A microbiome-directed therapeutic food for children recovering from severe acute malnutrition.

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.

Multiplexed immunohistochemical evaluation of small bowel inflammatory and epithelial parameters in environmental enteric dysfunction.

BACKGROUND: Environmental enteric dysfunction (EED) is characterized by reduced absorptive capacity and barrier function of the small intestine, leading to poor ponderal and linear childhood growth. OBJECTIVES: To further define gene expression patterns that are associated with EED to uncover new pathophysiology of this disorder. METHODS: Duodenal biopsies from cohorts of children with EED from Bangladesh, Pakistan and Zambia were analyzed by immunohistochemistry (IHC) to interrogate gene products that distinguished differentiation and various biochemical pathways in immune and epithelial cells, some identified by prior bulk RNA sequence analyses. Immunohistochemical staining was digitally quantified from scanned images and compared to cohorts of North American children with celiac disease (gluten-sensitive enteropathy) or with no known enteric disease and no pathologic abnormality (NPA) detected in their clinical biopsies. RESULTS: After multivariable statistical analysis, we identified statistically significant (P < 0.05, 2-tailed t-test) elevated signals representing cluster of differentiation 45 (80%; 95% confidence interval [CI]: 24%, 127%), lipocalin 2 (659%; 95% CI: 198%, 1838%), and regenerating family 1 beta (221%; 95% CI: 47%, 600%) and lower signals corresponding to granzyme B (-74%; 95% CI: -82%, -62%), and sucrase isomaltase (-58%; 95% CI: -75%, -29%) in EED biopsies compared with NPA biopsies. Computerized algorithms also detected statistically significant elevation in intraepithelial lymphocytes (49%; 95% CI: 9%, 105%) and proliferation of leukocytes (267%; 95% CI: 92%, 601%) in EED biopsies compared with NPA biopsies. CONCLUSIONS: Our results support a model of chronic epithelial stress that decreases epithelial differentiation and absorptive function. The close association of several IHC parameters with manual histologic scoring suggests that automated digital quantification of IHC panels complements traditional histomorphologic assessment in EED.

Histopathology underlying environmental enteric dysfunction in a cohort study of undernourished children in Bangladesh, Pakistan, and Zambia compared with United States children.

BACKGROUND: Environmental enteric dysfunction (EED) is an asymptomatic intestinal disorder associated with growth impairment, delayed neurocognitive development, and impaired oral vaccine responses. OBJECTIVES: We set out to develop and validate a histopathologic scoring system on duodenal biopsies from a cohort study of children with growth failure in Bangladesh, Pakistan, and Zambia ("EED") with reference to biopsies from United States children with no clinically reported histologic pathology (referred to hereafter as "normal") or celiac disease. METHODS: Five gastrointestinal pathologists evaluated 745 hematoxylin and eosin slide images from 291 children with EED (mean age: 1.6 y) and 66 United States children (mean age: 6.8 y). Histomorphologic features (i.e., villus/crypt architecture, goblet cells, epithelial and lamina propria acute/chronic inflammation, Brunner's glands, Paneth cells, epithelial detachment, enterocyte injury, and foveolar metaplasia) were used to score each histopathologic slide. Generalized estimating equations were used to determine differences between EED, normal, and celiac disease, and receiver operating characteristic curves were used to assess predictive value. RESULTS: Biopsies from the duodenal bulb showed higher intramucosal Brunner's gland scores and lower intraepithelial lymphocyte scores than from the second or third parts of the duodenum (D2/3), so only D2/3 were included in the final analysis. Although 7 parameters differed significantly between EED and normal biopsies in regression models, only 5 (blunted villus architecture, increased intraepithelial lymphocytosis, goblet cell depletion, Paneth cell depletion, and reduced intramucosal Brunner's glands) were required to create a total score percentage (TSP-5) that correctly identified EED against normal biopsies (AUC: 0.992; 95% CI: 0.983, 0.998). Geographic comparisons showed more severe goblet cell depletion in Bangladesh and more marked intraepithelial lymphocytosis in Pakistan. CONCLUSIONS: This scoring system involving 5 histologic parameters demonstrates very high discrimination between EED and normal biopsies, indicating that this scoring system can be applied with confidence to studies of intestinal biopsies in EED.

The Environmental Enteric Dysfunction Biopsy Initiative (EEDBI) Consortium: mucosal investigations of environmental enteric dysfunction.

Environmental enteric dysfunction (EED) is an asymptomatic acquired disorder characterized by upper small bowel inflammation, villus blunting, and gut permeability. It is a major contributor to poor growth in childhood as well as other highly consequential outcomes such as delayed neuorcognitive development. After decades of intermittent interest in this entity, we are now seeing a resurgence in the field of EED. However, recent studies have been hampered by a lack of investigation of the target tissue-the upper small bowel. In 2016, the EEDBI (Environmental Enteric Dysfunction Biopsy Initiative) Consortium was established as a common scientific platform across 3 independent EED biopsy cohort studies in Bangladesh, Pakistan, and Zambia. Two centers in the United States recruited comparison groups of children undergoing endoscopy for clinical indications. The EEDBI Consortium goal was to augment the contributions of the individual centers and answer high-level questions amenable to analysis and interpretation across the studies. Here, we describe the Consortium and its cohorts and recruitment procedures across studies. We also offer details applicable to all papers in this supplement, which describe EED mucosal histology, morphometry, immunohistochemistry, and transcriptomics as well as histology relationship to pathogens and biomarkers.

Anthropometry relationship with duodenal histologic features of children with environmental enteric dysfunction: a multicenter cross-sectional study.

BACKGROUND: Environmental enteric dysfunction (EED) is a precursor of growth faltering in children living in impoverished conditions who are frequently exposed to environmental toxins and enteropathogens, leading to small bowel inflammatory, malabsorptive, and permeability derangements and low-grade chronic systemic inflammation. OBJECTIVES: We explored the association between anthropometrics and duodenal histologic features of EED among children from 3 lower middle-income country centers. METHODS: In this cross-sectional study, Pakistani children (n = 63) with wasting, Bangladesh children (n = 116) with stunting or at risk for stunting (height-for-age Z score [HAZ] <-1 but ≥-2), and Zambian children (n = 108) with wasting or stunting received nutritional intervention. Children with anthropometric status refractory to intervention underwent endoscopy. Linear regression models included anthropometric around endoscopy, scores of histology parameters, and a global index score of EED-the total score percent-5 (TSP-5). Multivariable models were adjusted for center, age, sex, and histology slide quality. RESULTS: Intersite variation was observed while exploring the association between anthropometrics and the TSP-5; for example, Pakistani children had the worst HAZ, yet their median TSP-5 score was lower than that of the other 2 centers. Even within each site, no overall pattern of higher TSP-5 score was observed with worsening HAZ. During univariate analysis, TSP-5 (coefficient: 0.01; 95% confidence interval [CI]: 0, 0.02), goblet cell depletion (coefficient: 0.22; 95% CI: 0.06, 0.37), and Paneth cell depletion (coefficient: 0.14; 95% CI: 0.01, 0.27) were associated with HAZ scores; however, they lost statistical significance in the multivariable models, with study center most strongly confounding the relationships seen in univariate models between anthropometry and histology. CONCLUSIONS: This study contributes a crucial negative finding that duodenal morphological features did not associate with anthropometric phenotypes; hence, anthropometric measurements may not be a suitable outcome measure for use in EED trials. Trial outcomes may need to be defined by combining the functional and structural elements of the gut to monitor EED.

Enteric pathogens relationship with small bowel histologic features of environmental enteric dysfunction in a multicountry cohort study.

BACKGROUND: Environmental Enteric Dysfunction (EED) is an acquired disorder of asymptomatic altered gut function, the etiology of which is unknown. EED is postulated to be a major contributor to growth faltering in early childhood in regions where early-life enteropathogenic carriage is prevalent. Few studies have examined the critical organ (the upper small bowel) with enteropathogens in the evolution of small bowel disease. OBJECTIVES: The objective of this study was to determine if fecal enteropathogenic detection predicts subsequent EED histology. METHODS: Fecal samples were obtained from undernourished children aged <2 y without diarrhea enrolled in 3 cohort studies, who failed nutritional intervention and subsequently underwent endoscopy. Duodenal biopsies from 245 (Bangladesh n = 120, Pakistan n = 57, and Zambia n = 68) children were scored using a semiquantitative histologic grading protocol. Thirteen enteropathogens were sought in common across the 3 centers using TaqMan array cards (TAC) (Bangladesh and Pakistan) and the Luminex platform (Zambia). An additional 18 pathogens and 32 virulence loci were sought by TAC and included in sensitivity analyses restricted to TAC data. RESULTS: Multivariable linear regressions adjusting for study center, age at stool collection, and stool-to-biopsy interval demonstrated the following: 1) an association of norovirus and Shigella detection with subsequent enterocyte injury [ß 0.2 (95% CI: 0.1, 0.3); P = 0.002 and ß 0.2 (95% CI: 0.0, 0.3); P = 0.008, respectively], 2) association of Campylobacter with intraepithelial lymphocytes [ß 0.2 (95% CI: 0.0, 0.4); P = 0.046], and 3) association of Campylobacter and enterotoxigenic Escherichia coli with a summative EED histopathology index score [ß 4.2 (95% CI: 0.8, 7.7); P = 0.017 and ß 3.9 (95% CI: 0.5, 7.3); P = 0.027, respectively]. All but 2 of these associations (Shigella-enterocyte injury and Campylobacter-index score) were also demonstrated in TAC-only sensitivity analyses, which identified additional associations between other pathogens, pathogen burden, or virulence loci primarily with the same histologic parameters. CONCLUSIONS: The detection of some enteropathogens in asymptomatic infections is associated with subsequent EED histopathology. These novel findings offer a basis for future EED etiology and pathogenesis studies.

Duodenal transcriptomics demonstrates signatures of tissue inflammation and immune cell infiltration in children with environmental enteric dysfunction across global centers.

BACKGROUND: Environmental enteric dysfunction (EED) is an inflammatory condition of the small intestine that is prevalent in children residing in low- and middle-income countries. EED is accompanied by profound histopathologic changes in the small bowel, loss of absorptive capacity, increased intestinal permeability, increased microbial translocation, and nutrient loss. OBJECTIVES: We sought to identify dysregulated genes and pathways that might underlie pediatric EED. METHODS: RNA-sequencing libraries were generated from endoscopically obtained duodenal tissue from undernourished children with EED from 3 prospective cohorts of children with EED. The EED transcriptome was defined in comparison to North American children without EED. Weighted gene coexpression network analysis (WGCNA) was tested for gene modules associated with EED and its histologic features. RESULTS: The 1784 upregulated genes in EED were highly enriched for immune and inflammatory processes, including IL-17 and JAK-STAT signaling, and cytokine-cytokine receptor interactions. The 1388 downregulated genes included genes corresponding to xenobiotic metabolism, detoxification, and antioxidant capacities. A gene coexpression module enriched for antimicrobial responses and chemokine activity was significantly associated with villous blunting, goblet cell depletion, and overall histologic severity of EED. CONCLUSIONS: The transcriptome signatures of EED include specific innate and adaptive immune responses that are consistently elevated across study centers, coupled with reduced detoxification and antioxidant capacities. These data may have implications for targeted interventions to improve EED outcomes.

Impacts of climate change on diarrhoeal disease hospitalisations: How does the global warming targets of 1.5-2°C affect Dhaka, Bangladesh?

Dhaka is one of the world's densely populated cities and faces significant public health challenges including high burden of diarrhoeal diseases. Climate change is intensifying existing environmental problems including urban heat island effect and poor water quality. While numerous epidemiological studies have linked meteorological factors to diarrhoeal diseases in Bangladesh, assessment of the impacts of future climate change on diarrhoeal diseases is scarce. We provide the assessment of climate change impacts on diarrhoeal disease in Dhaka and project future health risks under climate change scenarios. About 3 million acute diarrhoea cases presenting to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b) during 1981-2010 were linked to daily temperature, rainfall and humidity and association investigated using time series adapted negative binomial regression models employing constrained distributed lag linear models. The findings were applied to climate projections to estimate future risks of diarrhoea under various global warming scenarios. There was a significantly raised risk of diarrhoea hospitalisation in all ages with daily mean temperature (RR: 3.4, 95% CI: 3.0-3.7) after controlling for the confounding effects of heavy rainfall, humidity, autocorrelations, day of the week effect, long-term time, and seasonal trends. Using the incidence rate ratio (IRR) of 1.034, temperature increases based on the global warming targets of 1.5-2°C could result in an increase of diarrhoea hospitalisations by 4.5-7.4% in all age groups by the 2100s. These effects were more pronounced among <5 children where the predicted temperature increases could raise diarrhoea hospitalisation by 5.7% - 9.4%. Diarrhoea hospitalisation will increase significantly in Dhaka even if the global warming targets adopted by the Paris Agreement is reached. This underscores the importance of preparing the city for management and prevention of diarrhoeal diseases.

Establishing human microbial observatory programs in low- and middle-income countries.

Studies of the human microbiome are progressing rapidly but have largely focused on populations living in high-income countries. With increasing evidence that the microbiome contributes to the pathogenesis of diseases that affect infants, children, and adults in low- and middle-income countries (LMICs), and with profound and rapid ongoing changes occurring in our lifestyles and biosphere, understanding the origins of and developing microbiome-directed therapeutics for treating a number of global health challenges requires the development of programs for studying human microbial ecology in LMICs. Here, we discuss how the establishment of long-term human microbial observatory programs in selected LMICs could provide one timely approach.

Is heat wave a predictor of diarrhoea in Dhaka, Bangladesh? A time-series analysis in a South Asian tropical monsoon climate.

While numerous studies have assessed the association between temperature and diarrhoea in various locations, evidence of relationship between heat wave and diarrhoea is scarce. We defined elevated daily mean and maximum temperature over the 95th and 99th percentiles lasting for at least one day between March to October 1981-2010 as TAV95 and TAV99 and D95 and D99 heat wave, respectively. We investigated the association between heat wave and daily counts of hospitalisations for all-cause diarrhoea in Dhaka, Bangladesh using time series regression analysis employing constrained distributed lag-linear models. Effects were assessed for all ages and children aged under 5 years of age. Diarrhoea hospitalisation increased by 6.7% (95% CI: 4.6%- 8.9%), 8.3% (3.7-13.1), 7.0 (4.8-9.3) and 7.4 (3.1-11.9) in all ages on a TAV95, TAV99, D95 and D99 heat wave day, respectively. These effects were more pronounced for under-5 children with an increase of 13.9% (95% CI: 8.3-19.9), 24.2% (11.3-38.7), 17.0 (11.0-23.5) and 19.5 (7.7-32.6) in diarrhoea hospitalisations on a TAV95, TAV99, D95 and D99 heat wave day, respectively. At lags of 3 days, we noticed a negative association indicating a 'harvesting' effect. Our findings suggest that heat wave was a significant risk factor for diarrhoea hospitalisation in Dhaka. Further research is needed to elucidate the causal pathways and identify the preventive measures necessary to mitigate the impacts of heat waves on diarrhoea. Given that no heat wave definitions exist for Dhaka, these results may help to define heat waves for Dhaka and trigger public health interventions including heat alerts to prevent heat-related morbidity in Dhaka, Bangladesh.

Risk or associated factors of wasting among under-five children in Bangladesh: A systematic review.

BACKGROUND AND OBJECTIVES: Wasting among under-five years old (U-5) children is a significant global public-health-nutrition burden. To effectively address this problem in Bangladesh, knowing its prevalence, caus-es and associated-factors are essential. This review aimed to identify evidences available in the existing-accessible literature/documents that describe the individual, socioeconomic, demographic, and contextual risk-factors associated with wasting among U-5 children in Bangladesh. METHODS AND STUDY DESIGN: Electronic-databases included were MEDLINE, EMBASE, CINAHL, WoS, and Cochrane-Library written in English and published until 29 February 2024. RESULTS: The search from the five databases yielded 167 publications. Of these, 50 papers/articles were duplicates and 108 were irrelevant, and nine have met the inclusion criteria. Additionally, 22 articles/documents were identified from other sources. Finally, a total of 31 articles/documents have been included in this review. The odds of childhood wasting observed were high for smaller birth-size, higher birth-order, male child, 12-24 months age-group, improper breastfeeding- and complementary-feeding practices, not-receiving DPT1 and/or measles vaccine, ≥1 sibling(s), maternal-undernutrition, less food-consumption during pregnancy, lack of maternal-education, lack of hand-washing practices by the mother/caregiver, paternal tobacco use, lower socioeconomic-status, food-insecurity, lack of access to hygienic-latrine and/or improved-water, Monsoon season (May-August), flood exposure, living es-pecially in Barishal, Rajshahi Chittagong and Rangpur-division and/or Eastern part of Bangladesh, and urban-slum. CONCLUSIONS: The risk/associated factors of wasting among U-5 children in Bangladesh were found at various multilevel. Rarely caused by any one factor alone, wasting in U-5 children results from an interplay between pregnant-mother's health and nutrition, child-caring practices, diets, poverty, and disease, which vary by context.

The Impact of Non-Dysentery Shigella Infection on the Growth and Health of Children over Time (INSIGHT)-A Prospective Case-Control Study Protocol.

(1) Shigella spp. (Shigella) is known for causing dysentery with blood in stool, but most children infected with Shigella have non-dysentery Shigella-associated diarrhea (NDSD). The World Health Organization recommends the use of antibiotics when diarrhea is bloody, leaving most NDSD cases untreated. The absence of dysentery may not indicate a low risk of death and severe morbidity. Rapid diagnosis and treatment of shigellosis in vulnerable, young children may be lifesaving. INSIGHT aims to determine the potential benefit of identifying NDSD cases (n = 296) and their outcomes compared to cases of Shigella dysentery [DS (n = 148)] and non-Shigella watery diarrhea [WD (n = 148)]. (2) Children seeking care at hospitals in Bangladesh will be enrolled and followed for 1 year (NDSD and DS) or 90 days (WD). We will determine the impact of NDSD on morbidity, mortality, gut health, nutritional status, and cognitive development compared to DS and WD in children and whether the simple "Rapid LAMP-based Diagnostic Test (RLDT)" can accelerate the detection and treatment of shigellosis in the clinical settings of rural Bangladesh. (3) INSIGHT will determine the impact of NDSD in children and determine if the treatment guidelines of shigellosis need to be revisited to improve clinical outcomes and the development of these children.

Effects of maternal exposure to biomass cooking fuel on birth size and body proportionality in full-term infants born by vaginal delivery.

It remains unclear whether and how maternal exposure to biomass fuel influences infant anthropometry or body proportionality at birth, which are linked to their survival, physical growth, and neurodevelopment. Therefore, this study seeks to explore the association between household-level exposure to biomass cooking fuels and infant size and body proportionality at birth among women in rural Bangladesh. A total of 909 women were derived from the Pregnancy Weight Gain study, which was conducted in Matlab, a rural area of Bangladesh. Infant's weight (g), length (cm), head circumference (cm), small for gestational age (SGAW), short for gestational age (SGAL), low head circumference for gestational age (SGAHC), ponderal index, and cephalization index at birth were the outcomes studied. Of the women, 721 (79.3%) were dependent on biomass fuel. Compared to infants born to mothers who used gas for cooking, those born to biomass users had lower weight (ß - 94.3, CI - 155.9, - 32.6), length (ß - 0.36, 95% CI - 0.68, - 0.04), head circumference (ß - 0.24, CI - 0.47, - 0.02) and higher cephalization index (ß 0.03, CI 0.01, 0.05) at birth. Maternal biomass exposure is more likely to lead to symmetric SGA, although there is evidence for some brain-sparing effects.

Development of machine learning models predicting mortality using routinely collected observational health data from 0-59 months old children admitted to an intensive care unit in Bangladesh: critical role of biochemistry and haematology data.

INTRODUCTION: Treatment in the intensive care unit (ICU) generates complex data where machine learning (ML) modelling could be beneficial. Using routine hospital data, we evaluated the ability of multiple ML models to predict inpatient mortality in a paediatric population in a low/middle-income country. METHOD: We retrospectively analysed hospital record data from 0-59 months old children admitted to the ICU of Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh. Five commonly used ML models- logistic regression, least absolute shrinkage and selection operator, elastic net, gradient boosting trees (GBT) and random forest (RF), were evaluated using the area under the receiver operating characteristic curve (AUROC). Top predictors were selected using RF mean decrease Gini scores as the feature importance values. RESULTS: Data from 5669 children was used and was reduced to 3505 patients (10% death, 90% survived) following missing data removal. The mean patient age was 10.8 months (SD=10.5). The top performing models based on the validation performance measured by mean 10-fold cross-validation AUROC on the training data set were RF and GBT. Hyperparameters were selected using cross-validation and then tested in an unseen test set. The models developed used demographic, anthropometric, clinical, biochemistry and haematological data for mortality prediction. We found RF consistently outperformed GBT and predicted the mortality with AUROC of ≥0.87 in the test set when three or more laboratory measurements were included. However, after the inclusion of a fourth laboratory measurement, very minor predictive gains (AUROC 0.87 vs 0.88) resulted. The best predictors were the biochemistry and haematological measurements, with the top predictors being total CO2, potassium, creatinine and total calcium. CONCLUSIONS: Mortality in children admitted to ICU can be predicted with high accuracy using RF ML models in a real-life data set using multiple laboratory measurements with the most important features primarily coming from patient biochemistry and haematology.

Correction: Role of L-Carnitine supplementation on rate of weight gain and biomarkers of Environmental Enteric Dysfunction in children with severe acute malnutrition: A protocol for a double-blinded randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pone.0275291.].

A microbiome-directed therapeutic food for children recovering from severe acute malnutrition.

Severe acute malnutrition (SAM), defined anthropometrically as a weight-for-length z-score more than 3 standard deviations below the mean (WLZ<-3), affects 19 million children under 5-years-old worldwide. Complete anthropometric recovery after standard inventions is rare with children often left with moderate acute malnutrition (MAM; WLZ -2 to -3). Here we conduct a randomized controlled trial (RCT), involving 12-18-month-old Bangladeshi children from urban and rural sites, who after hospital-based treatment for SAM received a 3-month intervention with a microbiota-directed complementary food (MDCF-2) or a ready-to-use supplementary food (RUSF) as they transitioned to MAM. The rate of WLZ improvement was significantly greater with MDCF-2 than the more calorically-dense RUSF, as we observed in a previous RCT of Bangladeshi children with MAM without antecedent SAM. A correlated meta-analysis of aptamer-based measurements of 4,520 plasma proteins in this and the prior RCT revealed 215 proteins positively-associated with WLZ (prominently those involved in musculoskeletal and CNS development) and 44 negatively-associated proteins (related to immune activation), with a significant enrichment in levels of the positively WLZ-associated proteins in the MDCF-2 arm. Characterizing changes in 754 bacterial metagenome-assembled genomes in serially collected fecal samples disclosed the effects of acute rehabilitation for SAM on the microbiome, its transition as each child achieves a state of MAM, and how specific strains of Prevotella copri function at the intersection between MDCF-2 glycan metabolism and the rescue of growth faltering. These results provide a rationale for further testing the generalizability of the efficacy of MDCF and identify biomarkers for defining treatment responses.

Development and Acceptability of Shelf-Stable Microbiota Directed Complementary Food Formulations.

BACKGROUND: A randomized controlled trial in Bangladeshi children aged 12 to 18 months with moderate acute malnutrition found that dietary supplementation with the microbiota-directed complementary food (MDCF-2) significantly improved weight gain and repaired gut microbiota compared to the ready-to-use supplementary food. However, the MDCF-2 formulation was made daily from locally available ingredients and the need for a packaged, nutritionally compliant, and organoleptically acceptable MDCF-2 prototype was essential for future large-scale clinical studies. OBJECTIVE: The study aimed to develop and assess the acceptability of 3 alternative foil-packaged formulations of MDCF-2 in comparison to current MDCF-2. METHODS: Of the 3 packaged formulations, the Jumpstart version was provided in 2 sachets, the other 2 formulations were provided in a retort-stable foil pouch extended by sterilization, and microbiological growth was monitored over 10 months. The acceptability study included 40 children aged 8 to 12 months living in an urban slum in Dhaka, and the organoleptic properties were assessed using a 7-point hedonic scale. RESULTS: In the 100 g distributed over the 2 sessions, children consumed 82.5 ± 7.84 g (mean ± SD) of kitchen-prepared MDCF-2, 85.4 ± 7.15 g of the "Jumpstart" MDCF-2 formulation, 85.4 ± 8.70 g of the MDCF-2 with green banana powder, and 86.2 ± 4.26 g of the MDCF-2 with sweet potato formulation. The "Jumpstart" MDCF-2 and MDCF-2 with sweet potato achieved the highest overall acceptability scores on the hedonic scale; although none of the shelf-stable formulations were significantly different from the kitchen-prepared MDCF-2. CONCLUSIONS: Packaged, shelf-stable prototypes of MDCF-2 exhibited comparable acceptability among Bangladeshi children aged 8 to 12 months to the original freshly prepared formulation.

Plain language titleDevelopment and Acceptability of Shelf-Stable Microbiota-Directed Complementary FoodsPlain language summaryCountries around the world are making progress in fighting malnutrition, but it may be challenging to achieve the global nutrition targets for undernourished children by 2025 at the current rate. To address this problem, we need special types of food that can help children grow, develop properly, and sustain their growth. Children with moderate acute malnutrition have imbalanced gut bacteria. By providing them with the right nutrition, we can restore the healthy bacteria in their gut using a special food called microbiota-directed complementary food (MDCF). Currently, this food is made daily in the icddr, b established field kitchen, which follows standard production measures to control the quality of MDCF preparation, but we need to create stable prototypes that can be stored and used in different settings. This study was designed to develop shelf-stable new formulations in industrial settings and check their acceptability among children with moderate acute malnutrition. The shelf life of the food was extended using a sterilization method, and its microbiological safety was monitored for a year. The actual consumption and acceptability of these foods were evaluated and all these formulations were acceptable by the children and their mother. The children consumed all 4 food formulations in substantial quantities, with consumption rates exceeding 80% for each formulation. This study showed positive results in Bangladesh, but more research is needed to see if these formulations work well in other geographies and over longer periods.

Enteric viral pathogens and child growth among under-five children: findings from South Asia and sub-Saharan Africa.

Enteric viral pathogens are associated with a significant burden of childhood morbidity and mortality. We investigated the relationship between viral pathogens and child growth among under-5 children. We analyzed data from 5572/22,567 children enrolled in the Global Enteric Multicenter Study across seven study sites (2007-2011). Multiple linear regression was used to examine the association between the viral pathogens and changes of length/height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length/height (WHZ) z-scores, stratified by diarrheal symptoms and adjusted for potential covariates. Rotavirus (18.51%) and norovirus (7.33%) were the most prevalent enteric viral pathogens among symptomatic and asymptomatic under-5 children, respectively. Infection with individual enteric viral pathogens hurts child growth in asymptomatic children. However, the relationship with HAZ was less clear and statistically non-significant. On the other hand, the combined viral pathogens demonstrated a strong negative influence on child growth [WAZ: ß coef.: - 0.10 (95%, CI - 0.15, - 0.05); P < 0.001 and WHZ: ß: - 0.12 (95% CI - 0.17, - 0.07); P < 0.001] among asymptomatic children. Infection with any viral pathogen was associated with growth shortfalls [HAZ: ß: - 0.05 (95% CI - 0.09, 0.00); P = 0.03 and WAZ: ß: - 0.11 (95% CI - 0.16, - 0.07); P < 0.001 and WHZ: ß: - 0.13 (95% CI - 0.18, - 0.09); P < 0.001], though the relationship with HAZ was less evident and became statistically non-significant in older children. Notably, among symptomatic children with moderate-to-severe diarrhea, individual enteric viral pathogens, as well as the combined effects of these pathogens [WHZ: ß: 0.07; (95% CI 0.01, 0.14); P = 0.03] and the presence of any virus [HAZ: ß: 0.09 (95% CI 0.05, 0.13) & WAZ: ß: 0.08 (95% CI 0.03, 0.12); P < 0.001], exhibited positive effects on child growth. While previous studies hypothesized that several viral pathogens had a conflicting controversial role in child growth, we find clear indications that enteric viral pathogens are associated with growth shortfalls, specifically among asymptomatic children. These findings highlight the need for preventive strategies targeting children with enteric viral pathogens, which could address the consequences of growth faltering.

Comprehensive study on the selection and performance of the best electrode pair for electrocoagulation of textile wastewater using multi-criteria decision-making methods (TOPSIS, VIKOR and PROMETHEE II).

The accelerating environmental impact of the textile industry, especially in water management, requires efficient wastewater treatment strategies. This study examines the effectiveness of various electrode pairs in the Electrocoagulation (EC) process for treating textile wastewater, focusing on removing of Total Suspended Solids (TSS), turbidity, Chemical Oxygen Demand (COD), and Total Organic Carbon (TOC). A comprehensive analysis was conducted using thirty-six electrode pair combinations, consisting of six materials: Aluminium (Al), Zinc (Zn), Carbon (C), Copper (Cu), Mild Steel (MS), and Stainless Steel (SS). The results demonstrated that different electrode pairs yielded varying removal efficiencies for various pollutants, with the highest efficiencies being 92.09% for COD (Al-C pair), 99.66% for TSS (Al-Cu pair), 99.17% for turbidity (Al-MS pair), and 70.99% for TOC (SS-SS pair). However, no single electrode pair excelled in removing all pollutant categories. To address this, three Multi-Criteria Decision Making (MCDM) methods such as TOPSIS, VIKOR, and PROMETHEE II were used to assess the most effective electrode pair. The results indicated that the Al-Zn combination was the most efficient, exhibiting high removal efficiencies for various pollutants (99.32% for TSS, 98.88% for turbidity, 68.62% for COD, and 57.96% for TOC). This study demonstrates that the EC process can effectively treat textile effluent and emphasizes the importance of selecting suitable electrode materials. Furthermore, pollutant removal was optimal with the Al-Zn electrode pair, offering a balanced and efficient approach to textile wastewater treatment. Thus, MCDM methods offer a robust framework for assessing and optimizing electrode selection, providing valuable insights for sustainable environmental management practices.

A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth.

BACKGROUND: Globally, stunting affects ∼150 million children under five, while wasting affects nearly 50 million. Current interventions have had limited effectiveness in ameliorating long-term sequelae of undernutrition including stunting, cognitive deficits and immune dysfunction. Disrupted development of the gut microbiota has been linked to the pathogenesis of undernutrition, providing potentially new treatment approaches. METHODS: 124 Bangladeshi children with moderate acute malnutrition (MAM) enrolled (at 12-18 months) in a previously reported 3-month RCT of a microbiota-directed complementary food (MDCF-2) were followed for two years. Weight and length were monitored by anthropometry, the abundances of bacterial strains were assessed by quantifying metagenome-assembled genomes (MAGs) in serially collected fecal samples and levels of growth-associated proteins were measured in plasma. FINDINGS: Children who had received MDCF-2 were significantly less stunted during follow-up than those who received a standard ready-to-use supplementary food (RUSF) [linear mixed-effects model, ßtreatment group x study week (95% CI) = 0.002 (0.001, 0.003); P = 0.004]. They also had elevated fecal abundances of Agathobacter faecis, Blautia massiliensis, Lachnospira and Dialister, plus increased levels of a group of 37 plasma proteins (linear model; FDR-adjusted P < 0.1), including IGF-1, neurotrophin receptor NTRK2 and multiple proteins linked to musculoskeletal and CNS development, that persisted for 6-months post-intervention. INTERPRETATION: MDCF-2 treatment of Bangladeshi children with MAM, which produced significant improvements in wasting during intervention, also reduced stunting during follow-up. These results suggest that the effectiveness of supplementary foods for undernutrition may be improved by including ingredients that sponsor healthy microbiota-host co-development. FUNDING: This work was supported by the BMGF (Grants OPP1134649/INV-000247).