Digital Babies Created To Simulate the First 180 Days of Life

Newborn infants have unique metabolic features that support their healthy growth and development.

“Babies need more energy for regulating body temperature due to, for example, their high surface-area-to-mass ratio, but they cannot shiver in the first six months of life, so metabolic processes must ensure the infant keeps warm,” Elaine Zaunseder, a researcher in the Engineering Mathematics and Computing Lab at Heidelberg University, said.

Whole-body models (WBMs) are computational models that integrate different types of multiomics data such as genomic, metabolic and proteomic insights, and have been created to simulate and study adult physiology and disease. WBMs for newborns, however, are currently lacking.

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Researchers led by Professor Ines Thiele, principal investigator of the Molecular Systems Physiology group at the University of Galway, have created the first sex-specific WBMs representing newborn and infant metabolism across 26 organs, 6 cell types and over 80,000 metabolic reactions.

The study, published in Cell Metabolism, will “allow researchers to investigate the metabolism of healthy infants as well as infants suffering from inherited metabolic diseases, including those investigated in newborn screening,” Thiele said.

Translating metabolic processes into mathematical concepts

Thiele and colleagues created 360 organ-resolved models in total, utilizing data on sex, birth weight and metabolite concentrations from 10,000 newborns for validation.

“An essential part of this research work was to identify these metabolic processes and translate them into mathematical concepts that could be applied in the computational model. We captured metabolism in an organ-specific manner, which offers the unique opportunity to model organ-specific energy demands that are very different in infants compared to adults,” Zaunseder, who is lead author of the study, said.

“As nutrition is the fuel for metabolism, we can use breast milk data from real newborns in our models to simulate the associated metabolism throughout the baby’s entire body, including various organs. Based on their nutrition, we simulated the development of digital babies over six months and showed that they will grow at the same rate as real-world infants,” she added.

The WBMs can be personalized, enabling scientists to investigate an individual infant’s metabolism for precision medicine research.

“When simulating the metabolism of infants with a disease, the models showed we can predict known biomarkers for these diseases,” Thiele said. “Furthermore, the models accurately predicted metabolic responses to various treatment strategies, showcasing their potential in clinical settings.”

Integrating microbiome data, which features in adult WBMs, is a natural next step for advancing the infant WBMs, the researchers said. This data could enable scientists to analyze the effects of birth mode on early development. A growing body of research suggests that vaginally delivered babies possess a similar gut microbiota to the vaginal microbiome, whereas babies delivered via C-section have a gut microbiota similar to the environment and their mother’s skin.

“This work is a first step towards establishing digital metabolic twins for infants, providing a detailed view of their metabolic processes. Such digital twins have the potential to revolutionise paediatric healthcare by enabling tailored disease management for each infant's unique metabolic needs,” Zaunseder concluded.

Reference: Zaunseder E, Mütze U, Okun JG, et al. Personalized metabolic whole-body models for newborns and infants predict growth and biomarkers of inherited metabolic diseases. Cell Metab. 2024. doi:10.1016/j.cmet.2024.05.006

This article is a rework of a press release issued by the University of Galway. Material has been edited for length and content.