Did you miss Probiota Copenhagen 2022? Catch up now!

With 400 registered and 60 people on the waiting list, this edition of Probiota, the first in-person since 2020, broke all records.

The event started with the best and only way it is meant to: a beautiful get-together poem by Stephen Daniells.

In the stunningly sunny center of Copenhagen, Asbjorn Overgaard from the non-profit organization Copenhagen Capacity introduced and welcomed the probiotics community to the Medicon Valley – a life sciences cluster across Norther Denmark and Southern Sweden considered one of the best places in the world for biomanufacturing, including a strong microbiome network.

Session 1: The Weight Management Question

The opening session focused on next-generation beneficial microbes in weight management, starting with renowned Prof. Patrice Cani talking about the journey from identification of differences in gut microbiota composition between a healthy state and metabolic syndrome, and the implication of gut barrier and mucus disturbances, and a lower prevalence of Akkermansia muciniphila. A long path started to grow the strain in a suitable medium and test it in mice and humans, where it showed a significant reduction in insulin resistance (10¹⁰ live and pasteurized, n=45).

Further work from UCLouvain led to a broad-scale screening and to the discovery of other high-potential next-generation strains such as Dysosmobacter welbionis, a butyrate producer.

He was followed by the presentation of Prof. Pierre Déchelotte, gastroenterologist, director of laboratory at the Inserm and co-founder of TargEDys, on Hafnia alvei as a weapon in the battle against obesity. Strikingly, Hafnia was back in its cradle in Copenhagen, as it bears its name from its first description in the 1950s by Danish Vagn Moller in this city, which Latin name was Hafnia. Pierre highlighted the links between eating disorders and obesity, and the key role played by the regulation of appetite, including by the microbiome. The journey started with the identification of microbial metabolite Caseinolytic peptidase B (ClpB) as a mimetic of satiety hormone alpha-MSH, able to induce the release of PYY and GLP-1. From there, Hafnia was developed and used as a vector of ClpB and confirmed in several obese mice models and in a clinical trial in humans to significantly support weight loss and associated metabolic benefits (10¹¹ cells/day, n=230). The product is on the market since over 2 years and was identified as the first example of a precision probiotic.

Transitioning from this innovative, bottom-up discovery journey, Kimmo Makinen, innovation director at Novozymes OneHealth shared insight on using AI to better develop future probiotics. “Data is the new oil” he said, and to avoid the translational black box between in vitro/animal studies and human setting, he advises using deep learning, big data, data science, machine learning, and data fusion for their strong predictive power. “These tools can help understand the mechanism of action, better stratify population, and better answering precise consumer insights” he suggests.

At Novozymes, AI is used to annotate the company’s huge strain collection with performance potential and facilitates going after new strains expressing traits of interest.

In the panel discussion, Patrice Cani and Pierre Déchelotte were joined by Dr. Johanna Maukonen from IFF, the owner of B. lactis B420 and answered many questions to better understand what lies behind the efficacy of pasteurized Akkermansia and the potential for purified recombinant ClpB, the dynamics, the mechanisms, and the debated relevance of the Firmicutes/Bacteroidetes marker.

Session 2: Fermented Foods

Dr. Bruno Pot, science director for Yakult Europe made a case for the recognition of dietary microbes as a category to be labelled, and with a Recommended Daily Intake established, which should be taken into account in the calculation of nutritional scores such as NutriScore in France.

Since our ancestral origins, several revolutions (birth of agriculture, industrial food and now processed sanitized food) led to sequential dramatic reductions in microbiota diversity, associated with a rise in non-communicable diseases. Because it is important to restore a diverse, resilient ecosystem, he proposed the creation of a category “dietary microbes” (similar as “dietary fiber” recently added to nutritional labels) defined as “live microorganisms ingested as part of the normal diet”.

This category is distinct from fermented foods, which do not require the microorganisms to be alive at the time of ingestion.

Prof. Paul Cotter, Head of Food Biosciences at Teagasc, is one of the most dedicated explorers of fermented foods, diligently working on the characterization and scientific description of these foods, their microbes, and their benefits. Metagenomics studies revealed tremendous heterogeneity within fermented foods. For example, only 30% of milk kefir tested could remove cholesterol. These studies show vast differences in benefits, and a huge untapped potential with the possibility to optimize and develop super fermented foods.

From a completely different standpoint, the sensory angle, Maciej Krol gave us a taste of fermentation as a tool to develop taste and texture – the traditional technology that led Copenhagen to host the best restaurants in the world, including the Noma. “4 of the best restaurants in the world have a fermentation department” he highlighted, helping to release umami power.

In the panel discussion, Bruno, Paul and Maciej discussed the challenges in communicating the benefits of the category, and the colossal amount of work remaining to do to understand the communities at play in so many different types of foods, to step up to the next level and advance efficacy. Bruno reckons it will yet be 5 to 10 years before the dietary microbes arrive on food labels. One of the levers is education, he says, with the telling example of children who were taught milk kefir as a Tamagotchi!

The day closed on a cocktail full of original fermented foods tasting opportunities.

For the brave, Day 2 started with a 7am run in the freezing capital. For others, the day lit up with the industry’s favorite: Ewa Hudson, director of insights at Lumina, who processed data on e-commerce probiotics to deliver always so relevant messages.

Probiotics supplements are still growing strong (+35% in 2020, with 1.5 billion USD, to 1.7 billion in 2021) and APAC is now the largest market before Americas. With a sudden diversification of the category’s number of brands and a surge by over 2000% in reviews between 2017 and 2020, Ewa asks “Have we seen the probiotics Big Bang?”

“Watch out for metabolic health” she also urges, as Google trends show the weight management category is way ahead of any other terms of searches in the past 12 months.

Fastest-growing categories include many mood & stress focus areas, and star ratings identify thyroid, blood glucose, weight management and menopause as leading disrupters. The number of searches for dogs was also tremendous. Ewa’s key message was the responsibility of our industry to offer probiotics helping people in the middle of the mental health crisis.

She was followed by Briana Kolowicz from Cargill who highlighted the unicity of each postbiotic and presented how the company aims to build a full dossier including metabolomics and mass spectrometry for example, as was done for EpiCor, for future postbiotic developments.

Session 3: Beyond pre- and pro

Dr. Simone Guglielmetti from the University of Milan challenged the new ISAPP consensus statement for the definition of postbiotics in 2021:

“Postbiotics are a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host”.

He proposes:

• To keep nonviable cells distinct from microbial factors, metabolites, and molecules, and to call parabiotic the first and postbiotic the second
• To avoid the term inanimate that is not supported by literature

Dr. Luis Gosalbez from consulting firm Sandwalk Bioventures looked at the meaning of the term postbiotic from a market perspective. He showed that about half of the postbiotic market is in foods, and in this space, they are mostly intended as inactivated cells, typically Lactobacillus-derived. In the 2^nd market (cosmetics, 30%) the term usually refers to fermented lysates, and in the drug segment (4% of the postbiotics market) they are isolated molecules. Across segments, there is a characteristic in common: postbiotics are considered to exert a health benefit.

Next, Marta Tortajada Serra from ADM focused on postbiotics as products, and on their development journey. For example, B. lactis BPL-1 comes from a screening in C. elegans worms based on the reduction of fat droplets. The heat-treated BPL-1 was still able to reduce fat contents in C. elegans and mice raised on a cafeteria diet. Teichoic acids were identified as triggers of insulin signaling pathway.

I apologize to the panelists (John Deaton, Luis Gosalbez, Simone Guglielmetti and Chyn Boon Wong from Morinaga) and to speaker Henrik Roager from the University of Copenhagen for not reporting on their contributions which I wasn’t able to attend.

Session 4: The Gut-Brain Axis

Dr. Siobhain O’Mahony from University College Cork was expected for insights regarding the interplay between the gut microbiota and the brain, behavior, and stress but had a last-minute flight mishap. She graciously agreed to record her presentation which will be available on NutraIngredients in the next few weeks.

Dr. Gregory Leyer from Chr. Hansen gave an overview of the market and research on the topic. As Ewa, he showed that people are increasingly needing mental health support and that in parallel there is an ever better understanding of the interplay between diet, microbiota, neurotransmitters, immune regulation, and mental wellbeing. Assessing studies quality, he suggests to better define inclusion criteria in clinical studies as a major lever to reduce variability.

Impressively, Gregory reported on a study using LGG and BB12 in hospitalized people with bipolar disorder or mania, and the probiotics treatment reduced by more than half recurring mental challenge and hospitalization relapses!

The group sees a big market demand and growing holistic health understanding and keeps investing in providing proof, launching two Gut-Brain Axis studies this year.

Pierre Déchelotte suggested another effective way to reduce bias and variability in clinical studies: deciphering a clear mechanism of action.

Session 5: The opportunities of Live Biotherapeutics / Pharmabiotics

With the Pharmabiotics conference at our doorstep, 20-21 April in Lyon, this session was like a teaser to the next event.

John Deaton from Deerland Probiotics & Enzymes presented the original and creative work conducted by the company to investigate spore germination dynamics in real-time, enrolling 11 patients with ileostomies – with their large intestine removed, and feces collected in an external pouch. In this way, researchers could observe germination and growth of B. subtilis DE111 after 2 to 4 hours from intake. John also highlighted key documented benefits and “the spore advantage” – the broad applications offered by spores’ resistance.

More into Live Biotherapeutic Products (LBPs), Dr. Magali Cordaillat-Simmons from the Pharmabiotic Research Institute introduced regulatory science and its importance in the emergence of innovative therapies. First, the regulatory framework under which to register a product depends on the intended use and target population. When it is to prevent or treat a disease, it falls under the drug framework and requires extensive documentation of quality, safety, and efficacy.

Regulatory science, Magali stresses, is not simply regulatory affairs: it is more proactive and requires the skills to adapt the scientific studies’ design to fit with regulatory expectations – helping reduce risks in the development of innovative medicinal products as are those derived from the microbiome.

The stakes are to educate and convince authorities that “yes, this category is an innovative field, but we master the science and implications”.

Ferring’s director of R&D Alliance Management Dr. Kristin Wannerberger provided an update on developments from one of the leading players in pharmaceutical microbiome-based developments. Applications range from supporting fertility and post-partum depression to addressing Inflammatory Bowel Diseases (IBD), antimicrobial resistance, pregnancy-related infections, and all these thanks to bacteria, phages, fungi, and metabolites produced by microorganisms.

The panel discussion had Magali and Kristin joined by Monica Olivares Martin from Biosearch Life, Staffan Stromberg from Infant Bacterial Therapeutics (IBT), and Luis Gosalbez.

Staffan Stromberg is the CEO of IBT, a company ahead of the game in LBP development, working on Bifidobacteria to reduce necro enterocolitis (NEC) in pre-term infants. He raised 100 million USD and opened new drug applications in 10 countries, paving the way for LBPs in the most vulnerable population on Earth, with the very concrete chance to save lives.

The panelists stressed the importance of standardization and robustness, especially in Omics studies.

With regards to investments in the space, Luis is optimistic: after a slowdown when times smelled of uncertainty, he says, since 2021 the rebound is present with over 50 microbiome drug developments ongoing, several companies entering phase 3, and more dynamism brought by acquisitions. In the early days, food companies were investing a lot. Now it’s more Venture Capitals and Big Pharma.

In the end, and as reminded by Dr. Shahram Lavasani from ImmuneBiotech, developing drugs in this sector is about engaging with FDA: there is no “us” and “them” – we need to step forward together.

When will we see new probiotic drugs in the EU? Magali expects Steffan’s to be the first, in maybe 3 more years if the studies go well.

Day 2 finished with a beautiful networking dinner mingling among sea creatures in the wave-shaped Copenhagen Aquarium.

Day 3 dawned onto a great look into the European regulatory situation, and the hope for light at the end of the tunnel. Tanne Severin Holm from the Danish Veterinary & Food Administration, teamed with consultants Brian Kelly and David Pineda Ereno to answer Stephen Daniells’ questions. Tanne was one of the leading voices enabling Denmark to allow the use of the term probiotic on food supplements labels since May 2021 and is now working on alliances with supportive countries including Italy (since 2013), Spain (since 2020) and other member states to persuade the European Commission to look at this question again. Bulgaria, Greece, Poland, and Malta also accept the term although they have not published an official statement, David reminded. In Germany, since a Supreme Court Case ruled against the term, it would be necessary to change the law to enable more tolerance. The real-time Slido survey revealed about half of the industry attendees still believe an EFSA claim for probiotics and prebiotics to be the holy grail.

The panelists looked beyond claims and to the implications of modern advertising, through influencers.

“If they are paid, you’re back under the health claims regulation”,

they warned.

The work by the International Probiotics Association with Codex is also ongoing, with a paper on minimum requirements and a labeling framework submitted, but the next meeting was postponed to March 2023.

Session 6: Start-Up Focus 

Michael Oredsson, CEO of the Akkermansia Company, the new name of A-Mansia, related the rollercoaster adventure it’s been for the company to study the strain, produce it, obtain the novel food approval, and now being able to come to market end of 2022.

Enbiosis, presented by its CEO Omer Ozkan, proposes to third parties their software offering personalization possibilities. Enter your microbiota analysis’ raw data and the list of all your strains, and the company says its software can define the fastest way towards increased microbial diversity and recommend the best of your products accordingly, for just 40€.

Lactobio’s CEO Soren Kjaerulff is building a direct-to-consumer model. The mission of the company is to address antimicrobial resistance surge through the inhibitory capacities of microbes. It is one of the first in the world proposing live bacteria in creams, for skin health.

Which is a great transition to the panel on the skin microbiome, in which Kacey Culliney, editor at CosmeticsDesign-Europe hosted Marie Drago, founder of Gallinee, and Margherita Patrucco, Innovation and product development at Probiotical. The panelists agreed that tomorrow, cosmetics will no longer be just creams, but also nutraceuticals, mobile phone apps, the built environment microbiome, and even probiotic-covered clothes. They see less interest from consumers in anti-aging and anti-wrinkle products and more in antioxidant properties, acne, dermatitis, scalp care, skin barrier, inflammation, balancing the microbiome…

They also questioned certifications proposing a “supporting the microbiome” type of claim, since it is still unclear what a healthy skin microbiome is.

Oral care is also part of skincare, they advise, and after decades fighting bad bacteria in the mouth, we are at the same stage as Martin Blaser in his fight against the overuse of antibiotics: we need to change the perception that all bacteria in the mouth are bad. Marie created the Microbiota Academy and said education is a very important part of what they do. For example, her message “People kissing all the time have a better skin” was very successful.

Final Panel: The Future of the Industry

Organizer Kavitha Sivasubramaniam hosted panelists Stephen Daniells, Ewa Hudson, George Paraskevakos, and Bruno Pot for closing remarks regarding the key trends in the space.

George named the proliferation of e-commerce, the explosion of science, and the metabolic health blossom. Bruno sees more and better products coming to market and asks how we will get the right claims across to consumers. Yakult has had a probiotic for over 20 years, backed with studies on several hundreds of millions of participants, he says, and deplores still not being able to communicate.

“The probiotics shelf in supermarkets is probably the shelf most studied, and it’s the most questioned”.

Ewa stressed the importance of mental wellness and of weight management:

“We desperately need products for weight management and satiety”,

as well as menopause. Stephen confirms the big trends as seen in Expo West shifted from immune to stress and sleep. George also noted the importance of the demand for pets.

Regarding the postbiotics trend, the panelists advocate for consensus on the term to do and communicate things properly. Ewa also asked for a list of ingredients considered as postbiotics so Lumina can start tracking them.

George raised a great point about the future of communication. Influencers’ marketing increased by x1000, and a study revealed that only 14% of information from influencers is accurate. He also emphasizes from a recent consumer survey that the key reasons for having used a probiotic were a science claim, a health claim, product efficacy, and natural formulation. It doesn’t feel right that Google and influencers, 3^rd parties can communicate while companies are refrained from labeling or referencing their own science.

“Educate your consumers through your channels or let Google do it”,

George warns. The IPA is investing in education on multiple fronts and is finishing a 24 hour probiotic course in a Master’s program for nutrition students, hoping to collaborate with more universities. SeedHealth is also a luminary of education in the field: they created SeedUniversity to train influencers before they go communicate on social media. There is a multiplicator effect from industry to healthcare professionals, influencers, and consumers.

And that brought us to the end of Day 3, as grateful satisfied social animals having quenched their thirst for bonding and industry updates. Follow NutraIngredients’ news for more interviews and deeper reporting on these presentations.

Thank you Stephen, Kavitha, Fiona, Tim, and all the speakers for such a great event, and you reader for getting to the bottom of this long chronicle.