Periodic Reporting for period 2 - MBSelect (A novel technology enabling efficient delivery of personalized probiotics to prevent gut-related diseases and recover damaged gut microbiota) Reporting period: 2021-06-01 to 2022-11-30 Summary of the context and overall objectives of the project Gut-microbiome has been recognized as an essential part of the human health and consequently gut-bacteria-imbalance has been recognized as a crucial factor in the development of many diseases but currently, there are several solutions with significant limitations. Probiotic products for instance, whether as a supplement or as an integrated food components cover only a small fraction of the overall microbiome diversity. In addition, tradiational and existing probiotic products mostly use bacterial strains that are easier to culture but not necessarily have co-evolved with the human host and therefor have limited health benefits. Such products are in many cases not that effective and fail of delivering sufficient number and variety of bacteria to the correct target location in the gut and have them colonize. Moreover, regulatory authorities do not tend to approve new strains and therefore the focus remains on limited part of the overall bacteria population necessary for the functionality of the whole microbiome. During the last decade, the scientific community in conjunction with the probiotics manufacturers are shifting their approach from “one size feats all” toward personalized and groups-oriented products. Thanks to technological progress and better understanding of the beneficial symbiotic bacteria that thrive in our body, companies are also develop Next Generation Probiotics (NGP) based on unique strains isolated from the human gut (fastidious anaerobic strains). However, the challenge to produce NGPs as well as safety and regulation requirements led to the fact that only one NGP strain was approved in the past 10 years, and only when delivered dead.MyBiotics Pharma is a clinical stage microbiome company that lunched the MBselect project supported by the EIC through the Horizon 2020 program. The MBselect project designed to develop for the first time a “personalized” and segmented Synbiotics which includes a combination of bacteria and prebiotic materials such as fibers in order to precisely boost commensal NGPs for: Kids, Adults and Elderly, inter alia, using its proprietary technologies: MyCrobeTM and MyLiveIn Screening System. The bacteria produced using MyCrobeTM technology are more resilient and potent probiotics and are based on human origin bacteria. The bacteria delivered using MBSelect will potentially colonize more easily, have better survival through the GI harsh conditions, exhibit a transient antibiotics resistance, better ability to compete with the existent disease-promoting population, helping to shift the unbalanced bacterial communities to a healthy and balanced state. The second and very important part of the products aims to modify and re-balance the consumer’s own microbiome, enhancing its beneficial commensal bacteria, by feeding them with precise approved elements (prebiotics) discovered using our unique MyLiveIn screening system. MyLiveIn screening system is an in-vitro biological platform fully integrated with a set of computational and analysis tools represents the ecosystem of the human microbiome. The ability to grow the human microbiome for several days while introducing various microbiome modulators / prebiotics offers high throughput and empirically way to find the precise effect of such modulators on the complex microbiome and therefore much more effective way to identify ways to correct dysbiosis. The system allows to find the holistic effect of various modulators such as medications and prebiotics on desired bacteria (such as beneficial NGP strains) in the complex microbiome ecosystem. MyLiveIn can be run on variety microbiome backgrounds such as different age groups, genders, geographic origin, healthy or dysbiotic depends on the targeted segment.The program successfully achieved its goals; optimized MyCrobe growth and powder formulation, discovered precise prebiotics to meet each age group needs, and ready for production in small industrial scale. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far As part of the MBselect project, MyBiotics has developed and examined dozens of bacterial strains cultured using MyCrobe© technology. Each strain exposed to a variety of stress conditions (e.g. acidic pH, high temperature and antibiotics) to evaluate their resistance during production and delivery. In addition, to evaluate the products shelf life, the dry substance stability over 18 months in 4c and 25c was measured and found stable. The results showed a clear advantage and survival of the MyCrobeTM over traditional fermentation. Additionally, the ability of selected strains to colonize the human gut was examined, showing an enhance attachment of MyCrobeTM compared to standard fermentation, potentially displaying superior potency and healing effect. The ability to scale the process was also evaluated in several scales while using food approved ingredients, meeting with the food supplements regulatory requirements. An additional important layer was the utilization of MyLiveIn screening system for demonstrating the effect of potential prebiotics on a healthy human microbiome. This process isolated the microbiome population from the environment and allowed MyBiotics to understand the actual dynamics in this complexed ecosystem. It may even considered a better way to identify the effect of the potential products without the need to run a huge human trial while targeting a very precise and defined need. Various GRAS materials and their ability to specifically support NGP taxa and the overall microbiome richness and health were examined. Based on the analysis, a precise prebiotic premix will be made to address each of the three age group health needs.The progress and discoveries accomplished during the MBselect project, allowed us to strengthen MyBiotics IPR both in the unique cultivation process and the development of the discovery platform. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) Health and wellness is becoming a significant target in order to maintain high quality life from childhood, through adulthood towards old age, a pattern that will continue in the next couple of decades, as the medical infrastructure is improving and a retirement is only one stop in our lifetime.Such developments are likely to have profound implications, not only for individuals, but also for governments, business and civil society, impacting, among others: health and social care systems, labor markets, public finances and pension entitlements. MyBiotics invest development efforts to contribute to these three sectors by address specific solution for relevant potential issues. We believe developing a line of products and particularly for the Elderly population has a high relevance and high potential as such products should improve their wellness and wellbeing by leverage the power of the microbiome for this purpose.By developing a functional product with strong clinical indication based on our proprietary technology, MyBiotics will be able to introduce a personalized wide range probiotics that actually and finally work. Acid resistance compared when applying MyBiotics with conventional fermentation
