A microbiota-directed complementary food prototype (MDCF-2) may be beneficial in children aged 12 to 18 months with moderate acute malnutrition, according to a study in the New England Journal of Medicine.

The randomized controlled trial compared MDCF-2 with a ready-to-use supplementary food (RUSF) in children living in an impoverished area in Mirpur, Bangladesh. The caloric density of MDCF-2 was 204 kcal per 50-g daily dose, compared with that of the RUSF, which was 247 kcal per 50-g daily dose. The supplementation was given twice daily for 3 months, and the children were followed up for 1 month.

Among the 123 children who underwent randomization, 61 received MDCF-2 (mean age, 15.4 ± 1.9 months; 57% girls) and 62 received RUSF (mean age, 15.5 ± 2.0 months; 58% girls). From the cohort, 59 in each group completed the 3-month intervention and 1-month follow-up.

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At 3 months, children in the MDCF-2 group had better outcomes than those in the RUSF group regarding the mean (SD) change in weight-for-length and weight-for-age z scores. The mean weekly change in the weight-for-length z score was 0.021 (95% CI, 0.014-0.029) in the MDCF-2 group and 0.010 (95% CI, 0.003-0.017) in the RUSF group (between-group difference of 0.011 [95% CI, 0.001-0.021]).

The mean weekly change in the weight-for-age z score was 0.017 (95% CI, 0.012-0.022) in the MDCF-2 group and 0.010 (95% CI, 0.004-0.015) in the RUSF group (between-group difference of 0.008 [95% CI, 0.001-0.015]).

For the 4-month period including the intervention and follow-up, the between-group difference in change from baseline was 0.010 (95% CI, 0.002-0.018) for the weight-for-length z score, 0.008 (95% CI, 0.002-0.013) for the weight-for-age z score, 0.004 cm (95% CI, 0.000-0.007) for the mid–upper-arm circumference, and 0.000 (−0.003-0.003) for the length-for-age z score.

The investigators also found that 714 proteins had significantly (Q <.10) higher or lower levels after MDCF-2 supplementation for 3 months, compared with 82 proteins that showed significant alterations after RUSF treatment. Of the proteins that showed increases after 3 months of supplementation with MDCF-2, 70 were significantly enriched and positively correlated with change in the weight-for-length z score (P <.001), compared with the proteins that showed increases after RUSF supplementation (P =.11).

Among 209 amplicon sequence variants that met the threshold for prevalence and abundance, 23 were significantly associated with the weight-for-length z score (WLZ-associated taxa) in a linear mixed-effects model, of which 21 were positively associated.

The levels of WLZ-associated taxa increased significantly more in the gut microbiota of children who received MDCF-2 than in those of children who received the RUSF (P <.001).

“We observed larger changes in plasma protein mediators of bone growth, neurodevelopment, and inflammation and more complete repair of the gut microbiota in children who received MDCF-2 than in those who received RUSF,” stated the researchers.

Disclosures: Some of the study authors have a pending patent, regarding microbiota-directed foods to repair an individual’s gut microbiota. Please see the original reference for a full list of authors’ disclosures.


Chen RY, Mostafa I, Hibberd MC, et al. A microbiota-directed food intervention for undernourished children. N Engl J Med. 2021;384(16):1517-1528.