Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-13T12:42:48.025Z Has data issue: false hasContentIssue false
  • English
  • Français

Environmental enteropathy is associated with cardiometabolic risk factors in Peruvian children

Published online by Cambridge University Press:  07 March 2017

G. O. Lee Open the ORCID record for G. O. Lee [Opens in a new window] ,
M. Paredes Olortegui ,
M. Siguas Salas ,
P. Peñataro Yori ,
D. Rengifo Trigoso ,
P. Kosek ,
M. L. Mispireta ,
R. Oberhelman ,
L. E. Caulfield  and
M. N. Kosek
G. O. Lee*
Affiliation:
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
M. Paredes Olortegui
Affiliation:
Asociación Benéfica PRISMA, Iquitos, Peru
M. Siguas Salas
Affiliation:
Asociación Benéfica PRISMA, Iquitos, Peru
P. Peñataro Yori
Affiliation:
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
D. Rengifo Trigoso
Affiliation:
Asociación Benéfica PRISMA, Iquitos, Peru
P. Kosek
Affiliation:
Oregon Analytics, Eugene, OR, USA
M. L. Mispireta
Affiliation:
School of Nursing, Division of Health Sciences, Idaho State University, Pocatello, ID, USA
R. Oberhelman
Affiliation:
Department of Global Community Health and Behavioral Sciences, Tulane School of Public Health and Tropical Medicine, New Orleans, LA, USA
L. E. Caulfield
Affiliation:
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
M. N. Kosek
Affiliation:
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
*
*Address for correspondence: G. O. Lee, Department of Epidemiology, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA. (Email golee@umich.edu)
Get access Rights & Permissions [Opens in a new window]

Abstract

Environmental enteropathy (EE) is a syndrome of altered small intestine structure and function hypothesized to be common among individuals lacking access to improved water and sanitation. There are plausible biological mechanisms, both inflammatory and non-inflammatory, by which EE may alter the cardiometabolic profile. Here, we test the hypothesis that EE is associated with the cardiometabolic profile among young children living in an environment of intense enteropathogen exposure. In total, 156 children participating in the Peruvian cohort of a multicenter study on childhood infectious diseases, growth and development were contacted at 3–5 years of age. The urinary lactulose:mannitol ratio, and plasma antibody to endotoxin core were determined in order to assess intestinal permeability and bacterial translocation. Blood pressure, anthropometry, fasting plasma glucose, insulin, and cholesterol and apolipoprotein profiles were also assessed. Extant cohort data were also used to relate biomarkers of EE during the first 18 months of life to early child cardiometabolic profile. Lower intestinal surface area, as assessed by percent mannitol excretion, was associated with lower apolipoprotein-AI and lower high-density lipoprotein concentrations. Lower intestinal surface area was also associated with greater blood pressure. Inflammation at 7 months of age was associated with higher blood pressure in later childhood. This study supports the potential for a relationship between EE and the cardiometabolic profile.

Keywords

cardiovascular riskenvironmental enteropathyPeru
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 8 , Issue 3 , June 2017 , pp. 337 - 348
Check for updates
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Kelly, P, Menzies, I, Crane, R, et al. Responses of small intestinal architecture and function over time to environmental factors in a tropical population. Am J Trop Med Hyg. 2004; 70, 412–419.Google Scholar
2. Salazar-Lindo, E, Allen, S, Brewster, DR, et al. Intestinal infections and environmental enteropathy: working group report of the second world congress of pediatric gastroenterology, hepatology, and nutrition. J Pediatr Gastroenterol Nutr. 2004; 39(Suppl. 2), S662–S669.Google Scholar
3. WHO, UNICEF. Progress on sanitation and drinking water. World Health Organization, 2013.Google Scholar
4. Mckay, S, Gaudier, E, Campbell, DI, Prentice, AM, Albers, R. Environmental enteropathy: new targets for nutritional interventions. Int Health. 2010; 2, 172–180.Google Scholar
5. Lunn, PG, Northrop-Clewes, CA, Downes, RM. Intestinal permeability, mucosal injury, and growth faltering in Gambian infants. Lancet. 1991; 338, 907–910.Google Scholar
6. Kosek, M, Haque, R, Lima, A, et al. Fecal markers of intestinal inflammation and permeability associated with the subsequent acquisition of linear growth deficits in infants. Am J Trop Med Hyg. 2012; 88, e2125.Google Scholar
7. Campbell, DI, McPhail, G, Lunn, PG, Elia, M, Jeffries, DJ. Intestinal inflammation measured by fecal neopterin in Gambian children with enteropathy: association with growth failure, Giardia lamblia, and intestinal permeability. J Pediatr Gastroenterol Nutr. 2004; 39, 153–157.Google Scholar
8. Peterson, KM, Buss, J, Easley, R, et al. REG1B as a predictor of childhood stunting in Bangladesh and Peru. Am J Clin Nutr. 2013; 97, 1129–1133.Google Scholar
9. Mondal, D, Minak, J, Alam, M, et al. Contribution of enteric infection, altered intestinal barrier function, and maternal malnutrition to infant malnutrition in Bangladesh. Clin Infect Dis. 2012; 54, 185–192.Google Scholar
10. Kosek, MN, Mduma, E, Kosek, PS, et al. Plasma tryptophan and the kynurenine-tryptophan ratio are associated with the acquisition of statural growth deficits and oral vaccine underperformance in populations with environmental enteropathy. Am J Trop Med Hyg. 2016; 95, 928–937.Google Scholar
11. Guerrant, RL, Deboer, MD, Moore, SR, Scharf, RJ, Lima, AA. The impoverished gut-a triple burden of diarrhoea, stunting and chronic disease. Nat Rev Gastroenterol Hepatol. 2012; 10, 220–229.Google Scholar
12. Campbell, DI, Elia, M, Lunn, PG. Growth faltering in rural Gambian infants is associated with impaired small intestinal barrier function, leading to endotoxemia and systemic inflammation. J Nutr. 2003; 133, 1332–1338.Google Scholar
13. Goto, R, Mascie-Taylor, CGN, Lunn, PG. Impact of intestinal permeability, inflammation status and parasitic infections on infant growth faltering in rural Bangladesh. Br J Nutr. 2008; 101, 1509–1516.CrossRefGoogle ScholarPubMed
14. Barker, DJP, Osmond, C, Forsén, TJ, Kajantie, E, Eriksson, JG. Trajectories of growth among children who have coronary events as adults. N Engl J Med. 2005; 353, 1802–1809.Google Scholar
15. Bhargava, S, Singh Sachdev, H, Fall, C, et al. Relation of serial changes in childhood body-mass index to impaired glucose tolerance in young adulthood. N Engl J Med. 2004; 350, 865–875.Google Scholar
16. Deboer, MD, Lima, AA, Oría, RB, et al. Early childhood growth failure and the developmental origins of adult disease: do enteric infections and malnutrition increase risk for the metabolic syndrome? Nutr Rev. 2012; 70, 642–653.Google Scholar
17. Smets, S, Spears, D, Vyas, S. Growing Taller Among Toilets: Evidence from Changes in Sanitation and Child Height in Cambodia, 2005-2010. 2013. Research Institute for Compassionate Economics (RICE): Amston, CT.Google Scholar
18. Buck, C, Simpson, H. Infant diarrhoea and subsequent mortality from heart disease and cancer. J Epidemiol Community Health. 1982; 36, 27–30.Google Scholar
19. DeBoer, MD, Chen, D, Burt, DR, et al. Early childhood diarrhea and cardiometabolic risk factors in adulthood: the Institute of Nutrition of Central America and Panama Nutritional Supplementation Longitudinal Study. Ann Epidemiol. 2013; 23, 314–320.Google Scholar
20. Margolis, R. The effects of early childhood diseases on young adult health in Guatemala. PARC Working Paper Series, Philadelphia, PA, No. WPS 08-07, 2008.Google Scholar
21. Lin, A, Arnold, BF, Afreen, S, et al. Household environmental conditions are associated with enteropathy and impaired growth in rural Bangladesh. Am J Trop Med Hyg. 2013; 89, 130–137.Google Scholar
22. Kelly, P, Shawa, T, Mwanamakondo, S, et al. Gastric and intestinal barrier impairment in tropical enteropathy and HIV: limited impact of micronutrient supplementation during a randomised controlled trial. BMC Gastroenterol. 2010; 10, 72–81.Google Scholar
23. Creely, SJ, Mcternan, PG, Kusminski, CM, et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab. 2007; 292, 740–747.Google Scholar
24. Pussinen, PJ, Havulinna, AS, Lehto, M, Sundvall, J, Salomaa, V. Endotoxemia is associated with an increased risk of incident diabetes. Diabetes Care. 2011; 34, 392–397.CrossRefGoogle ScholarPubMed
25. Teixeira, TFS, Souza, NCS, Chiarello, PG, et al. Intestinal permeability parameters in obese patients are correlated with metabolic syndrome risk factors. Clin Nutr. 2012; 31, 735–740.Google Scholar
26. Kaliannan, K, Hamarneh, SR, Economopoulos, KP, et al. Intestinal alkaline phosphatase prevents metabolic syndrome in mice. Proc Natl Acad Sci U S A. 2013; 110, 7003–7008.Google Scholar
27. Florén, C, Alm, P. Defective synthesis of apoliprotein AI in jejunal mucosa in coelic disease. Scand J Gastroenterol. 1988; 23, 856–860.Google Scholar
28. Brar, P, Kwon, GY, Holleran, S, et al. Change in lipid profile in celiac disease: beneficial effect of gluten-free diet. Am J Med. 2006; 119, 786–790.CrossRefGoogle ScholarPubMed
29. Lewis, NR, Sanders, DS, Logan, RF, Fleming, KM, Hubbard, RB, West, J. Cholesterol profile in people with newly diagnosed coeliac disease: a comparison with the general population and changes following treatment. Br J Nutr. 2009; 102, 509–513.Google Scholar
30. Siebel, AL, Heywood, SE, Kingwell, BA. HDL and glucose metabolism: current evidence and therapeutic potential. Front Pharmacol. 2015; 6, 1–7.Google Scholar
31. Thompson, A, Danesh, J. Associations between apolipoprotein B, apolipoprotein AI, the apolipoprotein B/AI ratio and coronary heart disease: a literature-based meta-analysis of prospective studies. J Intern Med. 2006; 259, 481–492.Google Scholar
32. Rodríguez-Moran, M, Aradillas-García, C, Guerrero-Romero, F. The ApoB/A-I ratio and metabolic syndrome in prepubertal children. Metab Syndr Relat Disord. 2013; 11, 115–120.Google Scholar
33. Idohou-Dossou, N, Wade, S, Guiro, AT, et al. Nutritional status of preschool Senegalese children: long-term effects of early severe malnutrition. Br J Nutr. 2003; 90, 1123–1132.Google Scholar
34. Veiga, GRS, Ferreira, HS, Sawaya, AL, Calado, J, Florêncio, TMMT. Dyslipidaemia and undernutrition in children from impoverished areas of Maceió, state of Alagoas, Brazil. Int J Environ Res Public Health. 2010; 7, 4139–4151.Google Scholar
35. Lunn, PG. The impact of infection and nutrition on gut function and growth in childhood. Proc Nutr Soc. 2000; 59, 147–154.Google Scholar
36. Crimmins, EM, Finch, CE. Infection, inflammation, height, and longevity. Proc Natl Acad Sci U S A. 2006; 103, 498–503.Google Scholar
37. From the MAL-ED Network Investigators. The MAL-ED project: a multinational and multidisciplinary approach to understand the relationship between enteric pathogens, malnutrition, gut physiology, growth, cognitive development and immune responses in infants/children in resource poor environments. Clin Infect Dis. 2014; 59(Suppl. 4), S193–S206.Google Scholar
38. Yori, PP, Lee, G, Olórtegui, MP, et al. Santa Clara de Nanay: the MAL-ED cohort in Peru. Clin Infect Dis. 2014; 59(Suppl. 4), S310–S316.Google Scholar
39. Kosek, M, Guerrant, RL, Kang, G, et al. Assessment of environmental enteropathy in the MAL-ED cohort study: theoretical and analytic framework. Clin Infect Dis. 2014; 59(Suppl. 4), S239–S247.CrossRefGoogle ScholarPubMed
40. Caulfield, LE, Bose, A, Chandyo, RK, et al. Infant feeding practices, dietary adequacy, and micronutrient status measures in the MAL-ED study. Clin Infect Dis. 2014; 59(Suppl. 4), 248–254.Google Scholar
41. Richard, SA, Barrett, LJ, Guerrant, RL, et al. Disease surveillance methods used in the 8-site MAL-ED cohort study. Clin Infect Dis. 2014; 59(Suppl. 4), S220–S224.Google Scholar
42. Barclay, GR. Endogenous endotoxin-core antibody (EndoCAb) as a marker of endotoxin exposure and a prognostic indicator: a review. Prog Clin Biol Res. 1995; 392, 263–272.Google Scholar
43. Prendergast, AJ, Rukobo, S, Chasekwa, B, et al. Stunting is characterized by chronic inflammation in Zimbabwean infants. PLoS One. 2014; 9, e86928.Google Scholar
44. Pickering, TG, Hall, JE, Appel, LJ, et al. Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans. A statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association council on High Blood Pressure Research. Hypertension. 2005; 45, 142–161.Google Scholar
45. Lohman, T, Roche, A, Martorell, R. Anthropometric Standardization Reference Manual. 1988. Human Kinetics Books: Champaign, IL.Google Scholar
46. Lee, GO, Kosek, P, Lima, AA, et al. The lactulose:mannitol diagnostic test by HPLC and LC-MSMS platforms: considerations for field studies of intestinal barrier function and environmental enteropathy. J Pediatr Gastroenterol Nutr. 2014; 59, 544–550.Google Scholar
47. Stewart, CP, Christian, P, Schulze, KJ, et al. Antenatal micronutrient supplementation reduces metabolic syndrome in 6- to 8-year-old children in rural Nepal. J Nutr. 2009; 139, 1575–1581.Google Scholar
48. Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA. 2014; 285, 2486–2497.Google Scholar
49. Daniels, SR, Greer, FR. Lipid screening and cardiovascular health in childhood. Pediatrics. 2008; 122, 198–208.Google Scholar
50. American Diabetes Association. Standards of medical care in diabetes–2014. Diabetes Care. 2014; 37(Suppl 1), S14–S80.Google Scholar
51. Falkner, B, Daniels, SR, Flynn, JT, et al. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004; 114, 555–576.Google Scholar
52. Matthews, DR, Hosker, JR, Rudenski, AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28, 412–419.CrossRefGoogle ScholarPubMed
53. van der Merwe, LF, Moore, SE, Fulford, AJ, et al. Long-chain PUFA supplementation in rural African infants: a randomized controlled trial of effects on gut integrity, growth, and cognitive development. Am J Clin Nutr. 2013; 97, 45–57.Google Scholar
54. Wessells, KR, Hess, SY, Rouamba, N, et al. Associations between intestinal mucosal function and changes in plasma zinc concentration following zinc supplementation. J Pediatr Gastroenterol Nutr. 2013; 57, 348–355.Google Scholar
55. World Health Organization. Child growth standards: anthropometry macros, 2011. Retrieved 1 February 2015 from http://www.who.int/childgrowth/software/en/index.htm.Google Scholar
56. Psaki, SR, Seidman, JC, Miller, M, et al. Measuring socioeconomic status in multicountry studies: results from the eight-country MAL-ED study. Popul Health Metr. 2014; 12, 1–11.Google Scholar
57. Imai, K, Keele, L, Tingley, D. A general approach to causal mediation analysis. Psychol Methods. 2010; 15, 309–334.Google Scholar
58. Hicks, R, Tingley, D. Causal mediation analysis. Stata J. 2009; 11, 1–14.Google Scholar
59. Naylor, C, Lu, M, Haque, R, et al. Environmental enteropathy, oral vaccine failure and growth faltering in infants in Bangladesh. EBioMedicine. 2015; 2, 1759–1766.Google Scholar
60. Kosek, M, Lee, GO, Guerrant, RL, et al., Age and sex normalization of intestinal permeability measures for improved assessment of permeability in infancy and early childhood: results from the MAL-ED study. J Pediatr Gastroenterol Nutr. 2017 (in press).Google Scholar
61. Platts-Mills, JA, Babji, S, Bodhidatta, L, et al. Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED). Lancet Glob Health. 2015; 3, e564–e575.Google Scholar
62. Mispireta, M, Caulfield, L, Zavaleta, N, et al., Effect of maternal zinc supplementation on the cardiometabolic profile of Peruvian children: results from a randomized clinical trial. J Dev Orig Health Dis. 2017; 8.1, 56–64.Google Scholar
63. Buitrago-Lopez, A, van den Hooven, EH, Rueda-Clausen, CF, et al. Socioeconomic status is positively associated with measures of adiposity and insulin resistance, but inversely associated with dyslipidaemia in Colombian children. J Epidemiol Community Health. 2015; 0, 1–8.Google Scholar
64. Kuzawa, CW, Adair, LS, Avila, JL, Cadungog, JHC, Le, N. Atherogenic lipid profiles in Filipino adolescents with low body mass index and low dietary fat intake. Am J Hum Biol. 2003; 15, 688–696.Google Scholar
65. Lazo-Porras, M, Bernabe-Ortiz, A, Málaga, G, et al. Low HDL cholesterol as a cardiovascular risk factor in rural, urban, and rural-urban migrants: PERU MIGRANT cohort study. Atherosclerosis. 2016; 246, 36–43.Google Scholar
66. Kelly, P, Besa, E, Zyambo, K, et al. Endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy. PLoS Negl Trop Dis. 2016; 10, e0004600.Google Scholar
67. Blanton, L V, Charbonneau, MR, Salih, T, et al. Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Science. 2016; 351, aa3311-1–aad3311-7.Google Scholar
68. Brown, EM, Wlodarska, M, Willing, BP, et al. Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model. Nat Commun. 2015; 6, 7806.Google Scholar
69. Cani, PD. The gut microbiota manages host metabolism. Nat Rev Endocrinol. 2013; 10, 74–76.Google Scholar
70. Camhi, SM, Katzmarzyk, PT. Tracking of cardiometabolic risk factor clustering from childhood to adulthood. Int J Pediatr Obes. 2010; 5, 122–129.Google Scholar
Supplementary material: Image

Lee supplementary material

Figure S1

Download Lee supplementary material(Image)
Image 850.6 KB
Supplementary material: File

Lee supplementary material

Tables S1-S4

Download Lee supplementary material(File)
File 28.5 KB