One solution to child malnutrition may lie in kids’ guts
Gut microbes might be just as important as the number of calories when it comes to rebuilding the health of malnourished children.
It’s hard to imagine how childhood malnutrition persists when much of the world is mired in a global obesity epidemic—but it remains a significant problem. Experts say that the solution goes beyond providing sufficient calories; the problem may be partly due to the community of microbes living in the guts of malnourished kids.
This hypothesis has led researchers to create food supplements designed to improve gut microbial populations in malnourished children and help them grow and thrive.
“If there’s evidence that perturbations in this [microbial] assembly lead to undernutrition, the goal is to develop a way to repair the poorly developed microbial communities of malnourished children and restore healthy growth,” says Jeffrey Gordon, a microbiome scientist and director of the Center for Genome Sciences and Systems Biology at the Washington University School of Medicine in St. Louis.
A couple of years ago Gordon and his colleagues published a study in The New England Journal of Medicine that showed that malnourished young children in Bangladesh who were fed a freshly prepared food supplement designed to boost growth-promoting gut microbes gained considerably more weight and grew taller than those who were given a standard ready-to-use food supplement.
“The early establishment of a child’s microbiome is critical for a child’s development,” notes Liping Zhao, a microbial ecologist and director of the Rutgers Center for Nutrition, Microbiome, and Health at the New Jersey Institute for Food, Nutrition, and Health. “Adequate microbiota are important for the full development of the gut and nutrient absorption—and to protect the gut from the invasion of pathogens that can cause infections.”
Based on Gordon’s previous research, a clinical trial is now underway to test the efficacy of shelf-stable prototypes of the microbiota-promoting food supplement—compared to the freshly prepared version—in children eight to 12 months old with moderate malnutrition in Bangladesh. Gordon’s team has expanded its research to include other countries, and they will follow children for several years to see if the weight gain and growth improvements that were found in the New England Journal of Medicine study are replicable and malnutrition can be reversed.
“Our hope is that if we can develop a culturally acceptable intervention, it could have generalizable effects in various geographic areas and age groups,” Gordon says.
The scope of the problem
In 2020, the World Health Organization estimated that globally 149 million children under age five were too short for their age (stunted) and 45 million were too thin for their height (a condition known as wasting.) Approximately 45 percent of deaths among kids under five are linked to undernutrition. Even if they survive, malnutrition can disrupt kids’ neurological, cognitive, and physical growth and development. It can also harm their immune system function, and raise their susceptibility to infections and long-term risk of developing conditions such as cardiovascular diseases, diabetes, and certain forms of cancer.
In Gordon’s 2021 NEJM study, researchers provided 123 moderately malnourished children, ages 12 to 18 months and living in an urban slum in Bangladesh, with either a microbiota-boosting supplement or a standard therapeutic food. The former contained a mixture of chickpea, peanut, soybean flour, green banana pulp, and various micronutrients; the latter was made from rice, lentils, powdered low-fat milk, and micronutrients and had about 20 percent more calories per serving. Both supplements were given twice a day for three months, and the mothers were advised to continue their usual breast-feeding and complementary feeding practices during the study.
The researchers found the rates of change in the children’s weight and height were greater in the group that received the microbiota-directed food supplement—even though its calorie content was 20 percent lower than the standard therapeutic food. In addition, blood levels of key proteins that are associated with bone growth and neurodevelopment increased significantly in this group.
The results suggest that repairing the gut microbiome is essential to healthy growth in these children, says Gordon, the study’s senior author.
In the past, “there have been some nutritional interventions where improvements in mother and infant nutrition have had less success than we’d hoped,” notes Justin Sonnenburg, a professor of microbiology and immunology at the Stanford University School of Medicine and co-author of The Good Gut: Taking Control of Your Weight, Your Mood, and Your Long-Term Health. “This leads us to wonder what other things are happening. It may have to do with resident microbes—the wrong ones there are driving disease, and the right ones are missing to drive health. Or it might have to do with how an infant’s gastrointestinal tract develops.”
A baby’s nutritional status and microbiome begin before birth. During pregnancy, many aspects of a mother’s microbiome are passed on to her infant, which is another reason a pregnant woman’s health and nutritional status are so important. “We start to become colonized with microbes in utero, then more so in the birth process, then more depending on whether a baby is fed with breastmilk or formula,” explains Gail Cresci, a nutritionist and gut microbiome researcher at the Cleveland Clinic Children’s Hospital. “If an insufficient diet is being delivered or there are unsanitary living conditions, that will impact the [child’s] microbiome.”
Unfortunate ripple effects
Once a child is born, the microbiome is malleable, but challenges may remain, depending on the microbes the gut contains. “Without the right kind of bacteria coming to a newborn’s gut from the beginning, the gut may not fully develop and that may impair nutrient absorption,” says Rutgers’ Zhao. “Malnutrition may occur for various reasons, but the end result is the same—a dysbiotic gut microbiome.”
Dysbiosis in the gut microbiome may reflect a decrease in the diversity of microbiota, a dearth of beneficial microbes, and/or overgrowth of harmful ones. In fact, research shows that the gut microbiota of children who have severe acute malnourishment (SAM) have a less diverse community of microbes compared to those in healthy children.
The trouble is, when a malnourished child’s gut microbiome develops poorly or suffers from dysbiosis, this can lead to inflammation and high levels of pathogens in the gut—such as C. difficile, Salmonella, or E. coli—that can cause diarrheal illnesses. “Widespread inflammation in the small intestine can cause malabsorption of nutrients because the lining doesn’t function properly,” Sonnenburg says. This can lead to problems with leaky gut, which also can lead to malnourishment, Cresci notes.
When the intestine is compromised, increased inflammation, gut dysbiosis, barrier dysfunction, and malnutrition can ensue.
The integrity of the small intestine is a key element of a healthy microbiome and it has a delicate balancing act to perform. “The small intestine needs to be absorptive and a barrier at the same time—to absorb nutrients and to keep microbes in the right place,” explains Sonnenburg. The goal isn’t to eliminate harmful bacteria but to keep them at bay by allowing beneficial microbes to dominate in the gut. That way, the right nutrients can be absorbed and the gastrointestinal tract can function effectively.
Rebooting the microbiome
One of the challenges in developing a microbiota-directed intervention for child malnutrition is that everyone’s microbiome is slightly different so even defining a healthy microbiome is tricky, Sonnenburg says. That said, certain gut bacteria are recognized as being part of a healthy microbiome in children. For example, Bifidobacterium infantis has been identified as a particularly beneficial strain in the infant gut.
Still, some experts question whether it’s possible to develop a supplement that would have widespread effects in curbing childhood malnutrition. “I think the best thing would be if we could see what someone’s microbiome looks like and what the person needs, in order to re-establish a healthy microbiome,” Cresci says. “It’s like personalized nutrition. I think that’s what we need to do.”
Zhao raises another concern. “If we use the right nutrition to change the microbiome, it can help some children with malnutrition,” he says, “but nutritional intervention may not work well for children if they’re lacking beneficial bacteria or a fully developed gut from the beginning.”
There’s also a question about the optimal timing for trying to repair a disturbed microbiome. After all, the composition of gut microbiota changes with a child’s age. A small study in the March 2023 issue of Nutrients examined the intestinal microbiota in malnourished children between the ages of three and 24 months in Pakistan and found that age was the biggest factor accounting for differences in the diversity of their gut microbial communities.
The optimal intervention “needs to be targeted to the state of development of the microbiome,” Gordon says.
Some experts say there’s reason to hope the microbiome could be repaired in ways that allow kids to absorb more nutrients from their food. “The microbiome is malleable, and it can adapt rapidly to a changing environment,” Sonnenburg says. “Diet is an incredibly powerful mediator of the microbiome’s impact. The intervention of the future will not just focus on microbes or diet but the combination.” Ultimately, that may be the one-two punch that’s needed to curb childhood malnutrition.
