2. Liu, L, Oza, S, Hogan, D, et al. (2015) Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet 385, 430–440.
4. DeBoer, MD, Lima, AAM, Oría, RB, et al. (2012) Early childhood growth failure and the developmental origins of adult disease: do enteric infections and malnutrition increase risk for the metabolic syndrome? Nutr Rev 70, 642–653.
5. Victora, CG, Adair, L, Fall, C, et al. (2008) Maternal and child undernutrition: consequences for adult health and human capital. Lancet 371, 340–357.
6. Blanton, LV, Barratt, MJ, Charbonneau, MR, et al. (2016) Childhood undernutrition, the gut microbiota, and microbiota-directed therapeutics. Science 352, 1533.
7. Drozdowski, LA, Thomson, AB & Clandinin, T (2010) Ontogeny, growth and development of the small intestine: understanding pediatric gastroenterology. World J Gastroenterol 6, 787–799.
8. Grantham-McGregor, S, Cheung, YB, Cueto, S, et al. (2007) Developmental potential in the first 5 years for children in developing countries. Lancet 369, 60–70.
9. Bhutta, ZA, Ahmed, T, Black, RE, et al. (2008) What works? Interventions for maternal and child undernutrition and survival. Lancet 371, 417–440.
10. Ziegler, A, Gonzalez, L & Blikslager, A (2016) Large animal models: the key to translational discovery in digestive disease research. Cell Mol Gastroenterol Hepatol 2, 716–724.
11. Garas, LC, Feltrin, C, Hamilton, MK, et al. (2016) Milk with and without lactoferrin can influence intestinal damage in a pig model of malnutrition. Food Funct 7, 665–678.
12. Masschalck, B & Michiels, CW (2003) Antimicrobial properties of lysozyme in relation to foodborne vegetative bacteria. Crit Rev Microbiol 29, 191–214.
13. Walker, A (2010) Breast milk as the gold standard for protective nutrients. J Pediatr 156, S3–S7.
14. Lönnerdal, B (2013) Bioactive proteins in breast milk. J Paediatr Child Health 49, Suppl. 1, 1–7.
15. Maga, EA, Shoemaker, CF, Rowe, JD, et al. (2006) Production and processing of milk from transgenic goats expressing human lysozyme in the mammary gland. J Dairy Sci 89, 518–524.
16. Maga, EA, Desai, PT, Weimer, BC, et al. (2012) Consumption of lysozyme-rich milk can alter microbial fecal populations. Appl Environ Microbiol 78, 6153–6160.
17. Cooper, CA, Brundige, DR, Reh, WA, et al. (2011) Lysozyme transgenic goats’ milk positively impacts intestinal cytokine expression and morphology. Transgenic Res 20, 1235–1243.
18. Cooper, CA, Garas Klobas, LC, Maga, EA, et al. (2013) Consuming transgenic goats’ milk containing the antimicrobial protein lysozyme helps resolve diarrhea in young pigs. PLOS ONE 8, e58409.
19. Garas, LC, Cooper, CA, Dawson, MW, et al. (2017) Young pigs consuming lysozyme transgenic goat milk are protected from clinical symptoms of enterotoxigenic Escherichia coli infection. J Nutr 147, 2050–2059.
20. Fairbrother, JM, Nadeau, E & Gyles, CL (2005)
Escherichia coli in postweaning diarrhea in pigs: an update on bacterial types, pathogenesis, and prevention strategies. Anim Health Res Rev 6, 17–39.
21. Smiricky, MR, Grieshop, CM, Albin, DM, et al. (2002) The influence of soy oligosaccharides on apparent and true ileal amino acid digestibilities and fecal consistency in growing pigs. J Anim Sci 80, 2433–2441.
22. Mon, KK, Saelao, P, Halstead, MM, et al. (2015)
Salmonella enterica Serovars Enteritidis infection alters the indigenous microbiota diversity in young layer chicks. Front Vet Sci 2, 61.
23. Nygard, A-B, Jørgensen, CB, Cirera, S, et al. (2007) Selection of reference genes for gene expression studies in pig tissues using SYBR green qPCR. BMC Mol Biol 8, 67.
24. Wang, F, Wang, J, Liu, D, et al. (2010) Normalizing genes for real-time polymerase chain reaction in epithelial and nonepithelial cells of mouse small intestine. Anal Biochem 399, 211–217.
25. Jensen, G, Frydendahl, K, Svendsen, O, et al. (2006) Experimental infection with Escherichia coli O149:F4ac in weaned piglets. Vet Microbiol 15, 243–249.
26. Caporaso, JG, Kuczynski, J, Stombaugh, J, et al. (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7, 335–336.
27. Bokulich, NA, Joseph, CML, Allen, G, et al. (2012) Next-generation sequencing reveals significant bacterial diversity of botrytized wine. PLOS ONE 7, e36357.
28. McDonald, D, Price, MN, Goodrich, J, et al. (2012) An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea. ISME J 6, 610–618.
29. Segata, N, Izard, J, Waldron, L, et al. (2011) Metagenomic biomarker discovery and explanation. Genome Biol 12, R60.
30. Ley, RE, Turnbaugh, PJ, Klein, S, et al. (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022–1023.
31. Subramanian, S, Huq, S, Yatsunenko, T, et al. (2014) Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature 510, 417–421.
32. Fan, P, Liu, P, Song, P, et al. (2017) Moderate dietary protein restriction alters the composition of gut microbiota and improves ileal barrier function in adult pig model. Sci Rep 7, 43412.
33. Monira, S, Nakamura, S, Gotoh, K, et al. (2011) Gut microbiota of healthy and malnourished children in Bangladesh. Front Microbiol 2, 228.
34. Dinh, DM, Ramadass, B, Kattula, D, et al. (2016) Longitudinal analysis of the intestinal microbiota in persistently stunted young children in south India. PLOS ONE 11, e0155405.
35. Smith, MI, Yatsunenko, T, Manary, MJ, et al. (2013) Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 339, 548–554.
36. Roccarina, D, Lauritano, EC, Gabrielli, M, et al. (2010) The role of methane in intestinal diseases. Am J Gastroenterol 105, 1250–1256.
37. Triantafyllou, K, Chang, C & Pimentel, M (2014) Methanogens, methane and gastrointestinal motility. J Neurogastroenterol Motil 20, 31–40.
38. Rose, R, Whipp, SC & Moon, HW (1987) Effects of Escherichia coli heat-stable enterotoxin b on small intestinal villi in pigs, rabbits and lambs. Vet Pathol 24, 71–79.
39. Liu, P, Piao, XS, Thacker, PA, et al. (2010) Chito-oligosaccharide reduced diarrhea incidence and attenuates the immune response of weaned pigs challenged with Escherichia coli K88. J Anim Sci 88, 3871–3879.
40. Yi, GF, Carroll, JA, Allee, GL, et al. (2005) Effect of glutamine and spray-dried plasma on growth performance, small intestine morphology, and immune responses of Escherichia coliI K88+-challenged weaned pigs. J Anim Sci 83, 634–643.
41. Souba, WW (1991) Glutamine: a key substrate for the splanchnic bed. Annu Rev Nutr 11, 285–308.
42. Huang, Y, Shao, XM & Neu, J (2003) Immunonutrients and neonates. Eur J Pediatr 162, 122–128.
43. Lykke, M, Hother, AL, Hansen, CF, et al. (2013) Malnutrition induces gut atrophy and increases hepatic fat infiltration: studies in a pig model of childhood malnutrition. Am J Transl Res 5, 543–554.
44. McKay, S, Gaudier, E, Campbell, DI, et al. (2010) Environmental enteropathy: new targets for nutritional interventions. Int Health 2, 172–180.
45. Korpe, PS & Petri, WA Jr (2012) Environmental enteropathy: critical implications of a poorly understood condition. Trends Mol Med 18, 328–336.
46. Ferraris, RP & Carey, HV (2000) Intestinal transport during fasting and malnutrition. Annu Rev Nutr 20, 195–219.
47. Blanton, LV, Charbonneau, MR, Salih, T, et al. (2016) Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Science 351, 6275.
48. Ghosh, TS, Gupta, SS, Bhattacharya, T, et al. (2014) Gut microbiomes of Indian children of varying nutritional status. PLOS ONE 9, e95547.
49. Liu, Y, Song, M, Che, TM, et al. (2014) Dietary plant extracts alleviate diarrhea and alter immune responses of weaned pigs experimentally infected with a pathogenic Escherichia coli
. J Anim Sci 91, 5294–5306.
50. Youmans, BP, Ajami, NJ, Jiang, ZD, et al. (2015) Characterization of the human gut microbiome during travelers’ diarrhea. Gut Microbes 6, 110–119.
51. Thomson, AW & Knolle, PA (2010) Antigen-presenting cell function in the tolerogenic liver environment. Nat Rev Immunol 10, 753–766.