Periodic Reporting for period 1 - GROWTH (Research and Training in Early Life Nutrition to Prevent Disease) Reporting period: 2019-06-01 to 2021-05-31 Summary of the context and overall objectives of the project The GROWTH programme is an Innovative Training Network focused on European Industrial Doctorates that aims to train young business-oriented researchers in developing pathological insights, biomarker diagnostics and personalized nutritional interventions for intestinal disease in neonates, (preterm) infants and adults. GROWTH is a multidisciplinary network that involves the participation of 7 non-academic and 5 academic partners that will attempt shortening the path from basic research to clinical applications. Importantly, this programme builds on the availability of large collections of biosamples, cutting edge experimental models and high-quality infrastructures that open a window of opportunity to enhance understanding of (early) intestinal development and pathogenesis. The GROWTH programme puts forward four research aims that will equip ESRs with a unique blend of scientific competences during their doctoral programme: 1. define the metabolic components in breast milk that directly modulate gut epithelia or mucosal immune cells, and which in turn protect infants from conditions such as sepsis or NEC.2. provide functional insights into the microbiota dysbiosis associated with preterm birth and to establish the role played by the gut microbiome in the metabolism of both breast milk and nutritional supplements provided in early life. 3. define bioactive microbial co-metabolites generated from intestinal or endogenous compounds that affect epithelia or mucosal immune cells in the gut, in relation to intestinal pathology. 4. analyse the metabolic profile data of longitudinally collected samples and develop novel bioinformatics approaches for studying microbiome-host-nutritional interactions in large scale omics data sets that allow for biomarker discovery and stratification of dietary interventions in neonates and preterm infants. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far The first part is at the heart of the programme and is concerned with the availability of a unique longitudinal collections of clinical biosamples with robust clinical data. This part will deliver knowledge of essential elements of the intestinal metabolic activity in relation to intestinal failure in (preterm) infants. Overall, this part aim to • identify nutritional and bioactive components in breast milk or formula fed preterm infants that affect microbiome composition/metabolism and can modulate intestinal mucosal immunity to protect, infants from conditions such as infection and inflammatory conditions (eg. sepsis and NEC).• provide functional insights into the microbiota dysbiosis and metabolism associated with preterm birth, risk of infection/inflammation. Through this approach novel targets may be identified for nutritional support using breast milk and/or specific nutrients and bioactive compounds early in life. In addition, we will study the neonatal mycobiome in early development. • define bioactive microbial co-metabolites generated from intestinal or endogenous compounds that affect mucosal immune processes in relation to intestinal pathology as well as long term protection against infection and inflammatory diseases.• analyse the metabolic profile data of longitudinally collected biosamples and develop novel bioinformatics approaches for studying microbiome-host-nutritional interactions in large scale omics data sets that allow for biomarker discovery and stratification of nutritional interventions in neonates and preterm infants.Here, four ESRs are actively working on highly complementary projects ranging from metabolomics studies, mechanistic studies on mucosal immunity, bioinformatics analysis and clinical research. The second part of the research is dedicated to the relevance of microbial, mycobial, and metabolic compositions in different intestinal pathologies present in early life and adulthood. Different experimental models such as animal models, 2D cell cultures, 3D organoids and gut-on-a-chip technology will be set-up and used to acquire a detailed understanding of the microbial changes and metabolic processes. The main objectives of WP2 are to:• identify factors in breast milk/formula that are relevant to microbial and metabolic activity in early life intestinal health. • identify metabolic and microbial signalling molecules that affect epithelial function. • set up of the different experimental models. • study the characteristics of (neonatal) innate immune cells exposed to bacterial, fungal, and metabolic components. In this part, also four ESRs have set-up unique experimental models and gained novel insights. 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) To progress beyond the state-of-the-art in early life nutrition and inflammatory bowel disease, a new generation of innovation-minded researchers is needed who are able to tackle present challenges and develop effective solutions for early detection of disease and development of new dietary interventions for the prevention of intestinal disease in preterm infants and colitis later in life. The GROWTH proposition is to create a network of young professionals, who (1) have an in-depth, yet wide understanding of the field of early life nutrition in relation to intestinal inflammatory disease, (2) are able to explore and translate pathogenic insights, (3) are confident in applying state-of-the-art tools and knowledge necessary to concretize clinical developments, including in vitro, in vivo and ex vivo models, (4) accelerate the identification of predictive biomarkers and the development of novel nutritional formulae, and (5) have open data science as well as enthusiastic industrial and regulatory mind-sets. At the same time, the deep industry-academia blended training will prepare students to succeed their career in health and life sciences, which will favour their individual education, increase their employability opportunities and create a large network of researchers. Moreover, the partaking of several companies is a clear support for the programme’s commercial potential, both in short- and long-term.The GROWTH programme outputs are expected to substantially impact the ESR careers. It will place them in the position to either choose for an academic (preclinical or clinical) or industrial career, both in small and large companies/research groups. Other job directions include academic technology transfer, bio partnering, grant writing, project and event management, teaching or regulatory affairs. ESRs who have successfully completed the GROWTH programme will demonstrate:• a good understanding of interfaces between epithelial biology, nutrition science, metabolomics, bioinformatics.• competences in applying some of the most elemental techniques necessary for research in molecular biology, stem cell biology, metabolic pathways, bioinformatics, mucosal immunology and other fields.• profound knowledge of (neonatal) intestinal pathology and nutritional requirements.• microbiome, mycobiome and metabolome analytical skills via unique IIPTC training courses.• research specialisation and related competences that directly relate to specific research projects, including abilities to run LC-MS and NMR analyses and next generation sequencing, and computer programming.