Advanced Topic: Can We Curate An Effective Probiotic to Manage SIBO?




Can We Curate An Effective Probiotic to Manage SIBO (Small Intestinal Bacterial Overgrowth)?


Summary

Conventional probiotics are haphazard collections of bacterial species/strains not targeted to achieving a specific benefit. Can we therefore curate probiotic species/strains carefully chosen for characteristics such as ability to colonize the upper gastrointestinal tract where SIBO occurs and ability to produce bacteriocins, i.e., natural peptide antibiotics effective against the species of SIBO? Since we now have the ability to track breath hydrogen gas, can we apply such a probiotic to avoid use of antibiotics and eradicate SIBO with use of probiotics alone and proven by reductions in breath H2? That is the question we would like to answer.

Proposed protocol for probiotic management of SIBO

  1. Anyone testing positive for H2 breath levels with the AIRE device per the Undoctored Protocol for SIBO (i.e., rise of 4 units or more over baseline after prebiotic fiber challenge) may benefit from this strategy. You should not be currently taking any antibiotic, herbal or conventional, nor have taken them in the preceding 4 weeks.
  2. Confirm breath H2 positivity with the AIRE device, I.e., rise of at least 4 units within 90 minutes of consuming prebiotic fiber, e.g., 10 grams inulin fiber
  3. Consume 1/2 cup SIBO yogurt per day for 4 weeks. Consider adding prebiotic fibers and continuing to consume other fermented foods.
  4. After 4 weeks, stop consumption of SIBO yogurt, then retest breath H2 after 2 weeks of no yogurt after repeat prebiotic fiber challenge. (This is to avoid the false-positive H2 readings provoked by L. reuteri at high counts.)
  5. Report your experience in the “SIBO yogurt” Forum under “Undoctored Protocols” in the Undoctored Inner Circle.

After completing your 4-week course of SIBO probiotic, resume basic efforts to cultivate healthy bowel flora: a high-potency multi-species probiotic (or yogurt fermented from a multi-species kefir, per the Undoctored recipe), fermented foods, and prebiotic fibers.

If we obtain enough participants with completed 4-week course of yogurt consumption, the evidence will be assessed. If positive, this may prompt performance of a formal clinical trial. If negative, we go back to the drawing board to construct or modify the composition of our presumptive SIBO yogurt.

SIBO yogurt: Background and rationale

In our Undoctored approach for SIBO and SIFO, we address undesirable bacterial and fungal species that have proliferated and ascended up the length of the gastrointestinal (GI) tract using herbal antibiotics and a variety of antifungal agents. We have not relied on probiotics to eradicate SIBO or SIFO, as they have only partial suppressive effects and do not typically achieve full eradication. High H2 breath readings, food intolerances, and fibromyalgia, for instance, usually persist despite probiotics. This should come as no surprise, as conventional probiotics are created haphazardly without attention to choosing species/strains for specific SIBO-eradicating effects, bacteriocin production, or upper GI-colonizing properties, aspects that have potential for advantage in a SIBO management program. We therefore resort to either conventional treatments such as rifaximin or the two herbal antibiotic regimens, Candibactin AR/BR and FC Cidal/Dysbiocide, that have been shown to match or exceed the efficacy of rifaximin. Neither conventional nor herbal antibiotics are 100% successful, typically generating successful responses in 35-70% of people. Also, rifaximin has shown only limited efficacy in people with irritable bowel syndrome (9% improvement over placebo), a condition that may be synonymous with SIBO.

Most commercial probiotics are created by combining several bacterial species that have been shown to be individually beneficial. Limited evidence has suggested moderate effects of such products on reducing SIBO and levels of breath hydrogen (H2) gas. Can we improve on partial responses by choosing our species/strains more deliberately?

What are the characteristics of probiotic species/strains that have SIBO-eradicating potential? Among the characteristics of microbial species/strains that would potentially yield SIBO-eradicating benefits are:

By identifying probiotic species/strains with such characteristics and combining them, can we increase the effectiveness of a probiotic effort to eradicate SIBO? Can we also exert suppressive effects on methanogenic SIBO and SIFO? Can we thereby avoid the use of antibiotics in some cases or even altogether?

Tentative composition of a SIBO probiotic

The following species/strains holds promise as candidates to include in our first-line effort to reduce/eradicate the species of SIBO:
  • Lactobacillus reuteri DSM 17938, ATCC PTA 6475—L. reuteri colonizes the upper GI tract and produces bacteriocins effective against the species of SIBO. By itself, L. reuteri is unlikely to overcome SIBO or SIFO, but may exert greater effects in the presence of other bacteriocin-producing species. L. reuteri has also been shown to reduce Archaea species that dominate in methanogenic SIBO.
  • Lactobacillus gasseri BNR17—L gasseri strains have been shown to produce at least 7 different bacteriocins and reduce the symptoms of irritable bowel syndrome that is virtually synonymous with SIBO. L gasseri is also able to colonize the small intestine.
  • Bacillus coagulans GBI-30,6086—Several strains of B. coagulans have been shown to reduce the symptoms of irritable bowel syndrome that is virtually synonymous with SIBO. B coagulans also produces bacteriocins.

We also have the ability to substantially amplify bacterial numbers, as we do with our fermenting projects such as making L. reuteri yogurt, increasing numbers from 100 million to nearly 100 billion for enhanced efficacy, potentially increasing potential for SIBO-suppressing effects.

There is reasonable hope that this three-species probiotic may have suppressive effects on H2- and perhaps methane-producing SIBO. However, the likelihood of a fungal-suppressing effect is less likely and specific efforts to reduce fungal populations will still likely be necessary until a more effective panel of antifungal bacterial species are identified.

Unlike antibiotics, probiotics tend to not introduce harmful effects, such as reduction or eradication of desirable bacterial species or irritative/inflammatory effects. Rifaximin, for example, comes with a small risk for C. difficile enterocolitis, while components of the herbal antibiotic regimen such as oil of oregano may carry other toxic effects.

Given the more benign nature of probiotic vs. antibiotic, should we pursue a lengthier probiotic course? Some evidence (below, using the B. coagulans MTCC 5856 strain) suggests that benefits continue with 90 days of supplementation and perhaps onwards.

Given our ability to now monitor breath hydrogen gas levels, we are able to assess whether SIBO responds to a specific combination of probiotic species/strains over time.

Supportive evidence


 Lactobacillus reuteri DSM 17938, ATCC PTA 6475

These two strains of L. reuteri exert a variety of effects that suggest they may play an important potential role in preventing/eradicating SIBO, including introducing beneficial shifts in bacterial species composition, reduction in SIBO species, reduction in constipation/methanogenic Archaea, production of bacteriocins, and production of biofilms in the upper GI tract. The DSM 17938 was originally sourced from the breast milk of a woman living in the Peruvian highlands and the 6475 isolated from breast milk of a woman from Finland. Human sourcing suggests potential for long-term residence.

L reuteri has potential to introduce beneficial changes to the composition of the gut microbiome including reduction in Proteobacteria that includes the species of SIBO.

L. reuteri DSM 17938 compared to placebo reduced symptoms of gas, abdominal discomfort, pain and bloating, and reduced complaints of incomplete defecation, i.e., symptoms of irritable bowel syndrome with constipation (IBS-C) or methanogenic SIBO.

Four weeks of L. reuteri DSM 17938 200 million CFUs per day resulted in partial improvement in constipation/frequency of bowel movements.

Four weeks of L. reuteri DSM 17938 administration in 20 adults was associated with a significant decrease of methane production determined by lactulose breath test (from 20.8 ± 15 to 8.9 ± 8.6; p < 0.0001 CI 95%) and of AUC value (from 5101.5 ± 3571.13 to 2128.4 ± 2110.8; p < 0.0001 CI 95%). Total disappearance of methane production was observed in 11 patients.

L reuteri 6475 is a vigorous former of biofilms that permit long-term residence and the 55730 (native strain related to 17938) produces the greatest quantity of reuterin, the main bacteriocin of this species, two qualities that enhance antibacterial effects.

L reuteri 17938 suppressed growth of 9 different strains of Candida in vitro.

Lactobacillus gasseri BNR17

Lactobacillus gasseri BNR17 is a microbe originally isolated from human breast milk. Sourcing from a human suggests that it may be a microbe that has potential for taking up long-term residence, unlike many other bacterial species/strains present in commercial probiotics that persist for only days to weeks. No toxic effects have been reported with “doses” as high as 50 billion CFUs per day.

L. gasseri is proving to be a multi-functional species with a number of important health benefits, including reduction of waist circumference and abdominal visceral fat with the BNR17 strain. L. gasseri BNR17 has also been shown to reduce the symptoms of irritable bowel syndrome (IBS), suggesting a favorable effect on small intestinal bacterial overgrowth, SIBO, since IBS is closely associated and/or may be synonymous with SIBO.

L. gasseri is a likely “keystone” or “foundational” species, i.e., a bacterial species that, by its presence and production of various metabolites, supports the proliferation of other beneficial bacterial species. L. gasseri, for instance, has been shown to support proliferation of Faecalibacterium prausnitzii, the most vigorous producer of butyrate among human-colonizing microbes, and other species, and also produces as many as 7 different bacteriocins against pathogenic species, properties that likely make it a key species in preventing SIBO or preventing SIBO recurrences. L. gasseri has also been shown to colonize the jejunum of the upper GI tract.

Lactobacillus gasseri BNR17, 10 billion CFUs per day for 4 weeks (but not lower “doses”), reduced symptoms of irritable bowel syndrome (which, you will recall, is likely synonymous with SIBO).

Similar findings were reported in another study with Lactobacillus gasseri BNR17, 10 billion CFUs per day for 8 weeks, resulted in reduced symptoms of irritable bowel syndrome such as abdominal pain, bloating, and frequent stools. In particular, intestinal transit time was dramatically slowed by probiotic from 5.4 hours at week 0 to 19.2 hours after 8 weeks. Bowel flora species became reduced in Proteobacteria (the species of SIBO). Fasting blood sugar was also modestly reduced in non-diabetic participants.

There is insufficient evidence for methanogenic- or fungal-inhibiting properties for L. gasseri BNR17.

Bacillus coagulans GBI-30,6086

B. coagulans is a spore-forming microbe that is typically taken in spore form, which then germinates in the GI tract 4-6 hours after ingestion. It is a vigorous producer of several bacteriocins. Most of the claims made about the benefits of spore-forming probiotics are due to the effects of this species. No toxic effects have been observed with ingestion of this microbe, even with doses as high as 95 billion CFUs.

Most commercial probiotics do not contain B. coagulans. Some of the spore-based probiotics such as Megasporebiotic and Terraflora contain B. coagulans but fail to specify strain. This is important because substantial benefits have been documented with only a few strains, but mostly the GBI-30,6086 and the 5856 strains. The GBI-30,6086 strain is available as the commercial product, Digestive Advantage from Schiff.

Adding Bacillus coagulans (unspecified strain) after conventional antibiotic therapy for SIBO led to marked increase in H2-breath negativity, 93.3% with B. coagulans vs. 66.7% without:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4311312/

B. coagulans GBI-30, 6086 2 billion CFUs per day for 4 weeks increased populations of Faecalibacterium prausnitzii, Clostridium lituseburense, and Bacillus spp. In vitro addition of prebiotic fibers resulted in greater production of acetate, proprionate, and beta-hydroxybutyrate. https://www.sciencedirect.com/science/article/abs/pii/S1075996414001231?via%3Dihub

B. coagulans GBI-30, 6086 2 billion CFUs per day for 4 weeks was associated with reduced gastrointestinal distress and gas vs. placebo in people with unexplained postprandial intestinal gas. https://bmcgastroenterol.biomedcentral.com/track/pdf/10.1186/1471-230X-9-85

B. coagulans GBI-30, 6086 1 billion CFUs per day for 4 weeks increased populations of Faecalobacterium prausnitzii and increased the anti-inflammatory cytokine IL-10. https://academic.oup.com/jn/article/145/7/1446/4589930

Another strain of B. coagulans, the MTCC 5856 strain, has also been shown to reduce symptoms of irritable bowel syndrome and associated symptoms of depression. Notably, supplementation with this strain, 2 billion CFUs per day, continued to provide progressive benefits up to 90 days of supplementation when the study ended: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034030/

The bacteriocin profile of the GBI-30, 6086 strain has not been characterized, but other strains have demonstrated antibacterial effects against E. coli, Klebsiella pneumoniae, Staphylococcus aureus, and Candida albicans. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025323/

There is insufficient evidence for methanogenic- or additional fungal-inhibiting properties for B. coagulans BNR17.

Mixed culture yogurt for SIBO

Because bacterial species/strains are typically sold to us at relatively low bacterial counts, we use fermentation to substantially increase counts. We ferment for extended periods to take advantage of the exponential increase in bacterial numbers that occurs around hour 30 and beyond, unlike the 4-8 hours of commercial yogurt or kefir fermentation. We also add prebiotic fibers to ensure that bacteria have plentiful sources of nutrition for proliferation and production of healthy metabolites.

Rather than fermenting three different species/strains separately, we are going to ferment all three together to generate our potentially anti-SIBO mix of probiotic species. While this will reduce the final bacterial counts of each species, it will still amplify bacterial counts from the much smaller starting numbers. (Should we have success with our formulation, then we will need to submit a sample for formal bacterial quantification.)

Because we need to choose the right species and strains, we start with three different initial sources. There is need to purchase each species/strain only once, as future batches can be made from a small quantity of a prior batch. Of course, organic half-and-half can be replaced by A2 milk, goat or sheep milk, or coconut milk. (See the Undoctored Inner Circle recipe for making yogurt with coconut milk that requires extra steps to improve mixing.)
  • 10 tablets BioGaia Gastrus tablets, crushed (total 2 billion CFUs), or 2 tablespoons of L. reuteri yogurt (curds and/or whey)
  • 2 capsules Lactobacillus gasseri BNR-17
  • 2 capsules Bacillus coagulans GBI-30,6086 (total 5 billion CFUs)
  • 2 tablespoons prebiotic fiber (inulin or raw potato starch)
  • 1 quart half-and-half or other liquid

In medium-sized ceramic or glass bowl, place crushed L. reuteri tablets and the emptied contents of L. gasseri and B. coagulans capsules. Add 2 tablespoons of inulin or raw potato starch, followed by 2-3 tablespoons organic half-and-half (or your choice of other liquid) and mix thoroughly. Add remaining liquid and stir.

Cover with plastic wrap or other method and maintain at 106? for 36 hours.

Sources of bacterial species/strains

The BioGaia Gastrus tablets are available through Amazon as well as BioGaia’s U.S. distributor Everidis. Likewise, Osfortis capsules are available through the same routes.

L. gasseri BNR-17 is available from Korean manufacturer, Acebiome. It’s pricey at around $62 and all materials are in Korean. While UAS in Madison, Wisconsin has licensed the right to manufacture it from the Korean manufacturer, their minimum orders are impractically large (as they typically are from manufacturers). A U.S. retailer may be making this available to us at less cost near-future.

B. coagulans is widely available as the Digestive Advantage product from Schiff that is widely available in many major retailers such as Meijer, Walmart, and online sources.

Medical Disclaimer

Note that this is not a formal clinical trial but discusses an experience you can choose to follow. The information contained herein is not intended to represent a medical diagnosis, treatment, or medical advice in any form, as it is general information and cannot be relied upon without consultation with your physician.

The information contained herein is not intended nor is it implied to be a substitute for professional medical advice. The Undoctored program requires that you consult with your physician and healthcare providers before implementing any portion of the Undoctored Program.

As medical information and your health can change rapidly, we strongly encourage you to discuss all health matters and concerns with your physician before beginning, stopping, or changing any diagnostic or treatment strategies.