Malnutrition stands as a primary factor in the fatalities of children below 5 years old, with approximately 150 million youngsters worldwide in this age bracket experiencing stunted growth due to insufficient nutrition. While a subpar diet is a significant factor, scientists at Washington University School of Medicine in St. Louis discovered more than ten years ago that malfunctioning communities of gut microbes significantly influence the onset of malnutrition.
Currently, through a partnership with the Salk Institute and UC San Diego, WashU Medicine researchers have found that toddlers in Malawi—one of the most severely impacted areas by malnutrition—exhibited less growth when their gut microbiome fluctuated, in contrast to children with a more consistent microbiome. All the children involved were at significant risk for stunting and acute malnutrition.
“We recognize that gut microbes play crucial roles in malnutrition,” stated Mark J. Manary, MD, the Helene B. Roberson Professor of Pediatrics at WashU Medicine, an internationally acknowledged specialist in malnutrition and co-corresponding author of the recent study. “By enhancing our understanding of how alterations in gut microbes directly lead to this condition, we create opportunities for innovative methods to diagnose and treat millions of affected children globally.”
The results, published on September 9 in Cell, establish a pediatric microbial genome repository—a public health database featuring complete genetic profiles of 986 microbes derived from fecal samples of eight Malawian children collected over nearly a year, which can be utilized for future research to aid in predicting, preventing, and treating malnutrition.
Enhanced growth with a stable gut microbiome
More than twenty years ago, Manary became instrumental in the introduction of a peanut butter-based therapeutic food aimed at addressing severe acute undernutrition in Malawi, a nation in sub-Saharan Africa where 37% of children suffer from stunting. He created and clinically evaluated the high-calorie, nutrient-dense paste, which has saved countless lives since becoming the global benchmark for severe acute malnutrition care.
Children who survive this condition often experience persistent challenges in metabolism, bone development, immune system function, and cognitive development. Simply providing sufficient nutrients for recovery is inadequate for their growth and wellbeing, explained Manary.
Malnutrition leads to dysregulation in the gut microbiome, the collection of bacteria and other microorganisms inhabiting the intestines, diminishing beneficial microbes and increasing pathogenic ones. The researchers hypothesized that enhancing the health of malnourished children might involve comprehending the transformations in a gut ecosystem comprising hundreds of bacterial species.
To investigate microbial trends associated with child growth, the researchers sequenced genomic material from 47 fecal samples collected over 11 months from eight toddlers, previously enrolled in a clinical trial assessing the impact of legume-based complementary foods on mitigating or reversing environmental enteric dysfunction, a chronic affliction of the small intestine that results in stunted growth.
The selected children were between 12 and 24 months old and exhibited either improving or deteriorating length-for-age scores (LAZ), an indicator of growth measuring children’s heights against established averages for their age and gender. The researchers observed that children with a stable collection of microbial genomes—indicating minimal drastic changes within the microbial population—demonstrated improved growth compared to those with fluctuating microbial compositions, implying that stability in the gut microbiome may aid in promoting growth in children. Tracking such changes, Manary indicated, could potentially be utilized to evaluate gut health.
Developing genomic libraries
The study employed a contemporary genetic sequencing technique known as long-read sequencing to reconstruct complete microbial pangenomes, encompassing the genetic makeup of all members within a microbial species. This method facilitated the capture of 50 times more complete microbiota genomes in comparison to conventional techniques and offered a more in-depth genetic perspective of microbial communities in children at high risk for stunting and acute undernutrition.
“Stunting and acute undernutrition are characterized by easily quantifiable physical metrics, which arise from intricate and diverse underlying mechanisms,” remarked co-senior author Kevin Stephenson, MD, an assistant professor of medicine at WashU Medicine. “Enhanced detail and precision in identifying microbial communities, understanding their changes, and discerning their functions may illuminate otherwise immeasurable aspects of undernutrition as well as the role the gut microbiome plays in its causation.”
The method enabled the creation of the study’s innovative pediatric microbial genome repository. The researchers refined a long-read sequencing workflow that can be adapted by other scientists to build genome libraries for various purposes, suitable for research conducted in remote laboratories located in hard-to-reach areas.
“When applied in remote, field-based molecular laboratories, the genome sequencing and pangenomic strategies we developed can provide real-time insights not only into disease surveillance, antibiotic resistance, and infectious illnesses, but also into agricultural efficiency, environmental assessments, and biodiversity preservation,” stated senior co-corresponding author Todd Michael, PhD, a research professor at Salk. “This is a significant technological advancement that broadens the scope of genomics and establishes a new benchmark for scientific research in the field.”
Minich JJ, Allsing N, Din MO, Tisza MJ, Maleta K, McDonald D, Hartwick N, Mamerto A, Brennan C, Hansen L, Shaffer J, Murray ER, Duong T, Knight R, Stephenson K, Manary MJ, Michael TP. Culture-independent meta-pangenomics enabled by long-read metagenomics reveals associations with pediatric undernutrition. Cell. September 9, 2025. DOI: 10.1016/j.cell.2025.08.020
The research received funding from the NOMIS foundation.
Declaration of Interests: Michael TP is a founder of the carbon sequestration firm CQuesta. Knight R is a member of the scientific advisory board, and a consultant for BiomeSense, Inc., holds equity and receives income. Knight R serves on the scientific advisory board and has equity in GenCirq. Knight R is a consultant and member of the scientific advisory board for DayTwo and receives income. Knight R has equity in and provides consultancy for Cybele. Knight R is a co-founder of Biota, Inc., and possesses equity. Knight R is a co-founder and member of the scientific advisory board of Micronoma and has equity. These arrangements have been reviewed and authorized by the University of California San Diego in accordance with its policies on conflicts of interest. No conflicts of interest, financial or otherwise, are disclosed by the remaining authors. Din MO holds equity in GenCirq.
About Washington University School of Medicine
WashU Medicine is a prominent institution in academic medicine, encompassing biomedical research, patient care and educational initiatives with 2,900 faculty members. Its National Institutes of Health (NIH) research funding portfolio ranks as the second largest among U.S. medical schools, having grown by 83% since 2016. Along with institutional support, WashU Medicine dedicates well over $1 billion annually to the advancement of basic and clinical research and training. Its faculty practice consistently ranks in the top five nationwide, with more than 1,900 faculty physicians operating at 130 locations. WashU Medicine physicians exclusively staff Barnes-Jewish and St. Louis Children’s hospitals—the academic facilities of BJC HealthCare—and provide care in BJC’s community hospitals in the region. WashU Medicine has a distinguished legacy in MD/PhD training, having recently allocated $100 million towards scholarships and curriculum revisions for its medical students and is home to exceptional training programs in every medical subspecialty, as well as physical therapy, occupational therapy, and audiology and communication sciences.
Originally published on the WashU Medicine website
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