Tthe best The treatment for childhood malnutrition may seem obvious: more and more nutritious food. And the standard approach is just that. Over the years, formulas for ready-to-use complementary foods (RUSF)—pasta bars and packages intended for moderate cases and made from rice, lentils, sugar, soybean oil, and powdered milk—and similar therapeutic foods (RUTF), a nut-based treatment has been developed for the most severe cases. These work. But Tahmeed Ahmed, chief executive of the awkwardly named icddr,b, a research institute in Dhaka, Bangladesh, and his team think they’ve found something better.
In collaboration with Jeffrey Gordon and his colleagues at Washington University in St Louis, Missouri, Dr. Ahmed’s team has produced a new mixture for the treatment of malnutrition. In addition to providing nutrients, this formulation also improves intestinal health. That provides benefits to the malnourished that the conventional approach does not. Now the World Health Organization (WHO) is testing the result, called MDCF-2, in Bangladesh, India, Mali, Pakistan and Tanzania.
errors in the system
Until recently, little attention was paid to the role played in digestion by the trillions of microbes, known collectively as the microbiota or microbiome, that live in the human gut. That changed in 2013 when Dr. Gordon compared the gut flora of pairs of twin boys in Malawi. He did so on the assumption that since they are born together and raised in the same households, the twins’ nutritional histories will be identical.
However, he came across a number of cases where one of the twins had a form of malnutrition called kwashiorkor, while the other remained healthy. And when this happened, he also discovered that his microbiomes differed in systematic ways. In addition to this, he discovered that when the insects in question were transplanted into laboratory mice that had been raised in a germ-free environment, the animals that received transplants from a twin with kwashiorkor developed the mouse equivalent of that disease.
Thus, it seemed likely that while the underlying cause of kwashiorkor is undoubtedly nutrient insufficiency, malnourished people who might otherwise remain free of its symptoms (bloated bellies, muscle loss, stunted growth, and brittle hair) ) may lie on the ground. edge by an unbalanced microbiome.
In 2014, in a follow-up to this work, Dr Ahmed, Dr Gordon and their respective teams compared the gut microbiomes of healthy children living in the slums of Dhaka with those of children treated for forms of severe acute malnutrition. such as kwashiorkor. They showed that eating more calories and protein made no difference to the children’s microbiomes. They also showed how children’s microbiomes mature and that malnourished children lack the bacteria needed to properly digest food and produce certain vitamins. At the age of three, a healthy child has a fully developed microbiome. A three-year-old child with severe acute malnutrition, by contrast, has a microbiome similar to that of a healthy one-and-a-half-year-old child.
Microbiomes are easily thrown out of balance. After cesarean deliveries, for example, babies are not exposed to bacteria from their mothers as they are during vaginal deliveries. Such transfers help determine the early microbial population of a child’s gut, and a third of Bangladeshi children are delivered by caesarean section, compared to around a quarter in wealthy Western countries.
Oral antibiotics can also damage the gut microbiomes by killing helpful bacteria along with disease-causing ones. In Bangladesh, where medicines are often used to compensate for poor sanitation, antibiotics can be bought in pharmacies and markets without a prescription. Doctors also distribute them generously.
No bar for success
Rebalancing microbiomes once they have become unbalanced is difficult. However, research by Dr. Ahmed and Dr. Gordon, published in 2019, found that it can be done through careful management of children’s diets. By examining the diets of children in the slums of Mirpur, a suburb of Dhaka, and correlating what individual children ate with the mix of bacteria in their microbiomes, the two researchers and their teams devised 14 different experimental diets that they thought that could promote the growth of desirable intestinal bacteria. They then fed them to mice and piglets that had first been inoculated with bacteria from the children in question.
These tests led them to three “microbiota-driven complementary food” diets, which they called MDCF-1, -2 and -3, which seemed to encourage the maturation of the animals’ microbiomes. They then tested this successful trio for a month on groups of malnourished children, while feeding a fourth group. RUSF as control. MDCF-2, made from bananas, chickpeas, peanuts and soybeans, stood out. At the end of the trial, the microbiomes of children in the other three groups resembled those of untreated malnourished children, while those of children fed MDCF-2 had microbiomes similar to those of a healthy child.
This, Dr Ahmed speculates, could explain why children fed conventional complementary foods such as RUSF they often relapse into malnutrition when they return to their original diets. A follow-up study published last year supports this hypothesis. Malnourished children from the slums of Mirpur fed MDCF-2 times a day for three months grew fatter and faster than a comparable fed group RUSFalthough MDCF-2 has 20% fewer calories. Their “weight for length” score, a standard measure of childhood growth, also increased more rapidly.
Also, children who eat MDCF-2 continued to make gains relative to the others after the intervention ended. Their microbiomes became more developed, with 21 types of bacteria associated with growth and vitamin production becoming more abundant. And their levels of 70 blood plasma proteins known to be markers of nutritional status also improved.
The next step is to test this elsewhere. And that’s what WHO is now trying to do. For the new five-country test to be realistic, those running programs within it must build from scratch. The team in each country has to find the exact equipment used in Bangladesh locally and source the ingredients locally as well, a challenge that led Karim Manji of the Muhimbili University of Health and Allied Sciences in Dar es Salaam, a veteran in the child nutrition field that is running the Tanzania trial, thinking when you first read the list, “Oh my gosh, are we ready to manufacture this?”
But Dr. Manji has quickly regained his savoir faire. He is “totally unique”, he says, referring to the trial, and could transform the global response to malnutrition. Currently, UNICEFthe United Nations agency responsible for dealing with child malnutrition, has RUTF, a factory-made product from which it buys about 80% of the world’s production. If, as this research hopes to prove, a homemade alternative that nourishes the gut microbiome does a better job of helping children thrive, UNICEF and others involved in the malnutrition business may want to change tactics.
However, moving from a focus on nutritional value to gut health is complex. Importing and distributing pre-packed bars is simpler (although more expensive) than doing things locally from scratch. Y MDCF-2 may not be a one-size-fits-all solution. The mix may need to be tailored to account for regional variations in what constitutes a healthy microbiome.
Diets and tastes also vary, as Dr. Manji has already discovered. Ishita Mostafa, another icddr,b researcher, says MDCF-2, which comes as a sticky brown paste, “tastes sweet like halwa” (halwa is a popular dessert in Bangladesh). He adds that “babies love it” and, therefore, mothers too. But the same might not be true in, say, Mali. Aware of this risk, Dr. Ahmed and his colleagues have begun testing substitutes, such as sweet potatoes for bananas, to see if the impact on the microbiome remains the same. But finding ingredients that have similar effects involves complicated laboratory tests. Aid programs would need to do this over and over again.
Additional research may make things easier, says Dr. Ahmed. He and his colleagues are still investigating what exactly he does. MDCF-2 work very well. That will help the search for substitute ingredients. They also hope to apply MDCF-2 to maternal malnutrition. This affects children because malnourished women (especially those malnourished during pregnancy) give birth to malnourished babies. So for many malnourished children in the future, Dr. Ahmed’s work could make a difference. ■
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