Probiotics are valuable tools in helping to balance the bacterial communities found in our digestive system. Many chronic health conditions are slowly having their roots traced back to this balance. An imbalance in gut bacteria has been connected to many chronic health conditions such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Chron’s Disease, arthritis, and depression.
This systemic connection between gut bacteria and health has led many to use probiotic supplements. Probiotics can impact every individual differently and should always be taken with mindful observation. Even the best probiotics on the market can cause unwanted, negative effects. There are many considerations to make when weighing the potential health benefits of probiotics. This article discusses some of the more influential characteristics of probiotic bacteria to help you better navigate these uncertain, but often very beneficial, waters.
D-Lactic Acid vs. L-Lactic Acid
Lactic acid is a compound produced naturally by the human body and is used in many processes such as energy production. This compound is found in nature in one of two isomer forms; D-Lactic Acid or L-Lactic acid. Both of these variations are found in the human body, but only L-Lactic acid is actually produced by the body naturally.
D-Lactic acid is produced by many different types of bacteria and is considered an accurate biomarker for bacterial overgrowth (when it’s found in excess). Much of the data we have for bacteria and lactic acid levels produced by them come from the study of food preservation. Eggs, for example, are thought to be past their shelf life when 200mg/kg of L-Lactic acid is observed (R). This illustrates how the measurement of lactic acid concentration can help assess bacterial presence. It’s an important system in food science but also has a place in assessing bacterial influences on human health.
Measuring the ratio between types of lactic acid is also a useful indicator to suggest pathogenic bacterial overgrowth. For example, patients suffering from Chronic Fatigue Syndrome have been found to have higher levels of D-Lactic acid in their blood (R).
Recent research has even shown that ME/CFS can be accurately predicted in 82% of cases by analyzing fecal bacteria and serum inflammatory biomarkers. The takeaway here; bacterial imbalances are more and more frequently being connected to chronic health conditions. These types of bacteria are often noted as producing high levels of D-type lactic acid, though many beneficial bacteria also produce it to some degree. This isn’t usually an issue but can become troublesome when these bacteria outnumber L-Lactic acid producers.
Another very important consideration to make when selecting a probiotic is the impact it will have on histamine levels. Histamine is a neuroregulatory molecule that our bodies use for a wide array of functions. It plays a role in cognitive function, digestion, and allergic reactions. Our bodies have several types of histamine receptors; H1, H2, H3, and H4. These sites are found in our body where histamine attaches to help facilitate some other process. Histamines are commonly associated with allergies and symptoms such as watery eyes, stuffy nose, and itchy skin.
These symptoms are natural reactions to foreign invaders such as pollen or black pepper—but also sometimes become chronic in response to a seemingly-unknown cause. There are several fairly common genetic mutations that can affect your body’s ability to regulate histamine. These may affect the histamine production and removal at any stage during its lifecycle—all ultimately having potential to underlie histamine intolerance. Histamine is produced through the conversion of histidine via the L-Histidine Carboxylase (HDC) enzyme. Other enzymes, Diamine Oxidase (DAO) and Histamine N-methyltransferase (HMT), are responsible for getting rid of histamine.
Any issues in the production of HDC, DAO, or HMT could potentially cause disturbances in histamine regulation. There are certain common genetic mutations known to be connected with these issues with DAO activity. Minor alleles for rs2052129, rs2268999, rs10156191, and rs1049742 are associated with lowered DAO activity while rs2071514, rs1049748, and rs2071517 are associated with more robust protective levels (R). These types of variants strongly influence the production and activity of DAO—and thus histamine—but aren’t enough to predict histamine intolerance alone.
The Bacteria Connection
Certain types of bacteria produce histamine at much higher levels than others. These aren’t necessarily bad bacteria, though they may cause great difficulty for those suffering from histamine intolerance issues. Many of these bacteria are common in consumer probiotics and include such names as Lactobacillus casei, Lactobacillus bulgaricus, and Lactobacillus rheuteri.
Other bacteria such as Lactobacillus Acidophilus are considered to be more histamine-neutral—but still, produce some levels of histamine. In the vast majority of multi-strain consumer probiotics, histamine producing, histamine neutral, and histamine reducing bacteria are all found together. This diversity is generally regarded as beneficial and supportive of optimal digestive health.
For those with histamine-related issues, however, these bacteria can cause existing symptoms to worsen. Adverse reactions to probiotics commonly regarded as beneficial can be a likely signal of histamine imbalance or gut bacteria dysbiosis. A careful examination of which types of probiotic bacteria are low-histamine producers or even histamine-lowering may offer viable options for those managing histamine issues.
Probiotic Bacteria Research
The amount of data present for differentiation among probiotic bacteria is sparse. The majority of data comes from food preservation sciences, some from animal studies, and only a small amount from human studies. Many different bacteria strains are present in consumer probiotics that haven’t been well studied in controlled environments. We took a quick survey of the 100 best-selling probiotics on Amazon.com and found nearly 100 unique bacteria types.
While such species as Lactobacillus Acidophilus are common among many, other rarities such as Azomonas agilis are found in only a handful. We consider the presence of multiple sources of data important when classifying anything, but especially in the classification of probiotic bacteria. For this reason, much consideration found in this article is focused on those most-commonly studied bacteria that were also found among the list of most-common consumer probiotics.
Even among individual bacteria species, there are variances in how unique strains perform with regards to histamine and lactic acid production. At this point, the following attempt to identify low-histamine and low d-lactic acid producers are really just a best guess.
Beneficial Bacteria for Sensitive Individuals
There are no sure-things when it comes to bacteria. In most cases, when it comes to estimating the influence a particular bacteria might have on health, one must make broad considerations and be ready to experiment. We do have some solid scientific data to help inform these guesses.
When it comes to trying to select probiotics for selective individuals, one such consideration is the net histamine contribution of a species. Some bacterium may lower overall histamine levels, others may increase them, and some may have no impact whatsoever.
Low Histamine Producers
In one study, investigating the presence of biogenic amines in cider, researchers investigated the potential of several bacterial strains to produce histamine, tyramine, and putrescine—all markers of food spoilage. Among the data, researchers noted that non-histamine producers included Lactobacillus brevis CECT216 and Lactobacillus plantarum (R).
In another study, investigating various biogenic amines produced by lactic acid bacteria, researchers also found Lactobacillus plantarum, Lactococcus lactis, Lactobacillus casei, and Lactobacillus bulgaricus to also not produce histamine (R). Additionally, researchers also found that Klebsiella oxytoca, Citrobacter freundii and Enterobacter cloacae all to produce large amounts of histamine. These bacteria are often found in higher amounts among patients suffering from gut dysbiosis (R).
Lactobacillus Rhamnosus was found to produce small amounts of [ both D and L lactic acid] but nearly 400% more L-Lactic acid
One study investigating the ability of Bifidobacterium longum spp. Infantis and Lactobacillus rhamnosus isolated certain amines produced by each. Bifidobacterium longum subsp. Infantis CECT 7210 was found to produce a near-zero amount of D-lactic acid and no histamine whatsoever.
Lactobacillus Rhamnosus was found to produce small amounts of each, but nearly 400% more L-Lactic acid (R). This study ultimately concluded that the Bifidobacterium longum subsp. Infantis strain showed strong potential as an antiviral and immunological enhancing therapy.
In a previous article on Bifidobacterium and histamine, we discussed a study that found both Bifidobacterium infantis and Bifidobacterium longum to exert histamine-lowering effects in animal studies (R). This benefit was seen in pretreatment in mice prior to allergen exposure. Researchers found that mice in the test group were seen to not only show lower overall levels of histamine but to also have a smaller degree of gene expression associated with histamine reactions.
One study found that several different Lactobacillus plantarum species were able to reduce histamines and other biogenic amines found in wine. It was ultimately found that the most beneficial strains of Lactobacillus plantarum in lowering histamine content were, in order of most effect, NDT 03, NDT 16 and NDT 21 (R). Lactobacillus Rhamnosus GG is a strain of bacteria that has been extensively studied compared to other types. This strain, in particular, has shown the ability to colonize up within the human GI tract (R).
Assuming that different subspecies will perform similarly is incorrect. Not to say that they wouldn’t—just that one can’t make the assumption. For example, Lactobacillus Rhamnosus GG has evidence of positively influencing human health. Other sub-species might also offer positive benefits but are likely to vary in their specific influence. Again, we’re left to wait in see.
MOS, FOS, & High-Fiber Foods
Additional ingredients found in probiotics should also be carefully scrutinized. Many probiotics contain pre-biotic ingredients such as Fructooligosaccharides (FOS), Mannanoligosaccharides (MOS), or insoluble fibers meant to help bacteria ferment and colonize. These materials are very effective in providing a food source for probiotic bacteria—but may also nourish any existing harmful bacteria.
These so-called prebiotic compounds have been attributed to significantly lowered all-cause mortality rates. That’s big news. Regular consumption of healthy dietary fibers has been scientifically proven to help extend and improve human life (R). It’s thought such compounds help maintain healthy levels of digestive bacteria species in the gastrointestinal tract (among many other favorable actions.)
What of the individuals with poor existing bacteria balances though? It’s likely that such compounds would also feed these species as well resulting in reinforcement of existing dysbiosis. Foods high in these types of compounds are known to stimulate bacterial fermentation, sometimes as much as 30 grams of bacterial for every 100 grams of fermented carbohydrate! When approaching such cases, one should do so with the understanding that addressing bad bacteria should at least be done simultaneously in addressing positive species. The tide that raises all ships and etc.
Probiotics for Sensitive Individuals
There are probiotics out there that have lots of scientific support and also a positive reputation among many health practitioners. Isolated species, the types found in dietary supplements, offer a most isolated testing ground to gauge reactions—as opposed to fermented foods that are host to any number of species. Considering the research discussed here, the following probiotic species are the likeliest to provide a positive influence on digestive health with minimal probability of unfavorable results:
- Lactobacillus rhamnosus,
- Bifidobacterium infantis
- Bifidobacterium longum
There were many bacteria that have been noted as being low-histamine producers but were still high D-lactic acid producers. Inversely, there are also many bacteria that are noted as being low D-lactic acid producers but high histamine producers. These three bacteria were among the most commonly studied in the data we’ve seen that exhibit an overall impact of not increasing histamine or D-Lactic acid.
Bifidobacterium infantis and Bifidobacterium longum have both been noted to reduce histamine levels, and also have do not increase D-lactic acid levels.
Lactobacillus rhamnosus does produce a small amount of D-lactic acid, but it’s a near-negligible amount. It is a high-producer of L-lactic acid and has been shown to lower histamine levels as well as downregulating the genes associated with mast cell activity (involved in histamine release) (R).
Bifidobacterium is regarded as being native colonizers to the human gut and are generally non-lactic acid producers. Most all Lactobacillus types produce lactic acid—hence the name. There are likely many other bacteria that should be considered for use among highly-sensitive induvial but these represent those best described in currently-available data.
Existing data describing the impact of common probiotics on histamine and lactic acid levels are sparse. This article draws on data spanning from the scientific study of food, animal, and human bacterial dynamics. There is much variation in data presentation as well as identification of study species.
Consideration for net histamine and D-lactic acid production, as a result of probiotic supplementation, is an essential consideration for those with higher expressed food sensitivities. Additionally, ingredients such as MOS, FOS, and high dietary fiber may also present challenges for those with high levels of unwanted bacteria. Avoiding probiotics that include these compounds may also be a favorable measure for those with sensitivities.