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Butler, Ross N.; Kosek, Margaret; Krebs, Nancy F.; Loechl, Cornelia U.; Loy, Alexander; Owino, Victor O.; Zimmermann, Michael B.; Morrison, Douglas J. (2017)
Publisher: Lippincott, Williams & Wilkins
Languages: English
Types: Article
Subjects: Article
The International Atomic Energy Agency convened a technical meeting on environmental enteric dysfunction (EED) in Vienna (28th – 30th October 2015; https://nucleus.iaea.org/HHW/Nutrition/EED_Technical_Meeting/index.html) to bring together international experts in the fields of EED, nutrition and stable isotope technologies. Advances in stable isotope labelling techniques open up new possibilities to improve our understanding of gastrointestinal dysfunction and the role of the microbiota in host health. In the context of EED, little is known about the role gut dysfunction may play in macro- and micronutrient bioavailability and requirements and what the consequences may be for nutritional status and linear growth. Stable isotope labelling techniques have been used to assess intestinal mucosal injury and barrier function, carbohydrate digestion and fermentation, protein derived amino acid bioavailability and requirements, micronutrient bioavailability and to track microbe-microbe and microbe-host interactions at the single cell level. The non-invasive nature of stable isotope technologies potentially allows for low-hazard, field deployable tests of gut dysfunction that are applicable across all age-groups. The purpose of this review is to assess the state-of-the-art in the use of stable isotope technologies and to provide a perspective on where these technologies can be exploited to further our understanding of gut dysfunction in EED.
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    • 1. 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):S239-47.
    • 2. Campbell DI, McPhail G, Lunn PG, et al. 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;39:153-7.
    • 3. Black RE, Victora CG, Walker SP, et al. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet 2013;382:427-51.
    • 4. Bhutta ZA, Das JK, Rizvi A, et al. Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost? Lancet 2013;382:452-77.
    • 5. Trehan I, Kelly P, Shaikh N, et al. New insights into environmental enteric dysfunction. Arch Dis Child 2016;101:741-4.
    • 6. Keusch GT, Denno DM, Black RE, et al. Environmental enteric dysfunction: pathogenesis, diagnosis, and clinical consequences. Clin Infect Dis 2014;59(suppl 4):S207-12.
    • 7. Romagnuolo J, Schiller D, Bailey RJ. Using breath tests wisely in a gastroenterology practice: an evidence-based review of indications and pitfalls in interpretation. Am J Gastroenterol 2002;97:1113-26.
    • 8. Klein PD, Klein ER. Applications of stable isotopes to pediatric nutrition and gastroenterology: measurement of nutrient absorption and digestion using 13C. J Pediatr Gastroenterol Nutr 1985;4:9-19.
    • 9. Leal YA, Flores LL, Fuentes-Panana EM, et al. 13C-urea breath test for the diagnosis of Helicobacter pylori infection in children: a systematic review and meta-analysis. Helicobacter 2011;16:327-37.
    • 10. Dror G, Muhsen K. Helicobacter pylori infection and children's growth: an overview. J Pediatr Gastroenterol Nutr 2016;62:e48-59.
    • 11. Butler RN. Measuring tools for gastrointestinal toxicity. Curr Opin Support Palliat Care 2008;2:35-9.
    • 12. Butler RN. Non-invasive tests in animal models and humans: a new paradigm for assessing efficacy of biologics including prebiotics and probiotics. Curr Pharm Des 2008;14:1341-50.
    • 13. Nguyen NQ, Chapman M, Fraser RJ, et al. Long-standing type II diabetes mellitus is not a risk factor for slow gastric emptying in critically ill patients. Intensive Care Med 2006;32:1365-70.
    • 14. Omari TI, Benninga MA, Sansom L, et al. Effect of baclofen on esophagogastric motility and gastroesophageal reflux in children with gastroesophageal reflux disease: a randomized controlled trial. J Pediatr 2006;149:468-74.
    • 15. Urita Y, Hike K, Torii N, et al. Efficacy of lactulose plus 13C-acetate breath test in the diagnosis of gastrointestinal motility disorders. J Gastroenterol 2002;37:442-8.
    • 16. Perman JA. Clinical application of breath hydrogen measurements. Can J Physiol Pharmacol 1991;69:111-5.
    • 17. Koetse HA, Stellaard F, Bijleveld CM, et al. Non-invasive detection of low-intestinal lactase activity in children by use of a combined 13CO2/ H2 breath test. Scand J Gastroenterol 1999;34:35-40.
    • 18. Misselwitz B, Pohl D, Fruhauf H, et al. Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment. United European Gastroenterol J 2013;1:151-9.
    • 19. Clarke JM, Pelton NC, Bajka BH, et al. Use of the 13C-sucrose breath test to assess chemotherapy-induced small intestinal mucositis in the rat. Cancer Biol Ther 2006;5:34-8.
    • 20. Pelton NS, Tivey DR, Howarth GS, et al. A novel breath test for the noninvasive assessment of small intestinal mucosal injury following methotrexate administration in the rat. Scand J Gastroenterol 2004;39:1015-6.
    • 21. Tooley KL, Saxon BR, Webster J, et al. A novel non-invasive biomarker for assessment of small intestinal mucositis in children with cancer undergoing chemotherapy. Cancer Biol Ther 2006;5:1275-81.
    • 22. Tran CD, Hawkes J, Graham RD, et al. Zinc-fortified oral rehydration solution improved intestinal permeability and small intestinal mucosal recovery. Clin Pediatr (Phila) 2015;54:676-82.
    • 23. Yazbeck R, Howarth GS, Borges L, et al. Non-invasive detection of a palifermin-mediated adaptive response following chemotherapy-induced damage to the distal small intestine of rats. Cancer Biol Ther 2011;12:399-406.
    • 24. Ritchie BK, Brewster DR, Davidson GP, et al. 13C-sucrose breath test: novel use of a noninvasive biomarker of environmental gut health. Pediatrics 2009;124:620-6.
    • 25. Ritchie BK, Brewster DR, Tran CD, et al. Efficacy of Lactobacillus GG in aboriginal children with acute diarrhoeal disease: a randomised clinical trial. J Pediatr Gastroenterol Nutr 2010;50:619-24.
    • 26. Schoeller DA. 2001 uses of stable isotopes in the assessment of nutrient status and metabolism. Forum Nutr 2003;56:310-1.
    • 27. Hiele M, Ghoos Y, Rutgeerts P, et al. Measurement of the rate of assimilation of oligo- and polysaccharides by 13CO2 breath tests and isotope ratio mass spectrometry. Biomed Environ Mass Spectrom 1988;16:133-5.
    • 28. Tanis AA, Rietveld T, Wattimena JL, et al. The 13CO2 breath test for liver glycogen oxidation after 3-day labeling of the liver with a naturally 13C-enriched diet. Nutrition 2003;19:432- 7.
    • 29. Jonderko K, Spinkova M, Kaminska M, et al. Ability to digest starch assessed noninvasively with a 13CO2 breath test - comparison of results obtained in two groups of different age. Med Sci Monit 2009;15:CR128- 33.
    • 30. Seal CJ, Daly ME, Thomas LC, et al. Postprandial carbohydrate metabolism in healthy subjects and those with type 2 diabetes fed starches with slow and rapid hydrolysis rates determined in vitro. Br J Nutr 2003;90:853- 64.
    • 31. Weaver LT, Dibba B, Sonko B, et al. Measurement of starch digestion of naturally 13C-enriched weaning foods, before and after partial digestion with amylase-rich flour, using a 13C breath test. Br J Nutr 1995;74:531- 7.
    • 32. Korach-Andre M, Roth H, Barnoud D, et al. Glucose appearance in the peripheral circulation and liver glucose output in men after a large 13C starch meal. Am J Clin Nutr 2004;80:881- 6.
    • 33. Vinoy S, Normand S, Meynier A, et al. Cereal processing influences postprandial glucose metabolism as well as the GI effect. J Am Coll Nutr 2013;32:79 - 91.
    • 34. Robertson MD, Livesey G, Mathers JC. Quantitative kinetics of glucose appearance and disposal following a 13C-labelled starch-rich meal: comparison of male and female subjects. Br J Nutr 2002;87:569-77.
    • 35. Boets E, Deroover L, Houben E, et al. Quantification of in vivo colonic short chain fatty acid production from inulin. Nutrients 2015;7:8916- 29.
    • 36. Lifschitz CH, Grusak MA, Butte NF. Carbohydrate digestion in humans from a beta-glucan-enriched barley is reduced. J Nutr 2002;132:2593- 6.
    • 37. Ghosh S, Suri D, Uauy R. Assessment of protein adequacy in developing countries: quality matters. Br J Nutr 2012;108(suppl 2):S77- 87.
    • 38. Semba RD, Shardell M, Sakr Ashour FA, et al. Child stunting is associated with low circulating essential amino acids. EBioMedicine 2016;6:246 - 52.
    • 39. Elango R, Levesque C, Ball RO, et al. Available versus digestible amino acids: new stable isotope methods. Br J Nutr 2012;108(suppl 2):S306- 14.
    • 40. Tome D. Criteria and markers for protein quality assessment: a review. Br J Nutr 2012;108(suppl 2):S222- 9.
    • 41. Bos C, Mahe S, Gaudichon C, et al. Assessment of net postprandial protein utilization of 15N-labelled milk nitrogen in human subjects. Br J Nutr 1999;81:221- 6.
    • 42. Mariotti F, Mahe S, Benamouzig R, et al. Nutritional value of [15N]-soy protein isolate assessed from ileal digestibility and postprandial protein utilization in humans. J Nutr 1999;129:1992- 7.
    • 43. Juillet B, Saccomani MP, Bos C, et al. Conceptual, methodological and computational issues concerning the compartmental modeling of a complex biological system: postprandial inter-organ metabolism of dietary nitrogen in humans. Math Biosci 2006;204:282- 309.
    • 44. Elango R, Humayun MA, Ball RO, et al. Protein requirement of healthy school-age children determined by the indicator amino acid oxidation method. Am J Clin Nutr 2011;94:1545- 52.
    • 45. Pennings B, Groen B, de Lange A, et al. Amino acid absorption and subsequent muscle protein accretion following graded intakes of whey protein in elderly men. Am J Physiol Endocrinol Metab 2012; 302:E992- 9.
    • 46. Pennings B, Groen BB, van Dijk JW, et al. Minced beef is more rapidly digested and absorbed than beefsteak, resulting in greater postprandial protein retention in older men. Am J Clin Nutr 2013;98:121-8.
    • 47. Engelen MP, Com G, Anderson PJ, et al. New stable isotope method to measure protein digestibility and response to pancreatic enzyme intake in cystic fibrosis. Clin Nutr 2014;33:1024-32.
    • 48. Tome D, Jahoor F, Kurpad A, et al. Current issues in determining dietary protein quality and metabolic utilization. Eur J Clin Nutr 2014; 38:537 - 8.
    • 49. NATIONS FAAOOTU. FAO Research Approaches and Methods for Evaluating the Protein Quality of Human Foods.NATIONS FAAOOTU; 2014:ISBN 978-92-5-108695-7.
    • 50. Kasumov T, Ilchenko S, Li L, et al. Measuring protein synthesis using metabolic (2)H labeling, high-resolution mass spectrometry, and an algorithm. Anal Biochem 2011;412:47- 55.
    • 51. Claydon AJ, Thom MD, Hurst JL, et al. Protein turnover: measurement of proteome dynamics by whole animal metabolic labelling with stable isotope labelled amino acids. Proteomics 2012;12:1194- 206.
    • 52. MacDonald AJ, Small AC, Greig CA, et al. A novel oral tracer procedure for measurement of habitual myofibrillar protein synthesis. Rapid Commun Mass Spectrom 2013;27:1769- 77.
    • 53. Ventrucci M, Cipolla A, Ubalducci GM, et al. 13C labelled cholesteryl octanoate breath test for assessing pancreatic exocrine insufficiency. Gut 1998;42:81 - 7.
    • 54. Amarri S, Harding M, Coward WA, et al. 13Carbon mixed triglyceride breath test and pancreatic enzyme supplementation in cystic fibrosis. Arch Dis Child 1997;76:349- 51.
    • 55. Nakamura H, Murakami Y, Morifuji M, et al. Analysis of fat digestive and absorptive function after subtotal gastrectomy by a 13C-labeled mixed triglyceride breath test. Digestion 2009;80:98-103.
    • 56. Chavez-Jauregui RN, Mattes RD, Parks EJ. Dynamics of fat absorption and effect of sham feeding on postprandial lipema. Gastroenterology 2010;139:1538 -48.
    • 57. Krebs NF, Miller L, Naake V, et al. The use of stable isotope techniques to assess zinc metabolism 1995;6:292- 301.
    • 58. Krebs NF, Miller LV, Hambidge KM. Zinc deficiency in infants and children: a review of its complex and synergistic interactions. Paediatr Int Child Health 2014;34:279- 88.
    • 59. Miller LV, Hambidge KM, Krebs NF. Zinc absorption is not related to dietary phytate intake in infants and young children based on modeling combined data from multiple studies. J Nutr 2015;145:1763- 9.
    • 60. Kastenmayer P, Davidsson L, Galan P, et al. A double stable isotope technique for measuring iron absorption in infants. Br J Nutr 1994;71:411- 24.
    • 61. Troesch B, Egli I, Zeder C, et al. Fortification iron as ferrous sulfate plus ascorbic acid is more rapidly absorbed than as sodium iron EDTA but neither increases serum nontransferrin-bound iron in women. J Nutr 2011;141:822- 7.
    • 62. Zimmermann MB, Hurrell RF. Nutritional iron deficiency. Lancet 2007;370:511- 20.
    • 63. Troesch B, Egli I, Zeder C, et al. Optimization of a phytase-containing micronutrient powder with low amounts of highly bioavailable iron for in-home fortification of complementary foods. Am J Clin Nutr 2009;89:539- 44.
    • 64. Zimmermann MB, Harrington M, Villalpando S, et al. Nonheme-iron absorption in first-degree relatives is highly correlated: a stable-isotope study in mother-child pairs. Am J Clin Nutr 2010;91:802- 7.
    • 65. de Souza N. Supplement on single-cell analysis. Nat Meth 2011;8:S1 - 1.
    • 66. de Souza N. Single-cell methods. Nat Meth 2012;9:35-135.
    • 67. Stecher B, Berry D, Loy A. Colonization resistance and microbial ecophysiology: using gnotobiotic mouse models and single-cell technology to explore the intestinal jungle. FEMS Microbiol Rev 2013;37:793- 829.
    • 68. Berry D, Stecher B, Schintlmeister A, et al. Host-compound foraging by intestinal microbiota revealed by single-cell stable isotope probing. Proc Natl Acad Sci USA 2013;110:4720 - 5.
    • 69. Berry D, Mader E, Lee TK, et al. Tracking heavy water (D2O) incorporation for identifying and sorting active microbial cells. Proc Natl Acad Sci USA 2015;112:E194 - 203.
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