Microbiome-Boosting Foods Could Help Treat Severe Malnutrition in Children
Improvements in malnourished children’s health linked to growth-associated gut microbiome species.
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Malnutrition is a global health challenge, with nearly half of deaths among children under five years of age linked to undernutrition. Common among children with moderate acute malnutrition (MAM) and severe acute malnutrition (SAM) is a perturbed gut microbiome – resembling those of chronologically younger children.
A three-month trial of a gut microbiome-directed food supplement in Bangladeshi children who recovered from SAM but suffer from MAM, has shown that microbiome-based therapies improve growth better than a more calorically dense, commonly used supplement.
The study, published in the journal Science Translational Medicine, also hints at the mechanism behind the improvements, linking this to changes in growth-associated gut microbiome species, most notably Prevotella copri (P. copri).
Finding a gut-boosting supplement
Standard treatments for children suffering from moderate malnutrition include ready-to-use supplementary foods (RUSFs), which are generally made with cereals, sugar, milk powder, vegetable oils, vitamins and minerals.
In 2014, researchers discovered that malnutrition in children also slowed the development of intestinal microbiomes with their microbiota resembling those of newborns. A follow-up study conducted in germ-free mice found that mice given the microbiome from malnourished children had impaired weight gain. The mice also displayed immune and metabolic abnormalities not observed in mice given the microbiome from healthy children.
These findings led researchers to look at possible supplements to stimulate the normal development of the gut microbiome, in the hope that repairing the microbiome might lessen the effects of malnutrition in children.
Using animal studies, researchers identified a food mixture containing components typically given to Bangladeshi children as infants (chickpea flour, soybean flour, peanut paste and green banana) that stimulated normal development of the gut microbiome. These efforts yielded microbiota-directed complementary food (MDCF) prototypes that altered the abundance and expressed metabolic activities of bacterial strains.
Tackling severe malnutrition
In the current study, the researchers aimed to test the use of an MDCF prototype (MDCF-2) for treating malnutrition in children who had completed a hospital-based program for SAM but were still suffering from MAM.
The team conducted the trial in 12- to 18-month-old children from urban and rural hospitals in Bangladesh. After initial hospital-based treatment for SAM, half the children received standard ready-to-use food for three months and half received MDCF-2.
The group who received the MDCF-2 gained weight faster and had heightened levels of blood proteins known to stimulate the growth of the skeleton, muscles and brain.
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Subscribe for FREE“Using a comparative meta-analysis of the levels of 4520 plasma proteins during the treatment phase of this study and in our previously reported primary MAM trial, we identified 259 shared biomarkers of recovery from MAM,” the researchers explained.
These results provide a rationale for identifying biomarkers to define treatment responses. “These 259 plasma proteins represent potential biomarkers to evaluate in future studies involving MDCFs in children with acute malnutrition living in different geographic locales and having varying degrees of disease severity, as well as in studies involving other therapeutic agents,” the researchers concluded.
Characterizing the abundance of 754 bacterial metagenome-assembled genomes from fecal samples collected over the course of treatment, provided evidence that P. copri is both a target of MDCF-2 and linked to the growth responses in both patient cohorts. These observations, combined with findings in germ-free mice dosed with microbiomes containing the species, led the researchers to hypothesize that the bacterium may help break down complex carbohydrates in the supplement into simpler ones for uptake by other beneficial bacteria and intestinal cells.
The researchers emphasize that further work is needed to define the microbial metabolites that mediate host responses to MDCF-2 treatment.
Reference: Hartman SJ, Hibberd MC, Mostafa I, et al. A microbiome-directed therapeutic food for children recovering from severe acute malnutrition. Sci Transl Med. 2024;16(767):eadn2366. doi: 10.1126/scitranslmed.adn2366
