Additional Common Bean in the Diet of Malawian Children Does Not Affect Linear Growth, but Reduces Intestinal Permeability

Agapova, Sophia; Stephenson, Kevin; Divala, Oscar; Kaimila, Yankho; Maleta, Kenneth; Thakwalakwa, Chrissie; Ordiz, M. Isabel; Trehan, Indi; Manary, Mark J.

doi:10.1093/jn/nxx013

Cited by 27 publications

(22 citation statements)

References 44 publications

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“…0.45, while among older children, aged 12-36 months, the fraction with %L !0.45 was 595/1521 (39%) (P ¼ 0.001). 17 The seven transcripts measured were segregated into three groups based on correlation with each other: (1) CDX1, HLA-DRA, MUC12, (2) CD53, S100A8, TNF, and (3) REG1A ( Table 3). Comparison of the copy number of each of the seven transcripts for infants with %L !…”

Section: Resultsmentioning

confidence: 99%

Detection and interpretation of fecal host mRNA in rural Malawian infants aged 6–12 months at risk for environmental enteric dysfunction

Ordiz

Wold

Kaimila

et al. 2018

Exp Biol Med (Maywood)

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Recent studies have suggested that environmental enteric dysfunction can be assessed in rural African children by measuring levels of fecal mRNA transcripts. The field collection of fecal samples is less invasive and cumbersome than administration of the lactulose:mannitol test, which is typically used to assess environmental enteric dysfunction. This study sought to determine if, as in children aged 12-60 months, an array of seven fecal host transcripts (CD53, CDX1, HLA-DRA, TNF, S100A8, MUC12, and REG1A) could predict environmental enteric dysfunction in rural African infants. Host fecal transcript abundance was correlated to the percentage of lactulose (%L) excreted in the urine for 340 samples from Malawian children aged 6-12 months. Permeability was categorized as not severe (%L < 0.45) and severe (%L ≥ 0.45). This study found the prevalence of severe environmental enteric dysfunction to be 114/834 (14%), lower than what was previously reported for 12-60 months old children, 595/1521 (39%, P = 0.001). In linear regression analysis with the seven host transcripts, two were associated with %L: β coefficients of -1.843 ( P = 0.035) and 0.215 ( P = 0.006) for CDX1 and REG1A, respectively. The seven fecal host transcripts in a random forest model did not predict severe environmental enteric dysfunction. Future models utilizing different transcripts identified from an untargeted, agnostic assessment of all potential host transcripts could provide accurate predictions of environmental enteric dysfunction in infants. Impact statement Environmental enteric dysfunction (EED) is associated with reduced linear growth. The dual sugar absorption test has been used as a non-invasive method to determine the gut health of individuals. Alternative methods using fecal host mRNAs as predictors of the gut health are promising. In older children, we have determined that seven transcripts can predict the gut health in a random forest model. Our current study determined that the host fecal mRNA is abundant in infants and toddlers alike. Severe EED in rural Malawian children is less prevalent in infants than in young children. REG1A and CDX1 are associated with gut health. Fecal host mRNA may well be a means to assess gut health in African infants, but the panel of transcripts used to do this will differ from that in older children.

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Section: Resultsmentioning

confidence: 99%

Detection and interpretation of fecal host mRNA in rural Malawian infants aged 6–12 months at risk for environmental enteric dysfunction

Ordiz

Wold

Kaimila

et al. 2018

Exp Biol Med (Maywood)

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“…We performed a secondary analysis of children who participated in two randomized controlled trials (RCTs) of common bean and cowpea flours addition as a part of the complementary food in Malawi. The details of the study protocols and principal clinical findings have been reported previously [13,14,27].…”

Section: Methodsmentioning

confidence: 99%

“…The full procedure for EED categorization has been previously published by the group [13,14,27]. Briefly, the dual sugar absorption method was used for categorizing EED; 20 mL of 1 g mannitol and 5 g lactulose solution was fed to the children after overnight fasting under the supervision of research personnel.…”

Section: Methodsmentioning

confidence: 99%

“…We supplemented the complementary diets of children aged 6–23 months for 6–12 months with common bean or cowpea flours as alternatives to CSB, and we used CSB flour as a control. In children aged 6–12 months, the cowpea flour added to the weaning food improved linear growth compared to common bean and CSB [13]; in 12–23-months-old children, the common bean supplement reduced lactulose excretion, a biomarker of gut health, but this did not result in better linear growth outcomes [14]. In a secondary analysis of these two cohorts, we found higher rates of stunting, wasting and EED, despite adequate macronutrient consumption in Masenjere, a region that had a higher consumption of energy, carbohydrates and fats, better food security and Water, Sanitation and Hygiene (WASH) outcomes than Limera [15].…”

Section: Introductionmentioning

confidence: 99%

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Consumption of Animal-Source Protein is Associated with Improved Height-for-Age z Scores in Rural Malawian Children Aged 12–36 Months

et al. 2019

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Linear growth faltering, caused by insufficient diet, recurrent infections and environmental enteric dysfunction (EED), continues to plague young children in low- and middle-income countries (LMICs). Diets in LMICs are primarily plant based, and thus have poor-quality protein and low levels of essential micronutrients. The aim of this study was to assess the association of the type and protein quality of food consumed with stunting, EED and acute malnutrition in children aged 6–36 months in Limera and Masenjere, two rural Southern Malawian communities. This is a secondary analysis of two randomized controlled trials that tested the effects of common bean and cowpea flour on stunting in children aged 6–36 months. We used data from two interactive 24-h dietary recalls conducted 12 weeks after enrolment into each trial. Food intakes were compared between the regions using Chi-square and Student’s t-test. There were 355 children that participated in the dietary recalls. The diets of children were of poor quality, but the children from Limera consumed more fish (54% vs. 35%, p = 0.009) and more bioavailable protein (26.0 ± 10.3 g/day vs. 23.1 ± 8.1 g/day, p = 0.018, respectively) than children in Masenjere. Food type and protein quality were not associated with any of the outcomes except an association between animal protein consumption and improvement in height-for-age z scores in children aged 12–36 months (p = 0.047). These findings support the notion that animal-source food (ASF) consumption in this vulnerable population promotes linear growth.

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“…Data from 622 children from two clinical trials conducted in rural Malawi were used. 17–19 This included L:M test measurements from children aged 6–12 months ( n = 815) and 12–36 months ( n = 1519). These children were apparently healthy, did not have acute malnutrition, a known or obvious chronic disability or disease, nor was diarrhea reported within 48 h of L:M testing.…”

Section: Methodsmentioning

confidence: 99%

EB 2017 Article: Interpretation of the lactulose:mannitol test in rural Malawian children at risk for perturbations in intestinal permeability

Ordiz

Davitt

Stephenson

et al. 2018

Exp Biol Med (Maywood)

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The dual sugar absorption test, specifically the lactulose:mannitol test, is used to assess gut health. Lactulose absorption is said to represent gut damage and mannitol absorption is used as a measure of normal small bowel function and serves as normalizing factor for lactulose. A underappreciated limitation of this common understanding of the lactulose:mannitol test is that mannitol is not absorbed to any substantial extent by a transcellular process. Additionally, this interpretation of lactulose:mannitol is not consistent with current understanding of paracellular pathways, where three pathway types exist: pore, leak, and unrestricted. Pore and leak pathways are regulated biological constructions of the small bowel barrier, and unrestricted pathways represent micropathological damage. We analyzed 2334 lactulose:mannitol measurements rigorously collected from 622 young rural Malawian children at high risk for poor gut health in light of the pathway model. An alternative method of normalizing for gut length utilizing autopsy data is described. In our population, absorbed lactulose and mannitol are strongly correlated, r = 0.68 P <0.0001, suggesting lactulose and mannitol are traversing the gut barrier via the same pathways. Considering measurements where pore pathways predominate, mannitol flux is about 14 times that of lactulose. As more leak pathways are present, this differential flux mannitol:lactulose falls to 8:1 and when increased numbers of unrestricted pathways are present, the differential flux of mannitol:lactulose is 6:1. There was no substantial correlation between the lactulose:mannitol and linear growth. Given that mannitol will always pass through a given pathway at a rate at least equal to that of lactulose, and lactulose absorption is a composite measure of flux through both physiologic and pathologic pathways, we question the utility of the lactulose:mannitol test. We suggest using lactulose alone is as informative as lactulose:mannitol in a sugar absorption testing in subclinical gut inflammation. Impact statement Our work integrates the standard interpretation of the lactulose:mannitol test (L:M), with mechanistic insight of intestinal permeability. There are three paracellular pathways in the gut epithelium; pore, leak, and unrestricted. Using thousands of L:M measurements from rural Malawian children at risk for increased intestinal permeability, we predict the differential flux of L and M through the pathways. Our findings challenge the traditional notions that little L is absorbed through a normal epithelial barrier and that M is a normalizing factor for L. Our observations are consistent with pore pathways allowing only M to pass. And that substantial amounts of L and M pass through leak pathways which are normal, regulated, cell-junctional adaptations. So M is a composite measure of all pathways, and L is not a measure solely of pathologic gut damage. Using L alone as a probe will yield more information about gut health than L:M.

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Additional Common Bean in the Diet of Malawian Children Does Not Affect Linear Growth, but Reduces Intestinal Permeability

Cited by 27 publications

References 44 publications

Detection and interpretation of fecal host mRNA in rural Malawian infants aged 6–12 months at risk for environmental enteric dysfunction

Detection and interpretation of fecal host mRNA in rural Malawian infants aged 6–12 months at risk for environmental enteric dysfunction

Consumption of Animal-Source Protein is Associated with Improved Height-for-Age z Scores in Rural Malawian Children Aged 12–36 Months

EB 2017 Article: Interpretation of the lactulose:mannitol test in rural Malawian children at risk for perturbations in intestinal permeability

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