Challenges ahead in the probiotic field – insights from Probiota2019

By Dr. Mariya Petrova, Microbiome insights and Probiotics Consultancy (MiP Consultancy), Bulgaria.

Recently, I attended the Probiota Conference, which brings together representatives from industry and academia on the topic of probiotics and related fields. The goal of many of the speakers at the conference was to provide insight about how to translate scientific discoveries for, and share commercial insights with, end consumers. I would like to share a few points that caught my attention.

Do good science. End-consumers rely on news coverage of science, which unfortunately is too often more sensationalist than accurate. Prof. Gregor Reid’s talk, “Disentangling facts from fake news,” noted that news article titles such as “Probiotics labeled ‘quite useless’” and “Probiotics ‘not as beneficial for gut health as previously thought’” – after research was published last year in Cell (here and here) – were misleading to end-users and of great concern to people in the field of probiotics who are familiar with the totality of the data. Researchers have a responsibility to situate their results in the context of existing evidence. However, Prof. Reid also observed that “too many products are called probiotics with strains not tested in humans”; “too many products are making un-verified claims”; “too many journalist don’t have expertise in science”; “too many rodent studies making association with human health”; “researchers making up their own terms without defining them”. So how do we solve this? Do good science and communicate results clearly, accurately and without bias – to journalists, to peers and to end-users. (See related ISAPP blogs here and here).

Understand the probiotic mode of action. Understanding probiotic modes of action may be the most challenging issues ahead of us. Currently, we have too little understanding of mechanisms by which probiotics provide health benefits. Probiotic strains are living microorganisms, which most likely work through multiple mechanisms and molecules, but we indeed need more in-depth research. When I reflect on my own experience and the struggles to do molecular studies, I can appreciate how difficult this research is. Although others may be focused on screening the microbiome and developing bioinformatics tools, I applaud the researchers trying to develop deeper understandings of how probiotics function, which will enable more rational approaches to probiotic selection and use. (See related ISAPP blog here.)

New names, new glory. The forthcoming reclassification of the Lactobacillus genus was discussed. We are faced with the largest taxonomic upheaval of this genus in history, including many economically important species. The current Lactobacillus genus will be split into at least ten genera. The species and strain names will not change, but many species will have different genus names. Researchers are expected to propose that all new genera names will begin with the letter “L.” The reclassification can help us better understand the mode of action of industrially important probiotics and help tailor probiotic applications. The changes will be communicated with regulatory bodies such as EFSA and FDA. Name changes could also have consequences for medical stakeholders and may lead to potential issues with intellectual properties. Consumers of probiotic products will likely be less affected by this change, but an educational website targeted to consumers could be beneficial. (See related ISAPP blog here.)

EFSA claims as expected. EFSA claims and regulations were also discussed. To date, approximately 400 health claims applications have been submitted to EFSA without any approved. Experts advised to keep the claims simple and easy. EFSA’s strict approach to claims may have the advantage of compelling industry to conduct studies that better support health claims. Responsible companies are adapting to regulatory requirements and are developing good products, and they will probably succeed in meeting claim standards. Nevertheless, it seems that although health claims are deemed important to companies and medical representatives, end-users of probiotics obtain information from other sources. Obtaining health claims is only one piece of the puzzle. Also important is providing science-based information to end-users, especially those keen on keeping their good health through nutrition.

Be transparent. Don’t forget to disclose the strains you use on product labels. Strains designation is one key way to distinguish your product and it is an important way to communicate to your consumer exactly what is in your product. Surprisingly still, some scientific papers fail to report the strains they used to perform their clinical trials. The field is moving towards more transparency with high-quality clinical trials, the best-selected strains for certain condition and clear designation of the probiotic strain on the label. (See related ISAPP infographics here, here and here)

Educate, educate and again educate. Often discussed at the conference was the subject of educating the end consumers. Companies should take a proactive approach to engage consumers and promote understanding of the available evidence where probiotics can promote health. It is difficult for consumers to differentiate science-based evidence from journalistic sensationalism or researcher self-aggrandizement. A major obstacle is also the ready availability in the marketplace of unproven products containing strains that have been tested only in animal models or not proven experimentally at all. Taking the need for reliable communications on probiotics and probiotics to end-users very seriously, ISAPP has developed a range of science-based videos and infographics. The infographics include topics such as how to read the labels of the probiotics products (USA and EU versions) and a probiotic checklist. Thanks to the enthusiastic work of many volunteers, some ISAPP infographics can now be found in 10 different languages.

Despite having great discussions, one thing keeps troubling my mind: Where is the field of probiotics going and how will it look like in 10 or 20 years? The fight for probiotics is not over, despite the progress we have made so far.

Role of citizen science in research on fermented foods

By Prof. Sarah Lebeer, Universiteit Antwerpen

Spontaneous vegetable fermentations, with their rich flavors and potential health benefits, are regaining popularity among chefs and the general public. Famous Michelin star chefs, such as Belgium’s Kobe Desramaults, have implemented fermented vegetables in their recipes and offer fermented vegetable juices as non-alcoholic alternatives to wine. Serendipity was surely at play when I made contact with Kobe and his team, and had the opportunity to explore the microbial life of many of his fermented food and beverages.

Thanks to this spontaneous collaboration, I became intrigued by fermented vegetables as a promising alternative to dairy probiotic matrices. They have several benefits:

  • they are lactose-free
  • they contain no milk allergens
  • they are naturally vitamin-, antioxidant- and fiber-rich
  • they are vegan, satisfying the growing dietary trend


Together with prof. L. De Vuyst – a fermented food specialist from the VUB University in Brussels – we attracted a talented PhD student Sander Wuyts to study Lactobacillus’ role in the spontaneous fermentation process of carrot juices. I admit that fermented carrot juice is not the tastiest beverage I ever drank, but the fermentation process turned out to be scientifically intriguing: it appeared to be a robust, man-made microbial ecosystem dominated by lactic acid bacteria. We now often use this fermentation process in my lab as a model to study various aspects of niche-adaptation and niche-flexibility of lactic acid bacteria (LAB). And if you mix carrot juice with another fresh vegetable juice, such as cucumber, you’ll be surprised by its interesting light acidic flavor!

But perhaps the most rewarding part about our fermented-vegetables project was that we managed to carry out a Citizen Science project with the Flemish name, Ferme Pekes. You could translate it as ‘Fantastic Carrots’ 😊. Forty citizens volunteered to set up their own carrot juice fermentations at home and delivered with great enthusiasm samples of different time points. The carrots originated from their own garden, the supermarket or organic stores. Our analysis indicated that origin or organic compared to conventional product did not impact the microbial community composition. But we also could show that the LABs – first Leuconostoc then Lactobacillus – out-competed the undesirable Enterobacteriaceae after 3 to 13 days of fermentation. Longer times were needed for carrots derived from winter storage.

Our analyses (phylogenetic placement and comparative genomics, which was recently published in Applied and Environmental Microbiology) also indicated that a high LAB diversity was achieved in the different spontaneous fermentations. This is of interest if you believe it is important to let our immune system come into contact with a large and naturally diverse dose of beneficial bacteria. This idea has been promoted through the years as the hygiene hypothesis or microbial deprivation theory and aligns perfectly with the surge of interest in the health benefits of naturally fermented foods. See the recent ISAPP blog from Prof. Colin Hill, who advocates for the idea of a recommended daily allowance of consumption of live microbes.  (See also a related ISAPP blog here.) Such guidelines should be taken with precaution: the fermentations must be done properly with regard to food safety (see ISAPP blog on Making Safe Fermented Foods at Home).

Citizen Science refers to projects where citizens are actively involved in scientific studies, although it has various definitions and descriptions. In our case, it allowed us to obtain a much larger and more diverse set of samples than we could have created in the lab. Furthermore, the opportunity to directly (on e.g. workshops for adults and kids or at delivery of their samples) or indirectly (as a response to articles in the popular press) communicate with citizens helped us greatly in identifying which other research questions might be of importance for the general public. This approach is increasingly implemented in the fermented food and microbiome field. There are examples of fantastic projects such as on sourdough from Rob Dunn, Benjamin Wolfe and colleagues, the Global FoodOmics initiative and the Flemish Gut Flora project, which will also be presented by Dr. Gwen Falony at our next ISAPP meeting in Antwerp. I am not aware of a Citizen Science project in the probiotic or prebiotic area, but it might be a good idea for a joint ISAPP initiative, for science communication, the creation of richer datasets, validation/confirmation of probiotic efficacy, inspiration for future research questions, for example.

East meets West at ISAPP’s first meeting in Asia

By Mary Ellen Sanders, PhD

The International Scientific Association for Probiotics and Prebiotics (ISAPP) recently convened its first meeting held in Asia, with the modern hub of Singapore as a host city. The meeting featured a two-day open registration meeting, attended by nearly 250 scientists, health professionals, and industry representatives, and a third day of smaller discussion groups by invitation. The meeting provided a rare opportunity for non-members to attend. It provided a dynamic forum for sharing different clinical experiences and regulatory nuances amongst the continents, as well as allowing attendees to better appreciate the research being performed in the Asian region.

Here are a few speaker highlights:


Mimi Tang MD

Tang presented the results of a double-blind, randomized controlled trial examining the effect of probiotic supplementation combined with oral immunotherapy (OIT) to decrease the risk of peanut allergy in children. Peanut allergy is one of the fastest growing food allergies in children. In the Probiotic and Peanut Oral ImmunoTherapy [PPOIT] study, children randomized to the intervention group had increased rates of sustained responsiveness to peanut several weeks after discontinuation of the treatment. Tang discussed the implications of the study, as well as current, larger clinical trials that are building upon these findings.


Dr. Bruno Pot

The Lactobacillus genus is taxonomically abnormally heterogeneous. Currently, the 231 Lactobacillus species range from a genome size of 1.23 – 4.91 megabases, have a GC content of 32-57% and an average nucleotide identity that is typical for a family or worse. Such ranges are far beyond what is acceptable for a bacterial genus. Experts are recommending that the current genus should be split into 12 new genera. Some well-known lactobacilli would be re-named, which may have important repercussions commercially and legally.


Profs. Colin Hill and Patrice Cani

Hill described how lactase in yogurt cultures improves lactose digestion; he emphasized how mechanisms that drive probiotic activity are complex. Some scientists are searching for a single molecule that drives probiotic health benefits—but it is unlikely to be found.

Hill noted even inactivated (non-living) microbes may have health effects—for example, a study showed that a dead Lactobacillus strain reduced anxious behavior, reduced cortisol levels, and impacted the microbiome in a mouse model. Work by Prof. Patrice Cani showed that heat-killed Akkermansia muciniphila were sufficient to ameliorate obesity and diabetes in mice. Does this suggest that we will need to start quantifying probiotics based on biomass as well as CFU?


Profs. Hani El-Nezami, Gregor Reid and Akihito Endo

These three speakers illustrated the important impact of environmental toxins (extremely potent aflatoxins, pesticides, and heavy metals) on humans and wildlife. They showed how certain probiotic strains can decrease aflatoxin absorption and even degrade them; sequester heavy metals and pesticides to reduce their uptake; and enhance resistance to honey bee colony collapse disorder that threatens the world’s food supply.


Prof. Wim Teughels

To date, 11 studies have been published on probiotics with a low ‘number needed to treat’ for prevention of dental caries in infants, toddlers, and adults. One study showed the benefits of administered L. reuteri, following children for nine years after they were treated as infants before any teeth had emerged. Also, data exist for probiotics influencing other oral health endpoints, including periodontal infections, oral candida infections, and halitosis.


The discussion groups on day three of the conference addressed a range of topics:

  • Possibilities to harmonize global probiotic and prebiotic regulations—Chaired by Seppo Salminen (Finland), Yuan Kun Lee (Singapore), and Gabriel Vinderola (Argentina)
  • Fermented foods for health: East meets West—Chaired by Bob Hutkins (USA), Paul Cotter (Ireland), and Liu Shao Quan (Singapore)
  • Potential value of probiotics and prebiotics to treat or prevent serious medical issues in developing countries—Chaired by Daniel Merenstein (USA), Reuben Wong (Singapore), and Colin Hill (Ireland)
  • Prebiotics as ingredients: How foods, fibres and delivery methods influence functionality—Chaired by Glenn Gibson (England) and Karen Scott (Scotland)


These workshops often produce peer-reviewed publications based on the discussion outcomes, so stay tuned for these developments. (See here for a list of ISAPP publications.)

The full meeting report is being developed and will be posted on the ISAPP website shortly.

The 2019 meeting will return to ISAPP’s normal format, hosted by Dr. Sarah Lebeer in Antwerp, Belgium.



ISAPP’s First Meeting in Asia is a Huge Success

June 5-7th 2018 ISAPP held it’s first Asian meeting in Singapore. This open registration meeting was a huge success with over 240 attendees from 34 countries.

Two days of plenary talks focused on the latest science featuring prebiotic and probiotic use in: pediatrics, oral health, allergy immunotherapy, the gut microbiome throughout life, synbiotics, liver disease, honey bee health, chronic gut disorders, and more. The meeting also featured an interesting talk about the changes coming in the nomenclature of the genus Lactobaccilus.

The plenary, open sessions were followed by a Discussion Forum on June 7th for invited experts and Industry Members. The discussion groups focused on:

  • Harmonizing Global Probiotic and Prebiotic Food/Supplement Regulation
  • Fermented Foods for Health: East Meets West
  • Potential Value of Probiotics and Prebiotics to Treat or Prevent Serious Medical Issues in Developing Countries
  • Prebiotics as Ingredients: How Foods, Fibres and Delivery Methods Influence Functionality

Finally, there were over 70 posters presented at the meeting featuring the latest prebiotic and probiotic research from around the world.

Next year, ISAPP will be hosting an invite-only meeting in Antwerp, Belgium – May 14-16, 2019. To attend this meeting, join ISAPP as an Industry Member.