More than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children with moderate acute malnutrition have perturbed development of their gut microbiota.
The study, which was conducted in Mirpur from November 2018 through December 2019, was approved by the ethics review committee at the International Centre for Diarrhoeal Disease Research, Bangladesh. Parents or guardians of all the study participants provided written informed consent.
Boys and girls with moderate acute malnutrition who were between 12 months and 18 months of age and who satisfied the inclusion and exclusion criteria were randomly assigned to receive MDCF-2 or RUSF (Figure 1A). The caloric density of MDCF-2 is lower than that of RUSF (204 kcal vs. 247 kcal per 50-g daily dose). Anthropometric features were measured every 15 days, and data regarding health complications were documented daily. Field research assistants monitored the children for any adverse events and treated them according to standard of care, if needed.
During the first month, the children’s mothers fed them two daily 25-g servings of MDCF-2 or RUSF at a local study center under the supervision of a health care provider; the amount that had not been consumed was determined by weighing. In the second month, one of the two daily feedings occurred at home, and the amount consumed was documented; in the third month, both daily feedings were provided at home. Other than being asked to avoid feeding their children during the 2-hour period before each visit, mothers were advised to continue their usual breast-feeding and complementary feeding practices throughout the study. After completing 3 months of the intervention, the children returned to their normal feeding routine but continued to be monitored; fecal samples and anthropometric data were collected 1 month after the discontinuation of treatment.
Outcome measures were the weekly rate of change in the weight-for-length z score, weight-for-age z score, mid–upper-arm circumference, length-for-age z score, medical complications, plasma proteomic profile, and gut microbiota configuration.
Scientists compared changes in ponderal growth between the two groups using linear mixed-effects models that included fixed effects to control for differences in characteristics between the children at baseline (age, sex, and the occurrence of illness 7 days before starting the intervention), the number of weeks of the intervention, treatment group, the interaction between the number of weeks of the intervention and the treatment group, and a random-effects coefficient for each child to account for the within-participant correlation; other anthropometric measures were assessed in a similar fashion. They used generalized linear mixed-effects models to analyze responses on the food-frequency questionnaire and data regarding medical complications. Because we tested the effects of the supplements on four measures of growth and did not correct for multiple testing, we have provided confidence intervals for each outcome.
Changes in levels of plasma proteins were analyzed with the use of an empirical Bayesian linear model framework12 and gene-set enrichment analysis,13 a method for quantifying whether a rank-ordered list of features (e.g., proteins that are ranked according to the changes in levels after treatment or by a correlation coefficient) are enriched for a subgroup of features of interest (e.g., a biologic pathway). We used linear mixed-effects models and gene-set enrichment analysis to quantify the effects of supplementation on microbial community configuration. For all statistical analyses, a P value of less than 0.05 was considered to indicate statistical significance. For analyses requiring adjustment for multiple hypotheses, significance was indicated by a false discovery rate–adjusted P value (Q value) of less than 0.10 for the comparison in the plasma proteomic data set and of less than 0.05 for the comparison in the fecal microbial data set. All reported P and Q values are two-sided.
A total of 118 children (59 in each study group) completed the intervention. The rates of change in the weight-for-length and weight-for-age z scores are consistent with a benefit of MDCF-2 on growth over the course of the study, including the 1-month follow-up. Receipt of MDCF-2 was linked to the magnitude of change in levels of 70 plasma proteins and of 21 associated bacterial taxa that were positively correlated with the weight-for-length z score (P<0.001 for comparisons of both protein and bacterial taxa). These proteins included mediators of bone growth and neurodevelopment.
These findings provide support for MDCF-2 as a dietary supplement for young children with moderate acute malnutrition and provide insight into mechanisms by which this targeted manipulation of microbiota components may be linked to growth.
Sherry
Phone: 
E-mail: 
Address: