We carry countless types of bacteria in our gut, but in malnourished children, many beneficial intestinal microbes lack the fuel to grow. Now, a clinical trial suggests that a new dietary supplement could help restore the intestinal bacteria of malnourished children, helping them gain weight and grow up healthy.
The trial took place in Mirpur district of Dhaka, Bangladesh, and researchers created a new dietary supplement from locally available ingredients, including chickpeas, soy flour, peanuts, green bananas, oil and sugar. Compared to children who received standard treatment for malnutrition – caloric “ready-to-eat supplements” (RUSF) – children received a new supplement weight and gained height faster.
Moreover, faecal samples of these children showed that it was their gut bacteria better suited to those of healthy children by the end of the study. This change in intestinal microbes is associated with the appearance of certain proteins in the blood; especially the key proteins involved in bone growth and brain development has increased, while markers of inflammation decreased, according to a study published on April 7 in New England Journal of Medicine.
Related: 5 Ways Intestinal Bacteria Affect Your Health
These findings suggest that “impact [microbial] the community extends beyond the gut wall to affect many systems, ”said senior author Dr. Jeffrey Gordon, director of the Edison Family Center for Gene Science and Systems Biology at Washington University School of Medicine in St. Louis.
It is exceptional that the standard RUSF treatment contains about 20% more calories rather than a new supplement, and yet, “this lower-calorie density intervention can actually improve weight gain in these children to a greater extent than something with higher calorie density,” said Ruairi Robertson, a postdoctoral researcher studying the gut microbiome at Queen Mary University in London. but was not included in the study. This result reverses the usual thinking about diet and calorie intake and emphasizes the importance of intestinal errors in a child’s development, he said.
However, more data is needed to confirm whether the supplement helps children grow in the long run and whether the observed changes in protein levels actually translate into strong bones and a healthy brain, Robertson said. For now, researchers do not know how long the observed benefits will last or whether the treatment can offer similar benefits to all of its malnourished children, Gordon said.
“A lot of work needs to be done, but the results, I think, are encouraging,” Gordon told Live Science.
The best fuel for intestinal bugs
Prior to the start of the clinical trial, Gordon and colleagues conducted extensive testing of human fecal samples, as well as laboratory tests of mice and pigs, to determine which foods could best fuel the microbiome of an malnourished child, a community of microbes living in the digestive system.
The team first sampled fecal matter from the children in different countries – including Venezuela, Malawi, USA and Bangladesh – and look for patterns of how their intestinal bacteria vary, depending on their location, age, diet, and nutritional status. They observed that healthy children accumulated a certain set of intestinal microbes during the first two years of life, while the intestinal microbiomes of malnourished children appeared to be “stunted”.
In other words, similar to organs in the body, the gut microbiome matures and changes over time, but the microbiome of malnourished children “looks‘ younger ’than you would expect,” Gordon said.
“After about two or three years, the intestinal microbiome stabilizes and looks pretty similar to that of an adult,” Robertson said. “We assume that if you have these distractions … in that critical window, it can actually disrupt the trajectory later,” in the sense that the child’s body matures.
Related: 70,000 never-before-seen viruses have been found in human intestines
The team tested the idea to see how microbiome clogging in this immature state could undermine a child’s development u mice. Certainly, when the team transplanted malnourished pediatric faecal specimens into animals, the rate of weight gain and bone growth worsened. They also began to develop metabolic dysfunction because, for example, the body began to break down amino acids for energy rather than sugars, among other problems seen in malnourished children.
The team wondered if a particular food could fix a stunted microbiome and potentially help children get back on track for normal development. Working with locally available food from Dhaka, the team tested how different combinations of ingredients affect the intestinal microbiome in their animal models and how these changes are related to growth.
By working with locally available food, “ideally, this is an intervention that can be produced locally and provided locally,” and is aligned with local cultural standards, Robertson said. “And that kind of creates a viable model for a good outcome overall.”
Seeing reliable results in their animal studies, the researchers conducted a small trial of their new dietary supplements in children, testing them three formulations. One of them stood out as particularly promising and worthy of a wider trial.
Put it to the test
In the current study, 118 children with moderate acute malnutrition completed the experiment, ranging in age from 12 months to 18 months. (By definition, children with moderate acute malnutrition fall two to three standard deviations below the average weight of their height, while children with severe acute malnutrition fall at least three below, according to the World Health Organization.)
Half of the children received RUSF, while the other half received a new dietary supplement, called the “microbiota-focused complementary food prototype” (MDCF). The RUSF used in the study also contained local ingredients – mostly rice and lentils – but the food was not specifically selected to feed the gut microbiome, as in the new MDCF, said first author Robert Chen, a medical and doctoral student at Gordon’s lab. And it all seems to matter, he added.
The children received the assigned supplement twice a day for three months and then underwent another month of follow-up. The researchers measured the weight, length and arm circumference of the children, tracking changes over time and found that children who received MDCF grew and gained weight faster.
“That thing certainly surprised us,” Chen said.
That said, although the improvements in weight and height were significant, overall they were relatively small, Robertson said. This could be related to the fact that the children were moderately malnourished, while the same treatment in severely malnourished children “could actually have more drastic effects,” he said. In any case, “we can never expect a full recovery in three months,” he added.
Related: 5 diets that fight disease
The team also collected blood samples, for the assessment of children’s plasma proteins and faecal samples, for the analysis of their intestinal bacteria. Children who received the new supplement showed higher increases in 70 developmental plasma proteins than children who received RUSF; they included key proteins for bone growth and nerve and brain development. An increase in these 70 proteins is associated with a significant increase in weight and height.
Although interesting, fluctuating protein levels cannot definitively suggest whether these children will grow healthy bones and brains; larger and longer clinical trials will be needed to see how these protein levels translate into actual health outcomes, Robertson said. But by refining proteins of interest, the current study provides “a treasure trove that other researchers could enter,” he said.
Similarly, in all children, the team identified 21 types of bacteria that appeared to be associated with significant growth growth, as well as two types of bacteria associated with poor growth. These last two bacteria are involved Escherichia coli ia Bifidobacterium type, a probiotic found in large quantities in breastfed infants.
“You want a lot of it there in the very early months of life because it breaks down and metabolizes sugars, and oligosaccharides in human milk, in breast milk,” Robertson said. “But intriguing, [the trial] it seemed to show that later on more of it was negatively linked to growth, “he said. So perhaps at this critical stage of infancy when children are weaned from breast milk, this once useful gut could become less abundant, allowing other microbes to take his place, he said.
Seeing that their new MDCF has helped children’s microbiomes get to a more mature state, Gordon and his team are now following the children to see how they grow over time. In the future, researchers want to better link the points between children’s diets, their intestinal bacteria, plasma proteins and their health outcomes.
These fine details should help scientists adjust their MDCF to meet the needs of children in different places, where the supplement may be made from different ingredients.
Originally posted on Live Science.