Abstract
Globally, millions of children suffer from undernutrition, with stunting affecting 150 million and wasting nearly 50 million under five years old. Current interventions have shown limited effectiveness in mitigating long-term consequences such as stunted growth, cognitive deficits, and immune dysfunction. Through this body of work, I investigated the efficacy of a microbiota- directed complementary food (MDCF-2) as a next generation therapeutic food to combat childhood stunting. Across two randomized controlled trials involving Bangladeshi children with either moderate acute malnutrition or post-severe acute malnutrition, MDCF-2 significantly outperformed standard ready-to-use supplementary foods (RUSF), leading to significantly improved ponderal and sustained linear growth over extended follow-up periods. Through the integration of plasma proteomic and metagenomic datasets using new computational approaches, I demonstrated that compared to RUSF, MDCF-2 produces an augmented response in the plasma levels of protein mediators and biomarkers of musculoskeletal and central nervous system development and how these mediators are linked to specific growth-promoting members of the microbiota. These findings establish MDCF-2 as a promising therapeutic approach for treating undernourished children and highlight the need to repair the gut microbiome to improve long- term health outcomes in children recovering from varying states of acute malnutrition. Collectively, these discoveries also set the stage for developing point-of-care biomarker panels for improved stratification of populations of children prior to treatment, improved assessment of the efficacy of current therapeutic leads, development of new therapeutic leads, identification of microbial molecular mediators of host responses, and expansion of our understanding of the complicated relationship between the gut microbiome and host systems physiology.
Committee Chair
Jeffrey Gordon
Committee Members
Daniel Goldberg; Megan Baldridge; Michael Province; Scott Handley
Degree
Doctor of Philosophy (PhD)
Author's Department
Biology & Biomedical Sciences (Computational & Systems Biology)
Document Type
Dissertation
Date of Award
8-12-2025
Language
English (en)
DOI
https://doi.org/10.7936/k6wz-gm42
Recommended Citation
Hartman, Steven J., "Computational and mathematical modeling of microbial community and host responses to microbiota-directed complementary foods administered to children with acute malnutrition." (2025). Arts & Sciences Theses and Dissertations. 3590.
The definitive version is available at https://doi.org/10.7936/k6wz-gm42