To examine the contributions of impaired gut microbial community development to childhood undernutrition, we combined metabolomic and proteomic analyses of plasma samples with metagenomic analyses of fecal samples to characterize the biological state of Bangladeshi children with severe acute malnutrition (SAM) as they transitioned, after standard treatment, to moderate acute malnutrition (MAM) with persistent microbiota immaturity. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes targeting weaning-phase bacterial taxa underrepresented in SAM and MAM microbiota were characterized in gnotobiotic mice and gnotobiotic piglets colonized with age- and growth-discriminatory bacteria. A randomized, double-blind controlled feeding study identified a lead MDCF that changes the abundances of targeted bacteria and increases plasma biomarkers and mediators of growth, bone formation, neurodevelopment, and immune function in children with MAM.

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 )

Characterizing the organization of the human gut microbiota is a formidable challenge given the number of possible interactions between its components. Using a statistical approach initially applied to financial markets, we measured temporally conserved covariance among bacterial taxa in the microbiota of healthy members of a Bangladeshi birth cohort sampled from 1 to 60 months of age. The results revealed an “ecogroup” of 15 covarying bacterial taxa that provide a concise description of microbiota development in healthy children from this and other low-income countries, and a means for monitoring community repair in undernourished children treated with therapeutic foods. Features of ecogroup population dynamics were recapitulated in gnotobiotic piglets as they transitioned from exclusive milk feeding to a fully weaned state consuming a representative Bangladeshi diet.

Persistent diarrhoea remains an important public health problem in children under-5 in Bangladesh. Algorithm-based dietary management with simple clinical guidelines was effective in most cases. This treatment is appropriate in low-income settings where resources are limited.

Background: Childhood undernutrition remains a significant global health challenge accounting for over half of all under 5 child mortality. Moderate acute malnutrition (MAM), which leads to wasting [weight-for-length z-scores (WLZ) between − 2 and − 3], affects 33 million children under 5 globally and more than 2 million in Bangladesh alone. We have previously reported that acute malnutrition in this population is associated with gut microbiota immaturity, and in a small, 1-month pre-proof-of-concept (POC) study demonstrated that a microbiota-directed complementary food formulation (MDCF-2) was able to repair this immaturity, promote weight gain and increase plasma biomarkers and mediators of healthy growth. Here we describe the design controlled feeding study that tests whether MDCF-2 exhibits superior efficacy (ponderal growth, host biomarkers of a biological state) than a conventional Ready-to-use Supplementary Food (RUSF) in children with MAM over intervention period of 3 months.Methods: Two separate cohorts of 12-18-month-old children will be enrolled: 124 with primary MAM, and 124 with MAM after having been treated for severe acute malnutrition (post-SAM MAM). We have established several field sites in an urban slum located in the Mirpur district of Dhaka, Bangladesh and at a rural site, Kurigram in the north of Bangladesh. The two groups of children receiving MDCF-2 and RUSF will be compared at baseline (preintervention), after 1 month, at the end of intervention (3 months), 1 month after cessation of intervention, and every 6 months thereafter for 4 years.Discussion: This study will determine whether daily, controlled administration of MDCF-2 for 3 months provides superior improvements in weight gain, microbiota repair, and elevated levels of key plasma biomarkers/mediators of healthy growth compared to the control RUSF formulation. The pathogenesis of MAM is poorly defined and there are currently no WHO-approved treatments; results from the current study of children with primary MAM and post-SAM MAM will shed light on the effects of the gut microbiota on childhood growth/development and will provide a knowledge base that may help improve complementary feeding practices.

AimThis study investigated the microbial quality of food and water consumed by children in four slums in Dhaka, the capital of Bangladesh, together with the associated risk factors.MethodsThis cross‐sectional study took place from December 2015 to May 2016 and focused on 360 children under the age of five. We recorded household food security, namely adequate food for a healthy life, socio‐economic and nutritional status, hygiene and feeding practices. Food and water samples were analysed.ResultsWe found that 63% of the children were malnourished and 58% were stunted. Yeast and moulds were detected in 86% of the food samples and coliforms in 73%. All the water samples were contaminated with faecal coliforms, yeasts and moulds and Staphylococcus. Food insecurity affected 83% of households. Children were twice as likely to be malnourished if they were born with a perceived low birthweight or their mothers did not wash their hands with soap after cleaning the child's bottom following defecation. Exclusively breastfed children were less likely to develop malnutrition.ConclusionChildren from the Dhaka slums were frequently stunted and malnourished and contaminated food and water was common. Integrated efforts are essential to create public awareness about hygiene.

Background: Vitamin A deficiency (VAD) is one of the most prevalent micronutrient deficiencies in the world. About 2% of all deaths among children under five years of age (U-5) are attributable to VAD. Currently evidence-based knowledge is grossly lacking about the factors associated with low coverage of VAS. Objective: This study aims to determine the factors affecting low coverage of the vitamin A supplementation program among the young children admitted to a diarrheal hospital. Methods: We extracted data from the Diarrhoeal Diseases Surveillance System (DDSS) on children aged 12-59 months admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, from 1996 to 2014. A logistic regression model was constructed to identify the factors that were significantly associated with non-compliance to vitamin A supplementation (VAS). Strength of association was determined by calculating adjusted odds ratios (aORs) and their 95% confidence intervals. Results: A total of 8649 children were enrolled and comprised the analyzable sample. Their mean ± SD age was 25.2 ± 12.8 months and 40% were female. Around 68% of them had received VAS in the previous 6 months. In the logistic regression analysis, older (>24 months) children (aOR: 1.38; 95% CI: 1.24-1.53), having an illiterate mother (aOR: 1.43; 95% CI: 1.27-1.64), having an illiterate father (aOR: 1.3; 95% CI: 1.16-1.50), coming from the two lowest wealth quintiles (aOR:1.13; 95% CI: 1.02-1.27), with an average monthly household income <10,000 BDT, (1 USD = 60 BDT) and children who had not received the measles vaccine (aOR: 1.87; 95% CI: 1.63-2.19) were more likely not to have received VAS in the preceding six months. We also observed an increase in coverage of VAS from 61% to 76% over the last 18 years (p < 0.001). Conclusions: Non-compliance to VAS was found to be associated with older children, parents without formal schooling, family with greater poverty, low family income, and lack of measles vaccination. Specific programmatic approaches including prioritizing vulnerable children may enhance vitamin A coverage.

ObjectivesMalnutrition remains a major problem among adolescents worldwide, but the types of nutritional problem impacting this group are changing significantly. This study aims to describe and analyse the trends in nutritional status and related epidemiological characteristics of 10 to 19 years old adolescent girls over time (2001 to 2018) in Bangladesh.MethodsWe extracted data from the Diarrhoeal Disease- Surveillance System of the International Centre for Diarrhoeal Disease Research Bangladesh. We performed χ2 test for trend to test for statistical significance of the changing trends of undernutrition and overnutrition among the study participants. Multivariable logistic regression model was fit to measure the strength of association, reported as adjusted OR (aOR) and corresponding 95% CIs.ResultsA total of 1224 and 628 adolescent females attended urban and rural treatment facilities, respectively, between 2001 and 2018. The proportion of stunting and thinness decreased substantially, whereas overweight has been observed to increase (1.7% to 7.4%, p<0.001) over the study period. Factors independently associated with stunting were illiteracy (aOR 2.39, 95% CI (1.68 to 3.39), p<0.001), monthly family income of less than US$100 (aOR 1.54, 95% CI (1.25 to 1.9), p<0.001) and family belonging to poorest wealth quintile (aOR 1.45, 95% CI (1.13 to 1.87), p=0.004). Younger participants (aOR 2.69, 95% CI (2.10 to 3.45), p<0.001), rural participants (aOR 1.71 95% CI (1.23 to 2.38), p<0.001), longer hospital stay (aOR 1.52, 95% CI (1.16 to 1.98), p=0.002) and monthly family income less than US$100 (aOR 1.44, 95% CI (1.09 to 1.89), p=0.009) were significantly associated with thinness. Conversely, overweight/obesity was associated with monthly family income more than US$100, duration of diarrhoea and rural participants.ConclusionUndernutrition in adolescent girls has decreased with time, but the burden of overweight has increased. Higher literacy and better wealth status were found to be associated with the improved nutritional status of the participants.