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1. Zinc Absorption and Endogenous Fecal Zinc Losses in Bangladeshi Toddlers at Risk for Environmental Enteric Dysfunction

   https://doi.org/10.1097/MPG.0000000000002361  

   Mondal, Prasenjit ; Long, Julie M. ; Westcott, Jamie E. ; Islam, M. Munirul ; Ahmed, Mondar ; Mahfuz, Mustafa ; Ahmed, Tahmeed ; Miller, Leland V. ; Krebs, Nancy F. ( June 2019 , Journal of Pediatric Gastroenterology and Nutrition)

   Environmental enteric dysfunction (EED) impairs zinc absorption from food, and zinc deficiency may contribute to the poor growth associated with EED. We examined zinc absorption from a standardized aqueous zinc dose, and habitual daily endogenous fecal zinc excretion (EFZ) and compared these outcomes between children grouped by the lactulose to mannitol ratio (L:M).

   Bangladeshi toddlers (18–24 months) with low (<0.09) and high (≥0.09) L:M were administered isotope‐labeled 3 mg aqueous zinc in the fasted state. Fractional absorption of zinc (FAZ) and EFZ were measured by dual stable isotope tracer method and an isotope dilution method, respectively. Secondary aims included examining relationships of biomarkers of systemic and intestinal inflammation and gut function with FAZ and EFZ.

   Forty children completed the study; nearly all had evidence of EED. No differences in zinc homeostasis measurements (mean ± SD) were observed between high and low L:M groups: FAZ was 0.38 ± 0.19 and 0.31 ± 0.19, respectively; both figures were within estimated reference range. Means of EFZ were 0.73 ± 0.27 and 0.76 ± 0.20 mg/day for high and low L:M, respectively, and were 10% to 15% above estimated reference range. Regression analyses indicated that biomarkers of systemic inflammation were directly associated with increasing FAZ, consistent with increased gut permeability. Biomarkers of intestinal inflammation were negatively associated with EFZ, consistent with low‐zinc intake and chronic deficiency.

   In these children at risk of EED, endogenous zinc losses were not markedly increased. Results suggest that efforts to improve zinc status in EED should focus on substantially improving zinc intakes.

    

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2. Markers of Environmental Enteric Dysfunction Are Associated With Neurodevelopmental Outcomes in Tanzanian Children

   https://doi.org/10.1097/MPG.0000000000001978  

   Etheredge, Analee J. ; Manji, Karim ; Kellogg, Mark ; Tran, Hao ; Liu, Enju ; McDonald, Christine M. ; Kisenge, Rodrick ; Aboud, Said ; Fawzi, Wafaie ; Bellinger, David ; et al ( June 2018 , Journal of Pediatric Gastroenterology and Nutrition)

   Chronic exposure to enteropathogens may result in environmental enteric dysfunction (EED), a subclinical condition associated with poor child growth. Growth faltering is strongly associated with poor neurodevelopment, and occurs during sensitive periods of postnatal brain development. We investigated the role of novel EED biomarkers, systemic inflammation, and micronutrient status on neurodevelopment in Tanzanian children.

   Non‐stunted subjects with 6‐week and 6‐month blood samples and neurodevelopmental measures (n = 107) were included in this study. Samples were tested for biomarkers of gastrointestinal function (citrulline, antibodies to lipopolysaccharide, and flagellin), micronutrient status (iron, retinol binding protein [RBP], and vitamin D), systemic inflammation (C‐reactive protein [CRP] and alpha‐1‐acid glycoprotein), and growth (insulin‐like growth factor and insulin‐like growth factor binding protein 3).

   Cognitive scores at 15 months were associated with higher concentrations of 6‐month anti‐lipopolysaccharide IgG (β = 1.95,P= 0.02), anti‐flagellin IgA (β = 2.41,P= 0.04), and IgG (β = 2.99,P= 0.009). Higher receptive language scores were positively associated with anti‐flagellin IgG (β = 0.95,P= 0.05), and receptive language and gross motor scores were positively associated with citrulline at 6 months (β = 0.09,P= 0.02; β = 0.10,P= 0.03, respectively). Gross motor scores were positively associated with RBP at 6 months (β = 1.70,P= 0.03). Markers of systemic inflammation were not significantly associated with neurodevelopment.

   Plasma citrulline, a marker of gastrointestinal mucosal surface area, and vitamin A status were associated with higher gross motor development scores. Novel markers for EED, but not inflammation, were positively associated with cognitive scores, suggesting a possible mechanistic pathway involving immune response and neuroprotection.

    

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3. Nutritional, inflammatory, and ecological correlates of maternal retinol allocation to breast milk in agro‐pastoral Ariaal communities of northern Kenya

   https://doi.org/10.1002/ajhb.22961  

   Fujita, Masako ; Lo, Yun‐Jia ; Brindle, Eleanor ( January 2017 , American Journal of Human Biology)

   Vitamin A (VA) is an essential micronutrient required for a range of biological functions throughout life. VA deficiency (VAD) claims an estimated 1 million preschool children's lives annually. Human milk is enriched with VA (retinol) from the maternal blood, which originates from the hepatic reserve and dietary intake. Secreting retinol into milk will benefit the nursing infant through breast milk, but retaining retinol is also important for the maternal health. Previous studies found that the public health intervention of high‐dose VA supplementation to lactating mothers did not significantly lower child mortality. The World Health Organization (WHO) recently acknowledged that our understanding about the principle of VA allocation within the maternal system and the secretion into milk is too incomplete to devise an effective intervention.

   We present a secondary analysis of data collected among lactating mothers in VAD endemic northern Kenya (n = 171), examining nutritional, inflammatory, and ecological factors that might associate with maternal retinol allocation. Regression models were applied using the outcome milk‐retinol allocation index: milk retinol/(milk retinol + serum retinol).

   Ten percent of the sample was identified as VAD. The average milk retinol concentration was 0.1 μmo/L, grossly below what is considered minimally necessary for an infant (1 μmol/L). VAD mothers and mothers with inflammation did not seem to compromise their milk retinol even though their serum retinol was lower than non‐VAD and noninflammation mothers. Breast milk fat concentration positively correlated with milk retinol but not with serum retinol.

   This exploratory study contributes toward an understanding of maternal retinol allocation.

    

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4. Health impacts of a randomized biomass cookstove intervention in northern Ghana

   https://doi.org/10.1186/s12889-021-12164-y  

   Abdo, Mona ; Kanyomse, Ernest ; Alirigia, Rex ; Coffey, Evan R. ; Piedrahita, Ricardo ; Diaz-Sanchez, David ; Hagar, Yolanda ; Naumenko, Daniel J. ; Wiedinmyer, Christine ; Hannigan, Michael P. ; et al ( December 2021 , BMC Public Health)

   Household air pollution (HAP) from cooking with solid fuels has adverse health effects. REACCTING (Research on Emissions, Air quality, Climate, and Cooking Technologies in Northern Ghana) was a randomized cookstove intervention study that aimed to determine the effects of two types of “improved” biomass cookstoves on health using self-reported health symptoms and biomarkers of systemic inflammation from dried blood spots for female adult cooks and children, and anthropometric growth measures for children only.

   Two hundred rural households were randomized into four different cookstove groups. Surveys and health measurements were conducted at four time points over a two-year period. Chi-square tests were conducted to determine differences in self-reported health outcomes. Linear mixed models were used to assess the effect of the stoves on inflammation biomarkers in adults and children, and to assess the z-score deviance for the anthropometric data for children.

   We find some evidence that two biomarkers of oxidative stress and inflammation, serum amyloid A and C-reactive protein, decreased among adult primary cooks in the intervention groups relative to the control group. We do not find detectable impacts for any of the anthropometry variables or self-reported health.

   Overall, we conclude that the REACCTING intervention did not substantially improve the health outcomes examined here, likely due to continued use of traditional stoves, lack of evidence of particulate matter emissions reductions from “improved” stoves, and mixed results for HAP exposure reductions.

   ClinicalTrials.gov(National Institutes of Health); Trial Registration Number:NCT04633135; Date of Registration: 11 November 2020 – Retrospectively registered.

   URL:https://clinicaltrials.gov/ct2/show/NCT04633135?term=NCT04633135&draw=2&rank=1

    

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5. Intervention and Mechanisms of Alanyl‐glutamine for Inflammation, Nutrition, and Enteropathy: A Randomized Controlled Trial

   https://doi.org/10.1097/MPG.0000000000002834  

   Moore, Sean R. ; Quinn, Laura A. ; Maier, Elizabeth A. ; Guedes, Marjorie M. ; Quetz, Josiane S. ; Perry, Madeline ; Ramprasad, Chethan ; Lanzarini Lopes, Gabriela M. L. ; Mayneris‐Perxachs, Jordi ; Swann, Jonathan ; et al ( July 2020 , Journal of Pediatric Gastroenterology and Nutrition)

   Determine the minimum dosage of alanyl‐glutamine (Ala‐Gln) required to improve gut integrity and growth in children at risk of environmental enteropathy (EE).

   This was a double‐blinded randomized placebo‐controlled dose‐response trial. We enrolled 140 children residing in a low‐income community in Fortaleza, Brazil. Participants were 2 to 60 months old and had weight‐for‐age (WAZ), height‐for‐age (HAZ), or weight‐for‐height (WHZ)z‐scores less than −1. We randomized children to 10 days of nutritional supplementation: Ala‐Gln at 3 g/day, Ala‐Gln at 6 g/day, Ala‐Gln at 12 g/day, or an isonitrogenous dose of glycine (Gly) placebo at 12.5 g/day. Our primary outcome was urinary lactulose‐mannitol excretion testing. Secondary outcomes were anthropometry, fecal markers of inflammation, urine metabolic profiles, and malabsorption (spot fecal energy).

   Of 140 children, 103 completed 120 days of follow‐up (24% dropout). In the group receiving the highest dose of Ala‐Gln, we detected a modest improvement in urinary lactulose excretion from 0.19% on day 1 to 0.17% on day 10 (P = 0.05). We observed significant but transient improvements in WHZ at day 10 in 2 Ala‐Gln groups, and in WHZ and WAZ in all Ala‐Gln groups at day 30. We detected no effects on fecal inflammatory markers, diarrheal morbidity, or urine metabolic profiles; but did observe modest reductions in fecal energy and fecal lactoferrin in participants receiving Ala‐Gln.

   Intermediate dose Ala‐Gln promotes short‐term improvement in gut integrity and ponderal growth in children at risk of EE. Lower doses produced improvements in ponderal growth in the absence of enhanced gut integrity.

    

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