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D-Lactate producing probiotic strains in Chronic Fatigue Syndrome

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There appears to be a growing concern surrounding the use of probiotic species which produce some D-lactic acid, as opposed to solely L-lactic acid or other acid types (e.g. butyric, propionic, acetic and succinic acids).

Limited human evidence exists on this topic, however a clear combination of symptoms do appear to be caused by the presence of excess D-lactic acid in the system. These symptoms tend to resemble those of chronic fatigue syndrome (CFS), with myalgia and mood and cognitive changes. Despite the most noted cases of acidosis occurring in individuals with short bowel syndrome, it has been hypothesised that this situation of acidity may arise in other circumstances, as a result of microbial imbalance within the gastrointestinal tract (GIT).

Lactic acid can be produced by certain microorganisms as either L-lactic acid or its stereoisomer D-lactic acid. The theory behind the acidosis concern is that L-lactic acid can be metabolised and utilised by the mitochondria for energy production, whilst humans tend to lack sufficient levels of the enzyme D-lactate dehydrogenase required to utilise D-lactic acid. 

Instead, when high amounts of D-lactic acid accumulate in the gut, altering the pH, gut integrity may be compromised and the acid allowed passage into the body. When D-lactic acid then enters the cell, it can be preferentially taken up in the place of L-lactic acid, compromising mitochondrial function, leading to toxicity, acidity and resultant symptoms. Controversy still exists around this story, however, as research has revealed that despite this past hypothesis, most humans do produce D-lactate dehydrogenase and only a very small portion of the population are unable to.[1]

Specific microbial species produce either L-lactate or D-lactate exclusively, whilst others produce a racemic mix. Small amounts of D-lactic acid are not a concern, however a significant imbalance may arise when, due to dietary and lifestyle factors, those species producing D-lactic acid exclusively notably out-number the other types. 

Some older research has suggested higher numbers of lactic acid producing lactobacillus species (e.g. L. plantarum) to be a key concern. However, in these studies, enterococcus and streptococcus numbers were not determined. Lactobacilli and bifidobacterium are known as “heterofermentative” species in that they produce not only lactic acid, but also ethanol and carbon dioxide and they exert numerous local and systemic benefits.[2] These species generally produce primarily L-lactic acid, or if D-lactic acid is produced it is done so in a racemic mix along with L-lactic acid.

A more recent investigation into the intestinal microbial balance of individuals with CFS found that there was a significant overgrowth of homofermentative D-lactic acid producing bacteria, Enterococcus faecalis and Streptococcus sanguinis, in combination with E. coli numbers significantly lower than that of healthy individuals.[2] 

E. coli is normally a dominant microorganism in the intestines, and produces many beneficial compounds (e.g. nutrients, acetic and succinic acids) and far less lactic acid than E. faecalis and S. sanguinis. Not surprisingly, significantly lower pH was seen in this imbalance (as the homofermentative E. faecalis and S. sanguinis produce a greater amount of the D-lactic acid type which is unable to be efficiently metabolised).[2]

Intestinal hyperpermeability stemming from dysbiosis (and excess acidity), insufficient fibre, nutritional deficiencies, stress and dietary antigens also allow a greater passage of gram-negative bacterial endotoxins.[2] These initiate widespread inflammatory response and potentially “cytokine sickness”, which may result in a similar subset of the symptoms to that of acidosis and CFS.[3,4] This is therefore a factor which should also be addressed in these individuals.

An ideal way to support healthy E. coli growth is via a prebiotic-rich diet and avoidance of foods that result in high D-lactate production (e.g. sugars including glucose, lactose and fructose). Certain strains of E. coli play a role in supporting gut motility and reducing constipation,[5] and thus a high fibre diet not only contributes to better bowel tone, but also via the feeding of E.coli will provide additional benefit. 

Dysmotility of the gut is a noted contributor to dysbiosis (e.g. small intestinal bowel overgrowth (SIBO) and small intestinal fungal overgrowth (SIFO)).[6] Keeping the intestines moving will minimise time available for fermentation by D-lactate producing organisms and an undesirable production of the compound,[1] which can be a causative factor in the local imbalance.

In conclusion, it appears that the following is the most ideal approach to addressing symptoms of potential D-lactic acidosis (e.g. CFS, mood changes, cognitive dysfunction and myalgia):

  • Restoration of microbial balance is paramount. Recommend a diet rich in prebiotic fibres (to feed E. coli and other beneficial species) and consider a broad spectrum probiotic, which does not contain strains which produce D-lactic acid exclusively; balance is key.
  • Keep the bowels moving with a high fibre diet, beneficial fats and good hydration (this reduces the opportunity for excessive fermentation by D-lactic acid producing microorganisms[1]) and attenuates SIBO.
  • Significantly reduce sugar (e.g. glucose, sucrose, fructose, maltose, lactose) in the diet, as it is fermentation of these which sees high D-lactic acid production.[1,2]
  • Heal and soothe the gut with sound nutrition (e.g. sufficient zinc, vitamins D and A, quercetin and glutamine), herbal (e.g. marshmallow, curcumin, cinnamon, mastic gum, deglyccherized liquorice) and microbial (e.g. Saccharomyces boulardii) support.
  • Reduce/remove dietary antigens which may contribute to increased intestinal permeability (e.g. gluten).
  • Support antioxidant status and mitochondrial function (e.g. ubiquinol and alpha-lipoic acid).

References

  1. Uribarri J, Oh MS, Carroll HJ. D-lactic acidosis. A review of clinical presentation, biochemical features, and pathophysiologic mechanisms. Medicine (Baltimore) 1998;77(2):73-82. [Abstract]
     
  2. Sheedy JR, Wettenhall RE, Scanlon D, et al. Increased d-lactic acid intestinal bacteria in patients with chronic fatigue syndrome. In Vivo 2009;23(4):621-628. [Full Text]
     
  3. Morris G, Anderson G, Galecki P, et al. A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior. BMC Med 2013;11:64. [Full Text]
     
  4. VanElzakker MB. Chronic fatigue syndrome from vagus nerve infection: a psychoneuroimmunological hypothesis. Med Hypotheses 2013;81(3):414-423. [Abstract]
     
  5. Chmielewska A, Szajewska H. Systematic review of randomised controlled trials: probiotics for functional constipation. World J Gastroenterol 2010;16(1):69-75. [Full Text]
     
  6. Jacobs C, Coss Adame E, Attaluri A, et al. Dysmotility and proton pump inhibitor use are independent risk factors for small intestinal bacterial and/or fungal overgrowth. Aliment Pharmacol Ther 2013;37(11):1103-1111. [Full Text]

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Belinda Reynolds

Belinda is a dietitian and Senior Educator at one of Australia's leading nutraceutical companies. She graduated with an Honours Degree in Nutrition and Dietetics, and has been involved in the complementary medicine industry for over 15 years. Her key interests are immune modulation, the human microbiome and the impact they have on overall health.