Path to personalized probiotics: Predicting nutrients that support bacterial growth

Scientists reveal that they can predict the nutritional adaptations of Bifidobacterium strains by analyzing the distribution of metabolic genes in thousands of genomes. They note their paper offers a “critical resource” for future research and the development of personalized probiotics. Probiotic treatment often includes Bifidobacterium strains, which are considered beneficial to human health.

The research highlights how carbohydrate metabolism strategies vary across and within species and how ecological factors, such as geographic location, host age, diet, and lifestyle, shape these. 

“With this encyclopedia of sugar utilization pathways in hundreds of strains with sequenced genomes, you can now confidently predict the nutrients that support their growth and those that do not,” says senior author Andrei Osterman, Ph.D., a professor at Sanford Burnham Prebys, US. 

“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.”

Benefiting infant health?

Bifidobacterium strains are abundant in infants’ guts, particularly in breastfed children. Due to their health benefits, scientists have sought to deliver the strains to infants suffering from malnutrition through probiotics. 

“Bifidobacteria confer multiple positive properties, beginning with inhibiting the growth of pathogenic bacteria by outcompeting them for space and nutrients,” details lead author Aleksandr Arzamasov, Ph.D., a postdoctoral associate at Sanford Burnham Prebys. “They also help develop an infant’s immune system.”

For example, Lallemand Health Solutions notes that its probiotic formula containing B. bifidum HA-132 supports maternal health during pregnancy and helps infants develop a healthy microbiome during breastfeeding. A recent review consolidated research on Novonesis’ B. animalis subsp. lactis BB-12 strain for digestion and infant health. 

In the US, around one in ten of the youngest preterm infants are treated with probiotics to promote healthy outcomes and prevent intestinal diseases. Studies indicate that these treatments can reduce all causes of mortality. 

However, contrary to expectations based on US testing, previous studies revealed that the beneficial bacteria did not find a “permanent home” in the microbiomes of Bangladeshi infants suffering from severe acute malnutrition when treated with Bifidobacterium probiotics. 

“We wondered if the strain was less effective because it was not adapted to the local diets of Bangladeshi children,” adds Osterman. “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.”

Uncovering sugar utilization pathways

For the study, published in Nature Microbiology, the research team needed to define the metabolic genes that enable the gut bacteria to break down specific carbohydrates to create energy. 

After mapping 68 metabolic pathways, the team trained an AI model to analyze genomes to predict their capability to process the associated glycans.“When we eat food, many of the dietary carbohydrates are not digested by our bodies, especially the more complex fibers,” explains Arzamasov. “Instead, they go straight to the large intestine, where gut bacteria can metabolize them.”

The researchers manually analyzed 263 Bifidobacterium genomes and integrated data from hundreds of previously published studies to reconstruct and map 68 metabolic pathways. These pathways determine if a bacterium can digest a specific carbohydrate. 

Using these findings, the team trained an AI model to analyze over 2,820 additional genomes to predict the encoded capability to process the 68 identified glycans — a chain-like structure composed of multiple sugar molecules. 

The team tested their resulting predictions on 30 geographically diverse Bifidobacterium strains. The scientists observed the strains’ growth ability when exposed to 43 carbohydrates corresponding to the predicted carbohydrate utilization pathways. 

The accuracy rate of predictions was over 94% when comparing predicted growth with actual growth. 

Identifying individual differences

The researchers found differences in how Bifidobacterium strains used carbohydrates based on geographic location, diet, and lifestyle. 

For example, strains isolated from fecal samples of Bangladeshi children had a unique capacity to digest carbohydrates from human milk and plant fibers. The team notes this may indicate that these strains had adapted to nutrient changes as infants moved from breast 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,” says 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.”