Key takeaways
- A study in Mumbai found that toddlers who ate iron- and zinc-biofortified pearl millet for nine months had improved gut microbiome activity without the negative side effects previously seen with iron supplements.
- Iron deficiency is widespread and harmful, especially for young children, but traditional supplements can disrupt gut health and cause digestive issues.
- The biofortified millet potentially could increase beneficial microbial functions (like pathogen-fighting and antioxidant activity) while reducing harmful bacteria.
- This food-based approach could offer a safer, more sustainable way to address nutrient deficiencies compared to supplements.
- Researchers say biofortified crops could have global applications and align with growing interest in nutrient-dense, whole foods.
Every day in the urban slums of Mumbai, hundreds of young children were fed a toddler-appropriate porridge, soft curry or fresh baked good. For some, these were made of ordinary pearl millet, an ancient grain common in the Indian diet. For others, it was a specially bred variety, packed with nearly three times the iron and more zinc than typical grain. The difference was largely imperceptible on the palate. But deep in the children’s guts, something meaningful was beginning to happen.
Iron deficiency is the most common nutritional disorder worldwide, affecting roughly a quarter of the global population. When you lack sufficient iron, your body cannot produce enough hemoglobin, leading to iron-deficiency anemia, which can cause a wide array of physical and cognitive problems.
Cornell Joan Klein Jacobs Center for Precision Nutrition and Health researchers and collaborators in India and at the University of California San Diego found that toddlers who ate iron- and zinc-biofortified pearl millet for nine months did not have adverse effects typically seen with increased iron intake; moreover, the high-iron millet developed gut microbiomes with distinct and potentially beneficial changes.
The findings, published July 30 in Nature Communications and set to be presented at the American Society for Nutrition’s annual meeting on July 25, represent what the researchers believe is one of the first studies ever to examine how biofortified crops affect the human gut microbiome.
“We thought that a food-based approach could help us move away from one-size-fits-all supplementation strategies to address population health, while also being a way to personalize nutritional interventions,” said Dr. Saurabh Mehta, founding director and Janet and Gordon Lankton Professor at the Jacobs center in the College of Human Ecology, and the principal investigator on the study. “So, we decided to test it.”
Boosting iron without disrupting the gut
Iron deficiency affects roughly one in four people worldwide and hits young children especially hard, slowing brain development and leaving the body vulnerable to infection. The standard fix – iron supplements – works. But it comes with a catch. Previous research has found that supplements can disrupt the gut’s bacterial ecosystem, boosting populations of harmful pathogens in the colon while inhibiting the growth of beneficial microbes, and also causing symptoms like diarrhea, constipation and tarry stools. That’s a particularly worrying tradeoff in infants and toddlers, whose gut microbiomes are still forming and are exquisitely sensitive to outside forces.
The trial enrolled 223 children between 12 and 18 months old in Mumbai’s urban slums, a setting where iron deficiency and anemia remain stubbornly common. Half of the children received foods made from the biofortified millet (8.7 mg of iron per 100 grams); the other half got standard millet (3 mg per 100 grams). Researchers collected rectal swabs at the start and end of the study and performed sequencing to map the microbial landscape of each child’s gut.
The logistics weren’t simple.
“We had to work with growers to develop the millet. Then we procured 38 tons of millet, split between the two types, and we had to identify storage facilities with the proper temperature and humidity,” said Samantha Huey, research associate in the Jacobs center and co-first author of the study. “We tested it for contamination and to make sure it had the iron and zinc we wanted it to have.”
The millet-based foods and recipes were developed with the help of SNDT Women’s University in India, and delivered to 20 different sites in partnership with the Centre for the Study of Social Change, a Mumbai-based NGO. A research assistant in each feeding center measured how much food was consumed by each child twice each day in the center (with one take-home meal), six days a week, for nine months.
“The sequencing technique that was used allowed us to delve deeper than just describing the types of bacteria present in these children’s guts – we could also understand what they were actually doing,” said co-first author Nathanial Cole, a postdoctoral associate in the Jacobs center.
“We compared the DNA from these children’s gut communities to reference DNA from other species with known functions, allowing us to predict what these microbes were doing based on genetic similarities,” he said. “This approach enabled us to track how the gut microbiome developed over time and how it responded to the biofortified pearl millet.”
Good news in the data
Results were encouraging. Children eating the biofortified millet showed increased activity in microbial pathways associated with fighting pathogens, including the production of natural antibiotic-like compounds, and with antioxidant metabolism, which helps maintain a healthier gut environment. At the same time, markers linked to harmful bacteria were lower in their guts by study’s end.
Across both groups, the researchers also observed that as the children aged, their microbiomes naturally grew more diverse and more metabolically capable, better equipped to handle a wider range of foods. This is the expected arc of a healthy gut coming online in the first years of life.
“Iron supplementation is usually given at high doses because it isn’t well absorbed, but excess ends up in the colon and can allow harmful bacteria to proliferate,” Huey said. “Biofortification increases the nutrient density of the plant via genetic engineering, agronomic practices or – what we used – traditional cross breeding.”
Unlike supplements, which require distribution infrastructure and depend on consistent behavior, biofortified crops can be grown and eaten the same way ordinary crops are. They are, in theory, a self-sustaining solution, Huey said.
Beyond Mumbai
While larger studies across diverse populations will be needed before biofortified crops can be confidently prescribed as gut-friendly, these crops have potential applications in both lower-to-middle income and developed nations. In the U.S., iron deficiency remains a major concern. Biofortification could strengthen U.S. agricultural systems while also providing climate-smart, high-yield and highly bioavailable staple crops already grown widely across the country.
It also fits in with current nutrition trends.
“The latest dietary guidelines are now stressing eating whole foods and limiting ultra-processed foods and additives,” Huey said. “Growing crops that are naturally more nutrient-dense, rather than relying on adding micronutrients back in during food manufacturing, aligns with these recommendations.”
This study was funded by the Agriculture and Food Research Initiative Grant from the USDA National Institute of Food and Agriculture. The parent trial was funded by a HarvestPlus grant, funded in part by the Bill & Melinda Gates Foundation. HarvestPlus is also supported by the John D. and Catherine T. MacArthur Foundation. Huey was supported by the National Institutes of Health as a trainee while working on this study.
