Probiota is set with the ambition to connect business and science of the microbiome space, build community, start conversations and inspire innovation, as very well expressed by Nathan Gray from William Reed.
Probiota this year started with the tour of Kerry’s Technology and Innovation Centre, and was followed in the afternoon by 5 talks on the implications of emerging research on the microbiome.
Dr. Francisco Guarner, consultant of gastroenterology at the University Hospital Vall d’Hebron in Spain traced back the history of our symbiosis with our microbes in the past 100 000 years to highlight how our changes in diet and environment have impoverished our microbial communities in a way that has become suboptimal for health. “Loss of microbial richness is the common feature of non-communicable diseases” he said – taking examples from the literature in cancer, type 1&2 diabetes, etc. Dr. Guarner concluded with 3 practical assertions:
- Maintaining diversity is a novel clinical target
- Increasing the abundance of fermentative taxa is a hard endpoint
- Probiotics with anti-oxidant, anti-inflammatory activity and prebiotics promoting butyrate producers are to be developed and tested for their capacity of recovering vulnerable gut microbiota in industrialized countries.
Dr. Cormac Gahan, Principal Investigator at the APC Microbiome in Ireland mined the gut microbiota for solutions to infectious disease and antibiotic resistance. A recent publication in the Lancet estimated the burden of infectious disease and sepsis at nearly 50 million cases in 2017 and 11 million deaths – twice the level of previous estimates. A randomized controlled trial (RCT) in India involving 4500 babies given a synbiotic (L. plantarum+ FOS) showed the intervention reduced sepsis by 40% and also reduced respiratory tract infection. The results were so dramatic the study was interrupted to generalize the use of the synbiotic. Mechanisms of action include colonization resistance, secondary bile acids and bacteriocin production by members of the microbiota.
Probiotics, Dr. Gahan concludes after several other examples, are a real prospect for preventing infectious disease and for decreasing the carriage of resistant bacteria.
Pr. Yolanda Sanz from the Spanish National Research Council investigated how intestinal bacteria restore endocrine and immune signaling in diet-induced obesity. “The discovery that the gut microbiota could play a role in obesity resets hopes for intervention”. Bacteroides uniformis CECT7771, selected for its anti-inflammatory profile, has reduced glucose intolerance in mice on a high fat diet. The mechanisms of action include the stimulation of toll-like receptor 5 (TLR5), the increase in butyrate producers and Bacteroides, and the decrease in Helicobacter. The group has also worked with the association of prebiotic fiber and on other bacteria selected for other mechanisms of action.
Dr. Greg Leyer, Chief Scientific Officer at UAS Labs, presented on the results of a new clinical study on the company’s strainsL. acidophilus DDS-1 and B. lactis UAB1a-12 compared to placebo on gastrointestinal symptoms in 330 participants. The strains were both selected based on anti-inflammatory activity and were delivered at the dose of 10 billion cfu/day for 6 weeks. Because IBS is known to present high placebo response, the excessive placebo responders (who saw their symptoms decrease by 25% or more) were screened out in the first 2 weeks.
Both strains were able to significantly reduce symptoms of IBS (-36% with DDS-1 and -22% with B. lactis, after 6 weeks), with clinically relevant improvement of bloating and bowel habits as well as reduced constipation and diarrhea.
Finally, Julian Mellentin, the founder of New Nutrition Business, provided insights for successful science commercialization. He advised companies in the field to:
- Strive to become experts both in science AND market – with a need to understand better consumers, their complexities and how to get the information to them;
- Help the consumers feel (or measure) the benefit
- Find the best product type to promote or endorse their science
- Give retail strategy as much importance as they give to science
- Consider Asia and America are THE place to be (health-conscious, open to innovation, willing to spend money on maintaining health)
- Avoid treating health claims as the answer and invest in other ways of communication.
Following Julian’s advice, Day 2 of Probiota started with 3 talks dedicated to consumer market insights.
Jen Thompson, Healthcare Regulatory Manager at Walgreens Boots Alliance, focused on consumer health. She notes that the chain of communication tends to start from authorities, like the NHS in the US that advises the use of probiotics when taking a course of antibiotics, leading to Doctors recognition and recommendation. In the US, over 90% of Doctors say probiotics have a beneficial effect for Antibiotic-Associated Diarrhea (AAD), and 74% of them have already recommended their patients to take probiotics. However, information available online doesn’t always match scientific evidence (Neunez et al., 2020), and the industry is left with a disconnect between the science and regulation, having thus difficulty explaining the science to consumers. The EU market is nagging behind the US due to the difference in legislation, while healthcare professionals are starting to truly understand probiotics science and endorse it in their practice, Jen says.
Ewa Hudson, Director of Insights of Lumina Intelligence, presented data on online probiotics sales in 25 countries, covering 1397 brands and nearly 4000 products. She confirmed the EU market is underperforming in comparison with Asia and the US. Of course reviews are of utmost importance and Ewa’s advice to brands is to listen to what consumers say about the products in their reviews and to modify them accordingly. A lot of innovation is finding its way to the marketplace and Probiotical was named among the most innovative suppliers. Fast-growth areas include the skin microbiome, men’s health and the gut-brain axis. E-commerce is living a transformation in which women are more empowered and active, but social isolation and depression are big questions and create an opportunity for gut-brain axis products, including for generation Z.
Sheelagh Pentony, Acting Market Team Lead at Kerry guided us through the who, what and where of probiotics consumers. Starting from the gut, consumer research shows 30% of people suffer with gas, constipation, bloating or stomach aches globally– some of them all the time. Their symptoms range from embarrassing to painful and they are highly motivated to find solutions. The purchase driver are:
- Immune system support (even more in this period)
- Healthy bones and joints
- Heart health
- Digestive health
- Improved energy
The preferred formats for their health products remain foods and drinks, followed by pills and capsules. 27% of interrogated people used probiotics in the past 6 months and 25% considered it – bringing the potential to 52% of the global population!
In terms of timing, 70% of consumers prefer to have their digestive benefits in the morning. They are eager for more information on digestive health and are ready to pay premium process for healthcare products, which paves the way for more research.
The next session focused on prebiotics and fermented foods. Glenn Gibson, Professor of Food Microbiology at the University of Reading, gave a talk full of humor on the gut microbiota and prebiotics, guiding the auditors across a review of prebiotics clinical studies. A blend of Galacto-OligoSaccharides (GOS) and inulin given to healthy infants for 2 months led to halved allergy, atopic dermatitis and rhino conjunctivitis at the 5 years follow-up (Moro e al., 2006). In both adults and infants, GOS were shown to promote the growth of Bifidobacteria. A trial in IBS with 3,6 or 7 g of GOS per day linearly increased Bifidobacteria and significantly decreased bloating and flatulence. In overweight adults, GOS decreased inflammation markers, triglycerides and total cholesterol/HDL cholesterol. In seniors, known to lose Bifidobacteria in aging, GOS increased Bifidobacteria, decreased pro-inflammatory cytokines and increased NK cell activity and phagocytose against E. coli. In travelers, GOS decreased significantly diarrhea’s prevalence and duration. The mechanism of action of GOS is thought to be through the selective proliferation of beneficial bacteria. There are also chances to explore gut-brain axis potential with prebiotics, Prof. Gibson concludes.
Prof. Paul Cotter, Principal Investigator at the APC Microbiome Ireland, reviewed health promoting properties of fermented foods. The fermentation market is living a boom, and its market value is expected to reach a staggering 900 billion USD by 2023. Fermented foods are rich in live microbes, which produce high value nutrients and decrease toxins. But can we speak of health benefits ? Fermented foods are highly variable in their composition, so studies are not reproducible or can’t be extrapolated from one product to another. In addition to difficulty in standardization is also the question of denomination and rules, with products on the market sold as kefir or kombucha often not respecting the composition and requirements for these drinks.
A mouse study showed that traditional, but not commercial kefir, led to weight loss and metabolic benefits. The Global Fermented Food Initiative is doing tremendous work sequencing fermented foods – and discovering new species, and acknowledges that “we are just scratching the surface”.
The following panel discussed commercial opportunities for prebiotics and fermented foods, identifying several areas of opportunities including skin health and heart health. While the panelists Tracy Armstrong, co-founder of KO Kombucha, Len Monheit, executive director of the Global Prebiotics Association, Stephen O’Hara, CEO of Optibiotix, and John Deaton, VP of Science and Technology at Deerland probiotics & enzymes agree that understanding the mechanisms of action is important, they also think simplification is necessary to pass the message – while avoiding the pitfall of presenting the products as magic bullets. The role of regulation will also be major – with the current ban in the EU of the term prebiotic alike the term probiotic – since this word is key to explaining the difference between dietary fiber and prebiotics.
After the traditional roundtable lunch, the afternoon sessions covered probiotics in foods and the big question of communication.
Kara Landau, CEO of Uplift Food and dietitian from Australia, told the story of her brand. Her company launched healthy cookies with taste and functionality (with resistant starch as a prebiotic, as well as a probiotic) and minimal sugar, and was supported by investments from Mondelez Internation’s Snack Futures Innovation Lab.
Katrina Borisjuk, marketing director of the said Snack Futures, further explained the objectives of the initiative: in a world with increasing demand for healthy snacking, especially for the gut, Mondelez aims to facilitate the pick-up of the scientific message to gut health influencers and to consumers. She mentioned 9 “tribes” around gut health, including for example the Super Moms, who take probiotic supplements to give the best possible life start to their children, and the Natural Healers, who are interested in natural foods and ayurvedic.
Both Kara and Katrina, as well as Julian Mellentin, gave insights on taking the microbiome mainstream. They indicate that some companies were looking at the space for a long time but the change is that now the consumer understanding is catching up and the market is more mature. Brands can help people understand the science in a more digestible way, and help people feel the benefits.
Communication and education in the microbiome field remain one of the biggest challenges. How can we decrease the confusion and improve feelings towards the category ? How can we tell the right, true stories and bring emotions in to talk about our science? Kristina Campbell, Science and medical writer specialized in the microbiome, identified key issues in the mishaps in communication we’ve seen in the past years, and proposed clear actions to improve the situation:
- To have more scientific content specialists involved in content creation and media training in specific scientific areas;
- For science and marketing teams to work together more closely, backing the words used;
- To reinforce specific points about the science:
- A body of scientific literature does exist on probiotics
- The right probiotic is needed for the right benefit (like drugs)
- Health effects are separate from effects on the microbiome
- Find opportunities to listen and calmly clarify what is and isn’t based on science.
“Be a resource for your community” she commends, “That will make people more resilient to the wrong message.”
Punchy DJ twins Lisa and Alana McFarlane, co-founders of the Gut Stuff, discussed how to avoid euphemisms and boredom in microbiome education. Sensitized to this world by participating to Tim Spector’s Twin UK study, they wanted to help pass the message on. The new generation is ready to think and act prevention but lacks basic information, so the sisters created an online platform to deliver bite-size messages from the world leading scientists. Contents were tailored according to polls in order to identify important topics and questions from people – like the effect of alcohol on the gut. When the audience knew more, people demanded products and the website evolved to include a selling platform. Their audience is reactive, with 70 000 people engaged on Instagram and half a million that saw their infographics.
Their advice for a better communication is to never patronize, to be playful, knowledgeable, accessible and revolutionary(only that!). But also to be honest on where the science is at, to teach people what are reputable sources to find the information and decide for themselves.
The speakers got together for a panel discussion and confirmed the need to listen to the people, create a sense of community and tap into the emotional side of the message. Government recommendations, researchers and practitioners can all help create trust in probiotics. The Revolution has to start from the grass root up – first with the understanding of benefits of the category, before they can arrive at the strains, they think. To make a difference in communication, the panelists advise to focus more on what is or is not science, work more together for a more unified voice and tell everyone that will listen about gut health !
Day 3 main focuses were the skin and beauty in the first part, followed by the prospect of better research, and concluded with the gut-brain axis session.
Dr. Audrey Gueniche from L’Oréal showed how “adapted cosmetics” can counter daily aggressions on the skin microbiota. Harsh cleaners decrease the bacterial load and diversity during at least 6 hours after use. A high tolerance product with prebiotics (polysaccharides) and Lactobacillus extracts allows a complete recovery after 6 hours. 14 days of use also decrease dryness, roughness and discomfort – because the skin microbiota is necessary for skin health.
The panel discussion on opportunities in the skin microbiome highlighted this is a very active sector: the number of cosmetics with probiotics has doubled since two years ago, Ewa Hudson remarked. Audrey Gueniche precised at the moment then company’s cosmetic products are not with live bacteria, and there are opportunities also for gut microbiota modulation for skin health. Luca Bucchini, owner of Hylobates Consulting, clarified that beauty claims are not health claims and not regulated by EFSA. However most skin problems fall into health category (spots, barrier function, dryness), says Dr. Gueniche, while only wrinkles are really beauty.
The Probiota Frontiers showcased a selection of 3 posters regarding the preclinical selection of strains (several isolated from Greek traditional foods) and their potential in diabetes, colitis, atherosclerosis and cholesterol reduction.
In the session aiming for better research, Olaf Larsen from Yakult and the Free University Amsterdam shared some insights he found based on computer simulations regarding the optimal setup of a clinical trial. In most cases, researcher try to get the population of subjects participating in the clinical trial as homogeneous as possible, for example by aiming to have all participants on the same diet and the same amount of exercise.However, it was shown that it is better to focus on another parameter when striving for statistical significance, namely minimizing the temporal fluctuations. Hence, it is not such a big deal to have the participants on different diets or amounts of exercise, as long as they stick to that lifestyle factors during the course of the trial.
Dr. Johanna Maukonen, Global Health and Nutrition Science leader at DuPont, also focused on clinical research in the microbiome era. Modulators of the microbiome, including antibiotics, diet and probiotics, are able to change the microbiome function rather than its composition, she argued. When conducting probiotics clinical trials, it’s important to register the study on clinicaltrials.gov and establish:
- The correct strain(s) and dose(s)
- The duration of the intervention
- The age of the host and target population, with which variations
- Power calculation
- The methods of analysis
- Following the good clinical practices
- The best Contract Research Organization
She mentioned a few studies conducted at DuPont, in weight management, bacterial vaginosis, and with a rhinovirus challenge.
The pioneers session was one of the most exciting moments of the event, with a showcase of real innovation in the field.
Matt Amicucci is founder of BCD Bioscience, which has created a carbohydrate encyclopedia of different oligosaccharides present in different foods, as well as a library of 800 different oligosaccharides which can be selected for combinations, not unlike Human Milk Oligosaccharides. There’s potential for scouting bacterial genomes and associating them with the right prebiotic, but also according to the production of certain metabolites in function of the association with the prebiotics.
Aline De Santa Izabel, founder of YoGutMe, proposes a smart yogut machine, focusing on plant-based symbiotic recipes, for intake of fresh yogurt with no additives. Better in taste, for health and for sustainability.
Leandro Barreiro, Co-founder and CEO of Microgenesis, links gut microbiota and fertility. 15% of couples suffer from infertility, 80% of them linked to auto-immunity or inflammation. The company proposes a test, Gynoma, analyzing microbiota markers, and provides recommendations for a personalized diet within 15 days. They have managed to increase by 60% pregnancies and by 78% the birth rate!
Last but not least: the final session was on the most fascinating topic: the gut-brain axis (GBA).
Dr. Harriett Schellekens of the APC Microbiome Cork looked at the microbiota-gut-brain-axis at the interface of appetite, food and mood. Alexis Martin, wounded in the stomach, gave the first scientific account in the 18thcentury that anger affects digestion. The microbiota indeed mediates appetite regulation through metabolites that can interact with receptors in the gut, by immunomodulation, and directly through the vagus nerve, for example. Prebiotics FOS and GOS in mice on a high-fat diet were able to decrease fat accumulation and leptin but also anxiety and depression. This knowledge allows to screen the APC culture collection for identified traits. Testing the strains in humans showed prospect of metabolic improvement (decrease in fasting blood glucose and cortisol, increase in ghrelin). The GBA signaling can influence appetite, eating behavior and stress.
Prof. John Bienenstock, director of the Brain-Body institute in Hamilton, worked on vagal stimulation, mood disorders and the identification of nerve targets for beneficial bacteria. He found an association between depression and butyrate producing bacteria. Mice studies showed the vagus nerve modulates BDNF expression and neurogenesis in the hippocampus. Like SSRIs, some probiotics effect on the brain is mediated through the vagus nerve. Sickness, sleep issues, cognition, memory and behavior are all affected by elevation of inflammatory biomarkers (C-reactive protein, TNF-α, IL-6) and their normalization is usually associated to curative outcomes.
“bacteria and SSRIs are speaking both to the immune system and the nervous system”, he says.
Dr. Jonathan Swann from Imperial College London focused on the biochemistry of depression and confirmed “it’s about the metabolites of our 39 trillion microbes”.
I would like to thank Nathan Gray for contributing this closing comment on the last session that he chaired.
“The final session of Probiota generally focuses on the future of the market”,
Nathan notes,
“looking at the opportunities and challenges facing the sector in the coming years. Featuring input from George Paraskevakos of the IPA, Brain Kelly from Covington & Burling LLP, Bruno Pot of Yakult Europe and Maria Kardakova at Atlas Biomed Group, discussions ranged from the impact of Brexit on the industry (and possible UK-USA relations in a post-Brexit world) to the upcoming changes to the Lactobacillus taxonomy, and the challenges associated with personal privacy and data protection in areas like microbiome testing and personalization. The panel highlighted emerging science linking the gut microbiome to mood, depression and other cognitive disorders as a very promising area, noting it is an area where microbiome-modulators like probiotics and prebiotics could potentially bring benefit to the millions of people who have sub-clinical mental health issues in the future.”
Thank you for reading and becoming a resource to your community too !
Nina Vinot
Before entering industry, Nina was involved in human nutrition research at Penn State University, USA, the French National Center for Scientific Research (CNRS) and the National Institute for Agronomic Research (now INRAe). She has an engineer degree from AgroParisTech, Paris Institute of Technology for Life, Food and Environmental Sciences. After over 6 years developing science-backed probiotic supplements sales across Europe for Probiotical, she is today international sales director for the French biotech TargEDys, the ambassador of precision probiotics.