The study has major shortcomings and inaccurate conclusions have been drawn by the author and media.
Comment on study by Rao et al. 2018, “Brain fogginess, gas and bloating: a link between SIBO, probiotics and metabolic acidosis”1
The results from the study has been interpreted in a way that suggest that probiotics are associated with brain fogginess. BioGaia argues that the study has major shortcomings and that inaccurate conclusions have been drawn by the author and media. We have received a lot of questions regarding the study and have compiled an official comment.
Requirements for a true probiotic
In the publication, see quote below, it is referred to ”probiotics” as if all probiotics were the same. The products that the subjects in the study were using are not specified on species level neither on strain or product level. Yoghurts were also included in the definition of “probiotics”.
“All patients in the BF group were taking probiotics (range 3 months to 3 years), some were taking 2–3 different varieties containing lactobacillus species, and/or bifidobacterium species or streptococcus thermophillus and others. Additionally 11 (36.7%) were using cultured yogurt daily, and 2 (6.7%) large amounts (20 oz.) of homemade cultured yogurt daily.”
It is generally agreed in the scientific community that probiotics need to be defined on strain level.2, 3, 4 Different probiotic strains have very different effects in the human body.
On the market you find many multi-strain probiotics that may contain up to 1×1010 – 5×1011 CFU. These products often contain many different species and have limited clinical support.5, 6, 7, 8
High quality probiotics are defined on strain level. For those products, clinical studies are performed with a stated amount of the particular strain/strains and are done for specific indications. As an example, L. reuteri DSM 17938 has been studied in 137 clinical trials including nearly 13 000 subjects. The recommended daily dose of L. reuteri DSM 17938 is 1-2×108 CFU for indications like acute gastroenteritis, colic and constipation. More than 30 safety studies have proven the safety and efficacy of the BioGaia patented L. reuteri strains.
Probiotics claimed association with SIBO, motility disturbances and brain fogginess
The argument from Dr. Rao that probiotics might contribute to problems like SIBO and motility disturbances, and thereby cause brain fogginess, has no support in the majority of published probiotic literature.
A summary of the study in Science Daily claims that “Probiotic use may be particularly problematic for patients who have known problems with motility, as well as those taking opioids and proton pump inhibitors, which reduce stomach acid secretion and so the natural destruction of excessive bacteria.”
Again, you have to define probiotics on strain level. For example, Indrio et al. showed that L. reuteri DSM 17938 increased gastric emptying rate in infants, resulting in improved gastrointestinal motility.9 L. reuteri DSM 17938 has also been shown to reduce the risk of SIBO in children with gastroesophageal reflux that take PPIs.10
Is production of D-lactic acid a problem?
Many probiotics, especially from the Lactobacillus genus, produce D-lactic acid. In certain individuals, for example in patients with short bowel syndrome, this is recognized as a problem.
In the introduction Dr. Rao writes: “…probiotic use has been implicated in the production of D-lactic acidosis, both in short bowel syndrome patients and in the first 2 weeks of life in infants who were fed probiotic-containing formula”, referring to a study by Papagaroufalis.11 The fact is that the study by Papagaroufalis on healthy infants showed no increase of D-lactate acidosis in blood. Although an initial increase in urinary D-lactate excretion was seen in the L. reuteri group versus control, this increase was only temporary and had no clinical implications.
In a safety study by Connolly et al. 200512 it was concluded that there was no difference in blood levels of D(-)-lactic acid between infants who had ingested L. reuteri for 6 or 12 months and those who had received placebo. Furthermore, in a study with children suffering from short bowel syndrome, D(-)-lactic acid producing L. plantarum299v was even demonstrated to reverse D-lactic acidosis.13
A poorly designed study, difficult to draw conclusions from
In addition to our comments on Dr. Rao‘s conclusions the study design has major shortcomings:
- Observational study (low level of scientific evidence)
- Heterogenous study population (unspecified reasons for gastrointestinal problems, different drugs and diets)
- Small study population (in total 38)
- Probiotics ingested before study start are not defined
- No statistical power
- Different methods of analysis were used
From BioGaia’s perspective a relation between specific probiotics and the claimed indications has not been proven in this study. If anything, the results emphasize the importance of choosing a well-studied probiotic strain, like L. reuteri DSM 17938.
Several randomized, double-blind, placebo-controlled studies performed with BioGaia probiotic products have demonstrated a positive effect on gut motility as well as SIBO.
We believe that this study might actually contribute to a healthy skepticism against multi-strain “probiotics” that contain high numbers of undefined strains and have no clinical support.
- Rao SSC et al. Brain fogginess, gas and bloating: a link between SIBO, probiotics and metabolic acidosis. Clin Transl Gastroenterol. 2018;9:162.
- Guarner F et al. Gut flora in health and disease. Lancet. 2003;361:512-9.
- World Gastroenterology Organisation (WGO) Global Guidelines – Probiotics and Prebiotics. 2017.
- Hill C et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the scope and appropriate use of the term probiotic. Hill, C. et al. Nat Rev Gastroenterol Hepatol. 2014;11:506-14.
- Temmerman R et al. Identification and antibiotic susceptibility of bacterial isolates from probiotic products. Int J Food Microbiol. 2003;81:1-10.
- Lewis ZT et al. Validating bifidobacterial species and subspecies identity in commercial probiotic products. Pediatr Res. 2016;79:445-52.
- Vanhee LM et al. Quality control of fifteen probiotic products containing Saccharomyces boulardii. J Appl Microbiol. 2010;109:1745-52.
- Indrio F et al. Lactobacillus reuteri accelerates gastric emptying and improves regurgitation in infants”. Eur J Clin Invest. 2011;41:417-22.
- Belei O et al. Is it useful to administer probiotics together with proton pump inhibitors in children with gastroesophageal reflux? J Neurogastroenterol Motil. 2018;24:51-57.
- Papagaroufalis K et al. A Randomized Double Blind Controlled Safety Trial Evaluating d-Lactic Acid Production in Healthy Infants Fed a Lactobacillus reuteri-containing Formula. Nutr Metab Insights. 2014;7:19-27.
- Connolly E et al. Safety of D(-)-lactic acid producing bacteria in the human infant. J Pediatr Gastroenterol Nutr. 2005;41:489-92.
- Vanderhoof JA et al. Treatment strategies for small bowel bacterial overgrowth in short bowel syndrome.” J Pediatr Gastroenterol Nutr. 1998;27:155-60.