Take-Home Messages from IPC 2024

It’s been 24 years that the International Scientific Conference on Probiotics, Prebiotics, Gut Microbiota and Health - IPC2025 welcomes students, researchers, industry and stakeholders of the biotic sector in a unique atmosphere that makes the conference both informative and feel like a gathering of friends. As Dr. Jiri Snaidr puts it, the IPC motto could be « work hard, play hard » with long scientific days and short nights !

This edition brought together over 300 attendees and started with IPC new President, Arthur Ouwehand, offering recognition for the figures who made the IPC in this generation : Prof. Alojz Bomba, for establishing and leading the IPC since 2000, Prof. Sin-Hyeog Im for enriching it to a East meets West hub, Prof. Wilhelm Holzapfel for his contributions to the program and mentoring of many young scientists, and Peter Kürti for his experience and advice to help the conference become among the most recognized in the sector. They received pretty microscope-radiophone awards, while today's lead organizer Norbert Bomba received a certificate of appreciation. Norbert is more than appreciated by all the attendance, as this gathering would not take place if it was not for his efforts, and would not feel so convivial without his presence.

This report is to give you the essence of the topics and insights discussed at this edition, but it is not exhaustive, and I apologize for the speakers who will not find reference to their work in this summary.

Metabolomic Session

Keynote speaker Dongryeol Ryu from Korea discussed the language of microbes, who communicate via gut-microbiota generated metabolites (GMGM), including urolithin A (UA) and polylactic acid (PLA). UA and PLA appear to extend the lifespan and healthspan of C. elegans nematodes and improve mitochondrial function, but they are not the only messengers of the gut microbiome.

Hiroshi Ohno from Japan also digged into the language and mechanism of action (MoA) of microbes and identified that propionate in neonates activate oesinophils through GPR-41 by upregulating TLR signaling, showing the importance of microbes and their metabolites in the predisposition of bronchial asthma.

Next-Generation Probiotics

Cancer researcher Susan Lesley Woods from Australia, works on engineered bacteria, more precisely bioluminescent E. coli Nissle, to colonize specifically the cancer tissues, detect and prevent colorectal tumors. The research is promising but still far from being authorized for use in patients.

Jiri Hdry from Czech Republic described the potential of E. coli 083:K24:H31 (the drug Colinfant NewBorn) to prevent colitis development in neonates. He described the bacterium’s immunomodulatory properties and promotion of gut barrier by upregulating the expression of tight junction protein.

Finally, Bentley Shuster, scientific affairs at US-based ZBiotics, described the innovative work of the company that brought to market the first genetically modified probiotics, B. subtilis ZB183. It is based on the inclusion of an acetaldehyde enzyme from C. necator, accompanied by an upregulating section, to detoxify alcohol and prevent hangover. In terms of safety, they say their approach is conservative as it uses co-occurring microbes from the soil (that could have naturally exchanged these genes), with as few edits as possible, and delivers an enzyme that is not stable outside of the bacteria. The demand is there, as the company has sold over 4 million bottles already !

Claudia Borgmeier from BRAIN in Germany sensitized the audience on the 50 shades of grey between naturally-occurring microbes and engineered ones, from selecting random mutations to gene edition and self-cloned strains.

IPC President and scientific committee Chair Arthur Ouwehand from IFF guided us through the process of selection of new candidate Next-Generation Probiotics (NGPs). Based on comparisons of fecal microbiota samples from healthy cohorts and diseases cohorts, the company identified 4 high-potential winners : Intestinimonas massiliensis, Segatella copri, Lachnospira eligens and Akkermansia muciniphila. Next, they assessed their benefits and mechanisms in mice and worked on industrial upscale and stability. The next step will be human clinical trials.

Akkermansia was also the hero of Vidya Probiotics' speaker Dr. Rishi Raj Triverdi who worked mostly on the industrial challenges to produce the mucin-lover. The company uses plant-based gum with a chemical structure similar to animal mucins for the growth and microencapsulation of the strain to enhance stability. They are now proceeding to clinical trials in digestion, cognition and glucose/cholesterol regulation.

Belgian researcher Jean-Paul Pirnay focused the electronic microscope to the even smaller scale – to bacteriophages. Phages’ advantages in treating infection are their selectivity and lesser risk to drive resistancecompared to antibiotics, but they are challenging to work with as they require a wide collection, and often, a phase of training or pre-adaptation, to reduce resistance. Phage treatment improved several infections eradication rate in association with antibiotics. At Queen Astrid Military Hospital, Pirnay is working on a prototype of on-site phage printer aimed for use in 2030.

« Phages can make antibiotics great again » - Jean-Paul Pirnay.

Simulating and Modeling Session : Gut, Body Parts, Organoids

Young Scientist Thi Thanh Truc Phung from Institut Agro Dijon in France screened 8 biopolymers to be used as coating materials for NGPs. Sodium alginate is the best candidate because its release dynamics in the gastrointestinal tract can be tuned, it does not impact the oxygen barrier, and its molecular weight is ideal for probiotics.

Institut Pasteur researcher Catherine Daniel strives to bring animal-free preclinical trials to the next level with biomimetic gut-microbiota-on-chip models with 3D printing and reproduction of a flow like in the lumen, which resembles more closely what is observed in the intestine and better study probiotics mechanisms of action and host-microbiota interactions.

Jana Stofilova from Slovakia also works on in vitro models to screen for probiotic strains efficacy. She focused on transwell-based models using different cell lines, and organoids, and she recommends Caco/HT-29 MTX to assess anti-inflammatory activity and gut barrier function.

« All models are wrong, but some are useful » she concludes with the quotation from George E. P. Box.

« All models are wrong, but some are useful » - George E. P. Box

AI in Probiotic Research

Olivia Colberg, industrial PhD student working with Novonesis, assessed the effects of Human Milk Oligosaccharides (HMOs) with or without B. infantis Bifin02, on gut microbiota composition and metabolites using i-TIM2 model. The effects of the 5 HMO mix depended if the gut microbiota samples had Bifidobacteria, showing benefits when Bifidobacteria were present, but unpredictable results in absence of the keystone species. The mix of 5 HMO + Bifin02 resolved this risk and maintained or increased Bifidobacteria and beneficial metabolites in all infants.

Then Gustav Lindved, senior scientific product manager at Clinical Microbiomics (now merged with CosmosID, MS Omics and DNA Sense and offering services from discover to clinical validation) showed how analysis at strain or clonal level enables clearer understanding of mechanisms of action and community dynamics, as well as helps to inform the design of NGPs based on strain propensity for engraftment in public databases.

Tim Hensen from the University of Galway, Ireland, investigated with metabolic gender-specific whole-body models using 1000+ fecal microbiota samples which metabolites correlate with Alzheimer’s Disease (AD) and global cognition score. He found that APOE allele presence correlates with deoxycholate production and risk of AD, mainly explained by Eggerthella lenta abundance.

Koen Venema, editor-in-chief of Beneficial Microbes and organizer of the Beneficial Microbes conference, now Microbiome Expert with Wageningen University, gave an inspiring overview of how AI empowers analysis and visualization of databases, especially microbiome databases. He is excited by interactive figures where one can pick the subset of data of interest, useful for e-journals, and reminds not to skip in-vitro models, biological explanations, and simplicity.

Immunology Session

Prof. Sin-Hyeog Im walked us through a journey in science and innovation from probiotics to Live Biotherapetic Products (LBPs), and reminded yet again the importance of the mechanism of action to interest big pharma in microbiome-based therapeutics targeting civilization diseases from asthma to skin, metabolic diseases and immune disorders and cancer. « Avatiome » is ImmuneBiome’s AI-based drug development process, that yielded for example a developing LBP as a co-therapeutic option for immunotherapy studied from mechanism (Prof. Im says it took 8 years to find the effector molecules) to animal models, and the next step is a clinical trial combining the live B. bifidum and L. plantarum, and the company will launch next month a food supplement based on these findings in Korea before it can be registered as a drug.

Maria Rescigno focused on postbiotics, taken in the sense of bacteria-produced metabolites, as a new frontier for healthcare which can deliver protective effects against leaky gut, inflammation and their associated symptoms, without risk of translocation. She discussed several studies in the gut-brain vascular axis and their mechanistic findings.

INRAe researcher Jean-Marc Chatel dived into the variety and mechanims of action of Faecalibacterium species and their potential for IBD (Inflammatory Bowel Disease) and cancer. In  particular, his lab characterized the microbiome anti-inflammatory molecule (MAM) – from its abundance and position in the microbiome to its structure and association with transporters on the genome – and they wonder if MAM is the S-layer protein of Faecalibacterium. The next steps are to continue characterizing this promising NGP, its MoA and proof of concept in human trials.

Lallemand Health Solutions sponsored Session

Clinical research lead at Lallemand Marie-Laure Oula delivered an impressive review presentation focusing on Lacidofil® (L. rhamnosus R-11 and L. helveticus R-52 at 4 billion cfu/dose) and its studies showing it increases the success rate of H. pylori eradication when used as an adjuvant to triple therapy (2 antibiotics and Proton Pump Inhibitors, PPIs) compared to triple therapy alone (90% vs. 75%) in multiple human trials. The probiotic formulation also improves gastrointestinal side effects of the treatment and quality of life.

(Pro)biotic Application Trends

George Paraskevakos, President of the 25-year old International Probiotics Association (IPA) explained why and how the association recently expanded its scope to a pan-biotic mission and the services delivered by and to its 113 member companies, from manufacturing guidelines and standards to regulatory harmonization efforts, and scientific, technical and education advances. With the arrival of prebiotics and postbiotics in the scope, the association experts are starting with the reconciliation of defintions, as the lack of consensus on current definitions create confusion for consumers and even to frame market sizes for these categories.

Following-up with prebiotics, Salwa Karboune from McGill University pointed to the use of levansucrase enzymes from bacteria to catalyze the production of next-generation prebiotics – fructooligosaccharides (FOS) with a wide spectrum, which associated with increased short chain fatty acids (SCFA) production.

Irina Spacova from the University of Antwerp discussed a recent paper she recently wrote in collaboration with the IPA to explain the technologies, intended uses and regulatory landscapes of the different categories for biotics – foods, dietary supplements, and LBPs. She stresses the importance of defining the intended use at the very beginning of a development as the applicable  regulation, claim and study design all depend on it.

Microvesicles Session

Maastricht University Frank Stassen is a microvesicles enthusiast who showed great pictures of these budding nano-sized vesicles from the outer membrane of Gram- bacteria and inner membrane of Gram+ bacteria. What these vesicles contain depends on how they formed. They can participate in stress response, recovery of nutrients, biofilm formation and interaction with host cells. Certain bacteria are high « vesiculators » (Bacteroidetes, Bacteroides, Alistipes, Barnesiella), and extracellular vesicles (EVs) from Firmicutes and Proteobacteria could participate in the pathogenesis of Crohn’s disease. Vesicles from pathogens exacerbate inflammatory diseases while those from the commensal microbiota contribute to host physiology and homeostasis.

INRAe Juliana Guimaraes Laguna dived into the world of EVs from Propionibacterium freudenreichii PF129 as part of the strain’s health-promoting roles, by mimicking the immunomodulatory properties of parent cells, modulating NF-kB transcription and mitigating LPS-induced IL-8 release.

Beyond Gut Session

I was the only speaker in this session aiming to integrate the concern for the gut microbiome with its roots, the soil microbiome, in a One Health approach. My name is Nina Vinot and I am a business developer for Bioprox Healthcare , French toll-manufacturer for probiotic strains, and its spin-off company Cybele Agrocare that offers bacteria for agriculture. As soil microbes hitchhike foods and become members of the gut microbiome, and contribute to the nutritional quality of crops and foods, themselves participating to gut microbiome diversity - beyond their many roles in crop nutrition, protection, health and resilience, there can be no gut health without soil health ! The growing interest in the soil microbiome is also a key lever to motivate better ecoagricultural practices. I gave the example of Azotilis, Cybele's leading nitrogen-fixing bacterium which helps reduce drastically the green house gas footprint of fertilization.

Unfortunately I could not attend the regulatory session which ran in parallel to the young scientist award candidates presentations. It looked at the EU Feed Additive authorization and EFSA’s risk assessment process, gave insights on the registration of mirobial products intended for feed and food, discussed the latest developments in the European Regulatory Framework for microbiome-based health products (SOHO), and applications including the development of genetically-engineered probiotic microbes.

In the Young Scientist session, I’ll introduce the presentations of our three winners. Victor Castañeda-Monsalve’s work on the impact of xenobiotics on the human gut microbiome was a highlight. Using the SIHUMix simplified gut microbiome model, he found that roughly half of the 90 plant protection products and food additives tested affected this microbiome, and recommended including gut microbiome analyses in the safety assessment of xenobiotics. Andrea Merchak used altered simplified flora (Schaedler flora) to modelize the gut microbiota of mice and observe its reactions to stress with and without Lactobacilli. She concluded that Lactobacilli can protect from stress and their mechanism involves IFN-γ. Finally, Marco Calvigioni built a new dynamic 3D model of the human gut microbiome allowing to add flow and peristalsis in the model, which changes biofilm formation, cross-feeding dynamics and microbiome behavior to ressemble more closely the in-vivo conditions.

Industry Session

On Thursday, we started with the trends in the biotics market with FMCG Gurus Will Cowling. Will showed that consumers are still being proactive about their health and the proportion of those that have taken probiotics in the past year continued to grow (to 67% in 2024), but they are less to do it for general wellbeing and when they don’t suffer from symptoms. They are also struggling with inflation and 64% wonder if they can keep consuming these products in the context of rising prices. Digestive health is their main ask and they seek claims and « clinically-proven » labeling.

Industry’s polar light Ewa Hudson commented on the continuous growth of e-commerce biotics and confirmed that on 3000+ products, over half are aimed at digestion, followed by microbiome diversity, immunity, wellbeing and skinbiotics. As Ewa loves to look at market gaps, she pointed to a successful product for sexual wellness in men specifically targeted to the LGBT community, to several products claiming GLP-1 boosts, to the Agnositol range supporting women’s health from fertility to menopause, to synbiotics and cellular aging including NAD and urolithin A – and pushed biotic makers to be part of this offering, since bacterial metabolites offer these actives and benefits.

George Paraskevakos stepped back on the stage for considerations on the making of probiotics, from pure culture mother cell banks to finished products, going through the many questions and required expertise to deliver a qualitative, effective, stable live probiotic that complies with local regulations – all the way to risks of fines if influencers make non-authorized claims on products.

Probiotic expert Marie-Eve Boyte continued with the advantages of culture-independent enumeration methods including DNA-based methods and flow cytometry. « Enumeration based on DNA are culture-independent and strain-specific, for single and multiple-strain formulations, and help see how strains perform in stability together », she says. They are also critical for quality control of NGPs and postbiotics.

To continue in analytics, amazing bacterial communicator Jiri Snaidr, CEO of vermicon (the company that makes bacteria shine !), proposed a combination of direct method FISH and digital PCR (dPCR) to identify bacteria at strain level, for a powerful analysis of live strains in a sample. « Strains are temporary states of a species », he elegantly stated.

 "Strains are temporary states of a species." Jiri Snaidr.

Postbiotics Are Not Dead (on Biotics, Dead or Alive)

IFF Arthur Ouwehand, also President of the IPC and Chair of the scientific committee, looked at the evolution of the postbiotics. While the word first appeared in 1975, it is since 2019 that internet searches for postbiotics boomed, and most of the clinical trials referring to postbiotics (a little over 30) were published in the past 3 years. While conceptually simply « killed probiotics », this "postbiotization" step is complex and can be conducted in many different ways with different outcomes and challenges. Arthur highlights that postbiotics, although not live microbes, still face deterioration during their shelf life – from oxydation and from the complex formulations they can be integrated to. The regulatory framework for postbiotics depends on the intended use.

Postbiotic key opinion leader Simone Guglielmetti presented a decisional tree to reconciliate the different definitions of postbiotics – over a dozen since 2009 (cf. Maria Rescigno’s interpretation of postbiotics as metabolites, and Arthur Ouwehand’s and ISAPP’s take as dead microorganisms). The tree offers 4 categories of postbiotics: dead cells non-purified from the medium (A1), dead cells purified from the medium (A2), dead cells together with the medium (category C), and purified compounds coming from microbial cells but without microbial cells (B). The paper will be submitted shortly.

Thi Thu Hao Van proposed cell-free supernatant of L. sakei F1 from kimchi as a postbiotic exerting antioxidant benefits, and Vasantha Rupasinghe used probiotics to ferment polymeric proanthyanidins (PPAC) into bioactive metabolites, then tested as postbiotics (class B) against non-alcoholic fatty liver disease (NAFLD) in mice. They were protective, possibly thanks to the mitigation of lipid accumulation and inflammation.

Alessandro Bernardinello studied the mechanism of action of Postbiotica ’s postbiotic L. paracasei CNCM-I-5220 fractions separated by chromatography. Two partially-purified fractions showed anti-inflammatory and immunomodulatory effects mediated by aqueous components.

I missed Aurora Meucci and Bodo Speckmann’s talks and the next ones reverted to live biotics.

Cheng Chung Yong from Morinaga discussed Human Residential Bifidobacteria (HRB) expressing tryptophan synthase β subunit (trpB) and aromatic lactate dehydrogenase (aldh) as able to orientate tryptophan metabolism towards indole-3-lactic acid rather than indoxyl sulfate, which leads to chronic kidney dysfunction.

Theodorus Eko Pramudito looked at tempeh as a postbiotic fermented by lactic acid bacteria (P. pentosaceus TL, Leuconostoc citreum TR, L. mesenteroides WA and L. mesenteroides WN) producing ExoPolySaccharides (EPS). These EPS adhere with enterotoxigenic E. coli (ETEC), which helps clear these agents of traveller’s diarrhea.

Sumin Kang from Nutrigenomics Hanyang University in South Korea introduced the effect and mechanism behind two undisclosed probiotic strains on the improvement of NAFLD. Strain B inhibited mTOR1 pathway (thus inhibiting nuclear SREBP1C expression), leading to a reduction in hepatic de novo lipogenesis, liver fat content, and serum triglycerides.

Winclove Probiotics Maria Slotaki spoke of probiotic supplementation to enhance vitamin K status. Vitamin K is a co-factor in reactions protecting from cardiovascular disease (CVD), neurodegeneration, and cancer. The research team screened their cell collection for production of menoquinones and tested a 4-strain blend in adults at high risk of CVD. They found improved vitamin K7 levels after 6 weeks and plasma dp-uc MGP (+10-15% compared to the placebo group).

Peter Myintzaw from the Teagasc Food Research Center in Ireland screened B. longum from vaginally-delivered babies for probiotic properties. He checked the absence of biogenic amines in silico and in vitro, the utilization of HMOs, the survival to previous phage attacks (robustness marker), growth rate, and absence of inhibition properties against other Bifidobacteria.

Shaghayegh Hemmati from Denmark hypothesized that a probiotic could help wound healing in mice with induced diabetes. The next step is to look at inflammatory biomarkers.

Lithuania-based Ashwinipriyadarshini Megur tested the synbiotic synergistic effects of L. paracasei 11w and GalactoOligoSaccharides (GOS) on psychobiotic and antidiabetic efficacy in mice. She confirmed potential mitigation effects and the synbiotic appears more effective than the probiotic alone. She will next test the gut microbiome responses.

Julia Rode worked on a review of the impact of probiotics on brain structure in adults, looking at neuroimaging studies. While she struggled with considerable heterogeneity of protocols and treatments, she concludes that probiotics modify the resting state in brain and functional connectivity, they mitigate the brain responses to negative emotional stimuli, improve stress quality, and generally correlate with the clinical outcome.

StrainInSight Eliza Depoorter presented the company’s private strain collection of nearly 50.000 bacterial strains from over 500 genera, and the exciting free-access dashboard they created to filter directly by the gene name, metabolite, protein sequence or metadata you’re interested in.

Radu Ghemis from Spain characterized mushroom extracts for prebiotics activity and immunomodulatory activity, and tested different conditions and doses of the product in 5 women with recently diagnosed breast cancer and 5 healthy controls. The results depended on individuals and point to the necessity of personalized treatments based on specific microbial and metabolic starting conditions.

Finally, Ioannis Giavasis from Greece presented a project of valorization of olive oil waste stream rich in polyphenols. The waste is processed to concentrate and purify the tannins, polyphenols and polysaccharides, then encapsulated into a strong prebiotic product called Medoliva, which enhances the growth rate, acid and bacteriocin production of several Lactobacilli, Streptococcus and Pediococcus strains, and was used in yogurt, salami and animal feed. The effects are so strong that dosage is important, an excessive dose can lead to opposite effects.

Conclusion

Overall, this was a fantastic edition of the IPC, where more and more mechanisms of action of probiotics come into the spotlight, where innovation finds implementation, where mentees find mentors, all in a pleasurable convivial atmosphere - like nowhere else. It is a place to be for academics in the probiotic space, for people in R&D and NPD roles in the biotic industry, and service providers tuned to research needs, from analytics to novel models. And now with George, Ewa and Will, it even answers business-oriented people with market data and consumer insights !

I hope to see you there next year ! Don't hesitate to reach out and let us know what topics you'd love to see on the agenda !