NPIcenter: Probiotics were first seen as being beneficial strictly for various intestinal conditions such as diarrhea. Then came immune function health area, based on the concept of gut-mediated immunity. Here now is a new study with Probio'Stick on stress. How is it that beneficial bacteria levels in the gut can help all these disparate health conditions?
Isabelle Champie: Beneficial bacteria can act through several mechanisms of actions. One of the most known is the competition/exclusion of pathogenic bacteria that is very efficient in the prevention/fighting of infections, especially gastro-intestinal infections. As science has progressed, we now know that two other major mechanisms of action are:
- the "barrier effect" where probiotics offer better preservation and restoration of the intestinal barrier and also decrease gut permeability
- the interaction with the immune system and the modulation of the production of cytokines
These two mechanisms prevent the entry of pathogens into the body and help prevent inflammation. Sixty percent of the immune cells are located in the gut as well as 60 percent of nerve fibers! Thus the effectiveness between the interactions with the microflora and probiotics is high.
A change in the gut permeability, with the microbiota composition or an imbalanced immune system, may lead to disparate health conditions such as IBS, increased susceptibility to cold and flu, increased neuro-inflammation (leading to anxiety symptoms). Science has now shown that an "imbalanced" microbiota could lead to a micro-inflammation that could also be linked to obesity and metabolic syndrome. As you can imagine, the areas where probiotics could be beneficial today and in the future are vast.
NPI: What are the health conditions that are of most interest to researchers these days? What about marketers – do these align with researchers'?
IC: Today, researchers are still very interested by the potential of probiotics in gastrointestinal disorders, especially IBS, and this is also a good opportunity for marketers as there is still an unmet need in this field – IBS is highly predominant in the population and you need a lot of drugs to target all symptoms of IBS. Some of these drugs have adverse effects, while probiotics offer a more holistic approach: They target the origin of the condition rather than the symptoms, and their long-term use is perfectly safe. Still, to date there are not a lot of probiotic strains that have shown their efficacy in this syndrome.
Another health condition of interest for researchers and marketers is obesity and metabolic syndrome, for the exact same reasons as IBS; however, more research still needs to be done in this field before bringing a product to market.
Finally, marketers and researchers are not in complete agreement as to the positive effect of probiotics on anxiety and depression. At Institut Rosell-Lallemand, our clinical and preclinical studies have shown that our probiotic products can be effective, and there is an ever-increasing need from the general public as it is confronted with more and more stress. Academic research is not enough, however, to create awareness and credibility of probiotics, but we are confident that as more and more researchers review our results, they will become increasingly interested in studying how probiotics are beneficial.
NPI: Regulatory bodies, in particular in Europe, are loathe to allow any health claims on probiotics. What are the steps a researcher or supplier needs to do in order to pass regulatory muster? It's more than just characterizing strains (though that's a start!). Must one also patent strains?
IC: The characterization is obviously the first step. You have to know your strain and its characteristic perfectly and how to produce it consistently before anything else. Then EFSA or FDA require evidence of safety (this can also be included in the characterization process).
Finally, they ask for evidence of efficacy, and here is the hurdle we, as manufacturers, but also researchers, find:
To keep being a food supplement or a food, the clinical trials have to be conducted on healthy people. This increases the cost of clinical trials dramatically as, for most indications, the population has to be huge in such trials. Moreover, we know by experience and by previous clinical trials that probiotics can be good to prevent or even treat some diseases, but this cannot be used for a claim within EFSA matrix.
Then the choice of the endpoints and biological markers are also very important to have in your study so that your claim can be accepted by regulatory bodies.
NPI: Is EFSA making marketing of probiotics in Europe a lost cause for the next decade?
IC: I wouldn’t say that, however we have lost some time over the past two years and it will probably continue to do so as long as EFSA does not have more precise guidelines for the protocols of randomized, controlled trials that would be acceptable as proof for the EFSA. I think that we are heading in the right direction and things are progressing, and the dialogue is opening in several countries so we should see some results in the near future.
NPI: Although the existing research on probiotics is compelling, it really is quite in its infancy, don't you think?
IC: The benefits of probiotics were discovered centuries ago, and the number of publications on Pubmed is increasing every year. Clinicians and some leading medical experts are convinced of the benefits and potential of probiotics, and manufacturers, distributors and consumers are becoming more and more aware of the potential of these products, the importance of the scientific data behind them and the specificity of the strains. In this respect, probiotic research is in its early stages, but I am confident it will grow very fast in the near future. As one of my colleagues mentioned in a conference recently, we can tell that probiotics are now teenagers.
NPI: From a marketer's perspective, has "probiotics" become so much of a household word that it almost doesn't matter that regulatory bodies prevent companies from ascribing any benefit to probiotics so long as the mere mention of the word is on the label – that is, consumers by now know probiotics are healthy.
IC: Yes, the word probiotic has indeed become a claim by itself, and that is why it is considered as a regulated claim. In Europe for instance, you cannot write it on your label or documentation without prior approval by EFSA. In other areas, it is not the case yet, and I agree that it is a sales tool by itself, but I do not think it is enough and I think that it will be better for consumer understanding when we have approved claims for documented products.
In terms of consumer awareness, probiotics today are where vitamins were decades ago. Consumers understand that they are healthy but are not aware of strain specificity. It’s a bit like vitamins in that we are now aware that there are all different kinds with very distinct effects. For example, consumers know the difference between vitamin D and vitamin C. The same is true for probiotics – each strain is different and can have very different, and even antagonist effects, and we need to educate consumers about the differences. When we finally have specific health claims, this should help.
NPI: Can any delivery system really compete with the payload of supplements? Part of the lawsuit against Dannon was that they must state that consumers need to eat three servings of DanActive a day to get the effect - a tall order! Might this compel companies to use efficacious doses in their non-supplement products?
IC: The dose is an important point. We know that we do not need to have thousands of billions to have efficacy. The studies we have performed were done with doses ranking from 1 to 20 billion CFU/day depending on the products, and this is the dose we usually have in one or two servings/day depending on the product. Usually these doses can be adaptable to the food matrix. At Rosell, all of our studies are done on a finished product therefore there won’t be a difference between dosage used in the clinical research and the finished product.
For the complete story on probiotics – pricing trends, supplier and finished product innovations, the forecast for the year ahead and much more – check out the Ingredient Intelligence Monograph: Probiotics report.