Unstable gut microbes can worsen child malnutrition

Malnutrition affects millions of young children. Nearly 150 million children under the age of five suffer from stunted growth due to poor nutrition. Poor food quality is not the only cause.

More than ten years ago, scientists at Washington University School of Medicine in St. Louis revealed another hidden factor: the gut microbiome.

When gut microbial communities become dysfunctional, they can worsen the effects of malnutrition. New research, in partnership with the Salk Institute and UC San Diego, builds on this understanding.

Gut microbes linked to stunted growth

Toddlers in Malawi, one of the hardest-hit regions, revealed critical insights. Those with unstable gut microbes showed poorer growth compared to those with stable communities.

All of the children studied already faced a high risk of stunting and acute malnutrition.

“We know gut microbes are important mediators of malnutrition,” said Dr. Mark Manary, a professor of Pediatrics at WashU.

“By contributing to our understanding of how changes in gut microbes directly contribute to the condition, we pave the way for new methods to diagnose and treat millions of affected children worldwide.”

Stable microbes aid children

The findings led to the creation of a pediatric microbial genome library. This resource contains complete genetic profiles of 986 microbes from fecal samples of Malawian children.

The data will help researchers predict, prevent, and treat malnutrition more effectively.

Manary has long worked on nutritional solutions in Malawi. Over 20 years ago, he played a key role in developing a peanut butter-based therapeutic paste.

This high-calorie, nutrient-rich food transformed care for severe malnutrition and has saved countless lives. Yet food alone is not always enough. Survivors often face challenges in growth, immunity, and cognitive development.

Malnutrition disrupts the delicate microbial balance inside the intestines. Harmful species multiply while beneficial ones diminish. This microbial instability may explain why nutritional recovery remains incomplete for many children.

Gut balance impacts nutrition

The new study builds on decades of work showing how the gut ecosystem interacts with nutrition. Malnourished children often display delayed microbial maturation, where their microbiome resembles that of younger children.

This immaturity may hinder nutrient absorption, metabolic signaling, and immune development. Theoretical models suggest that gut microbes directly shape energy harvest and growth by interacting with host pathways.

For example, certain bacteria regulate short-chain fatty acid production, which influences intestinal health and immune regulation. Disruption of these functions may worsen the cycle of malnutrition, even if dietary intake improves.

Microbes predict child growth

To investigate, the researchers analyzed 47 stool samples from eight Malawian toddlers over 11 months. These children were previously enrolled in a trial testing legume-based foods for intestinal health and growth.

The team focused on length-for-age scores (LAZ), a measure comparing a child’s height with expected averages. Children with stable microbial genomes tended to grow better.

Those with fluctuating microbial populations showed poorer outcomes. Stability in the microbiome, the study suggests, may serve as a crucial marker of growth potential.

Sequencing deepens gut research

The study employed long-read sequencing, a cutting-edge method that reconstructs entire microbial pangenomes. Unlike traditional techniques, this method captures far more genetic information, offering a clearer view of microbial ecosystems linked to child malnutrition.

“Stunting and acute undernutrition are defined by easily measured, physical measurements, which result from complex and diverse underlying processes,” said co-senior author Dr. Kevin Stephenson, an assistant professor of medicine at WashU.

“Improved resolution and accuracy in identifying microbial communities – how they change, and what they are doing – may shed light on otherwise unmeasurable facets of undernutrition as well as the role the gut microbiome plays in causing it.”

Creating microbial databases

The sequencing work enabled researchers to construct the novel microbial genome library. This public health resource may serve as a foundation for future studies.

Importantly, the optimized workflow is adaptable to remote laboratories, including those in low-resource regions where malnutrition is most severe.

“When applied in remote, field-based molecular laboratories, the genome-sequencing and pangenomic approaches we developed can deliver real-time insights,” said Dr. Todd Michael, a research professor at Salk.

“It’s a powerful technological advance that expands the reach of genomics and sets a new standard for scientific research in the field.”

Global impact of child malnutrition

Beyond its practical applications, the research deepens understanding of how microbiomes and human biology coevolve.

Theoretical work highlights that restoring microbial maturity may be as critical as food delivery in combating undernutrition.

Stability of microbial communities could serve as a therapeutic target, guiding interventions that go beyond calories to include probiotics, prebiotics, and microbial transplants.

Malnutrition remains one of humanity’s oldest battles. But with science turning its lens on the gut, there is new hope for children at risk today and for generations to come.

The study is published in the journal Cell.

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