Microbiota-directed food intervention showed benefits for undernourished children

1. A microbiota-directed complimentary food showed growth and developmental improvements for undernourished children compared to conventional ready-to-use supplementary food.

2. The improved outcomes were linked to the gut bacterial taxa previously demonstrated to correlate with healthy childhood development.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Childhood undernourishment remains a global health challenge with stunting growth and long-term sequelae in cognition, immunity, and metabolism. Conventional food interventions, without focusing on the microbiota, have shown limited success in treating malnourished children. As such, this study aimed at comparing the effects of twice-daily supplementation of microbiota-directed complimentary food prototype 2 (MDCF-2) and ready-to-use supplementary food (RUSF) on improving the growth of undernourished children. The study determined MDCF-2 provided superior improvements on weight-for-length and weight-for-age compared to RUSF. Furthermore, this difference was linked to changes in 70 plasma proteins and 21 bacterial taxa that have previously been associated with weight-for-length z-score. These proteins include markers of bone and nervous system development. The study was limited by not testing for composition through changes in fat mass and lean mass. Nonetheless, the study’s results are significant, as this study provided support for the microbiota-directed food supplementation as an efficacious therapy for childhood malnutrition.

Clicker to read the study in NEJM

Relevant Reading: Effects of microbiota-directed foods in gnotobiotic animals and undernourished children

In-Depth [randomized controlled trial]: This randomized controlled trial enrolled 123 children in Mirpur, Bangladesh. Children between 12 and 18 months of age and had moderate acute malnutrition, defined by the World Health Organization as weight-for-length two to three standard deviations below the age cohort median, were included in the study. Children classified with chronic malnutrition were excluded from the study. The children were randomized in a 1:1 ratio to receive either MDCF-2 or RUSF, respectively. The primary outcomes were weight-for-length z score and weight-for-age z score. The study found MDCF-2 resulted in better outcomes in weight-for-length and weight-for-age z score improvements over the study period. Specifically, the between-group differences in mean weekly change were 0.011 in weight-for-length z score (95% confidence interval [CI], 0.001 to 0.021) and 0.008 in weight-for-age z score (95% CI, 0.001 to 0.015). Among the plasma proteins examined, more proteins were significantly altered by MDCF-2 (714 proteins) than RUSF (82 proteins). Specifically, the proteins significantly enriched in the MDCF-2 group relative to RUSF were associated with weight-for-length z scores (WLZ), musculoskeletal, and nervous systems development (P<0.001). On the other hand, pro-inflammatory markers, heightened by malnutrition at the beginning of the study, were reduced to a larger extent by MDCF-2 supplementation. Bacteria taxa positively associated with WLZ, such as Facecalibacterium prausnitzii, were significantly increased by MDCF-2 than RUSF (P<0.001). Conversely, the Bifidobacterium species, negatively associated with WLZ, were significantly reduced by MDCF-2 (P<0.001). Overall, this study highlighted the potential benefits of the MDCF-2 approach and identified key plasma and microbiota biomarkers underlying these improvements.

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