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 journalArticle

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

Fingerprint

Micronutrients
Permeability
Inflammation
Food
Vitamin A
Neopterin
Lactulose
Mannitol
Ferritins
Peroxidase
Zinc
Anemia
Transferrin Receptors
Vitamin B 6
Malnutrition
Glycoproteins
Eating
Parturition
Diet
Calcium

Keywords

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

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

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

In: American Journal of Clinical Nutrition, Vol. 110, No. 4, 01.10.2019, p. 1015-1025.

Research output: Contribution to journalArticle

McCormick, BJJ, Murray-Kolb, LE, Lee, GO, Schulze, KJ, Ross, AC, Bauck, A, Lima, AAM, MacIel, BLL, Kosek, MN, Seidman, JC, Ambikapathi, R, Bose, A, John, S, Kang, G, Turab, A, Mduma, E, Bessong, P, Shrestra, SK, Ahmed, T, Mahfuz, M, Olortegui, MP, Bhutta, Z, Caulfield, LE, Acosta, AM, Burga, RRD, Chavez, CB, Flores, JT, Olotegui, MP, Pinedo, SR, Salas, MS, Trigoso, DR, Vasquez, AO, Ahmed, I, Alam, D, Ali, A, Bhutta, ZA, Qureshi, S, Rasheed, M, Soofi, S, Zaidi, AKM, Bodhidatta, L, Mason, CJ, Babji, S, George, AT, Hariraju, D, Steffi Jennifer, M, Kaki, S, Karunakaran, P, Koshy, B, Lazarus, RP, Muliyil, J, Raghava, MV, Raju, S, Ramachandran, A, Ramadas, R, Ramanujam, K, Roshan, R, Sharma, SL, Sundaram, SE, Thomas, RJ, Pan, WK, Daniel Carreon, J, Charu, V, Doan, V, Graham, J, Hoest, C, Knobler, S, Lang, DR, McGrath, M, Miller, MA, Mohale, A, Nayyar, G, Psaki, S, Rasmussen, Z, Richard, SA, Wang, V, Blank, R, Gottlieb, M, Tountas, KH, Amour, C, Bayyo, E, Mduma, ER, Mvungi, R, Nshama, R, Pascal, J, Swema, BM, Yarrot, L, Shamsir Ahmed, AM, Haque, R, Hossain, I, Islam, M, Mondal, D, Tofail, F, Chandyo, RK, Shrestha, PS, Shrestha, R, Ulak, M, Black, RE, Checkley, W, Yori, PP, Catharine Ross, A, Schaefer, B, Simons, S, Pendergast, L, Abreu, CB, Costa, H, Moura, AD, Filho, JQ, Havt, A, Leite, ÁM, Lima, NL, Lima, IF, Medeiros, PHQS, Moraes, M, Mota, FS, Oriá, RB, Quetz, J, Soares, AM, Mota, RMS, Patil, CL, Bessong, P, Mahopo, C, Maphula, A, Nyathi, E, Samie, A, Barrett, L, Dillingham, R, Gratz, J, Guerrant, RL, Houpt, E, Petri, WA, Platts-Mills, J, Scharf, R, Shrestha, B, Shrestha, SK, Strand, T & Svensen, E 2019, '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', American Journal of Clinical Nutrition, vol. 110, no. 4, pp. 1015-1025. https://doi.org/10.1093/ajcn/nqz151
McCormick, Benjamin J.J. ; Murray-Kolb, Laura E. ; Lee, Gwenyth O. ; Schulze, Kerry J. ; Ross, A. Catharine ; Bauck, Aubrey ; Lima, Aldo A.M. ; MacIel, Bruna L.L. ; Kosek, Margaret N. ; Seidman, Jessica C. ; Ambikapathi, Ramya ; Bose, Anuradha ; John, Sushil ; Kang, Gagandeep ; Turab, Ali ; Mduma, Estomih ; Bessong, Pascal ; Shrestra, Sanjaya K. ; Ahmed, Tahmeed ; Mahfuz, Mustafa ; Olortegui, Maribel Paredes ; Bhutta, Zulfiqar ; Caulfield, Laura E. ; Acosta, Angel Mendez ; Burga, Rosa Rios De ; Chavez, Cesar Banda ; Flores, Julian Torres ; Olotegui, Maribel Paredes ; Pinedo, Silvia Rengifo ; Salas, Mery Siguas ; Trigoso, Dixner Rengifo ; Vasquez, Angel Orbe ; Ahmed, Imran ; Alam, Didar ; Ali, Asad ; Bhutta, Zulfiqar A. ; Qureshi, Shahida ; Rasheed, Muneera ; Soofi, Sajid ; Zaidi, Anita K.M. ; Bodhidatta, Ladaporn ; Mason, Carl J. ; Babji, Sudhir ; George, Ajila T. ; Hariraju, Dinesh ; Steffi Jennifer, M. ; Kaki, Shiny ; Karunakaran, Priyadarshani ; Koshy, Beena ; Lazarus, Robin P. ; Muliyil, Jayaprakash ; Raghava, Mohan Venkata ; Raju, Sophy ; Ramachandran, Anup ; Ramadas, Rakhi ; Ramanujam, Karthikeyan ; Roshan, Reeba ; Sharma, Srujan L. ; Sundaram, Shanmuga E. ; Thomas, Rahul J. ; Pan, William K. ; Daniel Carreon, J. ; Charu, Vivek ; Doan, Viyada ; Graham, Jhanelle ; Hoest, Christel ; Knobler, Stacey ; Lang, Dennis R. ; McGrath, Monica ; Miller, Mark A. ; Mohale, Archana ; Nayyar, Gaurvika ; Psaki, Stephanie ; Rasmussen, Zeba ; Richard, Stephanie A. ; Wang, Vivian ; Blank, Rebecca ; Gottlieb, Michael ; Tountas, Karen H. ; Amour, Caroline ; Bayyo, Eliwaza ; Mduma, Estomih R. ; Mvungi, Regisiana ; Nshama, Rosemary ; Pascal, John ; Swema, Buliga Mujaga ; Yarrot, Ladislaus ; Shamsir Ahmed, A. M. ; Haque, Rashidul ; Hossain, Iqbal ; Islam, Munirul ; Mondal, Dinesh ; Tofail, Fahmida ; Chandyo, Ram Krishna ; Shrestha, Prakash Sunder ; Shrestha, Rita ; Ulak, Manjeswori ; Black, Robert E. ; Checkley, William ; Yori, Pablo Peñataro ; Catharine Ross, A. ; Schaefer, Barbara ; Simons, Suzanne ; Pendergast, Laura ; Abreu, Cláudia B. ; Costa, Hilda ; Moura, Alessandra Di ; Filho, José Quirino ; Havt, Alexandre ; Leite, Álvaro M. ; Lima, Noélia L. ; Lima, Ila F. ; Medeiros, Pedro H.Q.S. ; Moraes, Milena ; Mota, Francisco S. ; Oriá, Reinaldo B. ; Quetz, Josiane ; Soares, Alberto M. ; Mota, Rosa M.S. ; Patil, Crystal L. ; Bessong, Pascal ; Mahopo, Cloupas ; Maphula, Angelina ; Nyathi, Emanuel ; Samie, Amidou ; Barrett, Leah ; Dillingham, Rebecca ; Gratz, Jean ; Guerrant, Richard L. ; Houpt, Eric ; Petri, William A. ; Platts-Mills, James ; Scharf, Rebecca ; Shrestha, Binob ; Shrestha, Sanjaya Kumar ; Strand, Tor ; Svensen, Erling. / 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. In: American Journal of Clinical Nutrition. 2019 ; Vol. 110, No. 4. pp. 1015-1025.
@article{ec335a813de84e4ab70c8124ef0e99db,
title = "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",
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.",
keywords = "diet, environmental enteropathy, inflammation, intestinal barrier function, micronutrient status",
author = "McCormick, {Benjamin J.J.} and Murray-Kolb, {Laura E.} and Lee, {Gwenyth O.} and Schulze, {Kerry J.} and Ross, {A. Catharine} and Aubrey Bauck and Lima, {Aldo A.M.} and MacIel, {Bruna L.L.} and Kosek, {Margaret N.} and Seidman, {Jessica C.} and Ramya Ambikapathi and Anuradha Bose and Sushil John and Gagandeep Kang and Ali Turab and Estomih Mduma and Pascal Bessong and Shrestra, {Sanjaya K.} and Tahmeed Ahmed and Mustafa Mahfuz and Olortegui, {Maribel Paredes} and Zulfiqar Bhutta and Caulfield, {Laura E.} and Acosta, {Angel Mendez} and Burga, {Rosa Rios De} and Chavez, {Cesar Banda} and Flores, {Julian Torres} and Olotegui, {Maribel Paredes} and Pinedo, {Silvia Rengifo} and Salas, {Mery Siguas} and Trigoso, {Dixner Rengifo} and Vasquez, {Angel Orbe} and Imran Ahmed and Didar Alam and Asad Ali and Bhutta, {Zulfiqar A.} and Shahida Qureshi and Muneera Rasheed and Sajid Soofi and Zaidi, {Anita K.M.} and Ladaporn Bodhidatta and Mason, {Carl J.} and Sudhir Babji and George, {Ajila T.} and Dinesh Hariraju and {Steffi Jennifer}, M. and Shiny Kaki and Priyadarshani Karunakaran and Beena Koshy and Lazarus, {Robin P.} and Jayaprakash Muliyil and Raghava, {Mohan Venkata} and Sophy Raju and Anup Ramachandran and Rakhi Ramadas and Karthikeyan Ramanujam and Reeba Roshan and Sharma, {Srujan L.} and Sundaram, {Shanmuga E.} and Thomas, {Rahul J.} and Pan, {William K.} and {Daniel Carreon}, J. and Vivek Charu and Viyada Doan and Jhanelle Graham and Christel Hoest and Stacey Knobler and Lang, {Dennis R.} and Monica McGrath and Miller, {Mark A.} and Archana Mohale and Gaurvika Nayyar and Stephanie Psaki and Zeba Rasmussen and Richard, {Stephanie A.} and Vivian Wang and Rebecca Blank and Michael Gottlieb and Tountas, {Karen H.} and Caroline Amour and Eliwaza Bayyo and Mduma, {Estomih R.} and Regisiana Mvungi and Rosemary Nshama and John Pascal and Swema, {Buliga Mujaga} and Ladislaus Yarrot and {Shamsir Ahmed}, {A. M.} and Rashidul Haque and Iqbal Hossain and Munirul Islam and Dinesh Mondal and Fahmida Tofail and Chandyo, {Ram Krishna} and Shrestha, {Prakash Sunder} and Rita Shrestha and Manjeswori Ulak and Black, {Robert E.} and William Checkley and Yori, {Pablo Pe{\~n}ataro} and {Catharine Ross}, A. and Barbara Schaefer and Suzanne Simons and Laura Pendergast and Abreu, {Cl{\'a}udia B.} and Hilda Costa and Moura, {Alessandra Di} and Filho, {Jos{\'e} Quirino} and Alexandre Havt and Leite, {{\'A}lvaro M.} and Lima, {No{\'e}lia L.} and Lima, {Ila F.} and Medeiros, {Pedro H.Q.S.} and Milena Moraes and Mota, {Francisco S.} and Ori{\'a}, {Reinaldo B.} and Josiane Quetz and Soares, {Alberto M.} and Mota, {Rosa M.S.} and Patil, {Crystal L.} and Pascal Bessong and Cloupas Mahopo and Angelina Maphula and Emanuel Nyathi and Amidou Samie and Leah Barrett and Rebecca Dillingham and Jean Gratz and Guerrant, {Richard L.} and Eric Houpt and Petri, {William A.} and James Platts-Mills and Rebecca Scharf and Binob Shrestha and Shrestha, {Sanjaya Kumar} and Tor Strand and Erling Svensen",
year = "2019",
month = "10",
day = "1",
doi = "10.1093/ajcn/nqz151",
language = "English (US)",
volume = "110",
pages = "1015--1025",
journal = "American Journal of Clinical Nutrition",
issn = "0002-9165",
publisher = "American Society for Nutrition",
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}

TY - JOUR

T1 - Intestinal permeability and inflammation mediate the association between nutrient density of complementary foods and biochemical measures of micronutrient status in young children

T2 - Results from the MAL-ED study

AU - McCormick, Benjamin J.J.

AU - Murray-Kolb, Laura E.

AU - Lee, Gwenyth O.

AU - Schulze, Kerry J.

AU - Ross, A. Catharine

AU - Bauck, Aubrey

AU - Lima, Aldo A.M.

AU - MacIel, Bruna L.L.

AU - Kosek, Margaret N.

AU - Seidman, Jessica C.

AU - Ambikapathi, Ramya

AU - Bose, Anuradha

AU - John, Sushil

AU - Kang, Gagandeep

AU - Turab, Ali

AU - Mduma, Estomih

AU - Bessong, Pascal

AU - Shrestra, Sanjaya K.

AU - Ahmed, Tahmeed

AU - Mahfuz, Mustafa

AU - Olortegui, Maribel Paredes

AU - Bhutta, Zulfiqar

AU - Caulfield, Laura E.

AU - Acosta, Angel Mendez

AU - Burga, Rosa Rios De

AU - Chavez, Cesar Banda

AU - Flores, Julian Torres

AU - Olotegui, Maribel Paredes

AU - Pinedo, Silvia Rengifo

AU - Salas, Mery Siguas

AU - Trigoso, Dixner Rengifo

AU - Vasquez, Angel Orbe

AU - Ahmed, Imran

AU - Alam, Didar

AU - Ali, Asad

AU - Bhutta, Zulfiqar A.

AU - Qureshi, Shahida

AU - Rasheed, Muneera

AU - Soofi, Sajid

AU - Zaidi, Anita K.M.

AU - Bodhidatta, Ladaporn

AU - Mason, Carl J.

AU - Babji, Sudhir

AU - George, Ajila T.

AU - Hariraju, Dinesh

AU - Steffi Jennifer, M.

AU - Kaki, Shiny

AU - Karunakaran, Priyadarshani

AU - Koshy, Beena

AU - Lazarus, Robin P.

AU - Muliyil, Jayaprakash

AU - Raghava, Mohan Venkata

AU - Raju, Sophy

AU - Ramachandran, Anup

AU - Ramadas, Rakhi

AU - Ramanujam, Karthikeyan

AU - Roshan, Reeba

AU - Sharma, Srujan L.

AU - Sundaram, Shanmuga E.

AU - Thomas, Rahul J.

AU - Pan, William K.

AU - Daniel Carreon, J.

AU - Charu, Vivek

AU - Doan, Viyada

AU - Graham, Jhanelle

AU - Hoest, Christel

AU - Knobler, Stacey

AU - Lang, Dennis R.

AU - McGrath, Monica

AU - Miller, Mark A.

AU - Mohale, Archana

AU - Nayyar, Gaurvika

AU - Psaki, Stephanie

AU - Rasmussen, Zeba

AU - Richard, Stephanie A.

AU - Wang, Vivian

AU - Blank, Rebecca

AU - Gottlieb, Michael

AU - Tountas, Karen H.

AU - Amour, Caroline

AU - Bayyo, Eliwaza

AU - Mduma, Estomih R.

AU - Mvungi, Regisiana

AU - Nshama, Rosemary

AU - Pascal, John

AU - Swema, Buliga Mujaga

AU - Yarrot, Ladislaus

AU - Shamsir Ahmed, A. M.

AU - Haque, Rashidul

AU - Hossain, Iqbal

AU - Islam, Munirul

AU - Mondal, Dinesh

AU - Tofail, Fahmida

AU - Chandyo, Ram Krishna

AU - Shrestha, Prakash Sunder

AU - Shrestha, Rita

AU - Ulak, Manjeswori

AU - Black, Robert E.

AU - Checkley, William

AU - Yori, Pablo Peñataro

AU - Catharine Ross, A.

AU - Schaefer, Barbara

AU - Simons, Suzanne

AU - Pendergast, Laura

AU - Abreu, Cláudia B.

AU - Costa, Hilda

AU - Moura, Alessandra Di

AU - Filho, José Quirino

AU - Havt, Alexandre

AU - Leite, Álvaro M.

AU - Lima, Noélia L.

AU - Lima, Ila F.

AU - Medeiros, Pedro H.Q.S.

AU - Moraes, Milena

AU - Mota, Francisco S.

AU - Oriá, Reinaldo B.

AU - Quetz, Josiane

AU - Soares, Alberto M.

AU - Mota, Rosa M.S.

AU - Patil, Crystal L.

AU - Bessong, Pascal

AU - Mahopo, Cloupas

AU - Maphula, Angelina

AU - Nyathi, Emanuel

AU - Samie, Amidou

AU - Barrett, Leah

AU - Dillingham, Rebecca

AU - Gratz, Jean

AU - Guerrant, Richard L.

AU - Houpt, Eric

AU - Petri, William A.

AU - Platts-Mills, James

AU - Scharf, Rebecca

AU - Shrestha, Binob

AU - Shrestha, Sanjaya Kumar

AU - Strand, Tor

AU - Svensen, Erling

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

KW - diet

KW - environmental enteropathy

KW - inflammation

KW - intestinal barrier function

KW - micronutrient status

UR - http://www.scopus.com/inward/record.url?scp=85072746149&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072746149&partnerID=8YFLogxK

U2 - 10.1093/ajcn/nqz151

DO - 10.1093/ajcn/nqz151

M3 - Article

C2 - 31565748

AN - SCOPUS:85072746149

VL - 110

SP - 1015

EP - 1025

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

SN - 0002-9165

IS - 4

ER -