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

item ORDIZ, M - Washington University
item WOLD, KARL - Washington University
item KAIMILA, YANKHO - University Of Malawi
item DIVALA, OSCAR - University Of Malawi
item GILSTRAP, MADELINE - Washington University
item ZU, HENRY - Washington University
item MANARY, MARK - Children'S Nutrition Research Center (CNRC)

Submitted to: Experimental Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/15/2018
Publication Date: 8/12/2018
Citation: Ordiz, M.I., Wold, K., Kaimila, Y., Divala, O., Gilstrap, M., Zu, H.Z., Manary, M.J. 2018. Detection and interpretation of fecal host mRNA in rural Malawian infants aged 6-12 months at risk for environmental enteric dysfunction. Experimental Biology and Medicine.

Interpretive Summary: Environmental enteric dysfunction is associated with poor health and diminished growth. Gut health may be predicted by using an alternative noninvasive method based on fecal molecules as predictors. One fecal molecule was associated with severe gut health, which was less prevalent in 6-12 month old rural Malawian children. The study suggests that the predictor molecules associated with gut health in infants may be different than in young kids.

Technical Abstract: 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: B 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.