A Microbiota-Directed Food Intervention for Undernourished Children

Abstract

BACKGROUND More than 30 million children worldwide suffer from moderate acute malnutrition (MAM). Current treatments have limited effectiveness and much remains unknown about pathogenesis. Children with MAM exhibit perturbed development of their gut microbiota. METHODS Slum-dwelling Bangladeshi children, aged 12 to 18 months, with moderate acute malnutrition (n=124) received a microbiota-directed complementary food (MDCF-2) or an existing ready-to-use supplementary food (RUSF), twice daily for three months followed by a 1-month period of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age Z-scores and mid-upper arm circumference at baseline and fortnightly, through four months. We compared the rate of change of these related phenotypes between baseline and three months, and between baseline and four months. We also measured levels of 4,977 proteins in plasma plus 209 bacterial taxa in fecal samples. RESULTS 118 children completed the intervention (n=59/arm). The rate of change in weight-for-length Z-score (β-WLZ), weight-for-age Z-score, and mid upper arm circumference is consistent with a benefit of MDCF-2 on growth over the course of the study including the one-month follow-up. Receipt of MDCF-2 was linked to the magnitude of change in levels of 70 β-WLZ-positively correlated plasma proteins including mediators of bone growth, neurodevelopment and inflammation (gene set enrichment analysis [GSEA];p<0.001) and the abundances of 23 WLZ-associated bacterial taxa (GSEA;p<0.001). CONCLUSIONS These findings provide support for further clinical investigation of MDCF-2 as a dietary supplement for young children with MAM and provide insight into mechanisms by which this targeted manipulation of microbiota components may be linked to growth. (Supported by the Bill and Melinda Gates Foundation and the NIH; ClinicalTrials.gov identifier: NCT04015999 )

Lactobacillus reuteri Colonisation of Extremely Preterm Infants in a Randomised Placebo-Controlled Trial

“…The gut microbiota can influence the peripheral and central nervous system and host metabolism via production of neurotransmitters and short chain fatty acids [ 31 , 32 ]. A study in undernourished Bangladeshi infants at 12 to 18 months of age described changes in concentrations of blood plasma proteins linked to neurodevelopment due to manipulation of the gut microbiota [ 33 ]. Although the head growth of the infants in our trial was still inferior to the growth in utero, an increased head circumference growth rate might be associated with improved neurodevelopment of extremely preterm infants [ 34 ].…”

Gut Microbiota Shifts Favorably with Delivery of Handwashing with Soap and Water Treatment Intervention in a Prospective Cohort (CHoBI7 Trial)

“…Firmicutes to Bacteroidetes ratio (F/B ratio) has been shown to be correlated with obesity and other diseases in human and amimal studies 48 .The observed increase of Firmicutes over Bacteroidetes at day 8 was positive in the present study is consistent with our previous study which showed a higher proportion of Firmicutes (43 ± 4; mean ± SEM %) over Bacteroidetes (33 ± 3) with healthy children in Bangladesh 42 . A recent microbiota study carried out in Bangladesh showed tremendous success in improving child health by attracting bene cial gut microbiota via microbiota directed complementary foods (MDCF) 49 . Although the MDCF alone has succeeded in increasing weight for length Z score with positive changes in the level of some plasma proteins in study children, we would propose to combine MDCF study with the CHoBI7 WASH program to improve the gut microbiota composition of young children.…”

Significance of the Gut Microbiome for Viral Diarrheal and Extra-Intestinal Diseases

“…A microbiota-directed complementary food prototype was developed for 12–18 m old malnourished children and been found to be beneficial for weight and height gain, increase in plasma protein levels, and population by Faecalibacterium and Bifidobacterium spp. [ 69 ].…”