Scientists develop 'therapeutic food' that can repair gut microbes of malnourished children and boost healthy growth
Childhood malnutrition—a massive global health problem—can often cause irreversible damage, and around 45% of deaths (World Health Organization estimates) among children under five can be attributed to undernutrition.
However, researchers from the Washington University School of Medicine in St. Louis and the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh, now report an effective treatment strategy that could help millions of malnourished children globally.
A new type of therapeutic food, specially designed to repair the gut microbes of malnourished children, can help the children recover and boost healthy development, shows two studies published in the journal Science.
Results from the clinical trial show that the gut microbes in children who were given the therapeutic food - a mixture of nutrients from chickpea, soy, bananas, and peanuts - underwent a complete transformation and became healthy. The researchers say that malnourished children have incompletely formed gut microbial communities as compared with their healthy counterparts. Accordingly, they decided to design therapeutic food that could address and repair this immaturity.
“The gut microbial communities residing in the intestines of children receiving this therapeutic food had undergone a reconfiguration and more closely resembled microbial communities found in age-matched healthy children living in the same locale,” says the clinical trial findings.
It further states: “The results provide the first evidence that a therapeutic food, developed specifically to support growth and expansion of gut microbes linked to healthy microbiome development, has beneficial effects outside the gut related to many aspects of healthy growth. These effects involve key mediators of metabolism, and of bone, brain and immune system development - organ systems that have been very difficult to repair in malnourished children by supplementing their diet with traditional therapeutic foods.”
A longer and more extensive clinical trial is currently underway at two sites in Bangladesh to see if the new “Microbiome-Directed Complementary Food” has sustained benefits. This trial includes children with moderate malnutrition, and children with severe malnutrition who were treated with conventional therapy, but “left with incompletely repaired microbiomes, stunting and various other growth impairments.”
The WHO describes malnutrition as deficiencies, excesses, or imbalances in a person’s intake of energy and/or nutrients. It can lead to severe conditions that include wasting (low weight-for-height), stunting (low height-for-age), and underweight (low weight-for-age). Globally, in 2018, 149 million children under the age of five were stunted, 49 million wasted, and 17 million severely wasted, show the WHO estimates.
Conventional therapeutic foods inadequate
The study, based on the idea that healthy development of the gut community might be critical for normal growth, emanates from an earlier study by the team, which looks at gut microbial community development in healthy children living in Bangladesh. They reported that the gut microbiome normally ‘matures’ as an infant grows into a toddler. They found that children with acute malnutrition have impaired gut microbiota, leaving them with communities that appear younger or more ‘immature’ than those seen in healthy children of the same age.
The researchers also found that current therapeutic foods given to children with acute malnutrition were not able to repair this immaturity. “They have not been formulated based on knowledge of how they affect the developmental biology of the gut microbiota,” says the team. Moreover, say the researchers, the conventional therapeutic foods fail to address the long-term impact of malnutrition, which includes persistent stunting, neuro-development abnormalities, and immune dysfunction.
What did the researchers do?
To understand what malnourished children were missing, the researchers collected fecal samples from Bangladeshi children with severe acute malnutrition treated with standard therapy, as well as from healthy children. They transplanted the mature and immature microbes from children into mice that had been raised under sterile conditions. Results reveal that animals with immature communities had reduced weight gain, defective bone development, and abnormal metabolic and immune functions. “These findings provided early evidence that failure to form a normal microbial community may be a cause rather than simply an effect of malnutrition,” the findings say.
The researchers also developed a novel computational method, which provided better ways of characterizing the organization of human gut communities - their healthy development, what happens in disease states such as malnutrition, and how they respond to therapeutic interventions designed to repair them.
Studying the microbiomes of healthy Bangladeshi children sampled monthly from birth through five years, and using the new computational method, they identified a network of 15 gut bacterial community members that consistently interacted with one another. These were present in the gut of healthy children and the researchers called this network an eco-group. “The components of the eco-group provided an accurate way of describing normal gut development of infants and children living in Bangladesh as well as several other low-income countries. It served as an accurate way of determining how severely disrupted microbial communities are in children with moderate and severe malnutrition, and the degree to which they are repaired with various treatments,” says the findings.
Results from clinical trial in children
The researchers first used germ-free mice, and then germ-free piglets, colonized with gut microbial community members from Bangladeshi children to screen a series of diets that consisted of complementary food ingredients used in Bangladesh. They formulated Microbiome-Directed Complementary Food prototypes that could repair immature microbial communities from malnourished Bangladeshi children in both these animal models and improve the health of the animals. The prototypes were subsequently tested in children.
The clinical trial - which included 63 Bangladeshi children, 12-18 months of age, diagnosed with moderate acute malnutrition - was conducted by a team from the International Center for Diarrhoeal Disease Research. The foods for the trial were locally produced at this center. The team focused on using ingredients that are available locally, "culturally accepted”, and affordable.
There were four treatment groups, and the children were randomly assigned. Children in three of the groups each received one of the three newly designed therapeutic foods, while those in the fourth group received a standard therapeutic food that was not designed based on a consideration of its effects on the gut microbiome.
Children were brought twice daily to a nutritional rehabilitation center, where their mothers gave the therapeutic foods under the supervision of healthcare workers. One of the therapeutic foods that combined chickpea, soy, bananas and peanuts, stood out from the rest. “Measuring 1,300 blood proteins, including those intimately involved in directing bone growth, development of the brain, immune function, and metabolism in various tissues, revealed that this food prototype had produced a pronounced shift toward a healthy state compared with what was observed in the other three groups of children,” says the findings. This particular combination also improved the 15 gut bacteria that were present in the gut of healthy children, say the researchers, adding that their new approach of targeting gut microbes is "much superior" to standard treatment.
The two papers, which report the findings, are - effects of microbiota-directed foods in gnotobiotic animals and undernourished children and a sparse covarying unit that describes healthy and impaired human gut microbiota development.