Biology subjects

Monsonego-Ornan, E.

Publications and source records attributed to Monsonego-Ornan, E..

3 recordsLinked to original sources

bioRxiv2024

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

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.

physiology↗

bioRxiv2024

Local High-Protein, Plant-Based Ready-to-Use Therapeutic Food Enhances Recovery from Malnutrition in Rats

Infant child malnutrition is a major public health issue. We conducted a preclinical study with young rats to mimic the conditions of child malnutrition (combined wasting and stunting) and evaluate recovery using a novel plant-based ready-to-use-therapeutic food (RUTF) formulation. Three-week old female Sprague Dawley rats were assigned to six treatments groups in a 6-week experiment. The treatments included: 1) control balanced diet (CT), 2) A protein-deficient diet to induce malnutrition (MN), 3) and 4) A control balanced diet followed by either commercial RUTF (CT-PM) or a locally produced plant-based RUTF (CT-ChSMS), and 5) and 6) a protein deficient diet followed by either commercial RUTF (MN-PM) or locally produced plant based RUTF (MN-ChSMS), respectively. In treatments 3-6, rats were initially fed either a control-balanced or protein-deficient diet for 3 weeks, followed by 3 weeks of either the commercial or the locally plant-based RUTF. Results showed that rats in the CT-ChSMS group exhibited growth and weight comparable to CT group, while those in the MN-PM group showed no significant improvement compared to the MN group. Notably, rats in the MN-ChSMS group demonstrated significant catch-up growth, whereas those in the MN-PM group did not. Additionally, consumption of ChSMS and PM RUTFs differed significantly. ChSMS RUTF which contained 14% protein over total energy with better amino-acid composition and a higher Protein Digestibility-Corrected Amino Acid Score (PDCAAS), resulted in significantly greater weight gain and length compared to PM RUTF, which contained 10% protein over total energy. These findings indicate that a locally produced, culturally acceptable and affordable plant-based RUTF formulated with high protein quality and quantity may be effective in treating acute and chronic malnutrition in children.

physiology↗

bioRxiv2022

MMP2 loss leads to defective parturition and severe dystocia in mice

Parturition is the final step of mammalian reproduction and an essential process for the species survival. During pregnancy, the uterus is maintained quiescence which is important for fetal growth and development. However, at term, fundamental changes in myometrial contractility are initiated for efficient expulsion of the fetus. These changes involve tissue remodeling that requires changes in the extracellular matrix (ECM). The gelatinases subgroup of matrix metalloproteinases (MMPs), has only two members: MMP2 and MMP9, which are both known to participate in uterine ECM remodeling throughout the estrus cycle as well as during pregnancy, parturition and postpartum involution. Yet, no knowledge exists regarding their loss-of-function impact on the uterus. Here we investigated the effect of MMP2 and/or MMP9 genetic loss on parturition process. Single and double knockout (dKO) mice for MMP2 and/or MMP9 were used. We found high percentages of dystocia in mmp2-/-, mmp2-/-mmp9+/- and dKO females, but not in mmp9-/- females. Histological analysis of nulliparous uterine tissue of WT, mmp2-/-, mmp9-/- and dKO, at 8 weeks, 4 months and 8-9.5 months, revealed that the uterine tissue of mmp2-/- presents alterations in tissue size and structure, mainly when reaching to 8-9.5 months of age, including enlarged total tissue, myometrium, endometrium and luminal cavity. Additionally, Massons Trichrome staining suggested a mechanism of extensive fibrosis in mmp2-/- myometrium, which may lead to dystocia. Altogether, our research highlights a novel cause for dystocia pathology mediated by loss of MMP2 activity in uterine tissue during mammalian parturition.

physiology↗