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Research and Training in Early Life Nutrition to Prevent Disease

Periodic Reporting for period 2 - GROWTH (Research and Training in Early Life Nutrition to Prevent Disease)

Reporting period: 2021-06-01 to 2024-04-30

The GROWTH programme was a pioneering Innovative Training Network focused on European Industrial Doctorates, dedicated to nurturing young researchers with a business orientation. It aimed to develop comprehensive pathological insights, advanced biomarker diagnostics, and tailor-made nutritional interventions targeting intestinal diseases across various life stages, from neonates and preterm infants to adults. GROWTH was a collaborative effort, bridging seven non-academic and five academic partners to expedite the translation of foundational research into clinical practice. This programme leveraged extensive biosample collections, state-of-the-art experimental models, and high-caliber infrastructure, thereby significantly advancing our understanding of intestinal development and disease mechanisms from an early age.

The programme articulated four primary research objectives intended to endow Early Stage Researchers (ESRs) with a diverse array of scientific skills throughout their doctoral studies:

1. Identify metabolic elements in breast milk that influence gut epithelia or mucosal immune responses, providing protection against conditions like sepsis or necrotizing enterocolitis (NEC) in infants.
2. Explore the alterations in microbiota associated with preterm births, clarifying the gut microbiome's role in metabolizing breast milk and early-life nutritional supplements.
3. Characterize bioactive microbial co-metabolites from intestinal or endogenous sources that impact gut epithelia or immune cells, in relation to intestinal health and disease.
4. Analyze metabolic profiles from longitudinal sample collections and create innovative bioinformatics methods to study interactions between the microbiome, host, and nutrition in extensive omics datasets, facilitating biomarker identification and the optimization of dietary strategies for neonates and preterm infants.

With the completion of the GROWTH programme, a new chapter in the battle against intestinal diseases through personalized healthcare solutions such as early life nutrition has been firmly established.
The GROWTH programme has successfully concluded, achieving remarkable progress in research and training focused on intestinal health across various life stages. This initiative revolved around unique longitudinal collections of clinical biosamples complemented by robust data, which were instrumental in advancing our understanding of intestinal metabolic activity and its failures in preterm infants.

Key accomplishments of the programme include:

1. Identification of nutritional components: Researchers have successfully pinpointed crucial nutritional and bioactive elements in breast milk and formula that influence the microbiome's composition and metabolism. These components have been shown to enhance mucosal immunity, offering protection against infections and inflammatory conditions such as sepsis and NEC in preterm infants.
2. Insights into microbiota dysbiosis and metabolism: The programme provided new functional insights into the dysbiosis and metabolic changes associated with preterm birth, highlighting potential nutritional targets for early-life support using breast milk and specific nutrients.
3. Definition of bioactive microbial co-metabolites: Significant progress was made in identifying microbial co-metabolites that impact mucosal immune responses and offer long-term protection against infection and inflammatory diseases.
4. advanced metabolic profile analysis and bioinformatics: The development of innovative bioinformatics approaches has allowed for detailed analysis of metabolic profiles from biosamples, enhancing our capacity for biomarker discovery and the stratification of nutritional interventions.

Furthermore, the GROWTH programme also focused on the relevance of microbial, mycobial, and metabolic compositions in different intestinal pathologies from early life to adulthood. Through various experimental models—including animal models, 2D cell cultures, 3D organoids, this part provided a sophisticated understanding of microbial changes and metabolic processes. The main objectives were successfully met, resulting in:
- Identification of key factors in breast milk/formula
- Discovery of metabolic and microbial signalling molecules
- establishment of experimental models
- Study of neonatal innate immune responses
To surpass current benchmarks in early life nutrition and inflammatory bowel disease, the GROWTH programme was poised to cultivate a new cadre of innovation-driven researchers. These individuals are not only equipped to address current challenges but also poised to pioneer early detection methods and novel dietary strategies aimed at preventing intestinal diseases in preterm infants and mitigating colitis later in life. The GROWTH programme seeked to assemble a network of young professionals who:

1. Possess both deep and broad knowledge concerning early life nutrition and its links to intestinal inflammatory diseases.
2. Can adeptly navigate and translate pathogenic insights into actionable strategies.
3. Are skilled in deploying advanced tools and methodologies to drive clinical innovations using in vitro, in vivo, and ex vivo models.
4. Are focused on hastening the discovery of predictive biomarkers and formulating cutting-edge nutritional solutions.
5. Embrace open data science and possess a proactive mindset towards industry and regulatory engagements.

Furthermore, the programme's robust industry-academia collaboration is designed to enhance students' career prospects within the health and life sciences sectors, boosting their employability through specialized education and expanding their professional network. The engagement of multiple companies underscores strong commercial confidence in the programme’s potential for both immediate and future impact.

Expected outcomes for those completing the GROWTH programme include:
- A comprehensive understanding of the interfaces among epithelial biology, nutrition science, metabolomics, and bioinformatics.
- Mastery of essential research techniques in molecular biology, stem cell biology, metabolic pathways, mucosal immunology, among others.
- Deep insights into neonatal intestinal pathology and nuanced nutritional needs.
- Advanced analytical skills in microbiome, mycobiome, and metabolome assessment, bolstered by unique IIPTC training courses.
- Specialized research expertise and competencies that align directly with specific research initiatives, including proficiency in techniques like LC-MS, NMR analyses, next-generation sequencing, and computer programming.
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