Probiota Copenhagen 2019 broke a new record, going from 250 attendees last year to 350 and sold out! Why? Because of its unique approach to bringing together stakeholders from the industry, the academy, CROs and authorities representatives. Here’s what was talked about.
Day 1: The Microbiome through the life stages Prof. Tine Rask-Licht studied the impact of diet on gut microbes and revealed that if we don’t eat enough fiber, the colon inhabitants, in default of being able to ferment, increase protein catabolism, which is linked to putrefaction, proteolysis and carcinogenic compounds. Also, healthy non-celiac people on a gluten-free diet had less bloating but lost their Bifidobacteria.
DuPont Global Health and Nutrition leader Dr. Johanna Maukonen proposed to steer the microbiota in the right direction during the window of opportunity of the first 1000 days of life. L. rhamnosus HN001 in pregnancy was shown to significantly improve bacterial vaginosis symptoms and decrease the prevalence of gestational diabetes mellitus in women over 35 as well as post-partum depression and atopic dermatitis in the baby, including at the follow-up at 11 years! In addition, specific Human Milk Oligosaccharides (HMOs) like 2’FL could oppose E. coli, reduce NEC in preterm newborns and promote cognitive health.
Regarding a later phase of life, Prof. Dennis Sandris Nielsen identified from 2 cohort studies the parameters associated with frailty. To prevent a loss of bacterial diversity and “inflammaging”, he recommends a diversified diet (including cereals, that promote Akkermansia muciniphila and Bifidobacteria) and low consumption of alcohol. “The good senior life starts early and with the diet”.
Ewa Hudson of Lumina Intelligence looked at the probiotic market through the filter of consumer ages, and highlighted untapped potential in sports nutrition and seniors, notably in sarcopenia.
The day concluded with an interactive session organized by Peter Wennstrom, Founder and expert consultant at the Healthy Marketing Team. He described 4 subtypes of innovator profiles (the Explorer, the Developer, the Marketer and the Optimizer) and coordinated a brainstorm of the main challenges met in the sector, in the corresponding areas of Science, Product Development, Marketing and Commercial Optimization. Results here:
Day 2: From Population to Personalization: making sense of big data By analysing big (huge) data from the Flemish Gut Flora Project, Prof. Jeroen Raes and his team found 69 factors associated with microbiota variability. The main ones are diet, BMI, transit time, age, gender and drugs (especially antibiotics, laxatives, immunosuppressants, hormones and antidepressants). He also insisted on the importance of moving from relative to quantitative analysis to improve the quality of metagenomics interpretation. Density of bacteria, measured by flow cytometry, varies a lot even within the same person and same day, and shows an important impact on phenotype. Among the Bacteroides enterotype for example, the subgroup with extreme low cell count shows associations with Crohn disease, depression and a lower quality of life.
Dr. Xiaquan Su proposed a very exciting tool: the Microbiome Search Engine, to use as a telescope in the night sky of big data. Or less poetically, the Google of metagenomics. Encompassing over 100 000 samples from over 300 studies including HMP, MetaHIT and the Earth Microbiome Project, the tool can be used to screen previous databases for similar microbiome profiles, and to evaluate mainly two indexes:
The Microbiome Novelty Score (MNS), establishing how new the profile is (non-human samples are 6 times higher in novelty than human samples, strikingly indicating that we are approaching saturation in the human microbiome description and implying there is a big unknown universe to discover outside of us) The Microbiome Attention Score (MAS), identifying the hot spots that attract most attention.
While novelty when a microbiome is born is constant, the level of attention afterwards is variable: it’s amazing the MAS can actually be predicted by 4 years with 98.8% accuracy. Dr. Su reveals that the Sleeping Beauties which will get attention in the future are the marine environment, the indoor environment, and the mother-baby microbiomes.
Dr. Daniel Ramon Vidal got our attention back to the Earthly world of application, showing how Biopolis used genomics, transcriptomics, proteomics and metablomics to screen for novel strains. From metagenomics associations in atopics dermatitis, a blend of 3 strains with anti-inflammatory and anti-oxidant properties was developed and successfully tested in kids. With regards to metabolic syndrome, the company screened the strains thanks to C. elegans worms, obese Zucker rats and Wistar rats and finally in humans, showing a slight decrease of waist circumference and abdominal fat, and a concommittant increase in Akkermansia muciniphila, Bacteroides and Bifidobacteria.
Dr. Elisa Salvetti then gave an excellent and much needed update on the expected taxonomy change to the Lactobacillus genus, which will likely be split in 16-17 new genera by the end of 2019. The experts will aim to keep the first letter L, so that Lactobacillus casei for example could stay L. casei. The impacts for the stakeholders will be:
The need to update labelling on all technical, quality and commercial documentation – to be taken together with the opportunity for better understanding and communication of the strains activity, since the new classification will pool bacteria by their function, mode of action and metabolism;
The need to communicate to the consumers that strains remain the same; From a regulatory standpoint, a potential risk for the Qualified Presumption of Safety (QPS), though the EFSA said the QPS model won’t change and it is expected to simply update the names;
On the validity of patents deposited with species and strain name Literature searches will need to include both old names and new names. Bruno Pot reassuringly reminded us that B. lactis has become B. animalis subsp. lactis 15 years ago and there is still tolerance over the old name.
IPA and ISAPP will keep their members informed on the new names and timelines.
Also, Dr. Salvetti anticipates that the taxonomy review will surely touch Bifidobacteria as well in a next step.
Elinor McCartney signalled another important change of labeling to come: as of May 2022, the use of a brandname including “Probio” will no longer be authorized in the EU, unless substantiated by a probiotic approved health claim.
Marketing specialist Dr. Harini Venkataraman gave an overview in Microbiome-based new business opportunities. In the midst of the acquisition acceleration, she advises actors aiming to partner up to look for companies delivering the innovation suiting their products, to focus on academic research collaborations for fundamental research, and to look for ways to innovate up and down the value chain while always keeping in mind the end consumer (and his search for healthier food, convenience and personalization).
Real food was not left aside from the conference, and perfect examples of successes in fermented foods were introduced by Mats Lonne with Otto probiotic, organic unsweetened baby food, James Read with Kim Kong Kimchi and Lu Shao Quam with his probiotic beer business in Singapore.
3. The latest scientific developments
Dr. Angela Horvath from Graz university discussed the potential of selected probiotics to improve the quality of life in cirrhotic patients. Cirrhosis dysbiosis is characterized by a loss of SCFA producers, a rise in E. coli and a rise in inflammation and leaky gut. A clinical trial with Ecologic Barrier probiotic blend for 6 months increased butyrate producers. Importantly, Dr. Horvath highlights that Proton Pump Inhibitors (PPIs) are not as innocuous as previously thought when we start taking into account the microbiome: they decrease alpha-diversity and beneficial microbes, increase Small Intestinal Bacterial Overgrowth (SIBO) and oralization (less strict anaerobes), in link with inflammation and gut barrier dysfunction.
Probi’s research director Dr. Niklas Larsson entered another promising area for probiotics: bone loss prevention. A 12 months supplementation of healthy early postmenopausal women with the patented combination of L. plantarum Heal9, Heal19 and L. paracasei 8700:2 (ProbiOsteo) allowed a 78% reduction in bone loss compared to placebo (unpublished data). With 8,9 million fractures due to osteoporosis every year globally, the potential for probiotics to delay bone loss is a major finding.
Torben Solbeck Rasmussen created a WOW moment when he brought the revolutionary idea that Fecal Microbiota Transplant (FMT) efficacy in C. diff could be due to the bacteriophages present in the feces, rather than bacteria. He demonstrated the validity of this hypothesis by simply filtering the donor feces and obtaining the same efficacy as FMT in mice and he suggested to speak of Fecal Virome Transplant.
Dr. Anur Akilzhanova noticed from -omics analyses of 120 Kazakhs that lipid metabolism and markers of oxidative stress increase in older adults and in the obese group.
Keynote speaker Prof. Gregor Reid closed the second day of Probiota with a memorable, furious protest towards the recent sensationalist headlines against probiotics. He drew attention to the responsibility of the involved media in dissuading people from using probiotics that may really benefit them, and he pointed to the numerous weaknesses behind unfounded conclusions such as the ones of the 2 Cell papers (Suez J. et al. 2018; Zmora N et al. 2018), the brain fogginess (Rao et al. 2018) and the GG paper (Schnadower D et al., 2018). Prof. Reid advocates for more protest against such informational and dangerous failures – and more protest towards EFSA.
Day 3. Clinical Opportunities and Microbiome Therapeutics
APC Microbiome Dr. Lorraine Draper put again phages at the center of the attention. With over 90% of the phageome having unknown functions, with a quicker Microbiome recovery in mice when they were re-fed their phages, and in the light of Torben Rasmussen’s findings of therapeutic capacity in Cdiff, the phageome is an essential dimension of the microbiome that needs more research. More to come on this topic at the Pharmabiotics Conference in Paris 13-14 March.
In the microbial dimension, LNC Therapeutics is developing a next-generation probiotic to be registered as a drug for overweight people with metabolic syndrome. Christensenellaare associated with lean and healthy status and found in Italian and Korean healthy centenarians. A first clinical trial on Christensenella LNC01 led to a significant decrease in visceral fat while preserving lean mass in overweight people. CEO Dr. Rawadi says the study is now being reproduced in about 120 subjects.
Probiota Pioneers introduced 2 recent companies targeting gut health: Nouri, with a dietary supplement combining a sustainable plant-based omega 3 and 5 probiotic strains, and TROO, helping consumers fill the fiber gap with breakfast cereal bringing 10g fiber per bowl with a plastic-free packaging.
Workshop Claims vs Consumers
While Hannah Lester and Elinor McCartney from Pen&Tec think obtaining an EFSA claim for probiotics is possible if you “keep it simple” and describe well the mechanism (encouraged also by DuPont’s Dr. Arthur Ouwehand), Peter Wennstrom advises not to fall in the trap of treating probiotics as ingredients, but as a part of us that we can re-integrate if depleted. As well relayed by NutraIngredients after the conference, the addition of other ingredients for claims risks to confuse the consumers into thinking the probiotics are not the active component. Peter feels the industry should focus less on EFSA claims and more on their consumers and products. For example, belief-driven Millenials may respond more to emotional messages that reflect their values. Beyond claims, we need a paradigm shift in regulation to promote health and nut just heal or prevent disease – and there’s a huge role to play for probiotics to promote health.
It was great to have the European Commission represented by Dr. Dirk Hadrich, policy and program officer, reviewing important projects of the microbiome world funded by the EU, with budgets of 10-15 million € per project. EU funding gave us MetaHIT, MetaCardis, Syscid to look at chronic inflammatory diseases, and Eat2beNice looking on behavior. Now starting in 2019 are OncoBiome, researching signatures and therapeutic approaches from 9000 cancer patients, Microb-Predict in chronic liver failure, and Gemma regarding autism. Such EU projects give references, allow harmonization of protocols to increase data comparability, and start paving the way to precision medicine.
The BIG DEBATE gazed at the future, looking at the growth opportunities in the field. Dr. George Rawadi sees the funding going rather to therapeutic developments, while IPA Director George Paraskevakos emphasizes that one of the challenges for probiotics is that the Western cultures are not rewarding prevention. Michael Bush from GrowthWays thinks it would be ideal to include probiotics in everyday foods like breakfast cereal, to improve consumer daily compliance, and finally UAS Chief Scientific Officer Greg Leyer warns that exciting data is not causative data and joins Gregor Reid in denunciating probiotics sold for autism based only on animal data.
One of the editor’s takeaway messages was the beautiful opportunity to show people that their microbes are a part of their uniqueness, and to make them the hero of their health. My personal main take-away was the revelation from a poll showing 89% of people think that companies must also have a social / ethical mission beyond their products health benefits (up from 69% in 2017). That’s food for thought and for more action not just behind the products, but behind the values and ethical implementations of the company.