In a review article, the research team states for a bacterial strain or strains to be called a probiotic, it should be pure and properly named (or "characterised") and safe for its intended purpose.
Other criteria include support by at least one human clinical trial showing a health benefit; and kept alive in a high enough dose to convey its health benefits, all the way through the product’s shelf life.
“The term ‘probiotic’ poses a scientific problem,” says the International Scientific Association for Probiotics and Prebiotics (ISAPP), one of the organisations to take part in the review.
“It does not distinguish between bacterial strains that have a possible health benefit and strains that have a demonstrated health benefit, as shown in a human study.
“Correct use of the term probiotic, per these criteria, will give consumers better transparency about the benefits they can expect when they consume products that contain live microorganisms.
“It will also allow them to weigh the costs and benefits of different products in the marketplace.”
Writing in the Frontiers in Microbiology journal, the team outlines a minimum set of criteria needed for the proper use of the term probiotic, at a time where new “biotic” names are being introduced such as pharmabiotic, psychobiotic, postbiotic, synbiotic, amongst others.
Previous attempts to nail down a definitive definition occurred in 2002, where guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO).
The FAO/WHO definition of a probiotic was, "live microorganisms which when administered in adequate amounts confer a health benefit on the host".
In terms of characterisation the team, which also includes scientists from Danone, Chr. Hansen, Yakult, DuPont and the APC Microbiome Ireland, advise that probiotic strains follow currently bacterial nomenclature, based on the International Code of Nomenclature.
NutraIngredients-USA recently reported on taxonomic changes to the genus Lactobacillus, in which genetic analyses revealed many of these species could no longer be grouped under Lactobacillus.
According to the article, Lactobacillus is again limited to only 35 species. The other species have now been formally put into 23 new genera and Paralactobacillus.
The review goes on to recommend probiotic strain characterisation should support their probiotic activity.
“Such characterisations could include survival at relevant body sites, the production of lactic acid or other short chain fatty acids, adhesion to mucus or intestinal epithelial cells, interaction with human immune cells, resistance to digestive enzymes, bile or acid, antibacterial activity via competitive exclusion or production of bacteriocins or hydrogen peroxide,” the review says.
Regarding probiotic safety, the review goes on to discuss the importance of historical data in an overall assessment of safety for an intended use.
In its absence, the review advises that safety must be determined based on scientific principles, including the conduct of adequate phase one studies.
Here, human intervention studies allow for proper documentation of safety and tolerance of probiotics through rigorous monitoring and reporting of adverse events.
Biological and clinical parameters, including vital signs, can be monitored to collect valuable safety data. Unexpected deviations from baseline or standard values might indicate a possible safety concern.
The team points out that to date, only rare, mild, and transient probiotic-related adverse events have been reported in studies with healthy subjects.
Specific sensitive populations exist that include the young, old, pregnant, and immune compromised population must be considered, the team adds.
The researchers conclude that significant number of strains from Lactobacillus, Bifidobacterium, and yeast species have a long history of safe use having been the subject of thorough assessments and monitoring.
‘No major safety concerns’
“It can be concluded that there are no major safety concerns for their use in foods and dietary supplements for the general population,” the paper comments.
“Safety evaluations focus on the intended use, which here is food and dietary supplements; other uses may have different safety requirements e.g., depending on their delivery format or dose.”
The review also calls for probiotics to be supported by at least one human clinical trial preferably followed by confirmatory trial(s).
To correctly use the term “probiotic” to describe such strains, the review states the organism must be identified at strain level and shown to express the relevant trait.
“A valid demonstration of a health benefit depends both on the quality and soundness of the trial itself and on the capacity of the scientific community to critically appraise published trial results,” the paper says.
Finally, the team recommends quantification of probiotic strain viability using methods such as plating or Colony Forming Unit (CFU) counting on growth media, to determine its viability in a product at an efficacious dose during its shelf life.
Currently, faecal recovery is often used to reflect sufficient dose for gastrointestinal health targets with dose ranging possible for those probiotics which have a readily determined endpoint of efficacy (e.g., serum cholesterol levels).
However, the team points out that once again the issue of replication in situ could cause problems with interpretation.
For quantifying probiotic combinations, culture-independent metagenomics methods based on high-throughput next-generation sequencing are mentioned as are molecular approaches currently under development.
These include techniques such as propidium monoazide (PMA)-PCR, although as the review points out is experimental and currently not standardised.
“Probiotics are the subject of global investigative research, innovative product design, effective marketing, regulatory scrutiny, focused consumer interest and use by healthcare practitioners,” the team concludes.
“Some local regulatory contexts can define probiotics in a different manner, but it is the responsibility of the product manufacturer to produce and market probiotics that follow local rules and regulations and are in line with the above defined principles.”
Source: Front. Microbiol.
Published online: doi.org/10.3389/fmicb.2020.01662
“Criteria to Qualify Microorganisms as “Probiotic” in Foods and Dietary Supplements.”
Authors: Sylvie Binda et al.