Writing in the New England Journal of Medicine, a 3-month course of the supplement was enough to increase 21 types of beneficial bacteria numbers as well as a double the growth rate of the children.
Commenting on the proof-of-concept clinical trial, Senior Author Dr Jeffrey Gordon says, “Malnutrition has proven extraordinarily difficult to treat.
“Standard calorie-dense therapeutic foods have been shown to prevent the deaths of malnourished children but have been ineffective in overcoming growth stunting and other damaging effects of malnutrition, including impaired brain development, bone growth and immune function.”
“In an attempt to address this problem, we are investigating whether repairing the poorly developed microbial communities of malnourished children will impact their growth,” adds Dr Gordon, the Dr Robert J. Glaser Distinguished University Professor at Washington University School of Medicine.
“This is the first time that a microbiome-directed therapeutic food has been compared with a standard therapy in malnourished children; moreover, it produced a superior rate of weight gain, the key primary clinical outcome of the trial.”
The trial involved 118 children ages 12 months to 18 months who lived in an urban slum called Mirpur in Dhaka, Bangladesh.
All of these children had been diagnosed with acute malnutrition and half of them were randomly assigned to receive 25 grams (g) of the microbiome-directed food, twice daily for three months.
The food supplement contained a mixture of chickpeas, soy, bananas and peanuts, ingredients that the group had discovered in earlier preclinical models could repair the gut microbiome, among other components.
The other half also received 25g of a standard therapeutic food that was not designed to repair the gut microbiome, also for three months.
The children’s height, weight and mid-upper arm circumference were measured at regular intervals throughout the intervention period and for one month after treatment stopped.
Blood and stool specimens were also collected at various times to assess changes in the levels of nearly 5,000 proteins in the blood, and to quantify the food’s effects on beneficial microbe numbers in stool samples.
The team noted the rate of change in the children’s weight and mid-upper arm circumferences were greater in the group consuming the microbiome-directed food compared with the placebo food.
This growth continued even a month after the children had stopped receiving the nutritional intervention, which is the latest time point to be analysed so far.
‘A growth outcome improvement’
“When we look at the standard clinical measurement for assessing acute malnutrition — the weight-for-length z score — the difference between the two treatment groups was even more significant one month after we stopped the treatment,” said co-first author Robert Chen, a doctoral student in Dr Gordon’s lab.
“If this rate of growth was maintained for a year, we estimate an improvement in the weight-for-length z score of almost one full standard deviation.
“Children with acute malnutrition typically have declining or in the best-case stable weight, so if this extrapolation holds up, it would be a major clinically relevant improvement in growth outcomes,” he added.
Dr Gordon adds, “The rate of improvement in the weight of the children receiving the new therapeutic food designed with healthy gut microbes in mind was significantly greater even though its caloric density was 20% lower than the standard food.”
“This suggests that the repair of the gut microbiome, and not just additional calories, is key to healthy growth in these children.”
‘Overarching questions remain’
In an editorial accompanying the research, Dr Wendy Garrett from the Harvard Chan School of Public Health, remained reserved about the potential of these foods to restore optimal growth and development, given that the microbiome is itself stunted in children with severe acute malnutrition.
“Overarching questions that remain concern the durability of the effects of the intervention on the children’s growth trajectory, including potential microbiota repair and improved cognitive development, since the study ended in 2019,” she writes.
“The findings will also need to be replicated in a larger, phase 3 study. Regardless of the durability of this intervention, the documented correlation between gut microbiota and host plasma protein profiling with ponderal growth in malnourished children provides potential biomarkers for future studies of MDCF-2 and other locally sourced supplementary foods that are seeking clinical vetting.”
Source: New England Journal of Medicine
Published online: DOI: 10.1056/NEJMoa2023294
“A Microbiota-Directed Food Intervention for Undernourished Children.”
Authors: Robert Chen et al.