’t tolerate potato starch.

Biospora (Klaire Labs):

Soil-based species: B. coagulans, B. subtilis (no strain information; no response to my inquiry)

Colony-forming units: 2 billion CFU

Other ingredients: coconut oil powder

What they claim on their website:

“BioSpora™ is recommended for enhanced support of normal GI and immune function. […] Each lot of Bacillus species used in BioSpora™ undergoes independent DNA testing using 16S ribosomal RNA sequencing to verify genetic identity.”

What the science really says:

You can’t verify genetic identity with 16S rRNA gene sequencing at anything below the genus level – only occasionally can you get to the species level with this type of sequencing. So, the only thing they are “verifying” is that each lot has some form of Bacillus.

Verdict: Contains only well-studied species. Website claims are largely scientific, but their genetic identity verification is highly questionable. No studies on this formulation have been done and no strain information is provided. However, Klaire Labs is NSF certified, which means their products do undergo independent testing.

Proflora 4R (Bio-Botanical Research):

Soil-based species: B. coagulans, B. subtilis HU58, B. clausii (no response to my inquiry about strains)

Colony-forming units: 3 billion CFU cells

Other ingredients: 100mg quercetin, 100mg marshmallow root, and aloe vera extract

What they claim on their website: “Proflora 4R replaces beneficial flora: Evidence suggests that the increase of inflammatory gastrointestinal (GI) disorders and intestinal permeability may, in part, be attributed to a under-consumption of these vital spore-producing flora. The combination of Quercetin, Marshmallow Root, and Aloe Vera extract in Proflora 4R™ provide additional nutritional support for “leaky gut” and a healthy microbial balance, with just one capsule a day.”

Verdict: Contains a good selection of species, but strains are not provided or have not been studied in human clinical trials. Website claims are largely scientific, and the addition of quercetin, marshmallow root, and aloe may help soothe a damaged gut.

TOP CHOICE: RightBiotics RX (RealDose Nutrition)

Soil-based species: B. subtilis DE111, Bacillus coagulans Lactospore (MTCC 5856) (both clinically validated strains!)

Colony-forming units: 5.36 billion CFU soil-based organisms, 15 billion CFU other

Other probiotics: B. lactis B1-04, B. longum BB536, L. helveticus Lafti L10, L. gasseri Lg-36, L. acidophilus DDS-1, L. plantarum Lp-115, Gnosis® S. boulardii  (also all clinically validated strains) *Despite inclusion of Lactobacillus strains, this product should not cause histamine issues.

Other ingredients: vegetable capsule, organic rice bran extract, organic rice hull concentrate.

Allergens:RightBiotics Rx includes one probiotic strain (L. helveticus LAFTI® L10) that contains a trace amount of soy from the culture media and may contain a trace amount of milk (including lactose) as it is sourced from dairy, according to the product’s Allergen Statement. For this reason, the label includes a caution statement for people with soy or milk allergy.”

Website claims: “Like people, no two probiotic strains are exactly alike. Each has a unique genetic makeup that determines its special health benefits. Verifying the strain ID ensures the formula delivers the unique strains shown in clinical research to deliver health benefits.”

Manufactured in the USA and third-party lab tested for potency and purity: Our 3rd party laboratory is Atlas Bioscience Labs in Tucson, AZ. Atlas is DEA registered, and members of several industry-wide organizations including AOAC (Association of Official Analytical Chemists), and currently undergoing accreditation with ACLASS for ISO:17025 certification. We send every batch of product to Atlas Bioscience to test for active ingredients, as well as heavy metals, residual solvents, organochlorides, organophosphates and microbiology.”

Verdict: This is by far the best probiotic supplement I have seen on the market to date. I currently have NO affiliation with RightBiotics RX but am excited to have finally come across a product that is so well-supported by the evidence, independently tested, etc. I had not even heard of RealDose Nutrition before conducting this independent analysis, but if I continue to find success with this product with my clients, I may discuss affiliate options with RealDose Nutrition so that I can offer a discounted rate to my readers and clients.

For now, you can purchase it on their website or on Amazon.

Conclusion

To sum up, soil-based organisms are quite well studied and have been shown in randomized clinical trials to be efficacious for a wide range of conditions. However, I strongly advise choosing products that use high-quality manufacturing techniques and clinically-tested strains.

Currently, I am primarily using both Enterogermina and RightBiotics RX for myself and with my clients. I may occasionally try Probiotic-3 (BIO-THREE) in patients with low Clostridia or butyrate production. This is certainly subject to change, as more studies are available on particular species, strains, and formulas.

Note that every person will respond differently to probiotics. Response will depend on which probiotic you take, the dosage, which microbes you already have in your gut, and the health of your gut and immune system. This is part of the reason I recommend gut testing or working with someone with expertise in rebalancing the gut microbiota.

It’s possible that in some severe cases, we should look to heal the gut and treat gut pathologies before incorporating high-dose SBO probiotics. This may be especially true after antibiotics. I eagerly await more research on how individual strains and formulations of SBOs might impact the gut microbiota and gut environment in different contexts.

Of course, I also recommend getting exposure to SBOs the natural way – this means consuming organically grown vegetables and getting exposure to dirt through gardening or other outdoor activities where you’re getting your hands and feet in the dirt! It also means eating plenty of properly prepared fermented foods. Interestingly, I’ve noticed that many popular kombucha brands, such as GTs, contain Bacillus coagulans GBI-30, 6086.

I will plan to update and reevaluate this guide periodically as more research is published and as companies (hopefully) become more transparent with their strains and evidence-based in their marketing claims. To be notified of any future updates, be sure to subscribe to my newsletter.

What soil-based probiotics do you take? Will this influence which products you use? Share your thoughts in the comments below!

 

Sources:

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  15. Madempudi, R. S. & Kalle, A. M. Antiproliferative Effects of Bacillus coagulans Unique IS2 in Colon Cancer Cells. Nutr Cancer 69, 1062–1068 (2017).
  16. Majeed, M. et al. Bacillus coagulans MTCC 5856 supplementation in the management of diarrhea predominant Irritable Bowel Syndrome: a double blind randomized placebo controlled pilot clinical study. Nutr J 15, 21 (2016).
  17. Majeed, M., Nagabhushanam, K., Arumugam, S., Majeed, S. & Ali, F. Bacillus coagulans MTCC 5856 for the management of major depression with irritable bowel syndrome: a randomised, double-blind, placebo controlled, multi-centre, pilot clinical study. Food Nutr Res 62, (2018).
  18. Hong, H. A. et al. Bacillus subtilis isolated from the human gastrointestinal tract. Res. Microbiol. 160, 134–143 (2009).
  19. Graebner, H. F. [Supplemental treatment of radiogenic enterocolitis using Bacillus subtilis]. Med Klin 64, 1080–1084 (1969).
  20. Pillen, D. [Treatment of intestinal diseases with Bacillus strain 5832]. Med Welt 7, 266–268 (1971).
  21. Langman, C. B. et al. A Double-Blind, Placebo Controlled, Randomized Phase 1 Cross-Over Study with ALLN-177, an Orally Administered Oxalate Degrading Enzyme. Am. J. Nephrol. 44, 150–158 (2016).
  22. Toohey, J. C. et al. Effects of Probiotic (Bacillus subtilis) Supplementation During Offseason Resistance Training in Female Division I Athletes. J Strength Cond Res (2018). doi:10.1519/JSC.0000000000002675
  23. Townsend, J. R. et al. Effects of Probiotic (Bacillus subtilis DE111) Supplementation on Immune Function, Hormonal Status, and Physical Performance in Division I Baseball Players. Sports (Basel) 6, (2018).
  24. Cuentas, A. M., Deaton, J., Davidson, J., Ardita, C. & Khan, S. The Effect of <em>Bacillus subtilis</em> DE111 on the Daily Bowel Movement Profile for People with Occasional Gastrointestinal Irregularity. Journal of Probiotics & Health 5, 1–4 (2017).
  25. Lefevre, M. et al. Probiotic strain Bacillus subtilis CU1 stimulates immune system of elderly during common infectious disease period: a randomized, double-blind placebo-controlled study. Immun Ageing 12, 24 (2015).
  26. Lefevre, M. et al. Safety assessment of Bacillus subtilis CU1 for use as a probiotic in humans. Regul. Toxicol. Pharmacol. 83, 54–65 (2017).
  27. Hanifi, A. et al. Evaluation of Bacillus subtilis R0179 on gastrointestinal viability and general wellness: a randomised, double-blind, placebo-controlled trial in healthy adults. Benef Microbes 6, 19–27 (2015).
  28. Vuković, M. [Bacillus subtilis IP 5832 (Flonivin BS) shortens the duration of the carrier state in patients with acute non-typhoid salmonella enteritis]. Med. Pregl. 54, 62–68 (2001).
  29. Liu, Y.-P., Liu, X. & Dong, L. [Lactulose plus live binary Bacillus subtilis in the treatment of elders with functional constipation]. Zhonghua Yi Xue Za Zhi 92, 2961–2964 (2012).
  30. Choi, C. H. et al. Efficacy of combination therapy with probiotics and mosapride in patients with IBS without diarrhea: a randomized, double-blind, placebo-controlled, multicenter, phase II trial. Neurogastroenterol. Motil. 27, 705–716 (2015).
  31. Kim, Y. G., Moon, J. T., Lee, K. M., Chon, N. R. & Park, H. [The effects of probiotics on symptoms of irritable bowel syndrome]. Korean J Gastroenterol 47, 413–419 (2006).
  32. Lee, H. et al. A feasibility study of probiotics pretreatment as a bowel preparation for colonoscopy in constipated patients. Dig. Dis. Sci. 55, 2344–2351 (2010).
  33. Cenci, G., Trotta, F. & Caldini, G. Tolerance to challenges miming gastrointestinal transit by spores and vegetative cells of Bacillus clausii. J. Appl. Microbiol. 101, 1208–1215 (2006).
  34. Ghelardi, E. et al. Survival and persistence of Bacillus clausii in the human gastrointestinal tract following oral administration as spore-based probiotic formulation. J. Appl. Microbiol. 119, 552–559 (2015).
  35. Ciprandi, G., Vizzaccaro, A., Cirillo, I. & Tosca, M. A. Bacillus clausii exerts immuno-modulatory activity in allergic subjects: a pilot study. Eur Ann Allergy Clin Immunol 37, 129–134 (2005).
  36. Ciprandi, G., Vizzaccaro, A., Cirillo, I. & Tosca, M. A. Bacillus clausii effects in children with allergic rhinitis. Allergy 60, 702–703 (2005).
  37. Ciprandi, G., Tosca, M. A., Milanese, M., Caligo, G. & Ricca, V. Cytokines evaluation in nasal lavage of allergic children after Bacillus clausii administration: a pilot study. Pediatr Allergy Immunol 15, 148–151 (2004).
  38. Nista, E. C. et al. Bacillus clausii therapy to reduce side-effects of anti-Helicobacter pylori treatment: randomized, double-blind, placebo controlled trial. Aliment. Pharmacol. Ther. 20, 1181–1188 (2004).
  39. Gabrielli, M. et al. Bacillus clausii as a Treatment of Small Intestinal Bacterial Overgrowth. The American Journal of Gastroenterology 104, 1327–1328 (2009).
  40. EPA: Bacillus Licheniformis Final Risk Assessment – Biotechnology Program Under Toxic Substances Control Act (TSCA). Available at: http://widit.knu.ac.kr/epa/ebtpages/Pollutants/Toxics/Microorganisms/siteout/s1out8.htm. (Accessed: 21st September 2018)
  41. Park, M. R. et al. Bacillus licheniformis Isolated from Traditional Korean Food Resources Enhances the Longevity of Caenorhabditis elegans through Serotonin Signaling. J. Agric. Food Chem. 63, 10227–10233 (2015).
  42. Surono, I. S. et al. Novel probiotic Enterococcus faecium IS-27526 supplementation increased total salivary sIgA level and bodyweight of pre-school children: a pilot study. Anaerobe 17, 496–500 (2011).
  43. Agudelo Higuita, N. I. & Huycke, M. M. Enterococcal Disease, Epidemiology, and Implications for Treatment. in Enterococci: From Commensals to Leading Causes of Drug Resistant Infection (eds. Gilmore, M. S., Clewell, D. B., Ike, Y. & Shankar, N.) (Massachusetts Eye and Ear Infirmary, 2014).
  44. Mego, M. et al. Prevention of febrile neutropenia in cancer patients by probiotic strain Enterococcus faecium M-74. Pilot study phase I. Neoplasma 52, 159–164 (2005).
  45. Hlivak, P. et al. One-year application of probiotic strain Enterococcus faecium M-74 decreases serum cholesterol levels. Bratisl Lek Listy 106, 67–72 (2005).
  46. Hlivak, P. et al. Long-term (56-week) oral administration of probiotic Enterococcus faecium M-74 decreases the expression of sICAM-1 and monocyte CD54, and increases that of lymphocyte CD49d in humans. Bratisl Lek Listy 106, 175–181 (2005).
  47. Mego, M. et al. Prevention of febrile neutropenia in cancer patients by probiotic strain Enterococcus faecium M-74. Phase II study. Support Care Cancer 14, 285–290 (2006).
  48. Lo Skiavo, L. A., Gonchar, N. V., Fedorova, M. S. & Suvorov, A. N. [Dynamics of contamination and persistence of Clostridium difficile in intestinal microbiota in newborn infants during antibiotic therapy and use of probiotic strain enterococcus faecium L3]. Antibiot. Khimioter. 58, 13–18 (2013).
  49. Kawashima, M., Nakamura, S., Izuta, Y., Inoue, S. & Tsubota, K. Dietary Supplementation with a Combination of Lactoferrin, Fish Oil, and Enterococcus faecium WB2000 for Treating Dry Eye: A Rat Model and Human Clinical Study. Ocul Surf 14, 255–263 (2016).
  50. Loguercio, C. et al. Long-term effects of Enterococcus faecium SF68 versus lactulose in the treatment of patients with cirrhosis and grade 1-2 hepatic encephalopathy. J. Hepatol. 23, 39–46 (1995).
  51. Cavallini, D. C. U. et al. Probiotic Soy Product Supplemented with Isoflavones Improves the Lipid Profile of Moderately Hypercholesterolemic Men: A Randomized Controlled Trial. Nutrients 8, (2016).
  52. Shimbo, I. et al. Effect of Clostridium butyricum on fecal flora in Helicobacter pylori eradication therapy. World J Gastroenterol 11, 7520–7524 (2005).
  53. Imase, K. et al. Efficacy of Clostridium butyricum preparation concomitantly with Helicobacter pylori eradication therapy in relation to changes in the intestinal microbiota. Microbiol. Immunol. 52, 156–161 (2008).
  54. Yasueda, A. et al. The effect of Clostridium butyricum MIYAIRI on the prevention of pouchitis and alteration of the microbiota profile in patients with ulcerative colitis. Surg. Today 46, 939–949 (2016).
  55. Nomura, T. et al. Probiotics reduce infectious complications after pancreaticoduodenectomy. Hepatogastroenterology 54, 661–663 (2007).
  56. Chen, C.-C. et al. Probiotics have clinical, microbiologic, and immunologic efficacy in acute infectious diarrhea. Pediatr. Infect. Dis. J. 29, 135–138 (2010).
  57. Yoshimatsu, Y. et al. Effectiveness of probiotic therapy for the prevention of relapse in patients with inactive ulcerative colitis. World J Gastroenterol 21, 5985–5994 (2015).
  58. Ren, Y.-F. & Wang, L.-L. [Effects of probiotics on intestinal bacterial colonization in premature infants]. Zhongguo Dang Dai Er Ke Za Zhi 12, 192–194 (2010).
  59. Liao, H.-Y. et al. Clostridium butyricum in combination with specific immunotherapy converts antigen-specific B cells to regulatory B cells in asthmatic patients. Sci Rep 6, (2016).
  60. Kanai, T., Mikami, Y. & Hayashi, A. A breakthrough in probiotics: Clostridium butyricum regulates gut homeostasis and anti-inflammatory response in inflammatory bowel disease. J. Gastroenterol. 50, 928–939 (2015).
  61. Tsuda, H., Ochiai, K., Suzuki, N. & Otsuka, K. Butyrate, a bacterial metabolite, induces apoptosis and autophagic cell death in gingival epithelial cells. J. Periodont. Res. 45, 626–634 (2010).
  62. Horie, H. et al. Probiotic mixture decreases DNA adduct formation in colonic epithelium induced by the food mutagen 2-amino-9H-pyrido[2,3-b]indole in a human-flora associated mouse model. Eur. J. Cancer Prev. 12, 101–107 (2003).
  63. Hua, M.-C. et al. Probiotic Bio-Three induces Th1 and anti-inflammatory effects in PBMC and dendritic cells. World J. Gastroenterol. 16, 3529–3540 (2010).
  64. McFarlin, B. K., Henning, A. L., Bowman, E. M., Gary, M. A. & Carbajal, K. M. Oral spore-based probiotic supplementation was associated with reduced incidence of post-prandial dietary endotoxin, triglycerides, and disease risk biomarkers. World J Gastrointest Pathophysiol 8, 117–126 (2017).

The complete guide to soil-based probiotics

 BY LUCY MAILING, MD/PHD STUDENT

Soil-based probiotics have been touted for their ability to improve digestion, stimulate the immune system, and help maintain a healthy gut microbiota. On the other hand, some people believe that SBOs should be avoided at all costs, due to their spore-forming nature and ability to compete with resident gut microbes. So, should you be taking soil-based probiotics? If so, which formula or brand is best? Read on to find out.

Until recently, I recommended Prescript Assist as the best soil-based probiotic. While some of the microbes in the old probiotic formula were not well-studied, Prescript Assist had been used in several clinical trials with excellent results and no reported adverse events.1,2 It was also well tolerated, even by those with SIBO, severe gut dysbiosis, or other gut pathologies.

In late 2017, the manufacturer made major changes to the ingredients of Prescript Assist, so it is no longer using the formulation that was studied in clinical trials. While the original formula contained 29 different strains, the new formula contains 28 strains, only 9 of which are from the original formula. There’s very limited evidence for most of the strains included in the new formula.

I’ve been asked by many people what my new recommended alternative to Prescript Assist is, so I decided to do some digging. This guide is a result of 50+ hours of independent research on soil-based organisms and the products commercially available today.

First, though, I’ll review what soil-based organisms are, the controversy, and the evidence for the most commonly used strains.

What are soil-based organisms?

The term soil-based organism (SBO) encompasses over 100 different species of microbes naturally found in soil. Some of these have been isolated and adapted for use as probiotics. Most SBO used in soil-based probiotics are spore-forming. This means that when they replicate, they form a small spore that is protected by a hard coating, making them resistant to heat, acid, and most antibiotics. This also means that they are more likely to survive the upper gastrointestinal tract and reach the large intestine compared to other commonly used probiotic strains.

The controversy and the evidence

There is currently a lot of debate within health circles about the safety of SBOs. Advocates claim that they are probiotics that normalize bowel function, aid in digestion, beneficially stimulate the immune system, and help re-seed the gut microbiota. They also praise SBOs for their ability to resist stomach acid and the lack of need for refrigeration.

On the other hand, opponents of SBOs argue that because of their spore-forming nature, they proliferate rapidly, and may compete with our resident gut microbes, rather than helping to bring the gut microbiota back to normalcy. In some individuals, opportunistic SBOs could overgrow, with the potential to become pathogenic.

My take: Several individual SBO strains have been shown to be beneficial, with no adverse effects, in dozens of randomized, placebo-controlled, human clinical trials. However, other strains have very limited or no clinical evidence and may be able to cause infection in people with a compromised immune system.

Rather than labeling all SBOs as good or bad, I think we need a more nuanced discussion – one that considers the evidence for each particular strain, microbe, and formula. That’s what I’ll try to provide in the next few sections. If you just want to see my recommendations, feel free to skip down to the “Conclusions” section at the end.

Common soil-based species used in probiotics:

Before I do an analysis of the soil-based probiotic formulations on the market, it’s important to understand which species are most commonly used.

I searched PubMed and Google Scholar for every available human clinical trial on the seven most commonly used soil-based microbes:

Bacillus coagulans

Bacillus subtilis

Bacillus clausii

Bacillus indicus

Bacillus licheniformis

Enterococcus faecium

Clostridium butyricum

Before I share my findings below, it’s important to note that microbes are denoted by their genus, species, and strain. The list above provides the genus and species but does not tell you anything about the strain. Strain is incredibly important since two strains of the same species can have very different characteristics.3 Unfortunately, most probiotic formulations do not provide information about which strains they contain.

To see my full analysis of the available clinical trial literature for each strain, click here to download my Excel spreadsheet. For just the key findings, read on:

Bacillus coagulans

Bacillus coagulans is a gram-positive bacterium that produces L-lactic acid and, as a result, was formerly misclassified as Lactobacillus sporogenes. It exhibits many characteristics typical of the Lactobacillaceae family, but unlike most lactic acid bacteria, B. coagulans can form spores.

There are three strains of B. coagulans that have been heavily studied:

GBI-30, 6086 (“Ganeden BC30”): with over 8 human randomized, placebo-controlled trials, this is one of the most well-studied Bacillus strains. GBI-30, 6086 has been shown to improve IBS,4–6 immune function,7,8 and beneficially modulate the gut microbiota.9,10 In cell culture experiments, this strain has been shown to stimulate production of anti-inflammatory cytokines and regenerative markers.11

Unique IS-2 (“ProDURA”): three human clinical trials have found this strain to be efficacious for bacterial vaginosis12 and children with IBS.13,14 Cell culture studies have also found that it inhibits the proliferation of cancer cells.15

MTCC 5856 (“LactoSpore”): two randomized controlled trials showed that MTCC 5856 significantly reduced bloating, abdominal pain, and depressive symptoms in IBS patients.16,17

Verdict: These three strains of Bacillus coagulans appear to be safe, well-tolerated, and may be especially beneficial for those with IBS.

Bacillus subtilis

Bacillus subtilis is recognized as a normal inhabitant of the human gut.18 Even before the introduction of antibiotics, cultures of B. subtilis were popularly used worldwide as an immune stimulant to aid in the treatment of urinary tract and gastrointestinal disease.19,20

B. subtilis produces an enzyme that can degrade oxalate, which may be particularly helpful for people with hyperoxaluria,21 and may also produce small amounts of Vitamin K-2. B. subtilis is found naturally in natto, a traditional Japanese food made from fermented soybeans.

Only four strains of B. subtilis have been studied in humans:

DE111: two placebo-controlled RCTs of Division 1 athletes during off-season training found that B. subtilis DE111 was well tolerated. Female athletes saw greater reductions in body fat percentage; male athletes saw reduced blood TNFalpha, a marker of inflammation. There were no effects on physical performance.22,23 Another study found that DE111 improved bowel irregularity in otherwise healthy adults.24

CU1 (“LifeinU”): one placebo-controlled RCT found that ten-day supplementation with B. subtilis CU1 was well tolerated and improved immune function (fecal and salivary sIgA) in elderly adults.25 It does not exhibit any antibiotic resistance and was shown to be absent of toxigenic activity in vitro.26

R0179: one study found B. subtilis R0179 to be well tolerated in healthy adults at a dose of 1 or 10 billion CFU per day, and confirmed that it survived passage through the GI tract.27

IP 5832: one Croatian study found that B. subtilis IP 5832 given during parenteral rehydration therapy for acute nontyphoid Salmonella gastroenteritis reduced patient-weeks of carrier state and resulted in fewer positive stool cultures at week four.28

Several studies for which I could not find strain information also showed benefits from B. subtilis: One Chinese study found that B. subtilis plus lactulose was more effective at treating functional constipation than lactulose alone.29 Several other studies found that B. subtilis + Enterococcus faecium reduced IBS-related abdominal pain30,31 and improved bowel preparation for colonoscopy.32

Verdict: Commonly studied strains of B. subtilis appear to be safe, well-tolerated, and with no adverse effects. Some strains appear to be particularly beneficial for improving immune function and bowel regularity.

Bacillus clausii

Bacillus clausii has been studied extensively and used for many years as the Italian pharmaceutical preparation Enterogermina for the treatment of a wide range of gastrointestinal diseases. B. clausii has been shown to have antimicrobial activity against Staphylococcus aureus and Clostridium difficile.

Enterogermina is the only formulation of B. clausii that has been studied in controlled human clinical trials and is made up of four different strains (OC, NR, SIN, and T). These strains have been shown to be acid and bile resistant,33 and can be recovered in stool for up to 12 days after a single administration.34

Enterogermina has found to be particularly beneficial for those with allergies, reducing nasal congestion and the need for anti-histamines.35–37 It has also been shown to reduce side effects during antibiotic treatment for H. pylori.38

One study of 40 SIBO patients found that taking Enterogermina for 1 month resulted in a normalization of glucose breath test result in 47 percent of patients!39 This is astounding and comparable to the rate observed with many antibiotics commonly used for SIBO treatment. Only one patient reported a side effect of constipation.

Verdict: Very well-studied and well-tolerated, with clear efficacy documented in several randomized, placebo-controlled trials. May be particularly beneficial for those with allergies or SIBO. Since beginning this analysis, I have also tried Enterogermina myself and noticed improved tolerance to foods.

Enterogermina can be purchased from international online pharmacies as either capsules or liquid vials. Shipment should not be an issue since B. clausii is extremely heat-stable and does not require refrigeration.

Bacillus indicus:

Bacillus indicus has been touted for its ability to potently stimulate the immune system and produce high levels of carotenoids, vitamins, and quinols.

However, after an exhaustive search of the literature, I could find no scientific studies of Bacillus indicus in humans (with the exception of one study that used a preparation of 5 Bacillus strains – see “MegaSporeBiotic” section below).

Verdict: Currently lacking scientific evidence. This does not necessarily mean that B. indicus is not beneficial – it just means we have little to no evidence to speak to its safety and efficacy in humans.

Bacillus licheniformis

Bacillus licheniformis is commonly used in the fermentation history. Of all soil-based species used in probiotics, B. licheniformis is perhaps the most controversial. According to some reports, B. licheniformis may be an opportunistic pathogen and can cause infection in immunocompromised hosts. However, other reports have concluded that the virulence of B. licheniformis is very low: “In order to achieve an infection, either the number of microorganisms must be very high or the immune status of the host low.”40

The same EPA report further notes: “While there have been cases of acute, self-limited gastroenteritis associated with the isolation of large numbers of this species, a toxic or direct effect on intestinal epithelia has not been demonstrated. It is difficult to ascertain whether the species in these reported cases, which are quite limited in number, actively participated in the infection or were isolated in conjunction with an unidentified pathogen.”40

A literature search only revealed only three human studies of Bacillus licheniformis – two from Russia and one from China – none of which were placebo-controlled. I could not determine which strain was used in any of these studies, and the results were largely unimpressive.

Nonetheless, B. licheniformis is found in many fermented foods traditionally consumed in Korean culture. Certain strains found in these foods have been found to enhance the longevity of worms by upregulating serotonin signaling.41

Verdict: While traditional fermented foods containing B. licheniformis are almost undoubtedly safe, I believe there is currently insufficient evidence to support high-dose supplementation of isolated B. licheniformis. I think it’s best to err on the side of caution and avoid probiotics that contain this species, especially if they can provide no strain information and/or do not regularly test the genetic identity of their strains.

Enterococcus faecium

Enterococcus faecium is a normal resident of the human gut, metabolizing carbohydrates and producing lactic acid as a byproduct. Some strains of E. faecium can be found in traditional fermented foods, such as dadih, an Indonesian fermented buffalo milk.42

However, it can also be pathogenic, causing diseases like neonatal meningitis and endocarditis. Many strains of this bacterium have developed multi-drug antibiotic resistance and virulence factors that allow it to aggregate and form biofilms. In the United States, 80-90 percent of medical device-associated infections can be attributed to antibiotic-resistant E. faecium.43 Thus, there are concerns about its use as a probiotic.

Many different strains have been studied:

M-74: This strain has the most “randomized” clinical trials associated with it, but every single one gave the probiotic in conjunction with 50 micrograms of selenium.44–47 Many probiotics point to these studies to suggest that E. faecium can “reduce cholesterol”, but the lack of a selenium control group means that it’s entirely plausible that the selenium alone was reducing cholesterol levels.

L3: one Russian randomized controlled trial found that this strain of E. faecium reduced the frequency of infectious complications in premature infants on antibiotic therapy, reduced persistence of C. difficile, and increased abundance of Bifidobacterium and Lactobacillus spp.48

IS 27526: one Indonesian randomized, placebo-controlled study found that this strain of E. faecium increased salivary sIgA and weight gain in underweight preschool children.42

WB 2000: one Japanese study found that a combination of E. faecium with fish oil, lactoferrin, and several vitamins and minerals improved clinical symptoms of dry eye.49 However, the effects of probiotic cannot be separated because it was not adequately controlled.

SF68: one Italian randomized crossover study found that cirrhosis patients taking this strain of E. faecium had a greater reduction in blood ammonia than those taking lactulose.50 There was no control group taking neither E. faecium or lactulose.

CRL 183: one study performed in Brazil found that a combination of isoflavone-supplemented soy fermented with E. faecium and Lactobacillus helveticus was better than soy alone at improving total cholesterol, but again, we cannot separate out the effects of E. faecium from L. helveticus and the isoflavone supplementation.51

As mentioned above, several studies found that B. subtilis + E. faecium reduced IBS-related abdominal pain30,31 and improved bowel preparation for colonoscopy,32 but I could not determine which strains were used in these studies.

To make matters more complicated, Streptococcus faecium was reclassified to Enterococcus faecium several years ago. However, Enterococcus faecalis (previously known as Streptococcus faecalis) is an entirely separate organism. Unfortunately, I believe this delineation has been smudged in studies of these organisms.

Verdict: Very few well-designed RCTs have demonstrated the efficacy of E. faecium, and all seem to use different strains. E. faecium also has the potential to acquire multi-drug antibiotic resistance and cause infection. Until more studies can be performed, I would exercise caution with high doses of isolated E. faecium.

Clostridium butyricum

Clostridium butyricum is a natural resident of the human GI tract. It is one of the many important microbes in the gut that ferments dietary fiber and produces the beneficial short-chain-fatty acid butyrate. Butyrate is an important source of energy for colon epithelial cells, helps maintain the gut barrier, has anti-inflammatory effects, and protects against colon cancer.

MIYAIRI 588: This strain of C. butyricum has been used as a probiotic in Asia since as early as 1963. It does not carry any genes encoding any known toxins or virulence factors.

Two randomized controlled trials showed that this strain alone reduces side effects for abdominal symptoms and diarrhea incidence in patients undergoing H. pylori eradication therapy.52,53 Another randomized, placebo-controlled trial in ulcerative colitis patients found that fewer subjects in the group receiving MIYAIRI 588 developed pouchitis, though the effects were not statistically significant, and the placebo given was lactose, which can exacerbate colitis in many people.54

TO-A: this strain of C. butyricum, in combination with E. faecium and B. subtilis, has been heavily used and somewhat well studied as a probiotic in Asia. The combined product is called BIO-THREE and has been shown in randomized controlled trials to reduce postoperative infections in patients undergoing surgery55 and shorten hospital stay for children with acute diarrhea.56

In cell culture studies, C. butyricum TO-A has been shown to reduce expression of TLR4, a gene involved in the inflammatory immune response. One randomized trial of ulcerative colitis patients found lower relapse rates in the group receiving BIO-THREE, but the difference was not statistically significant.57 No changes were observed in SCFA levels with probiotic supplementation.

Several studies for which I could not find any strain information found that C. butyricum reduced the incidence of sepsis and diarrhea in premature infants,58 and improved antigen-specific immunotherapy.59 In animal studies, C. butyricum has been shown to improve intestinal homeostasis and attenuate colitis.60

Verdict: I really like the idea of being able to supplement with isolated C. butyricum. It’s a normal inhabitant of the gut, appears to be safe and well-tolerated in randomized trials, and could help increase butyrate levels in a way that is unlikely to induce toxicity.

Unfortunately, isolated forms of either of the strains listed above are not currently available in the United States, and I haven’t been able to find any international sources that I trust. The only alternative is to use the three-probiotic formulation BIO-THREE, which I’ll discuss more in the next section.

Product analysis

Note: I have no affiliation with any of these companies or products. This is the objective analysis that I used to determine which products I wanted to use for myself and with my clients.

Like all supplements, probiotics are not regulated by any governing agency (FDA, FTC, etc.), so it’s important to do your homework regarding their claims, sourcing, etc. Many companies that sell probiotics use species and strains that lack clinical evidence, make unsubstantiated statements, and cite highly questionable “research”.

In this section, I break down the ingredients, quality, claims, and evidence of the top eight most popular SBO products on the market.

While you might argue that a company’s marketing is less important than its ingredients or strains, I think it’s a key component. If they can’t provide evidence-based claims on their website or even sound remotely scientific, I don’t trust them to be manufacturing a high-quality product that I’m going to take on a daily basis and recommend to my readers and clients.

Probiotic-3 (Advanced Orthomolecular Research)

Soil-based species: Bacillus subtilis TO-A, E. faecium T-100, and C. butyricum TO-A, (also known as BIO-THREE)

Colony-forming units: 19.2 million CFU

Other ingredients: contains lactose, polyvinyl alcohol, and potato starch (may be an issue for many with gut symptoms

What they claim on their website:

“Probiotic-3 is a probiotic formula that has been used clinically for more than 50 years in Japan and across Asia.”

  • Reduces the growth of pathogenic bacteria while promoting the growth of beneficial bacteria
  • Normalizes the inflammatory response, promotes detoxification and supports immunity

They reference several studies of BIO-THREE.61–63

Verdict: Inclusion of E. faecium is questionable, but the formula has shown benefits in several randomized clinical trials. Not recommended for those sensitive to lactose, alcohol, or potato starch.

MegaSporeBiotic (Microbiome Labs)

Soil-based species: B. coagulans SC-208, B. subtilis HU58, B. clausii SC-109, B. indicus HU36, and B. licheniformis

Colony-forming units: 4 billion CFU

What they claim on their website: “MegaSporeBiotic™ is the first 100% spore-based, broad-spectrum probiotic clinically shown to improve leaky gut by 60% in just 30 days. This unique all-spore formula effectively RECONDITIONS the gut by increasing microbial diversity and encouraging the growth of key health-promoting, commensal gut bacteria. MegaSporeBiotic™ boasts a 5-year shelf-life, does not require refrigeration, and maintains efficacy during antibiotic therapy.”

What their single research study actually found: In a “randomized”, placebo-controlled trial, 30 days of supplementation with MegaSporeBiotic reduced endotoxin (a measure of bacterial translocation into the blood) by 42 percent after a high-fat cheese pizza meal, compared to a 36 percent increase in endotoxin in the group receiving placebo. However, the subjects included in the “randomized” trial were really a hand-picked group of endotoxin hyper-responders.64 So yes, MegaSporeBiotic may reduce leaky gut by 60 percent if you are a dietary endotoxin hyper-responder and you happen to eat cheese pizza regularly.

Furthermore, there is NO evidence that this particular formulation increases microbial diversity, promotes health-promoting, commensal gut bacteria, or maintains efficacy during antibiotics.

Verdict: Inclusion of B. licheniformis and B. indicus is questionable, as few studies have been performed on the safety and efficacy of these strains. One clinical trial showed some benefit in hyper-responders, but the findings are heavily exaggerated on their website.

Just Thrive (Microbiome Labs)

Soil-based species: B. coagulans, B. subtilis HU58, B. clausii, B. indicus HU36

Colony-forming units: 3 billion CFU

What they claim on their website:

 “With Just Thrive™ […] the body becomes a super-antioxidant factory right in the digestive system at the site where these important nutrients are most needed and absorbed.”

“Just Thrive® is the only product on the shelf to contain the patented Bacillus Indicus HU36®, a strain that produces high levels of antioxidants.”

What the evidence says:

There is absolutely no evidence to suggest that your gut becomes a “super-antioxidant factory”. In fact, any antioxidants produced by this probiotic are likely negligible if you consume a nutrient-dense diet rich in fruits and vegetables.

Moreover, Just Thrive is not the only product on the shelf to contain Bacillus indicus HU36, since MegaSporeBiotic also contains this strain.

Verdict: Contains B. indicus, which has little clinical evidence. Their website makes some pretty glorified claims that are clearly not backed by any real evidence. Supposedly they have about 10 clinical trials underway, so I’ll be happy to reevaluate Just Thrive when I see the data.

Primal Probiotics (Primal Blueprint):

Soil-based microbes: B. coagulans, B. subtilis, B. clausii (no strain information; quality assurance team said it was proprietary information)

Other probiotics: B. bifidus, L. plantarum, S. boulardii

Colony-forming units: 5 billion CFU soil-based, 5 billion CFU other probiotics

Other ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide, and 50 mg potato starch. Potato starch may be an issue for some people with gut issues. Resistant starch deserves an article on its own, but for now, I’ll say that I do not recommend supplementing with raw potato starch if you have gut dysbiosis, intestinal permeability, or autoimmunity.

What they claim on their website:

Like every probiotic, they make some lofty claims, such as:

A simple daily dose of Primal Probiotics can help rebalance and restore gut health and improve immune function*”.

However, they are careful to note that:

“* There is no guarantee of specific results and results can vary from person to person.”

Verdict: A good mix of species with high CFU count but no strain information. No supporting clinical evidence for this formula, and not suitable for those who can’t tolerate potato starch.

Biospora (Klaire Labs):

Soil-based species: B. coagulans, B. subtilis (no strain information; no response to my inquiry)

Colony-forming units: 2 billion CFU

Other ingredients: coconut oil powder

What they claim on their website:

“BioSpora™ is recommended for enhanced support of normal GI and immune function. […] Each lot of Bacillus species used in BioSpora™ undergoes independent DNA testing using 16S ribosomal RNA sequencing to verify genetic identity.”

What the science really says:

You can’t verify genetic identity with 16S rRNA gene sequencing at anything below the genus level – only occasionally can you get to the species level with this type of sequencing. So, the only thing they are “verifying” is that each lot has some form of Bacillus.

Verdict: Contains only well-studied species. Website claims are largely scientific, but their genetic identity verification is highly questionable. No studies on this formulation have been done and no strain information is provided. However, Klaire Labs is NSF certified, which means their products do undergo independent testing.

Proflora 4R (Bio-Botanical Research):

Soil-based species: B. coagulans, B. subtilis HU58, B. clausii (no response to my inquiry about strains)

Colony-forming units: 3 billion CFU cells

Other ingredients: 100mg quercetin, 100mg marshmallow root, and aloe vera extract

What they claim on their website: “Proflora 4R replaces beneficial flora: Evidence suggests that the increase of inflammatory gastrointestinal (GI) disorders and intestinal permeability may, in part, be attributed to a under-consumption of these vital spore-producing flora. The combination of Quercetin, Marshmallow Root, and Aloe Vera extract in Proflora 4R™ provide additional nutritional support for “leaky gut” and a healthy microbial balance, with just one capsule a day.”

Verdict: Contains a good selection of species, but strains are not provided or have not been studied in human clinical trials. Website claims are largely scientific, and the addition of quercetin, marshmallow root, and aloe may help soothe a damaged gut.

TOP CHOICE: RightBiotics RX (RealDose Nutrition)

Soil-based species: B. subtilis DE111, Bacillus coagulans Lactospore (MTCC 5856) (both clinically validated strains!)

Colony-forming units: 5.36 billion CFU soil-based organisms, 15 billion CFU other

Other probiotics: B. lactis B1-04, B. longum BB536, L. helveticus Lafti L10, L. gasseri Lg-36, L. acidophilus DDS-1, L. plantarum Lp-115, Gnosis® S. boulardii  (also all clinically validated strains) *Despite inclusion of Lactobacillus strains, this product should not cause histamine issues.

Other ingredients: vegetable capsule, organic rice bran extract, organic rice hull concentrate.

Allergens:RightBiotics Rx includes one probiotic strain (L. helveticus LAFTI® L10) that contains a trace amount of soy from the culture media and may contain a trace amount of milk (including lactose) as it is sourced from dairy, according to the product’s Allergen Statement. For this reason, the label includes a caution statement for people with soy or milk allergy.”

Website claims: “Like people, no two probiotic strains are exactly alike. Each has a unique genetic makeup that determines its special health benefits. Verifying the strain ID ensures the formula delivers the unique strains shown in clinical research to deliver health benefits.”

Manufactured in the USA and third-party lab tested for potency and purity: Our 3rd party laboratory is Atlas Bioscience Labs in Tucson, AZ. Atlas is DEA registered, and members of several industry-wide organizations including AOAC (Association of Official Analytical Chemists), and currently undergoing accreditation with ACLASS for ISO:17025 certification. We send every batch of product to Atlas Bioscience to test for active ingredients, as well as heavy metals, residual solvents, organochlorides, organophosphates and microbiology.”

Verdict: This is by far the best probiotic supplement I have seen on the market to date. I currently have NO affiliation with RightBiotics RX but am excited to have finally come across a product that is so well-supported by the evidence, independently tested, etc. I had not even heard of RealDose Nutrition before conducting this independent analysis, but if I continue to find success with this product with my clients, I may discuss affiliate options with RealDose Nutrition so that I can offer a discounted rate to my readers and clients.

For now, you can purchase it on their website or on Amazon.

Conclusion

To sum up, soil-based organisms are quite well studied and have been shown in randomized clinical trials to be efficacious for a wide range of conditions. However, I strongly advise choosing products that use high-quality manufacturing techniques and clinically-tested strains.

Currently, I am primarily using both Enterogermina and RightBiotics RX for myself and with my clients. I may occasionally try Probiotic-3 (BIO-THREE) in patients with low Clostridia or butyrate production. This is certainly subject to change, as more studies are available on particular species, strains, and formulas.

Note that every person will respond differently to probiotics. Response will depend on which probiotic you take, the dosage, which microbes you already have in your gut, and the health of your gut and immune system. This is part of the reason I recommend gut testing or working with someone with expertise in rebalancing the gut microbiota.

It’s possible that in some severe cases, we should look to heal the gut and treat gut pathologies before incorporating high-dose SBO probiotics. This may be especially true after antibiotics. I eagerly await more research on how individual strains and formulations of SBOs might impact the gut microbiota and gut environment in different contexts.

Of course, I also recommend getting exposure to SBOs the natural way – this means consuming organically grown vegetables and getting exposure to dirt through gardening or other outdoor activities where you’re getting your hands and feet in the dirt! It also means eating plenty of properly prepared fermented foods. Interestingly, I’ve noticed that many popular kombucha brands, such as GTs, contain Bacillus coagulans GBI-30, 6086.

I will plan to update and reevaluate this guide periodically as more research is published and as companies (hopefully) become more transparent with their strains and evidence-based in their marketing claims. To be notified of any future updates, be sure to subscribe to my newsletter.

What soil-based probiotics do you take? Will this influence which products you use? Share your thoughts in the comments below!

 

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By |2018-09-21T19:06:58+00:00September 21st, 2018|

14 Comments

  1. Nita Jain September 21, 2018 at 7:29 pm - Reply

    Enterogermina is also available on Amazon for those who may not want to risk customs clearance issues when purchasing from international pharmacies: https://www.amazon.com/gp/offer-listing/B07H7QTPCM/

    • Lucy Mailing September 24, 2018 at 1:07 pm - Reply

      I didn’t realize that, thanks Nita!

  2. Alyssa September 21, 2018 at 7:35 pm - Reply

    This is freaking awesome! You rock Lucy. I had been taking Just Thrive for a few months after meeting a rep at AHS last year and looking at the study they did on leaky gut. Did you see that one? The results seemed pretty impressive, but I’ll admit I more or less trusted the face-value results and didn’t dig deeper into how impressive they actually were (apparently I’m not as much of a skeptic as I thought!).

    Anyway, I haven’t noticed any huge difference while taking it (I never really do with probiotics), so I might skip a month and instead try the two you recommended. Thanks so much for doing the hard leg-work!

    • Lucy Mailing September 24, 2018 at 1:11 pm - Reply

      Thanks, Alyssa! Just Thrive and Megasporebiotic are actually both manufactured by Microbiome Labs, so the leaky gut study that I discussed under the Megasporebiotic section is the same as the one cited on the Just Thrive website. My biggest issue is that they hand-picked dietary endotoxin hyper-responders for the study (not a big deal in and of itself) but then used the study to say that it is “clinically proven to improve leaky gut in 30 days”.

      I’d love to hear what your experience is if you try these two!

      • Alyssa October 12, 2018 at 2:47 pm - Reply

        Ah, interesting! Well I’ve ordered both of the probiotics you recommended, and I’ll definitely let you know if I notice a difference!

  3. Kelsey September 22, 2018 at 12:22 am - Reply

    Great article! I’ll add the B. clausii UBBC 07 as another potential option besides Enterogermina. Certainly not as much research as those strains, but possibly useful. Here’s one of their studies on the strain: https://www.wageningenacademic.com/doi/abs/10.3920/BM2012.0034

    • Lucy Mailing September 24, 2018 at 1:19 pm - Reply

      Thanks, Kelsey! I have seen that study and did include it in my analysis, but it isn’t a controlled study. They gave 27 patients with acute diarrhea B. clausii UBBC 07, and their diarrhea resolved over time, but we have no idea if the B. clausii improved recovery since there was no placebo or control group that did not receive the probiotic. And as I’m sure you’re well aware, most acute diarrhea resolves on its own with time and fluids. I’m certainly keeping my eye out for more controlled studies on that strain, though!

      • Kelsey October 10, 2018 at 6:57 pm - Reply

        Yeah, I’m looking forward to more research too. It would be nice to have another B.clausii option on the market if it actually worked!

  4. Gary Kling September 22, 2018 at 8:43 pm - Reply

    Lucy, thank you for providing this very insightful research into SBO options available.
    As with most topics surrounding gut health these days, there are alternative opinions. I was wondering if you have considered comments made by Natasha Trenev of Natren and others surrounding the unknown, long-term impact of SBO’s A friend of mine has a site discussing related topics and reviews Natasha’s comments here: https://fixyourgut.com/hso-probiotics-not-as-safe-as-they-are-believed-to-be/
    Thanks…

    • Lucy Mailing September 24, 2018 at 1:24 pm - Reply

      Thanks for offering your perspective, Gary. I have read the entire HSO series on fixyourgut.com and am familiar with the arguments made there. As I mentioned in the article, I think we need a more nuanced discussion as “all good” or “all bad”, since there are clearly certain strains that show efficacy in RCTs with no significant adverse events, and some of these species are normal inhabitants of the human gut microbiome.

  5. Jake September 23, 2018 at 12:40 am - Reply

    Great work!I too was impressed by Prescript Assist and disappointed when the formulation was changed. The one that I see missing is Bifidobacterium infantis and apparent benefits for those with autism not just infants.

    • Lucy Mailing September 24, 2018 at 1:27 pm - Reply

      Absolutely. My intention with this article was to focus solely on soil-based species, but I will certainly be doing a similar analysis in the future that will discuss the benefits of Lactobacillus and Bifidobacterium-based probiotics 🙂

  6. Ronnie September 25, 2018 at 11:07 am - Reply

    Any thoughts on Progurt probiotics? They’re human-derived (isolated from breast milk, from what I can gather) and contain 1 trillion Colony-Forming Units. Said to colonise better than SBOs because the microbes are intuitive to the human GIT. Apparently Progurt is favoured by a number of practitioners/clinicians who report great results. Have personally used them and felt the benefits. Interested in your professional take.

    • Lucy Mailing September 25, 2018 at 4:44 pm - Reply

      Hi Ronnie. Progurt isn’t soil-based, it contains Lactobacillus and Bifidobacteria, so I did not include it in this post. I am planning to do a deep dive on the best species and strains of Lactobacillus and Bifidobacterium in the near future, so I’ll be able to speak more to it then!

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