Effect of Gut Microbiota-Directed Complementary Food Supplementation on Fecal and Plasma Biomarkers of Gut Health and Environmental Enteric Dysfunction in Slum-Dwelling Children with Moderate Acute Malnutrition.

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.

Effects of Different Doses, Forms, and Frequencies of Zinc Supplementation on Biomarkers of Iron and Zinc Status among Young Children in Dhaka, Bangladesh.

Young children in resource-constrained settings are susceptible to zinc deficiency and its deleterious health effects. The objective of this secondary analysis was to evaluate the effects of the following six interventions on biomarkers of iron and zinc status among a subgroup of young children in Dhaka, Bangladesh, who participated in the Zinc in Powders Trial (ZiPT): (1) standard micronutrient powders (MNPs) containing 4.1 mg zinc and 10 mg iron, daily; (2) high-zinc (10 mg) and low-iron (6 mg) (HiZn LoFe) MNP, daily; (3) HiZn (10 mg) and LoFe (6 mg)/HiZn (10 mg) and no-iron MNPs on alternating days; (4) dispersible zinc tablet (10 mg), daily; (5) dispersible zinc tablet (10 mg), daily for 2 weeks at enrollment and at 12 weeks; (6) placebo powder, daily. At the end of the 24 week intervention period, children in the daily dispersible zinc tablet group exhibited a mean serum zinc concentration (SZC) of 92.5 µg/dL, which was significantly higher than all other groups except the HiZn LoFe MNP alternating group (81.3 µg/dL). MNPs containing 10 mg and 6 mg of iron had a similar impact on biomarkers of iron status, with no evidence of an adverse interaction with zinc.

Zinc Kinetics Correlate With Length-for-Age z Scores in Bangladeshi Infants.

OBJECTIVES: Stunting [length-for-age z score (LAZ) <-2] has multiple causes and is prevalent in areas with low dietary zinc (Zn) intake. Zinc kinetics from non-stunted infants were used in a published model for predicting linear growth; here, we directly measure zinc kinetics in stunted infants. METHODS: Zinc kinetics were determined in 9-month-old Bangladeshi infants (n = 10), who were non-wasted [weight-for-length z score (WLZ) > -2], ranging in LAZ from -2.9 to -0.43. Stable isotopes were administered 2 hours after a meal as oral ( 70 Zn) and intravenous ( 67 Zn) tracers. After isotope administration, blood was sampled within 5 hours and all urine and feces were collected for 24 hours. Urine was sampled twice-daily out to 9 days. Data were analyzed by compartmental modeling. Daily zinc intake was estimated by the model as the sum of zinc used for growth plus that lost via urine and feces. Zinc absorbed (the amount required to maintain steady state) was the sum of zinc used for growth plus urine and endogenous fecal excretions. RESULTS: The LAZ score correlated with serum zinc concentration ( R = 0.77, P = 0.001), urinary zinc excretion ( R = 0.66, P = 0.010), and fractional zinc absorption from calculated daily intake ( R = 0.58, P = 0.030). In stunted infants (n = 8), the amount of zinc absorbed did not increase with calculated zinc intake unlike published values for non-stunted infants. CONCLUSIONS: Zinc kinetics in Bangladeshi infants correlate with LAZ and show that malabsorption of supplemental sources of zinc may occur in stunted infants.

Exchangeable Zinc Pool Size Reflects Form of Zinc Supplementation in Young Children and Is Not Associated with Markers of Inflammation.

A sensitive and reliable biomarker of zinc status has yet to be identified, but observational research suggests that the exchangeable zinc pool (EZP) size may be a possible biomarker. This randomized, placebo-controlled trial aimed to compare the change in EZP size from baseline to endline in 174 children who were preventatively supplemented with 10 mg of zinc as part of a multiple micronutrient power (MNP) or as a standalone dispersible tablet for 24 weeks versus a placebo powder. The effects of systemic inflammation on EZP size were also evaluated. Zinc stable isotopes were administered intravenously to children at baseline and endline, and the EZP was measured by the urine extrapolation method. A total of 156 children completed the study with the zinc dispersible tablet group having the greatest increase in EZP (14.1 mg) over 24 weeks when compared with the MNP group (6.8 mg) (p < 0.01) or placebo group (2.0 mg) (p < 0.001). Median EZP size was not different between children with normal or elevated serum inflammatory markers. EZP size was responsive to longitudinal zinc supplementation and reflected the expected difference in bioavailability for two forms of supplementation. The apparent absence of an effect of inflammation on EZP size may offer an advantage for use as a biomarker for group comparisons between different interventions.

Different Doses, Forms, and Frequencies of Zinc Supplementation for the Prevention of Diarrhea and Promotion of Linear Growth among Young Bangladeshi Children: A Six-Arm, Randomized, Community-Based Efficacy Trial.

BACKGROUND: Children in resource-limited settings remain vulnerable to zinc deficiency and its consequences. OBJECTIVES: To evaluate the effects of different doses, durations, and frequencies of zinc supplementation on the incidence of diarrhea and change in linear growth among young children. METHODS: We conducted a randomized, partially double-blind, controlled, 6-arm, community-based efficacy trial in Dhaka, Bangladesh. Children aged 9-11 mo were randomly assigned to receive 1 of the following interventions for 24 wk: 1) standard micronutrient powder (MNP) containing 4.1 mg zinc and 10 mg iron, daily; 2) high-zinc (10 mg), low-iron (6 mg) (HiZn LoFe) MNP, daily; 3) HiZn (10 mg) LoFe (6 mg)/HiZn (10 mg), no-iron MNPs on alternating days; 4) dispersible zinc tablet (10 mg), daily; 5) dispersible zinc tablet (10 mg), daily for 2 wk at enrollment and 12 wk; 6) placebo powder, daily. Primary outcomes were incidence of diarrhea and change in length-for-age z-score (LAZ) over the 24-wk intervention period. Home visits were conducted twice weekly to assess diarrhea and other morbidity. Incidence and prevalence outcomes were compared among groups with Poisson regression; continuous outcomes were compared using ANCOVA. RESULTS: A total of 2886 children were enrolled between February 2018 and July 2019. The mean incidence and prevalence of diarrhea among all participants was 1.21 episodes per 100 d and 3.76 d per 100 d, respectively. There were no differences in the incidence or prevalence of diarrhea across intervention groups. The decline in LAZ was slightly smaller among children in the daily HiZn LoFe MNP group compared with the placebo powder group (P < 0.05). CONCLUSIONS: The dose of zinc in MNPs as well as the duration and frequency of supplementation evaluated in this trial were not effective in reducing diarrhea; however, the daily HiZn LoFe MNP formulation offered modest improvements in linear growth among young children. This trial was registered at clinicaltrials.gov as NCT03406793.

Zinc Supplementation with or without Additional Micronutrients Does Not Affect Peripheral Blood Gene Expression or Serum Cytokine Level in Bangladeshi Children.

Preventive zinc supplementation provided as a stand-alone dispersible tablet, or via home fortification as multiple micronutrient powders (MNPs), has been considered a potential strategy to prevent zinc deficiency and improve health (including immune) outcomes among children in low- and middle-income countries. However, the impact of zinc supplementation on immune profiles has not been well characterized. We sought to define the effect of zinc supplementation on peripheral blood gene expression and cytokine levels among young children in Dhaka, Bangladesh. In a sub-study of a large randomized, controlled, community-based efficacy trial where children 9-11 months of age received one of the following interventions on a daily basis for 24 weeks: (1) MNPs containing 10 mg of zinc; (2) dispersible tablet containing 10 mg zinc; or (3) placebo powder, we used RNA sequencing to profile the peripheral blood gene expression, as well as highly sensitive multiplex assays to detect cytokine profiles. We profiled samples from 100 children enrolled in the parent trial (zinc MNPs 28, zinc tablets 39, placebo 33). We did not detect an effect from either zinc intervention on differential peripheral blood gene expression at the end of the intervention, or an effect from the intervention on changes in gene expression from baseline. We also did not detect an effect from either intervention on cytokine concentrations. Exploratory analysis did not identify an association between undernutrition (defined as stunting, underweight or wasting) and peripheral blood gene expression. Zinc interventions in children did not produce a gene expression or cytokine signature in the peripheral blood. However, this study demonstrates a proof of principle that sensitive multi-omic techniques can be applied to samples collected in field studies.

Designing of Epitope-Focused Vaccine by Targeting E6 and E7 Conserved Protein Sequences: An Immuno-Informatics Approach in Human Papillomavirus 58 Isolates.

Human papillomavirus (HPV) is a DNA virus that belongs to the papillomavirus family and is capable of infecting humans. Currently, few vaccines are available to prevent infection by HPV. However, they are not so much effective and provide little benefit to women who have already been infected with HPV. The aim of this study was to design epitope-based vaccines of HPV58 by targeting E6 and E7 proteins of HPV58. Proteomic sequences were retrieved from different isolates at different time periods and later analyzed by performing alignment of these sequences. To ensure the capacity of humoral and cell-mediated immunity, both B cell and T cell immunity were checked for the peptides. For E6 protein, the peptide sequence from 48 to 54 amino acids and one 9-m epitope ETSVHEIEL were the most potential B cell and T cell epitopes, respectively. This peptide could interact with as many as eight MHC-1 alleles and showed high population coverage up to 90.31 %. On the other hand, the peptide region for the E7 protein ranged from 27 to 33 amino acids and two 9-m epitopes QAQPATANY, SSDEDEIGL were found as the most potential B cell and T cell epitopes, respectively. The peptide sequences could interact with as many as seven MHC-1 alleles and showed population coverage up to 90.31 %. Furthermore, conservancy analysis was also performed using in silico tools and showed a conservancy of 100 % for all the selected epitopes. In addition to this, the allergenicity of the epitopes was also evaluated. Although the study requires further in vitro and in vivo screening, this epitope-focused peptide vaccine designing opens up a new skyline that holds a prospective future in HPV research.