Volume 86, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



A spectrum of enteropathies, characterized by small intestinal inflammation, reduced absorptive capacity, and increased intestinal permeability, commonly affect people in developing countries. This subclinical intestinal pathology facilitates microbial translocation across the compromised intestinal barrier, leading to chronic systemic inflammation that may adversely impact health. Environmental enteropathy (EE), ubiquitous among people living in unhygienic conditions, likely mediates two interlinked public health problems of childhood, stunting and anemia, and underlies poor oral vaccine efficacy in developing countries. Human immunodeficiency virus (HIV) enteropathy, which frequently overlaps with EE, may contribute to immune activation and modulate HIV disease progression. The interacting effects of infection and enteropathy drive a vicious cycle that can propagate severe acute malnutrition, which underlies almost half of under-5-y deaths. Enteropathies are therefore highly prevalent, interacting causes of morbidity and mortality in developing countries. Interventions to prevent or ameliorate enteropathies have potential to improve the health of millions of people in developing countries.


Article metrics loading...

Loading full text...

Full text loading...



  1. Desai HG, Borkar AV, Pathare SM, Dighe PK, Jeejeebhoy KN, , 1969. ‘Flat’ jejunal mucosa in the tropics. Indian J Med Sci 23: 15.
  2. Schenk EA, Samloff IM, Klipstein FA, , 1968. Morphology of small bowel biopsies. Am J Clin Nutr 21: 944961.
  3. Lindenbaum J, Harmon JW, Gerson CD, , 1972. Subclinical malabsorption in developing countries. Am J Clin Nutr 25: 10561061.
  4. Menzies IS, Zuckerman MJ, Nukajam WS, Somasundaram SG, Murphy B, Jenkins AP, Crane RS, Gregory GG, , 1999. Geography of intestinal permeability and absorption. Gut 44: 483489.[Crossref]
  5. Campbell DI, Elia M, Lunn PG, , 2003. Growth faltering in rural Gambian infants is associated with impaired small intestinal barrier function, leading to endotoxemia and systemic inflammation. J Nutr 133: 13321338.
  6. Lunn PG, Northrop-Clewes CA, Downes RM, , 1991. Intestinal permeability, mucosal injury, and growth faltering in Gambian infants. Lancet 338: 907910.[Crossref]
  7. Black RE, Allen LH, Bhutta ZA, Caulfield LE, de Onis M, Ezzati M, Mathers C, Rivera J, Maternal and Child Undernutrition Study Group, 2008. Maternal and child undernutrition: global and regional exposures and health consequences. Lancet 371: 243260.[Crossref]
  8. Victora CG, de Onis M, Hallal PC, Blossner M, Shrimpton R, , 2010. Worldwide timing of growth faltering: revisiting implications for interventions. Pediatrics 125: e473e480.[Crossref]
  9. Kelly P, Menzies I, Crane R, Zulu I, Nickols C, Feakins R, Mwamsa K, Mudenda V, Katubulushi M, Greenwald S, Farthing M, , 2004. Responses of small intestinal architecture and function over time to environmental factors in a tropical population. Am J Trop Med Hyg 70: 412419.
  10. Baker SJ, , 1976. Subclinical intestinal malabsorption in developing countries. Bull World Health Organ 54: 485494.
  11. Gerson CD, Kent TH, Saha JR, Siddiqi N, Lindenbaum J, , 1971. Recovery of small-intestinal structure and function after residence in the tropics. II. Studies in Indians and Pakistanis living in New York City. Ann Intern Med 75: 4148.[Crossref]
  12. Lindenbaum J, Gerson CD, Kent TH, , 1971. Recovery of small-intestinal structure and function after residence in the tropics. I. Studies in Peace Corps volunteers. Ann Intern Med 74: 218222.[Crossref]
  13. Veitch AM, Kelly P, Zulu IS, Segal I, Farthing MJ, , 2001. Tropical enteropathy: a T-cell-mediated crypt hyperplastic enteropathy. Eur J Gastroenterol Hepatol 13: 11751181.[Crossref]
  14. Dhaliwal W, Bajaj-Elliott M, Kelly P, , 2003. Intestinal defensin gene expression in human populations. Mol Immunol 40: 469475.[Crossref]
  15. Dewey KG, Adu-Afarwuah S, , 2008. Systematic review of the efficacy and effectiveness of complementary feeding interventions in developing countries. Maternal and Child Nutrition. Blackwell Publishing Ltd: Program in International and Community Nutrition, University of California, Davis, CA.
  16. Black RE, Brown KH, Becker S, , 1984. Effects of diarrhea associated with specific enteropathogens on the growth of children in rural Bangladesh. Pediatrics 73: 799805.
  17. Checkley W, Epstein LD, Gilman RH, Cabrera L, Black RE, , 2003. Effects of acute diarrhea on linear growth in Peruvian children. Am J Epidemiol 157: 166175.[Crossref]
  18. Rowland MG, Rowland SG, Cole TJ, , 1988. Impact of infection on the growth of children from 0 to 2 years in an urban West African community. Am J Clin Nutr 47: 134138.
  19. Assis AM, Barreto ML, Santos LM, Fiaccone R, da Silva Gomes GS, , 2005. Growth faltering in childhood related to diarrhea: a longitudinal community based study. Eur J Clin Nutr 59: 13171323.[Crossref]
  20. Moore SR, Lima AA, Conaway MR, Schorling JB, Soares AM, Guerrant RL, , 2001. Early childhood diarrhoea and helminthiases associate with long-term linear growth faltering. Int J Epidemiol 30: 14571464.[Crossref]
  21. Checkley W, Buckley G, Gilman RH, Assis AM, Guerrant RL, Morris SS, Mølbak K, Valentiner-Branth P, Lanata CF, Black RE, Childhood Malnutrition, Infection Network, , 2008. Multi-country analysis of the effects of diarrhoea on childhood stunting. Int J Epidemiol 37: 816830.[Crossref]
  22. Fewtrell L, Kaufmann RB, Kay D, Enanoria W, Haller L, Colford JM, Jr, 2005. Water, sanitation, and hygiene interventions to reduce diarrhoea in less developed countries: a systematic review and meta-analysis. Lancet Infect Dis 5: 4252.[Crossref]
  23. Bhutta ZA, Ahmed T, Black RE, Cousens S, Dewey K, Giugliani E, Haider BA, Kirkwood B, Morris SS, Sachdev HP, Shekar M, Maternal and Child Undernutrition Study Group, 2008. What works? Interventions for maternal and child undernutrition and survival. Lancet 371: 417440.[Crossref]
  24. Briend A, Hasan KZ, Aziz KM, Hoque BA, , 1989. Are diarrhoea control programmes likely to reduce childhood malnutrition? Observations from rural Bangladesh. Lancet 2: 319322.[Crossref]
  25. Moy RJ, de C Marshall TF, Choto RG, McNeish AS, Booth IW, , 1994. Diarrhoea and growth faltering in rural Zimbabwe. Eur J Clin Nutr 48: 810821.
  26. DeMaeyer E, Adiels-Tegman M, , 1985. The prevalence of anemia in the world. World Health Stat Q Rep. 38: 302316.
  27. Levine MM, , 2010. Immunogenicity and efficacy of oral vaccines in developing countries: lessons from a live cholera vaccine. BMC Biol 8: 129.[Crossref]
  28. Armah GE, Sow SO, Breiman RF, Dallas MJ, Tapia MD, Feikin DR, Binka FN, Steele AD, Laserson KF, Ansah NA, Levine MM, Lewis K, Attah-Poku M, Ojwando J, Rivers SB, Victor JC, Nyambane G, Hodgson A, Schödel F, Ciarlet M, Neuzil KM, , 2010. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomized, double-blind, placebo-controlled trial. Lancet 376: 606614.[Crossref]
  29. Zaman K, Dang DA, Victor JC, Shin S, Yunus M, Dallas MJ, Podder G, Vu DT, Le TP, Luby SP, Le HT, Coia ML, Lewis K, Rivers SB, Sack DA, Schödel F, Steele AD, Neuzil KM, Ciarlet M, , 2010. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Asia: a randomized, double-blind, placebo-controlled trial. Lancet 376: 615623.[Crossref]
  30. Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, Abate H, Breuer T, Clemens SC, Cheuvart B, Espinoza F, Gzillare P, Innis BL, Gervantes Y, Linhares AC, López P, Macias-Parra M, Ortega-Barria E, Richardson V, Riveria-Medina DM, Rivera L, Salinas B, Pavia-Ruz N, Salmerón J, Rüttimann R, Tinoco JC, Rubio P, Nuñez E, Guerrero ML, Yarzábal JP, Damaso S, Torniepporth N, Sáez-Llorens X, Vergara RF, Vesikari T, Bouckenoogle A, Clemens R, De Vos B, O'Ryan M, Human Rotavirius Vaccine Study Group, 2006. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med 354: 1122.[Crossref]
  31. Vesikari T, Matson DO, Dennehy P, Van Damme P, Santosham M, Rodriguez Z, Dallas MJ, Heyse JF, Goveia MG, Black SB, Shinefield HR, Christie CD, Ylitalo S, Itzler RF, Coia ML, Onorato MT, Adeyi BA, Marshall GS, Gothefors L, Compens D, Karvonen A, Watt JP, O'Brian KL, DiNubile MJ, Boslego JW, Offit PA, Heaton PM, Rotavirus Efficacy and Safety Trial (REST) Study Group, 2006. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med 354: 2333.[Crossref]
  32. Petri WA, Jr, 2011. Genetic Basis of Malnutrition. Malnutrition, Gut-Microbial Interactions and Mucosal Immunity to Vaccines. November 7–11, New Delhi, India.
  33. Serwadda D, Mugerwa RD, Sewankambo NK, Lwegaba A, Carswell JW, Kirya GB, Bayley AC, Downing RG, Tedder RS, Clayden SA, Bayley AC, Downing RG, Tedder RS, Clayden SA, , 1985. Slim disease: a new disease in Uganda and its association with HTLV-III infection. Lancet 2: 849852.[Crossref]
  34. Keating J, Bjarnason I, Somasundaram S, Macpherson A, Francis N, Price AB, Sharpstone D, Smithson J, Menzies IS, Gozzard BG, , 1995. Intestinal absorptive capacity, intestinal permeability and jejunal histology in HIV and their relation to diarrhoea. Gut 37: 623629.[Crossref]
  35. Kapembwa MS, Fleming SC, Sewankambo N, Serwadda D, Lucas S, Moody A, Griffin GE, , 1991. Altered small-intestinal permeability associated with diarrhoea in human-immunodeficiency-virus-infected Caucasian and African subjects. Clin Sci (Lond) 81: 327334.[Crossref]
  36. Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, Blazar BR, Rodriguez B, Teixeira-Johnson L, Landay A, Martin JN, Hecht FM, Lederman MM, Deeks SG, Douek DC, , 2006. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12: 13651371.[Crossref]
  37. Kelly P, Davies SE, Mandanda B, Veitch A, McPhail G, Zulu I, Drobniewski F, Fuchs D, Summerbell C, Luo NP, Pobee JO, Farthing JM, , 1997. Enteropathy in Zambians with HIV related diarrhoea: regression modelling of potential determinants of mucosal damage. Gut 41: 811816.[Crossref]
  38. Batman PA, Miller AR, Forster SM, Harris JR, Pinching AJ, Griffin GE, , 1989. Jejunal enteropathy associated with human immunodeficiency virus infection: quantitative histology. J Clin Pathol 42: 275281.[Crossref]
  39. Cummins AG, LaBrooy JT, Stanley DP, Rowland R, Shearman DJ, , 1990. Quantitative histological study of enteropathy associated with HIV infection. Gut 31: 317321.[Crossref]
  40. Miller AR, Griffin GE, Batman P, Farquar C, Forster SM, Pinching AJ, Harris JR, , 1988. Jejunal mucosal architecture and fat absorption in male homosexuals infected with human immunodeficiency virus. Q J Med 69: 10091019.
  41. Bjarnason I, Sharpstone DR, Francis N, Marker A, Taylor C, Barrett M, Macpherson A, Baldwin C, Menzies IS, Crane RC, Smith T, Pozniak A, Gazzard BG, , 1996. Intestinal inflammation, ileal structure and function in HIV. AIDS 10: 13851391.[Crossref]
  42. Veazey RS, DeMaria M, Chalifoux LV, Shvetz DE, Pauley DR, Knight HL, Rosenzweig M, Johnson RP, Desrosiers RC, Lackner AA, , 1998. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280: 427431.[Crossref]
  43. Brenchley JM, Paiardini M, Knox KS, Asher AI, Cervasi B, Asher TE, Cervasi B, Asher TE, Scheinberg P, Price DA, Hage CA, Kholi LM, Khoruts A, Frank I, Else J, Schacker T, Silvestri G, Douek DC, , 2008. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood 112: 28262835.[Crossref]
  44. Nazli A, Chan O, Dobson-Belaire WN, Ouellet M, Tremblay MJ, Gray-Owen SD, Arsenaulat AL, Kaushic C, , 2010. Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS Pathog 6: e1000852.
  45. Redd AD, Gray RH, Quinn TC, , 2011. Is microbial translocation a cause or consequence of HIV disease progression? J Infect Dis 203: 744745, author reply 746.[Crossref]
  46. Lester RT, Yao XD, Ball TB, McKinnon LR, Omange WR, Kaul R, Wachihi C, Jaoko W, Rosenthal KL, Plummer FA, , 2009. HIV-1 RNA dysregulates the natural TLR response to subclinical endotoxemia in Kenyan female sex-workers. PLoS ONE 4: e5644.[Crossref]
  47. Redd AD, Dabitao D, Bream JH, Charvat B, Laeyendecker O, Kiwanuka N, Lutalo T, Kigozi G, Tobian AA, Gamiel J, Neal JD, Oliver AE, Margolick JB, Sewankambo N, Reynolds SJ, Wawer MJ, Serwadda D, Gray RH, Quinn TC, , 2009. Microbial translocation, the innate cytokine response, and HIV-1 disease progression in Africa. Proc Natl Acad Sci USA 106: 67186723.[Crossref]
  48. Cassol E, Malfeld S, Mahasha P, van der Merwe S, Cassol S, Seebregts C, Alfano M, Poli G, Rossouw T, , 2010. Persistent microbial translocation and immune activation in HIV-1-infected South Africans receiving combination antiretroviral therapy. J Infect Dis 202: 723733.[Crossref]
  49. Sandler NG, Wand H, Roque A, Law M, Nason MC, Nixon DE, Pedersen C, Ruxrungtham K, Lewin SR, Emery S, Neaton JD, Brenchley M, Deeks SG, Sereti I, Douek DC, INSIGHT SMART Study Group, 2011. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis 203: 780790.[Crossref]
  50. Hunt PW, Cao HL, Muzoora C, Ssewanyana I, Bennett J, Emenyonu N, Kembabazi A, Neilands TB, Bargsberg DR, Deeks SG, Martin JN, , 2011. Impact of CD8+ T cell activation on CD4+ T cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy. AIDS 25: 21232131.[Crossref]
  51. Jiang W, Lederman MM, Hunt P, Sieg SF, Haley K, Rodriguez B, Landay A, Martin J, Sinclair E, Asher AI, Deeks SG, Douek DC, Brenchley JM, , 2009. Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection. J Infect Dis 199: 11771185.[Crossref]
  52. Marchetti G, Bellistri GM, Borghi E, Tincati C, Ferramosca S, La Francesca M, Morace G, Gori A, Monforte AD, , 2008. Microbial translocation is associated with sustained failure in CD4+ T-cell reconstitution in HIV-infected patients on long-term highly active antiretroviral therapy. AIDS 22: 20352038.[Crossref]
  53. Behrens RH, Lunn PG, Northrop CA, Hanlon PW, Neale G, , 1987. Factors affecting the integrity of the intestinal mucosa of Gambian children. Am J Clin Nutr 45: 14331441.
  54. Guerrant RL, Oria RB, Moore SR, Oria MO, Lima AA, , 2008. Malnutrition as an enteric infectious disease with long-term effects on child development. Nutr Rev 66: 487505.[Crossref]
  55. Mata LJ, , 1978. The Children of Santa Maria Cauque: A Prospective Field Study of Health and Growth. Cambridge, MA: MIT Press.
  56. Kotloff KL, , 2011. “Top 5” attributable pathogens of moderate and severe diarrhea (by age, study site and clinical presentation) and mortality and linear growth consequences. 60th Annual Meeting of the American Society of Tropical Medicine and Hygiene, Philadelphia, PA.
  57. Black RE, Brown KH, Becker S, , 1984. Malnutrition is a determining factor in diarrheal duration, but not incidence, among young children in a longitudinal study in rural Bangladesh. Am J Clin Nutr 39: 8794.
  58. Palmer DL, Koster FT, Alam AK, Islam MR, , 1976. Nutritional status: a determinant of severity of diarrhea in patients with cholera. J Infect Dis 134: 814.[Crossref]
  59. Tomkins A, , 1981. Nutritional status and severity of diarrhoea among pre-school children in rural Nigeria. Lancet 1: 860862.[Crossref]
  60. Schorling JB, McAuliffe JF, de Souza MA, Guerrant RL, , 1990. Malnutrition is associated with increased diarrhoea incidence and duration among children in an urban Brazilian slum. Int J Epidemiol 19: 728735.[Crossref]
  61. Mondal D, Minak J, Alam M, Liu Y, Dai J, Korpe P, Liu L, Haque R, Petri WA, Jr, 2011. Contribution of enteric infection, altered intestinal barrier function, and maternal malnutrition to infant malnutrition in Bangladesh. Clin Infect Dis 54: 185192.[Crossref]
  62. Wuehler SE, Peerson JM, Brown KH, , 2005. Use of national food balance data to estimate the adequacy of zinc in national food supplies: methodology and regional estimates. Public Health Nutr 8: 812819.[Crossref]
  63. Koo SI, Turk DE, , 1977. Effect of zinc deficiency on the ultrastructure of the pancreatic acinar cell and intestinal epithelium in the rat. J Nutr 107: 896908.
  64. Bahl R, Bhandari N, Hambidge KM, Bhan MK, , 1998. Plasma zinc as a predictor of diarrheal and respiratory morbidity in children in an urban slum setting. Am J Clin Nutr 68 (Suppl 2): 414S417S.
  65. Lukacik M, Thomas RL, Aranda JV, , 2008. A meta-analysis of the effects of oral zinc in the treatment of acute and persistent diarrhea. Pediatrics 121: 326336.[Crossref]
  66. Manary MJ, Abrams SA, Griffin IJ, Quimper MM, Shulman RJ, Hamzo MG, Chen Z, Maleta K, Manary MJ, , 2010. Perturbed zinc homeostasis in rural 3–5-y-old Malawian children is associated with abnormalities in intestinal permeability attributed to tropical enteropathy. Pediatr Res 67: 671675.[Crossref]
  67. Gong YY, Egal S, Hounsa A, Turner PC, Hall AJ, Cardwell KF, Wild CP, , 2003. Determinants of aflatoxin exposure in young children from Benin and Togo, West Africa: the critical role of weaning. Int J Epidemiol 32: 556562.[Crossref]
  68. Bouhet S, Oswald IP, , 2005. The effects of mycotoxins, fungal food contaminants, on the intestinal epithelial cell-derived innate immune response. Vet Immunol Immunopathol 108: 199209.[Crossref]
  69. Gong YY, Cardwell K, Hounsa A, Egal S, Turner PC, Hall AJ, Wild CP, , 2002. Dietary aflatoxin exposure and impaired growth in young children from Benin and Togo: cross sectional study. BMJ 325: 2021.[Crossref]
  70. Diamant M, Blaak EE, de Vos WM, , 2011. Do nutrient-gut-microbiota interactions play a role in human obesity, insulin resistance and type 2 diabetes? Obes Rev 12: 272281.[Crossref]
  71. Hotamisligil GS, Erbay E, , 2008. Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol 8: 923934.[Crossref]
  72. Baalwa J, Byarugaba BB, Kabagambe KE, Otim AM, , 2010. Prevalence of overweight and obesity in young adults in Uganda. Afr Health Sci 10: 367373.
  73. Shayo GA, Mugusi FM, , 2011. Prevalence of obesity and associated risk factors among adults in Kinondoni municipal district, Dar es Salaam Tanzania. BMC Public Health 11: 365.[Crossref]
  74. Wee BS, Poh BK, Bulgiba A, Ismail MN, Ruzita AT, Hills AP, , 2011. Risk of metabolic syndrome among children living in metropolitan Kuala Lumpur: a case control study. BMC Public Health 11: 333.[Crossref]
  75. Salazar-Lindo E, Allen S, Brewster DR, Elliott EJ, Fasano A, Phillips AD, Sanderson IR, Tarr PI, Latin American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, 2004. Intestinal infections and environmental enteropathy: Working Group report of the second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 39 (Suppl 2): S662S669.[Crossref]
  76. Gartner LM, Morton J, Lawrence RA, Naylor AJ, O'Hare D, Schanler RJ, Eidelman AI, American Academy of Pediatrics Section on Breastfeeding, 2005. Breastfeeding and the use of human milk. Pediatrics 115: 496506.[Crossref]
  77. Trehan I, Shulman RJ, Ou CN, Maleta K, Manary MJ, , 2009. A randomized, double-blind, placebo-controlled trial of rifaximin, a nonabsorbable antibiotic, in the treatment of tropical enteropathy. Am J Gastroenterol 104: 23262333.[Crossref]
  78. Galpin L, Manary MJ, Fleming K, Ou CN, Ashorn P, Shulman RJ, , 2005. Effect of Lactobacillus GG on intestinal integrity in Malawian children at risk of tropical enteropathy. Am J Clin Nutr 82: 10401045.
  79. Kerac M, Bunn J, Seal A, Thindwa M, Tomkins A, Sadler K, Bahwere P, Collins S, , 2009. Probiotics and prebiotics for severe acute malnutrition (PRONUT study): a double-blind efficacy randomised controlled trial in Malawi. Lancet 374: 136144.[Crossref]
  80. Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI, , 2011. Human nutrition, the gut microbiome and the immune system. Nature 474: 327336.[Crossref]
  81. Smith MI, , 2011. Metagenomic Studies of Humanized Gnotobiotic Mice Harboring the Gut Microbiomes of Malawian Twins Discordant for Kwashiorkor. Malnutrition, Gut-Microbial Interactions and Mucosal Immunity to Vaccines. November 7–11, 2011, New Delhi, India.

Data & Media loading...

  • Received : 30 Nov 2011
  • Accepted : 06 Feb 2012

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error