Probiotic Guide

This is an excerpt of the forthcoming 2nd Edition of The Keystone Approach

Chapter 2. Rebalancing the Microbiome with Probiotics

Probiotics are one of the best tools we have to rebalance the microbiome.  While we cannot simply take a supplement to replace the bacteria that are depleted, new research suggests that probiotics can actually shift the balance of the microbiome as a whole — both lowering the abundance of harmful species and raising the level of whole groups of beneficial bacteria. The right probiotics can ultimately make the microbiome of someone with autoimmune disease more closely resemble that of healthy individuals

Using Probiotics to Boost Other Beneficial Bacteria

Only certain species of probiotics possess the remarkable ability to boost the population of other anti-inflammatory species already present in our microbiome. We know, for example that L. Rhamnosus GG (sold as Culturelle®) has this property, because a 2016 study found that it significantly increased the population of butyrate-producing bacteria such as Roseburia and Blautia.[1] In infants given L. Rhamnosus GG, the boost to these other important species resulted in higher butyrate levels and greater immune tolerance (reflected in reduced rate of cow’s milk allergy).

The best explanation for how certain probiotics can help other good bacteria proliferate is by way of “cross-feeding.”[2] In short, different bacteria are good at performing different steps in the fermentation of fiber to short-chain fatty acids such as butyrate. The bacteria that are good at early steps in the process effectively feed the downstream butyrate-producing bacteria. Supplement with a probiotic that provides fuel for other dependent species, and you will raise the population of those downstream species.[3]

The bacteria that are best at cross-feeding the butyrate-producers are the Bifidobacteria. [4] Several clinical trials have reported that supplementing with Bifidobacteria probiotics can boost the population of other species that lower inflammation.[5]

Bifidobacteria are in fact critical to the development of a healthy microbiome. These species are among the first to colonize the human gut, typically constituting 95 percent of the total bacterial population in healthy breast-fed infants. The population then drastically declines, making up only 3–6 percent of the microbiome by middle age.[6] Common Bifidobacteria species found in healthy humans include B. longum, B. breve, B. bifidum, and B. infantis.[7] These species are also readily found in probiotic supplements.

One of the defining characteristics of Bifidobacteria is the production of acetate (whereas Lactobacilli primarily produce lactate). Acetate is important because it is the preferred food source of many of the butyrate producers. If we want to truly help the butyrate-producers flourish, we therefore need to look at the whole ecosystem.  It is important to not only provide sufficient dietary fiber, but also ensure adequate numbers Bifidobacteria, to turn that fiber into a more useable energy source.[8] Bifidobacteria are therefore considered keystone species, because they have a disproportionately large influence on the bacterial ecosystem as a whole.[9]

When it comes to choosing a probiotic supplement to support the butyrate-producing species, the recommended bifido species include:

  • B. infantis
  • B. longum
  • B. breve

Any Bifidobacteria stain will likely be able to perform the cross-feeding function, but these three species have other anti-inflammatory benefits, as will be discussed further below. Lactobacillus rhamnosus GG (found in Culterelle) is another good choice for promoting butyrate-production and thereby calming the immune system.

Using Probiotics to Suppress Harmful Species

The second way in which probiotics can help to rebalance a microbiome in disarray is by inhibiting the growth of harmful bacteria such as Klebsiella, E. coli, Streptococcus, and other species implicated in inflammatory diseases.[10] Almost all probiotics will combat these pathogens to some degree, by competing with the harmful species for nutrients. Lactobacilli and Bifidobacteria are also generally helpful in suppressing pathogenic bacteria and yeast purely as a function of their general metabolism.  That is because these species naturally produce acids that will lower the pH in the gut and thereby suppress many harmful species.

Against this backdrop, some probiotic species appear to have a particularly good ability to inhibit the growth of pathogenic bacteria: [11]

  • B. breve
  • B. infantis
  • B. longum
  • L. rhamnosus
  • L. plantarum

A probiotic supplement including some combination of these species is a good starting point in the fight to reclaim territory from the pathogens that contribute to inflammation.  Yet there are even more potent options available, if we take advantage of the fact that even within the same species, some very specific strains of probiotics have pathogen-fighting properties that exceed that of other strains.

For example, within the L. reuteri species, the strain L. reuteri DSM 17938 appears to be particularly good at outcompeting pathogens. As a result, this particular strain (sold as BioGaia Protectis®) is often given to preterm infants to prevent serious infections.[12] As further evidence of its ability to suppress pathogens, the strain helps to reduce the number of episodes and duration of infectious diarrhea in young children attending day care centers.[13] A recent study also suggest that this strain is effective in combatting constipation-dominant SIBO, by reducing the population of methane-producing bacteria in the small intestine.[14]

Within the L. rhamnosus species, the Culterelle® strain L. rhamnosus GG also has a slight edge in preventing opportunistic infections after antibiotics.[15] It also outperformed many other probiotics in a study focused on reducing the severity and duration of infectious diarrhea in children.[16] This strain is a particularly good choice because it helps to calm inflammation, boost the butyrate producers and restore the gut barrier.

Culturelle and BioGaia Protectis are therefore good options to consider. These products are widely available in many countries and are relatively inexpensive.

Advanced Pathogen-Fighting Probiotics

For a more aggressive approach to combating overgrowths of harmful bacteria or yeasts, we can turn to even more potent probiotics. Namely, the pathogen-fighting probiotics that been proven effective in preventing or treating serious infections such as post-antibiotic C.difficile infection and adherent-invasive E.coli.  These probiotics are:

  • BioK+® ( acidophilus CL1285, L.casei LBC80, L.rhamnosus CLR2)
  • Mutaflor® (E. coli Nissle 1917)
  • Florastor® (S. Boullardii CNCM I-745)

These products are typically more expensive and not as widely available as other probiotics, but they are supported by clear evidence from multiple randomized clinical trials.[17] These pathogen-fighting strains are exceptionally good at combating overgrowths of harmful bacteria because they have the unique ability to produce specific anti-microbial compounds. They can also block other organisms from adhering to the gut lining, which makes it more difficult for the harmful species to take up residence.

If testing shows you have an overgrowth of inflammatory species such as Candida, E.coli, Streptococcus, or Klebsiella, it may be worth using one of these advanced pathogen-fighting options for one or two months to help clear the overgrowth. When it comes to choosing between these options, each has different advantages and availability in different countries.

BioK+

BioK+ contains three proprietary strains: L. acidophilus CL1285, L.casei LBC80, and L.rhamnosus CLR2.  It is available in capsule form, or in dairy, rice, or soy-based drinks in WholeFoods and other health food stores in the United States and Canada. It is unfortunately difficult to obtain in other countries at time of writing.

The strains were originally isolated in the 1970s from the stools of a healthy infant. Dr Francois-Marie Luquet isolated a variety of bacterial strains then identified three strains with the strongest antimicrobial activity against various pathogenic bacteria.  After several years of research to optimize culture conditions and gastrointestinal survival of the strains, the Bio-K+ product was developed.[18]

Since that time, it has been used extensively in hospitals to prevent C. difficile infections. Following an outbreak of potentially fatal C.difficile infections in one hospital in Montreal in 2004, doctors began providing Bio-K+ to all patients there treated with antibiotics.

Multiple randomized, double-blind, placebo-controlled trials have now confirmed that Bio-K+ reduces the risk of developing the infections that cause antibiotic-associated diarrhea.[19] For example, one study found that 44% of patients treated with antibiotics alone developed diarrhea and 24% developed C.difficile infection, whereas of the patients taking taking two capsules per day of BioK+, only 15% developed diarrhea and only 1% developed C.difficile infections.[20]

These findings are important because beyond C.difficile, many of the other infections that cause diarrhea in those taking antibiotics correspond to the infections that contribute to systemic inflammation, such as Klebsiella, E.coli and Candida.[21]  The strains found in BioK+ may therefore be helpful to combat overgrowths of these pathogens.

Laboratory studies have also found that the strains used in Bio-K+ have strong antimicrobial activity against E. coli O157:H7, Salmonella, Staphylococcus, Listeria, and Enterococcus faecalis, all of which are strongly inflammatory.[22]

BioK+ has many other advantages, including a long history of use in hundreds of thousands of patients. The manufacturer also performs extensive quality control to verify strain identity and potency in each batch of the final product and the strains have demonstrated survival in the gastrointestinal environment. [23]  The drink formulations are certified gluten free and available in dairy-free forms (either rice or soy fermented drinks). These factors, along with its proven effects in protecting against serious gut infections, make BioK+ a good choice for a short-term pathogen-fighting protocol.

Mutaflor

Mutaflor contains an extensively studied strain of E.coli, called E.coli Nissle 1917. This particular strain was originally isolated from a soldier in World War I who escaped a severe outbreak of diarrhea affecting his regiment. The strain is thought to have protected the soldier from infection by Shigella. Unlike many other strains of E.coli, Nissle 1917 does not produce any known toxins or elicit an inflammatory response.[24]

Soon after the strain was isolated, it became apparent that it could not only help to prevent infections, but also treat other intestinal conditions. It began being used as a probiotic supplement in Europe in the 1920s, under the trade name Mutaflor.  Since then, research has confirmed the value of this particular probiotic strain in the treatment of diarrhea, constipation, and ulcerative colitis.

In patients with ulcerative colitis, two clinical studies have found that Mutaflor shows efficacy in maintaining remission equivalent to the gold standard treatment, mesalazine.[25] As a result of these studies, Mutaflor is actually one of the few probiotics licensed as a medicine in Europe.  A clinical trial in Crohn’s disease also reported a lower relapse rate after 12 months receiving steroid treatment in combination with Mutaflor.[26]

Importantly, there is good reason to believe that in these conditions, Mutaflor works in part by suppressing pathogenic E.coli. [27] As discussed previously, there is a growing body of research linking many cases of Crohn’s, ulcerative colitis, and spondyloarthritis to a particularly aggressive form of E.coli, called “Adherent-invasive E.coli” (AIEC). Researchers have now found that E.coli Nissle 1917 can effectively inhibit the adhesion and invasion of various AIEC strains isolated from patients with Crohn’s disease.[28] In laboratory studies, E.coli Nissle 1917 can in fact outcompete a range of pathogenic E. coli strains.[29] It also appears to be particularly good at inhibiting the growth of Klebsiella and preventing invasion by Salmonella, Yersinia, Shigella, Listeria, and various other species known to cause serious gut infections.[30] When given to newborns, E.coli Nissle 1917 colonizes the gut and reduces infection by pathogenic bacteria.[31]

Beyond suppressing harmful bacteria, E.coli Nissle 1917 may also directly calm inflammation and help to repair the gut barrier.[32] Mutaflor is readily available in capsule form in Europe, Canada, Australia, and the United Kingdom. Unfortunately the FDA barred Mutaflor from sale in the United States in 2011 because it does not fall within the technical definition of a “dietary ingredient,” unlike other probiotic species that have long been included in foods such as yogurts.[33] To be sold in the U.S., Mutaflor would therefore have to be approved as a drug, which is a long and expensive endeavor. Until the situation is resolved, many people in the U.S. have resorted to ordering from online Canadian pharmacies.

Florastor

Saccharomyces Boulardii is a species of yeast distantly related to bakers yeast. In recent years, it has become a popular probiotic, particularly in the context of treating Candida yeast and preventing the opportunistic infections that often arise after antibiotic use. Although there are now many products available containing S. Boulardii, it is important to note that all of the clinical studies showing efficacy in combatting pathogens have been performed with a specific strain, known as S. Boulardii CNCM I-745 or the Biocodex strain. This particular strain is sold under the trade name Florastor.

The Biocodex strain of S. boulardii was discovered in Southeast Asia in 1920 by the French microbiologist Henri Boulard. He was searching for new strains of yeast to use in fermentation and happened to be visiting an area during a cholera outbreak. He noticed that people drinking a tea made from the skins of lychees were able to resist the cholera infection. Eventually, he isolated a specific strain of yeast from the surface of the lychees and found that it was this yeast that conferred protection against cholera.[34]

Since that time, more than 50 randomized clinical studies have been performed to investigate the extraordinary properties of this strain, with many showing that it can protect against a variety of infections.[35]

For example, numerous controlled trials have found that those taking S. boulardii during antibiotic treatment are about 50% less likely to develop antibiotic-associated diarrhea, which is usually caused by opportunistic infections. [36] [37]  A 2017 study found that taking S.boullardii in conjunction with antibiotics leads to less overgrowth of E.coli.[38]

Supplementing with S. boulardii does not just prevent gastrointestinal infections but can also help to reduce the severity of infections that are already established.[39] Studies have found that S.boulardii can reduce the severity of infectious diarrhea, which is often caused by pathogens such as E. coli or Salmonella.[40]  It has also been shown to directly inhibit other specific pathogens most often associated with inflammation and SIBO.[41] One way in which S.boulardii can reduce the severity of gut infections is by blocking or breaking down the toxins they produce, such as lipopolysaccharide.[42]

Furthermore, S. boulardii is particularly well known for its activity against a variety of species of Candida yeast.[43] In addition to suppressing the growth of Candida, it has a strong negative effect on the ability of Candida to adhere to surfaces and form protective biofilms.[44] This ability to combat Candida is invaluable because Candida overgrowths in the GI tract are very common and highly inflammatory.[45] Higher levels of intestinal Candida are often seen in those with Crohn’s disease and ulcerative colitis.[46] It has been suggested that inflammation in the gut makes it easier for Candida to colonize, which then triggers further inflammation in a vicious cycle.[47]  Supplementing with S. boulardii could be one step towards breaking this cycle.

In addition to suppressing harmful bacteria and yeasts, S. boulardii can also help to restore the intestinal barrier. This was evident from a study of patients with Crohn’s disease, who still show abnormal intestinal permeability even when the disease is in remission. When a group of patients took S. boulardii for three months, their intestinal permeability improved.[48]

The effect of S. boulardii in Crohn’s disease does not end there. It also significantly reduces symptoms and the risk of relapse. When patients with Crohn’s disease in remission took S. boulardii for six months, only 6% relapsed, compared to 38% not taking the probiotic.[49]  In another placebo-controlled study, S. boulardii significantly reduced the severity of Crohn’s disease in those with continuing moderate symptoms.[50] Again, this likely occurs by suppressing pathogens that would otherwise antagonize the immune system. S. boulardii may therefore be able to play a similar role in dialing back other related autoimmune diseases.

  1. boulardii is not suitable for everyone, however. Isolated cases of S. boulardii entering the bloodstream and causing infection have been reported in seriously ill patients and those with central venous lines.[51] S. boulardii should probably also be avoided by those with an allergy or hypersensitivity to baker’s yeast (Saccharomyces cerevesiae), because the two are closely related.

If you decide to try S. boulardii, it is best to choose the Florastor brand if you can because this product contains the specific strain used in the clinical trials discussed above. The dose used in most studies is 500-1000 mg per day, which corresponds to two-four capsules per day.

Probiotics and SIBO

The value of probiotics in treating small intestinal bacterial overgrowth (SIBO) is hotly debated. Some take the view that if SIBO is caused by an excess of bacteria in the small intestine, then adding further bacteria in the form of probiotics is counterproductive. In addition, those with SIBO often find that probiotics can worsen symptoms such as bloating and histamine reactions, at least in the short term.

The alternate view is that the inflammation and damage caused by SIBO is often driven by particular species of unfriendly bacteria and probiotics can be a key weapon in suppressing those species in the long term. Probiotics may also combat SIBO in other ways, such as improving the speed of transit through the digestive system, which reduces the opportunity for bacterial overgrowth.

The clinical studies that have been done so far do indicate that probiotics can be somewhat helpful in treating SIBO. For example, we saw earlier that the BioGaia Protectis strain of L. reuteri appears to be effective in combatting methane-dominant SIBO. Another study found that four weeks of treatment with a probiotic combination that included several Bifidobacteria and Lactobacillus species was able to eradicate SIBO in a quarter of patients.[52]  A similar probiotic combination was able to produce a clinical improvement in 80% of patients with SIBO, whereas only 52% of patients taking antibiotics improved.[53] Other probiotic species that have been found helpful for SIBO include Lactobacillus casei, Bacillus clausii, and Bacillus coagulans.[54] These species are not necessarily the best choices for those with autoimmunity though, because they can be somewhat inflammatory.

Two other types of probiotics are often recommended to those with SIBO:  soil-based organisms and so called “D-lactate-free” probiotics.  There is little to no clinical evidence supporting the use of soil-based organisms and these products should be considered high-risk, given the possibility that they can colonize the gut long term.

The benefit of D-lactate free probiotics may also be oversold.  The supposed advantage of these probiotics is based on the fact that in some cases, SIBO can involve an excess of D-lactate.[55]  Although the body has mechanisms to quickly metabolize lactate, extreme excess is though to cause fatigue, weakness, and cognitive impairment.[56] Companies have therefore marketed probiotics that produce very little D-lactate as more suitable for those with SIBO. Yet the original studies linking D-lactate to SIBO were done in the context of severe SIBO caused by surgical shortening of the small intestine. This is a very unique situation and the findings cannot be extrapolated to ordinary SIBO.  Very little is known about the role of D-lactate is producing symptoms of SIBO in those with intact digestive systems. Nevertheless, if you do notice worsening fatigue or cognitive impairment with lactobacillus probiotics, note that Bifidobacteria species typically produce very little D-lactate.

In the end, our choice of probiotic in the context of SIBO should focus on the ultimate goal of reducing the burden of pathogens in the small intestine. Bifidobacteria are likely helpful in this context, but we may see even more benefit from the specialist pathogen-fighting strains discussed above: BioGaia Protectis, Mutaflor, BioK+, and Florastor. These have all been studied extensively in clinical trials and have been found to suppress a range of pathogens that are common culprits in causing SIBO. They also share the important properties of reducing overall inflammation and helping to repair the gut barrier, which are the other key goals of probiotic treatment.

Using Probiotics to Restore the Integrity of the Gut Barrier

Probiotics that suppress harmful species of yeast and bacteria will go a long way towards healing leaky gut. That is because pathogen overgrowth is often one of the root causes of increased intestinal permeability.[57] By addressing the cause of the problem, we give the natural repair mechanisms a chance to work.

Yet probiotics can also help to directly support the healing process itself. That is because butyrate is in fact the main energy source for the cells lining the intestines. It powers the repair and regeneration of every component of the intestinal barrier.[58]  Because probiotics such as Bifidobacteria and L. rhamnosus GG help to support butyrate-production, they can therefore help to reverse leaky gut.[59] Other strains of probiotics can also promote repair and regeneration of the intestinal lining in more direct ways.  E.coli Nissle 1917 and B. infantis, for example, have both been found to produce compounds that directly up regulate the production of tight junction proteins.[60]

Overall, the probiotics that are particularly good at reversing leaky gut include:[61]

  • B. infantis
  • B. breve
  • L. rhamnosus GG
  • E. coli Nissle 1917
  • L. plantarum
  • L. acidophilus.

Anti-inflammatory vs. Inflammatory Probiotics

All the beneficial effects of probiotics discussed so far have the net effect of reducing inflammation. But probiotics can also directly modulate the immune system, for better or worse. That is because different probiotics can shift the dial on the immune system in different directions.  Some can reduce the production of inflammatory mediators, which makes the immune system more tolerant and less likely to overreact to perceived threats.  Other probiotics activate components of the immune system that fight infection, but in the process may increase the production of inflammatory mediators.

Probiotics that are known to be anti-inflammatory include: [62]

  • B. infantis
  • B. breve
  • B. longum
  • L. rhamnosus GG (Culturelle)
  • L. reuteri DSM 17938 (BioGaia Protectis)
  • B. infantis 35624 (Align)
  • E. coli Nissle 1917 (Mutaflor)
  • S. boulardii CNCM I-745 (Florastor)
  • L. acidophilus

At the cellular level, these probiotics have been shown to reduce a wide variety of inflammatory mediators, including the mediators involved in psoriasis and arthritis.[63] Clinical studies also show that these probiotics can reduce the severity of inflammatory conditions such as ulcerative colitis, allergy, and eczema.[64]

In contrast, certain other probiotics can tend to promote immune activation and could potentially undermine our efforts to lower inflammation.  There are two main ways in which this can occur in the autoimmune context.  The first is by activating immune cells called T helper 17 cells (Th17), which produce powerful inflammatory mediators. The second is by producing large amounts of histamine, which can trigger the innate immune system.

Th17 cells, IL-17, and Probiotics

Th17 cells are specialized helper immune cells that have recently been recognized as playing a significant role in driving autoimmune disease.[65] Th17 cells produce a cytokine called Interleukin 17 (IL-17).  This is an immune-stimulating mediator that ordinarily plays an important role in combatting gut infection, but can also orchestrate the inflammation involved in some autoimmune diseases, particularly ankylosing spondylitis, psoriatic arthritis, and psoriasis. In fact, the newest generation of biologics used to treat these conditions (such as Cosentyx and Taltz) actually work by blocking IL-17.

Given that IL-17 plays a key role in driving inflammation, it stands to reason that we should try to minimize anything that boosts IL-17. Some species of bacteria and yeasts are very strong inducers of IL-17. This includes Klebsiella, Candida albicans, Campylobacter, Enterococcus and other common gut pathogens, but also species occasionally found in probiotic supplements, such as B. adolescentis.[66]

Research in this area has only just begun, so for many species of probiotics, we have no information about how they influence Th17 cells and IL-17 production. Yet we do know that some probiotics can actually calm inflammation by reducing IL-17 production, while many others have very little direct effect on IL-17. At time of writing, the best available information we have is as follows:

Mild suppressors of IL-17: [67]

  • L. rhamnosus GG
  • B. longum subspecies infantis 35624
  • L. acidophilus
  • L. reuteri DSM17938.

Little to no direct effect on IL-17: [68]

  • B. breve
  • B. infantis
  • B. longum
  • B. lactis
  • L. rhamnosus
  • L. casei
  • S. boulardii

Possible inducers of IL-17:[69]

  • B. bifidum
  • B. coagulans

Strong inducers of IL-17: [70]

  • B. adolescentis
  • Klebsiella pneumoniae
  • Enterococcus Faecalis
  • Campylobacter jejuni
  • Candida albicans
  • Citrobacter species
  • Salmonella species

Until more is known, the most cautious approach is to strictly avoid probiotics that contain B. adolescentis. What is less clear is whether we need to avoid probiotic combinations that contain B. bifidum. On its own, this species appears to be a mild-to-moderate inducer of IL-17 in laboratory studies.[71] But in at least one animal study, a probiotic combination that included B. bifidum decreased IL-17 production overall (and also suppressed experimental Inflammatory bowel disease and rheumatoid arthritis).[72]  B. bifidum is particularly good at combatting infections, so in real life it may ultimately lower IL-17 levels by suppressing other inflammatory bacteria or yeasts.

A similar effect has been seen with B. breve and L. casei.  On their own, these species have no direct effect on IL-17 production. But in the real world context, they significantly reduce the IL-17 production triggered by other infections.[73]

Ultimately, the major cause of high levels of IL-17 in those with autoimmune disease is likely to be the overgrowth of species such as Klebsiella, E.coli, and Candida. Addressing these overgrowths with pathogen fighting probiotics is probably the one of the best tools we have to naturally lower IL-17. Other strategies that can help to reduce IL-17 production include getting adequate amounts of vitamin A and vitamin D and supporting our resident butyrate-producing microbes.[74]

Histamine production by probiotics

The second way in which probiotics can potentially promote inflammation is by producing histamine.  Some species of bacteria produce large amounts histamine by degrading dietary amino acids.  In sensitive individuals, this histamine then activates mast cells, which triggers an increase in intestinal permeability, along with a variety of allergy-like symptoms, such as itching, flushing, fatigue, and headaches.

The probiotic species typically regarded as the worst when it comes to histamine production are S. thermophilus and L. bulgaricus.[75] There is unfortunately a lack of reliable data about histamine production by many other species. Even within the same species, different strains may produce different amounts of histamine. We do know that in general, Bifidobacteria are less likely to produce histamine than lactobacilli.  Within the lactobacilli species, L. acidophilus and L. rhamnosus are not typically histamine producers.[76]

The fact that a probiotic combination contains some histamine-producing species is not necessarily a deal-breaker, however.  This is because other strains in the combination may be good at degrading histamine, and the combination as a whole may be good at suppressing histamine-producing bacteria naturally resident in your gut. The high potency combination probiotic VSL#3, for example, contains the high-histamine producers S. thermophilus and L. bulgaricus. Some people will tolerate this probiotic, while others will not. (Note that researchers have recently raised quality concerns with VSL#3, following a change in manufacturing).

If you find you are particularly sensitive to histamine-producing strains of probiotics, the root cause may be an overgrowth of histamine producing or immune-stimulating microbes in your gut. Recent studies have found that certain of gut microbes can produce a massive amount of histamine. This includes Citrobacter and Morganella morganii. (Overgrowths of these particular species can be detected on stool tests, such as the GI-Map). Other pathogens in the gut can also stimulate the immune system itself to release histamine. This includes Candida yeast, for example.  The net effect is that an overgrowth of pathogens can heighten sensitivity to additional histamine from probiotics.  Yet probiotics that combat these pathogens may be the best long-term solution to histamine intolerance.

 

Probiotic Buyers Guide

 

Level 1 Probiotics:

The best place to start for most individuals is likely a combination that includes several Bifidobacteria species. That is because Bifidobacteria strains are typically the best at cross-feeding the butyrate producers, restoring the gut barrier, and calming inflammation. Within the Bifidobacteria, the best species are:

  • B. infantis
  • B. longum
  • B. breve

Recommended combination products that have one or more of these species include:

The Jarrow product may be best for those with significant dairy allergies, while the Klaire or Probiotic Pearls products are better options for those who need to strictly avoid starch.

Each of these combinations also contain lactobacillus species that may provide some further help in suppressing harmful bacteria and restoring the gut barrier. For example, L. acidophilus is known for its ability to combat leaky gut, while three of the specific strains used in the Jarrow Allergen Free combination are particularly good at suppressing E.coli (namely, L. plantarum LP01, L. rhamnosus LR-04, and B. breve BR-03).

As an alternative to a multi-strain probiotic (or even in addition), Culturelle and BioGaia Protectis are also good choices for basic probiotics. It is a matter of personal preference and experimentation to determine what works best for you.

All of these Level 1 probiotics are good options for long-term maintenance, to continue supporting our beneficial microbes while providing less opportunity for undesirable species to take up residence. If however you do not see sufficient improvement with one of these probiotics, or you already know you have a significant pathogen overgrowth, you may see better results with one of the more potent probiotics detailed below.

Level 2: Probiotics

If we want a combination that includes a larger number of Bifidobacteria species, and are willing to include B. bifidum, there are many other good Bifidobacteria combinations products available, such as:

Among these products, Gut Pro and Renew Life are the best options for those sensitive to dairy or starch.

Because these probiotics contain B. bifidum, they may be slightly more effective than other Bifidobacteria combinations at combating pathogens.  Yet once pathogen overgrowth is reduced, it may be preferable to return to one of the level 1 probiotic options above, for the greatest reduction in inflammation.

Level 3: Advanced Pathogen- Fighting Probiotics

For the most aggressive strategy to combat pathogens, the best probiotics are:

For those with severe inflammation, a known pathogen overgrowth of species such as Klebsiella, or a diagnosis of SIBO, it may be best to start with one or two months of treatment with one of these specialist probiotics. This intensive treatment phase will help control harmful bacteria and yeasts and you can then switch to one of the basic maintenance probiotics for long-term use.

Other Factors Influencing Probiotic Choice

Ultimately, the best option in your particular case may depend on many factors, including your budget, country, and ability to tolerate trace amounts of starch, dairy, or other ingredients.

Probiotics without fillers containing starch, prebiotics, or maltodextrin include:

Dairy free probiotics include:

Probiotics available outside the United States

Culturelle Health and Wellness: UK, CA.

Blackmores Probiotics + Eczema Relief (same L. rhamnosus GG strain as Culturelle) AU*

Mutaflor: AU, UK, CA (also ships to US)

BioGaia Protectis: US. UK. CA AU*

Probiotic Pearls Digestion and Immunity: UK.

Jarro-Dophilus Allergy Free: UK.

Florastor: AUCA , UK

References

[1] Canani, R. B., Sangwan, N., Stefka, A. T., Nocerino, R., Paparo, L., Aitoro, R., … & Nagler, C. R. (2016). Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants. The ISME journal, 10(3), 742-750.

[2] Falony, G., Vlachou, A., Verbrugghe, K., & De Vuyst, L. (2006). Cross-feeding between Bifidobacterium longum BB536 and acetate-converting, butyrate-producing colon bacteria during growth on oligofructose. Applied and environmental microbiology, 72(12), 7835-7841.

[3] Rios-Covian, D., Gueimonde, M., Duncan, S. H., Flint, H. J., & Clara, G. (2015). Enhanced butyrate formation by cross-feeding between Faecalibacterium prausnitzii and Bifidobacterium adolescentis. FEMS microbiology letters, 362(21), fnv176.

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