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 (pre-intervention), 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. Trial registration: The primary MAM and post-SAM MAM trials are registered in Clintrials.gov (NCT04015999 and NCT04015986, registered on July 11, 2019, retrospectively registered).

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.

Globally, severe acute malnutrition (SAM), defined as a weight-for-length z -score more than three SDs below a reference mean (WLZ < −3), affects 14 million children under 5 years of age. Complete anthropometric recovery after standard, short-term interventions is rare, with children often left with moderate acute malnutrition (MAM; WLZ −2 to −3). We conducted a randomized controlled trial (RCT) involving 12- to 18-month-old Bangladeshi children from urban and rural sites, who, after initial hospital-based treatment for SAM, received a 3-month intervention with a microbiome-directed complementary food (MDCF-2) or a calorically more dense, standard ready-to-use supplementary food (RUSF). The rate of WLZ improvement was significantly greater in MDCF-2–treated children ( P = 8.73 × 10 ⁻³ ), similar to our previous RCT of Bangladeshi children with MAM without antecedent SAM ( P = 0.032). A correlated meta-analysis of plasma levels of 4520 proteins in both RCTs revealed 215 positively associated with WLZ (largely representing musculoskeletal and central nervous system development) and 44 negatively associated (primarily related to immune activation). Moreover, the positively associated proteins were significantly enriched by MDCF-2 ( q = 1.1 × 10 ⁻⁶ ). Characterizing the abundances of 754 bacterial metagenome-assembled genomes in serially collected fecal samples disclosed the effects of acute rehabilitation for SAM on the microbiome and how, during treatment for MAM, specific strains of Prevotella copri function at the intersection between MDCF-2 glycan metabolism and anthropometric recovery. These results provide a rationale for further testing the generalizability of MDCF efficacy and for identifying biomarkers to define treatment responses.

Objectives: Malnutrition 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. Methods: We extracted data from the Diarrhoeal Disease- Surveillance System of the International Centre for Diarrhoeal Disease Research Bangladesh. We performed χ ² 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. Results: A 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. Conclusion: Undernutrition 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.

Dietary supplementation with a gut microbiota-directed complementary food (MDCF-2) significantly improved weight gain and repaired gut microbiota, as reported in a recent randomized controlled trial on Bangladeshi children with moderate acute malnutrition (MAM). Environmental enteric dysfunction (EED) is a small bowel disorder, and recent evidence shows that it is linked to growth failure in children. Therefore, we intended to investigate whether supplementation with MDCF-2 has any role in modifying gut health by changing the levels of biomarkers of EED and gut inflammation in children with MAM. We randomly assigned 124 children aged 12–18 months to one of two intervention diets, either MDCF-2 or ready-to-use supplementary food (RUSF). Approximately 50 g of the diet was administered in two feeding sessions daily for 12 weeks. Stool and plasma biomarkers were assessed to evaluate intestinal health. Results showed that the average change in citrulline concentration (µmol/L) significantly increased among children who consumed MDCF-2 compared to those who consumed RUSF (mean difference-in-differences: 123.10; 95% CI: 3.60, 242.61; p = 0.044). The research findings demonstrated that MDCF-2 might have a beneficial effect on improving the gastrointestinal health of malnourished children.

Background: Recent evidence suggests that measures of maternal gut enteropathy are associated with unfavorable fetal outcomes. It is, therefore, crucial to identify and treat the features of intestinal enteropathy among reproductive-age women living in areas where enteropathy is highly prevalent. However, there is a lack of non-invasive diagnostic tests to determine EED, making it difficult to identify the disease in field settings. In this study, we tested the potential of fecal pH as a biomarker of gut enteropathy and investigated its relationship with fecal biomarkers of intestinal enteropathy in reproductive-age women living in resource-limited environments. Methods: Data on socio-demographic information, anthropometry, and biological samples were collected from 78 apparently healthy women aged between 20 and 27 years from November 2018 to December 2019. The association of stool pH with two fecal biomarkers of gut enteropathy (i.e., intestinal alkaline phosphatase [IAP] and fecal lipocalin-2 [LCN-2] was investigated using multiple linear regression models after adjusting for relevant covariates. Results: In the adjusted models, alkaline stool pH (pH > 7.2) was found to be significantly associated with a decrease in the fecal IAP level by 1.05 unit (95% CI: -1.68, -0.42; p < 0.001) in the log scale, and acidic stool pH (pH < 6) was found to be significantly associated with an increase in the fecal LCN-2 level by 0.89 units (95% CI: 0.12, 1.67; p < 0.025) in the log scale. Conclusions: The study findings demonstrated an association of fecal pH with biomarkers of gut enteropathy indicating its applicability as a simple tool for understanding intestinal enteropathy among reproductive-age women living in resource-limited settings.