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D-lactate producing probiotics

No reason for concern

A recently published publication: Brain fogginess, gas and bloating: a link between SIBO, probiotics and metabolic acidosis, has caused quite a stir among scientists in the field (1).  A panel of experts warns physicians not take alarm from, according to them, non-founded conclusions. Expressing their concerns in a letter to the journal’s editor, they even come to an alternative conclusion, which is; SIBO patients sought relief from their gut symptoms by using probiotics rather then probiotics being the cause of their symptoms (2). In view of this, what do you need to know about d-lactate producing probiotics?

 

 

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Lactic acid types

Lactate occurs naturally in the form of two optical isometric forms; L-lactate and D-lactate. L-lactate is the predominant form in the human body and is a natural product of glucose and amino acid metabolism. D-lactate is far less abundant in the human body and mostly originates from a diet rich in fermented foods such as yoghurt or pickled vegetables. D-lactate is also a typical end-product of intestinal microbiota metabolism.

 

Bacteria that are naturally present in the gastrointestinal tract may produce D-lactate, L-lactate, or both the isomers, and some of them also have the ability to convert one isomer into the other.

 

 

D-lactate producing probiotics No reason for concern_2016

The type of lactic acid that is produced is specifically tied to the bacteria species (3,4). L-lactate and D-lactate are metabolized by respectively the enzymes L-lactate and D-lactate dehydrogenase. Even when D-lactate dehydrogenase is lacking, the body can still effectively metabolize large amounts of D-lactate, although slower than its isomer. (5,6)

 

 

Acidosis

In the rare case when D-lactate is insufficiently processed, too much acid can accumulate in the body fluids, resulting in acidosis. Clinical symptoms of metabolic acidosis included impaired consciousness, changes in behavior and neurological disturbances (7). It should be noted that a massive, 100-fold increase in the blood D-lactic acid concentration must occur before a patient develops D-lactic acidosis. The development of acidosis is therefore unlikely in individuals with an intact gastrointestinal tract and D-lactic acidosis has mainly been observed in subjects with short bowel syndrome (8). There is some evidence that babies in their first three months of life could have difficulties in processing small amounts of D-lactate. However, an infant’s gastrointestinal tract is colonized by many species of bacteria shortly after birth, including those producing D-lactic acid (9). Nevertheless, the World Health Organization's Codex Alimentarius currently only allows the use of L-lactic acid producing cultures in infant formulas.

 

 

 

In people with a normal gut, D-lactate produced by members of the gut microbiota – including some probiotics – is metabolized by other members of the gut microbiota and does not accumulate. Thus, under normal circumstances, D-lactic acidosis does not result from consumption of D-lactic acid-producing probiotics.

 

 

Safety studies

Extensive research is going on assessing the safety of probiotics use in infants and small children. A recently published review has summarized the available knowledge on the ingestion of D-lactic acid producing bacteria as a potential cause of pediatric D-lactic acidosis (10). The authors identified five randomized controlled trials from 2005-2017, covering 544 healthy infants up to 12 months of ages. All of these trials showed that probiotics did not cause D-lactic acidosis in healthy children and no clinically relevant adverse effects of the interventions were observed. The documented cases of pediatric D-lactic acidosis only occurred in a specific group of children, suffering from short bowel syndrome.   

 

 

These findings are in sharp contrast with the conclusions from Rao and colleagues. The experts explain the contradictive results by stating that the observational nature of the Rao study precludes any conclusive link between probiotic consumption and symptoms observed. Moreover they add; The patients in the Rao et al. study showed very low levels of D-lactic acid, calling into question if these SIBO patients were even acidotic. Moreover, the D-lactic acid that was present was not proven to be a result of probiotic growth. This is important, as intestinal bacteria including Escherichia coli also produce D-lactic acid. In cases of SIBO, numerous metabolites are produced in the small intestine (including alcohol), leading to a variety of SIBO symptoms, possibly including the poorly defined phenomenon of “brain fogginess”. Many issues that should have been were not addressed in the Rao et al. paper.

Winclove bacteria and

D-lactate production

The scientific view on D-lactate producing strains has changed in recent years and has in fact become a non-issue. Even though there is no conclusive scientific evidence linking D-lactic acidosis to probiotic supplementation, all of Winclove’s bacteria are screened for their capability to produce L-lactic acid and/or D-lactic acid. 

  

 

References

1 Rao, S. S. C., Rehman, A., Yu, S. & Andino, N. M. Brain fogginess, gas and bloating: a link between SIBO, probiotics and metabolic acidosis. Clin. Transl. Gastroenterol. 9, 162 (2018).

2 Eamonn M. M. Quigley, Bruno Pot, Mary Ellen Sanders. ‘Brain Fogginess’ and D-Lactic Acidosis: Probiotics Are Not the Cause. Clin. Transl. Gastroenterol. 9, 187 (2018)

3. Connolly E, Lonnerdal B. D(−)-lactic acid-producing bacteria. Safe to use in infant formulas. Nutrafoods 2004; 3: 37-49.

4. Hove H, Mortensen PB. Colonic lactate metabolism and D-lactic acidosis. Dig Dis Sci 1995; 40: 320-30.

5. Connor H, Woods HF, Ledingham JG. Comparison of the kinetics and utilisation of D(-)-and L(+)-sodium lactate in normal man. Ann Nutr Metab 1983; 27: 481-7.

6. de Vrese M, Koppenhoefer B, Barth CA. D-lactic acid metabolism after an oral load of DL-lactate. Clin Nutr 1990; 9: 23-8.

7. Ku WH, Lau DC, Huen KF. Probiotics provoked D-lactic acidosis in short bowel syndrome: Case report and literature review. Hong Kong J Paediatr 2006; 11: 246-54.

8. Reddy VS, Patole SK, Rao S. Role of probiotics in short bowel syndrome in infants and children--a systematic review. Nutrients 2013; 5: 679-99.

9 Bjorksten B, Sepp E, Julge K, Voor T, Mikelsaar M. Allergy development and the intestinal microflora during the first year of life. J Allergy Clin Immunol 2001; 108: 516- 20.

10 Łukasik J, Salminen S, Szajewska H. Rapid review shows that probiotics and fermented infant formulas do not cause d-lactic acidosis in healthy children. .Acta Paediatr. 2018 Aug;107(8):1322-1326. 

 

D-lactate producing probiotics No reason for concern

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