Intestinal permeability and inflammation mediate the association between nutrient density of complementary foods and biochemical measures of micronutrient status in young children: Results from the MAL-ED study

Benjamin J.J. McCormick, Laura E. Murray-Kolb, Gwenyth O. Lee, Kerry J. Schulze, A. Catharine Ross, Aubrey Bauck, Aldo A.M. Lima, Bruna L.L. MacIel, Margaret N. Kosek, Jessica C. Seidman, Ramya Ambikapathi, Anuradha Bose, Sushil John, Gagandeep Kang, Ali Turab, Estomih Mduma, Pascal Bessong, Sanjaya K. Shrestra, Tahmeed Ahmed, Mustafa MahfuzMaribel Paredes Olortegui, Zulfiqar Bhutta, Laura E. Caulfield, Angel Mendez Acosta, Rosa Rios De Burga, Cesar Banda Chavez, Julian Torres Flores, Maribel Paredes Olotegui, Silvia Rengifo Pinedo, Mery Siguas Salas, Dixner Rengifo Trigoso, Angel Orbe Vasquez, Imran Ahmed, Didar Alam, Asad Ali, Zulfiqar A. Bhutta, Shahida Qureshi, Muneera Rasheed, Sajid Soofi, Anita K.M. Zaidi, Ladaporn Bodhidatta, Carl J. Mason, Sudhir Babji, Ajila T. George, Dinesh Hariraju, M. Steffi Jennifer, Shiny Kaki, Priyadarshani Karunakaran, Beena Koshy, Robin P. Lazarus, Jayaprakash Muliyil, Mohan Venkata Raghava, Sophy Raju, Anup Ramachandran, Rakhi Ramadas, Karthikeyan Ramanujam, Reeba Roshan, Srujan L. Sharma, Shanmuga E. Sundaram, Rahul J. Thomas, William K. Pan, J. Daniel Carreon, Vivek Charu, Viyada Doan, Jhanelle Graham, Christel Hoest, Stacey Knobler, Dennis R. Lang, Monica McGrath, Mark A. Miller, Archana Mohale, Gaurvika Nayyar, Stephanie Psaki, Zeba Rasmussen, Stephanie A. Richard, Vivian Wang, Rebecca Blank, Michael Gottlieb, Karen H. Tountas, Caroline Amour, Eliwaza Bayyo, Estomih R. Mduma, Regisiana Mvungi, Rosemary Nshama, John Pascal, Buliga Mujaga Swema, Ladislaus Yarrot, A. M. Shamsir Ahmed, Rashidul Haque, Iqbal Hossain, Munirul Islam, Dinesh Mondal, Fahmida Tofail, Ram Krishna Chandyo, Prakash Sunder Shrestha, Rita Shrestha, Manjeswori Ulak, Robert E. Black, William Checkley, Pablo Peñataro Yori, A. Catharine Ross, Barbara Schaefer, Suzanne Simons, Laura Pendergast, Cláudia B. Abreu, Hilda Costa, Alessandra Di Moura, José Quirino Filho, Alexandre Havt, Álvaro M. Leite, Noélia L. Lima, Ila F. Lima, Pedro H.Q.S. Medeiros, Milena Moraes, Francisco S. Mota, Reinaldo B. Oriá, Josiane Quetz, Alberto M. Soares, Rosa M.S. Mota, Crystal L. Patil, Pascal Bessong, Cloupas Mahopo, Angelina Maphula, Emanuel Nyathi, Amidou Samie, Leah Barrett, Rebecca Dillingham, Jean Gratz, Richard L. Guerrant, Eric Houpt, William A. Petri, James Platts-Mills, Rebecca Scharf, Binob Shrestha, Sanjaya Kumar Shrestha, Tor Strand, Erling Svensen

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Environmental enteric dysfunction (EED) is thought to increase the risk of micronutrient deficiencies, but few studies adjust for dietary intakes and systemic inflammation. Objective: We tested whether EED is associated with micronutrient deficiency risk independent of diet and systemic inflammation, and whether it mediates the relation between intake and micronutrient status. Methods: Using data from 1283 children in the MAL-ED (Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health) birth cohort we evaluated the risk of anemia, low retinol, zinc, and ferritin, and high transferrin receptor (TfR) at 15 mo. We characterized gut inflammation and permeability by myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT) concentrations from asymptomatic fecal samples averaged from 9 to 15 mo, and averaged the lactulose:mannitol ratio z-score (LMZ) at 9 and 15 mo. Nutrient intakes from complementary foods were quantified monthly from 9 to 15 mo and densities were averaged for analyses. α-1-Acid glycoprotein at 15 mo characterized systemic inflammation. Relations between variables were modeled using a Bayesian network. Results: A greater risk of anemia was associated with LMZ [1.15 (95% CI: 1.01, 1.31)] and MPO [1.16 (1.01, 1.34)]. A greater risk of low ferritin was associated with AAT [1.19 (1.03, 1.37)] and NEO [1.22 (1.04, 1.44)]. A greater risk of low retinol was associated with LMZ [1.24 (1.08, 1.45)]. However, MPO was associated with a lower risk of high transferrin receptor [0.86 (0.74, 0.98)], NEO with a lower risk of low retinol [0.75 (0.62, 0.89)], and AAT with a lower risk of low plasma zinc [0.83 (0.70, 0.99)]. Greater nutrient intake densities (vitamins A and B6, calcium, protein, and zinc) were negatively associated with EED. Inverse associations between nutrient densities and micronutrient deficiency largely disappeared after adjustment for EED, suggesting that EED mediates these associations. Conclusions: EED is independently associated with an increased risk of low ferritin, low retinol, and anemia. Greater nutrient density from complementary foods may reduce EED, and the control of micronutrient deficiencies may require control of EED.

Original languageEnglish (US)
Pages (from-to)1015-1025
Number of pages11
JournalAmerican Journal of Clinical Nutrition
Volume110
Issue number4
DOIs
StatePublished - Oct 1 2019

Keywords

  • diet
  • environmental enteropathy
  • inflammation
  • intestinal barrier function
  • micronutrient status

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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