Probiotics’ Part I: A branching definition

Probiotics have a well-known definition that has been cited for over a decade: ‘Live microorganisms which when administered in adequate amounts confer a health benefit on the host’. Written in a 2001 joint report of the Food and Agriculture Organization of the United Nations and the World Health Organization (FAO/WHO), it is a definition that served well at the time, despite its generality.

“Not every live microorganism is a probiotic. Only those live microorganisms that produce a health benefit,” says Dr. Francisco Guarner, gastroenterologist and head of the Experimental Laboratory at the University Hospital Vall d’Hebron in Barcelona.

Then some difficult question arise: What counts as a health benefit? What scientific evidence is required to prove it? These are critical issues, especially for clinicians who may face potential therapeutic uses for probiotics on a daily basis.

Questions like these prompted Guarner and a group of eleven fellow scientists to sit down and revisit the definition of a probiotic, about twelve years after the original FAO/WHO report. Their meeting, organized by The International Scientific Association for Probiotics and Prebiotics (ISAPP), was the latest co-ordinated step in trying to refine the concept of probiotics — which microorganisms are in the category and which are out.

The ISAPP group decided that the scientific evidence prompts some new subcategories of probiotics: essentially, a further branching of the probiotic family tree. Guarner, along with two others on the panel, Lorenzo Morelli and Mary Ellen Sanders, spoke with GMFH about the must-know ideas that emerged out of the meeting.

“The science has expanded on [probiotics],” says Mary Ellen Sanders, ISAPP Executive Science Officer. “What you saw back in Metchnikoff’s day really was an observation that people who consume [certain] fermented beverages seem to live long, healthy lives.”

Indeed, the field has evolved dramatically since Élie Metchnikoff famously studied elderly Bulgarians in the late 1800s and connected fermented milk with “the prolongation of life”. Now, Sanders explains, a higher level of scientific scrutiny is required in order to say that particular health benefits are attributable to probiotics, rather than to a population’s genes, for example, or the climate in which they live. “You have to take that to the next level where you say, ‘Well, what kind of data do we have to support the hypothesis?’ Where we are today is in a position where we really do have more data.”

The number of studies on the topic, which is one measure of scientific interest, started to rise in the early 1990s and reached over 1500 studies in 2013. “Over the past five, six, seven years we’ve got all this really interesting information that’s come out of the effort to understand the human microbiome,” says Sanders. “I think that that has fuelled an interest in probiotics.”

Prof. Lorenzo Morelli, Chair of Food Microbiology and Biotechnology at the Istituto di Microbiologia Università Cattolica S.C., in Piacenza, Italy, agrees. In his four-decade career, he has seen a big shift in the way bacteria are studied, as metagenomic analysis techniques became more widely used. “Now, we have a totally different view of the composition of the microbiota,” he says.

The scientists at the ISAPP meeting agreed on several points of clarification on probiotics. First of all, they said, in order to call something a probiotic you must know its name — that is, you must characterize it. “If, in a product, there are live microorganisms that are not characterized, that you don’t know what is inside, for example [naturally occurring] in a cheese or in a food product… these will never be probiotics,” says Guarner. Sanders adds that while traditional fermented foods are certainly components of a healthy diet, the science doesn’t allow them to fall under the definition.

Moreover, says Guarner, the panel decided that fecal transplants, which are growing in clinical popularity, do not fall under the definition. “Fecal transplant is not going to be acceptable as probiotic because it’s uncharacterized,” he says.

Then, they decided on three probiotic subcategories. First, there is a category for the ‘usual suspect’ probiotics which, from a long history of study, are known to provide some general health benefits: according to the report, “a healthy digestive tract and a healthy immune system”. Guarner says, “There are already many data that these are good for health. Particularly for digestive health… In this category, you don’t need to repeat more and more studies, because these species are already very well known. Scientifically, [it] is already well accepted.”

Next comes a category of probiotics that are found useful for treating very specific health conditions such as antibiotic-associated diarrhea. “In this situation, the benefit is linked to the strain, not only to the species,” explains Guarner. “When you have a special health benefit… you need to go to human studies to demonstrate the particular health benefit associated with the consumption of this particular strain.”

Finally, the experts agreed on a third category of probiotics where most of the innovation is expected to occur in the next decade: probiotics from the human body that can be harvested and used therapeutically. “The last category is [using] probiotics as drugs,” says Guarner. “You have to go through the procedure to demonstrate efficacy and safety. In this last group, probably we will be accepting bacteria coming from the human gut, like Faecalibacterium prausnitzii or Akkermansia muciniphila: many bacteria that have not been used traditionally in food. So therefore they need a lot of studies for safety.”

All three experts underlined that the new categories of probiotics have far-reaching implications for how people can and should access live microorganisms for their own health. Some of the implications will only become evident over time, as more studies appear in the journals. They are convinced, however, that the definition and its new branches are faithful to the scientific evidence to date.

GMFH Editing Team
GMFH Editing Team