Toward Holistic Solutions to Undernutrition: A Comprehensive Preclinical Protocol for Novel Ready-to-Use Therapeutic Foods Testing

Utume, L.; Janssen, J. N.; Akomo, P.; Shaw, D.; Edwards, W. J. S.; Muleya, M.; Nikolaou, C. K.; Schneider, A.; Westby, A.; Reifen, R.; Tsaousis, A. D.; Monsonego-Ornan, E.; Benchoff, A.

doi:10.1101/2024.11.28.625813

bioRxiv · 10.1101/2024.11.28.625813

Toward Holistic Solutions to Undernutrition: A Comprehensive Preclinical Protocol for Novel Ready-to-Use Therapeutic Foods Testing

Utume, L.·Janssen, J. N.·Akomo, P.·Shaw, D.·Edwards, W. J. S.·Muleya, M.·Nikolaou, C. K.·Schneider, A.·Westby, A.·Reifen, R.·Tsaousis, A. D.·Monsonego-Ornan, E.·Benchoff, A.

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Abstract

Severe acute malnutrition (SAM) affects over 45 million children under five worldwide. Ready-to-Use Therapeutic Foods (RUTFs), the cornerstone of treatment, reach only 30% of children in need due to high production costs and reliance on imports. RUTF formulations developed from local ingredients have shown varying efficacy levels focusing primarily on weight gain, overlooking critical factors like micronutrient status, skeletal development, and gut health. The presented study establishes a comprehensive protocol for preclinical testing of novel RUTF formulations using a validated juvenile rat model replicating key features of malnutrition in children. Beyond the standard anthropometric measurements (body weight, length, and food consumption), bone quality is assessed through micro-computed tomography and mechanical testing, providing insights into microstructure and functionality beyond standard anthropometric measurements. Concurrently, gut microbiome dynamics are analysed using 16S rRNA sequencing coupled with metabolomic profiling of stool and serum to monitor gut health and systemic recovery.By addressing critical gaps in traditional RUTF evaluations and emphasising locally sourced, cost-effective formulations, this protocol offers a transformative framework for developing accessible and impactful malnutrition treatments. The findings generated through this multidisciplinary approach will guide RUTFs optimisation, strengthen their scientific foundation, and pave the way for evidence-based clinical trials to improve global malnutrition treatment strategies.

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Utume, L., Janssen, J. N., Akomo, P., Shaw, D., Edwards, W. J. S., Muleya, M., Nikolaou, C. K., Schneider, A., Westby, A., Reifen, R., Tsaousis, A. D., Monsonego-Ornan, E., Benchoff, A.. 2024-12-03. Toward Holistic Solutions to Undernutrition: A Comprehensive Preclinical Protocol for Novel Ready-to-Use Therapeutic Foods Testing. https://doi.org/10.1101/2024.11.28.625813

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