Lactobacillus probiotics provide little relief for diarrhoea

A recent meta-analysis has showed little evidence supporting the use of probiotics containing a combination of Lactobacillus acidophilus and L. bulgaricus for the treatment of diarrhoea.

After a systematic search of the online databases of PubMed, Embase, Cochrane, CINAHL, Web of Science, and Clinicaltrials.gov, four studies were found eligible for the meta-analysis, with a cumulative sample of 2,411 patients. Three distinct diarrhoea outcomes were assessed: antibiotic-associated diarrhoea, traveller’s diarrhoea, and diarrhoea caused by enterotoxigenic Escherichia coli.

Meta-analysis of the probiotic intervention revealed significant heterogeneity of evidence (p<0.0001), though Begg’s test (p=0.1742) and Egger’s test (p=0.1448) indicated no publication bias. [Front Gastroenterol 2022;doi:10.3389/fgstr.2022.983075]

Generalized linear regression analysis showed a significant effect (p<0.0001), though this was mostly attributed to differences across the studies included. No significant effect was attributed to the treatment (p=0.5081) nor to the interaction term between treatment and article (p=0.4941).

Prediction profiling analysis further confirmed that the lactobacillus-containing probiotic had no significant clinical benefit. Linear graphs showed similar slopes between the treatment and placebo groups, with considerable overlaps in their 95 percent confidence intervals.

In relative terms, patients treated with the probiotic only saw a 3.5-percent drop in the prevalence of diarrhoea as opposed to placebo comparators, a difference that fell short of statistical significance (p=0.5081). Additionally, this 3.5-percent difference was also deemed to be clinically insignificant.

“To demonstrate that this lower percentage would be statistically significant would require 3,133 placebo and L. acidophilus and L. bulgaricus articles,” the researchers. The unselected pool of studies for the present meta-analysis contained only 2,316 articles.

In addition, the present findings point to a need to re-evaluate the value of pushing for nationwide uptake of L. acidophilus and L. bulgaricus probiotics. While these are inexpensive interventions, there is currently no data to support such campaigns.

“At the very least, this warrants more current, large-scale studies to assess the efficacy of L. acidophilus and L. bulgaricus more accurately. However, in the absence of that data, L. acidophilus and L. bugaricus should be used judiciously, or not at all,” the researchers noted.

“Finally, there are questions about the effectiveness of probiotics in general,” they added, pointing out that while there does appear to be an increase in the bacterial levels post-treatment, these seem to normalize to baseline quickly, possibly due to the action of gastric acid, which interferes with colonization. [Am J Clin Nutr 1981;34:514-519; Clin Nutr ESPEN 2022;47:70-77]

“Any studies that look to the effectiveness of an L. acidophilus and L. bulgaricus formulation should also address the issues of colonization as there are numerous confounding variables at play,” the researchers said.

Aside from the inherent ambiguity surrounding lactobacillus-based probiotics, and probiotics in general, several other limitations hound the present analysis. Chief of these is the weak literature landscape surrounding lactobacillus probiotics. Of the more than 2,000 initial studies reviewed, only four were deemed eligible for inclusion, none of which had been conducted in the last 10 years. Moreover, papers have used varied definitions of diarrhoea, making direct comparisons difficult. Future efforts to deepen knowledge in this field are needed.