Probiotics: A Guide For Those With Food Sensitivities

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 this balance. Gut bacteria have been shown capable of physically altering the composition of our brain, influencing emotions, and have been connected to chronic health conditions such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). This systemic connection between gut bacteria and health has led many to use probiotic supplements. Some of the best probiotics will affect many people differently and, in some cases, those heralded as most-beneficial may actually make things worse. This article discusses some important considerations to make before deciding whether probiotics may offer you benefit, which types may be most-beneficial and why.

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 difference types of bacteria, and is considered an accurate biomarker for bacterial overgrowth when 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 [2]. This type of science highlights that bacteria are commonly known to produce types of lactic acid, and that measurements of lactic acid can indicate amount of growth.

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 [1]. 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 is that a disproportionate increase of certain types of intestinal bacteria is associated with chronic health issues. 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.

Histamine Intolerance

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 [14]. 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 in much higher levels than others. These aren’t necessarily bad bacteria, though they may cause great difficulty for those suffering with 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 Acidophillus 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, they can cause 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 under 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 Acidophillus 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 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 is really just a best guess.

Beneficial Bacteria

In one study investigating the presence of biogenic amines in cider generated a considerable amount of data related to histamine production. This study 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 [5]. 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 not produce histamine [6]. 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 [6].

Lactobacillus Rhamnosus was found to produce small amounts of each, but nearly 400% more L-Lactic acid

One study investigating the ability of Bifidobacterium longum spp. Infantis and Lactobacillus rhamnosus was also able to isolate 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. While Lactobacillus Rhamnosus was found to produce small amounts of each, but nearly 400% more L-Lactic acid [7]. 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 [8]. 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 genetic expression associated with histamine reactions.

One study found that several different Lactobacillus plantarum species were able to actually 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 [9]. 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 [10]. For anyone trying to establish a stronger presence of beneficial bacteria, this would likely be experienced as a positive aspect. These species-specific clarifications aren’t always made in consumer probiotics, illustrating how different brands may offer different results based on no other merit than ingredient source. In addition to impact probiotics potentially have on lactic acid and histamine levels, there are other considerations to make as well.

Oligosaccharides & Inulin Fibers

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. As an example, consider gut bacteria as a balance. On one side of the scale you have good bacteria—on the other side you have the bad bacteria. If you take prebiotic-containing probiotics, there’s a chance that for every increase you see in good bacteria—you’ll also see an increase in existing bad bacteria. This would help introduce new good bacteria, but not work to counterbalance bad bacteria effectively. This might result in a net-increase of lactic acid or histamine—ultimately worsening your existing condition.

The ability of FOS and MOS type compounds to sustain bacteria is well established and often used in laboratory simulations as well in consumer goods. The assertion we’re making that it could present as a hurdle along the path towards restoring gut-bacteria balance is not well-studied. This notion should only be considered as conversational at best. For otherwise healthy individuals, these types of compounds are beneficial in helping to maintain existing bacterial balances. That’s to say; if you’re happy where you are these compounds will likely work to reinforce your current bacterial profile. For those with a strong presence of dangerous bacteria or low diversity of good bacteria, these are likely to impact them negatively.

High Fiber Fruits & Vegetables

Fibrous fruits and vegetables are often regarded as essential to digestive health. They contain many minerals and vitamins essential to health like magnesium, calcium, and vitamin D. These types of foods have been shown in research to help address several digestive issues such as constipation, traveler’s diarrhea, and irritable bowel syndrome [11].  High fiber diets have also been associated with lower rates of any type of death—referred to as all-cause mortality [12]. High fiber diets have been found to be very beneficial in most circumstances, but for those with bacterial dysbiosis they have the potential to cause great harm.

We enter another area of discussion not supported by current data—though worth consideration. Our digestive tract is host to a yet unknown amount of bacteria, both beneficial and potentially harmful. Much of their primary energy is derived from undigested carbohydrates including celluloses, fruit pectins, gums, oligosaccharides, and sugar alcohols [13]. 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! Carbs, sugars, and fiber can all help sustain bacterial growth in our digestive tract. In the presence of favorable bacterial balance such diets will help sustain their presence. It’s likely that such high-fiber diets would help sustain any bacterial balance—even if it were largely comprised of potentially harmful types like  Klebsiella or Citrobacter.

Food Intolerances & Probiotics

Many times those suffering from food intolerances find themselves on woefully-restrictive diets. Giving up carbs, alcohol, sugar and grains seem like huge steps for most. For those suffering from food intolerances these concessions are often only distant memories. Foods like broccoli, carrots, eggs, and especially fruits can wreak all kinds of havoc. One potential explanation is that high fiber diets promote the growth of bad bacteria just as much as they do good bacteria. Such cases are likely found among those with very few types of bacteria, and large proportions of high histamine or D-lactic acid producers. In these cases, many probiotics often cause constipation, acidic stomach, and brain fog. To make this consideration, we’re assuming if fiber can cause good bacteria to grow, it will also cause bad bacteria to grow. Another assumption we’re making is that if you take probiotics and have a bad reaction it may be due to increases in histamine levels or D-lactic acid. Neither of these two notions is well-substantiated by data, but we believe both to be important considerations for those struggling finding an effective probiotic.

The Best Probiotics for Sensitive Individuals

Picking a quality probiotic is a lot of guess work, even when adequately educated. Different strains have been shown to provide dramatically different impacts on levels of histamine and lactic acid. Among the many data sources we’ve cataloged, it seems the best probiotics for sensitive individuals are as follows:

  • 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) [15].  Bifidobacterium are regarded as being native colonizers to the human gut, and are generally regarded as non-lactic acid producers. Most all Lactobacillus types produce lactic acid—having been named for such. 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.

Final Considerations

Existing data describing the impact of common probiotics on histamine and lactic acid levels is sparse. This article draws on data spanning from food science, to human study, and also among animals. There is a high degree of variation in how this data is presented among researchers, as well as how they’ve chosen to identify specific bacteria strains. Probiotics offer a strong hope in the ability to help address many health conditions. Research has tied imbalances of bacteria to chronic health conditions such as ME/CFS, allergies, and even anxiety. It seems safe to say better health is seen among those with a well-balanced microbiome. For those working towards establishing or maintaining such a balance, there are often many unknown hurdles that impede progress. Histamine and D-lactic acid are two compounds with the potential to cause many issues. Making careful consideration of how probiotics impact levels of these compounds may help overcome many issues. Additionally, ingredients such as MOS, FOS, and high dietary fiber may also present challenges for those with high levels of unwanted bacteria.  If you are struggling to rebuild your gut health and have been struggling with probiotics, the above-mentioned bacteria are likely all excellent choices for you to further investigate. There is always the possibility they will impact you negatively as well, and consultation with your doctor and quality laboratory analysis is the only way to truly diagnose your particular circumstance.

References

  1. Sheedy JR, Wettenhall RE, Scanlon D, Gooley PR, … DE Meirleir KL. (2009). Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome. In Vivo, 23(4):621-8. http://iv.iiarjournals.org/content/23/4/621.long
  2. Megazyme International. (2014). D-Lactic Acid and L-Lactic Acid Assay Procedures. https://secure.megazyme.com/files/Booklet/K-DLATE_DATA.pdf
  3. Manome A, Okada S, Uchimura T, Komagata K. (1998) The ratio of L-form to D-form of lactic acid as a criteria for the identification of lactic acid bacteria. J Gen Appl Microbiol, 44(6):371-374. http://doi.org/10.2323/jgam.44.371
  4. Takahashi, K., Terashima, H., Kohno, K., & Ohkohchi, N. (2013). A Stand-Alone Synbiotic Treatment for the Prevention of D-Lactic Acidosis in Short Bowel Syndrome. International Surgery, 98(2), 110–113. http://doi.org/10.9738/CC169
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  6. Bover-Cid S, Holzapfel WH. (1999). Improved screening procedure for biogenic amine production by lactic acid bacteria. Int J Food Microbiol. 53(1):33-41. https://doi.org/10.1016/S0168-1605(99)00152-X
  7. Moreno Muñoz, J. A., Chenoll, E., Casinos, B., Bataller, E., Ramón, D., Genovés, S., … Rivero, M. (2011). Novel Probiotic Bifidobacterium longum subsp. infantis CECT 7210 Strain Active against Rotavirus Infections. Applied and Environmental Microbiology, 77(24), 8775–8783. http://doi.org/10.1128/AEM.05548-11
  8. Dev S, Mizuguchi H, Das AK, Matsushita C, Maeyama K, et al. (2008). Suppression of histamine signaling by probiotic Lac-B: a possible mechanism of its anti-allergic effect. J Pharmacol Sci. 107(2):159-66. Epub 2008 Jun 5. http://doi.org/10.1254/jphs.08028FP
  9. Capozzi, V., Russo, P., Ladero, V., Fernández, M., Fiocco, D., Alvarez, M. A., … Spano, G. (2012). Biogenic Amines Degradation by Lactobacillus plantarum: Toward a Potential Application in Wine. Frontiers in Microbiology, 3, 122. http://doi.org/10.3389/fmicb.2012.00122
  10. Kontula, P., Nollet, L., Saarela, M., … Von Wright, Atte., (2009). The Effect of Lactulose on the Survival of Lactobacillus rhamnosus in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) and in vivo. Microbial Ecology in Health and Disease 14(2), 90-96 http://www.tandfonline.com/doi/abs/10.1080/08910600260081739
  11. Cummings JH, Christie S, Cole TJ. (2001) A study of fructo oligosaccharides in the prevention of travellers’ diarrhoea. Aliment Pharmacol Ther. 15(8):1139-45. http://doi.org/10.1046/j.1365-2036.2001.01043.x
  12. Chuang SC, Norat T, Murphy N, Olsen A, … Vineis P.(2012) Fiber intake and total and cause-specific mortality in the European Prospective Investigation into Cancer and Nutrition cohort. Am J Clin Nutr. 96(1):164-74. http://doi.org10.3945/ajcn.111.028415.
  13. Slavin, J. (2013). Fiber and Prebiotics: Mechanisms and Health Benefits. Nutrients, 5(4), 1417–1435. http://doi.org/10.3390/nu5041417
  14. Maintz L, Yu CF, Rodríguez E, Baurecht H, Bieber T, Illig T, Weidinger S, Novak N.(2011). Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities. Allergy. 66(7):893-902. http://doi.org.10.1111/j.1398-9995.2011.02548.x
  15. Oksaharju, A., Kankainen, M., Kekkonen, R. A., Lindstedt, K. A., Kovanen, P. T., Korpela, R., & Miettinen, M. (2011). Probiotic Lactobacillus rhamnosus downregulates FCER1 and HRH4 expression in human mast cells. World Journal of Gastroenterology : WJG, 17(6), 750–759. http://doi.org/10.3748/wjg.v17.i6.750

The Article Probiotics: A Guide For Those With Food Sensitivities was originally published on the Isotrope website

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