Personalizing Infant Probiotics Through Genome Analysis

Probiotics are emerging tools used by neonatal intensive care units to promote healthy outcomes and prevent intestinal diseases such as necrotizing enterocolitis. Approximately one in ten of the youngest preterm infants in the US are treated with probiotics, and studies show that this therapy can reduce all causes of mortality.

“We wondered if the strain was less effective because it was not adapted to the local diets of Bangladeshi children,” said Andrei Osterman, PhD, a professor in the Center for Data Sciences at Sanford Burnham Prebys and vice dean and associate dean of Curriculum in the Graduate School of Biomedical Sciences. “And we thought we may be able to predict which strains will thrive in different conditions, allowing us to match probiotics to children based on where they live and what they eat.”

Osterman, Arzamasov and colleagues at Washington University School of Medicine, Sabanci University and the University of California San Diego published findings July 16, 2025, in Nature Microbiology, demonstrating the ability to predict the nutritional adaptations of Bifidobacterium strains by analyzing the distribution of hundreds of metabolic genes in thousands of Bifidobacterium genomes.

The scientists followed up by putting their predictions to the test on 30 geographically diverse Bifidobacterium strains by observing their ability to grow when feasting (or not) on 43 carbohydrates corresponding to the predicted carbohydrate utilization pathways. When comparing the predicted growth to actual growth in these validation experiments, the accuracy rate of predictions was more than 94 percent.

The group uncovered differences in carbohydrate utilization based on geographic location, diet and lifestyle. For example, they discovered distinguishing features of Bifidobacterium strains isolated from fecal samples of Bangladeshi children. These strains had a unique capacity to digest both carbohydrates from human milk and plant fibers, which may indicate that these strains had adapted to changes in nutrients as an infant weans from milk to other foods.

“We found that these Bangladeshi isolates have unique gene clusters and unique metabolic phenotypes not found in any other genomes of strains isolated from other parts of the world,” said Arzamasov. “This reinforces the importance of studying the gut microbiomes in understudied populations around the world in a culturally sensitive way, as they have unique biological diversity which is currently underappreciated.”

By showing how carbohydrate metabolism strategies vary across and within Bifidobacterium species and are shaped by ecological factors — including host age, diet and lifestyle — Osterman, Arzamasov and their colleagues have provided a critical resource for future research and the development of personalized probiotics.

“With this encyclopedia of sugar utilization pathways in hundreds of strains with sequenced genomes, you can now confidently predict what are the nutrients that support their growth and what are the nutrients that do not support their growth,” said Osterman, the senior and co-corresponding author of the study. “In addition to a compendium of hundreds of already known bacterial isolates, we built a tool that can be used to provide the same type of predictions for thousands and thousands more.”

“You can use this knowledge to select the strains as probiotic candidates for a given situation,” said Arzamasov. “And you can define very precisely what nutrients would support these probiotic strains to guide the rational development of supplementary foods to make them even more effective.”

Reference: Arzamasov AA, Rodionov DA, Hibberd MC, et al. Integrative genomic reconstruction reveals heterogeneity in carbohydrate utilization across human gut bifidobacteria. Nat Microbiol. 2025:1-17. doi: 10.1038/s41564-025-02056-x

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