REFERENCES
1. Roura E, Müller M, Campbell RG, Ryoo M, Navarro M. Digestive physiology and nutrition of swine. In: Chiba LI, Editors. Sustainable swine nutrition. Hoboken, NJ, USA: Wiley-Blackwell; 2022. pp. 1-36.
2. Kim SW, Duarte ME. Understanding intestinal health in nursery pigs and the relevant nutritional strategies. Anim Biosci. 2021;34:338-44.
3. Sinkora M, Stepanova K, Butler JE, et al. Ileal Peyer’s patches are not necessary for systemic B cell development and maintenance and do not contribute significantly to the overall B cell pool in swine. J Immunol. 2011;187:5150-61.
4. Kim YS, Ho SB. Intestinal goblet cells and mucins in health and disease: recent insights and progress. Curr Gastroenterol Rep. 2010;12:319-30.
5. Blikslager AT, Moeser AJ, Gookin JL, Jones SL, Odle J. Restoration of barrier function in injured intestinal mucosa. Physiol Rev. 2007;87:545-64.
6. Adhikari B, Kim SW, Kwon YM. Characterization of microbiota associated with digesta and mucosa in different regions of gastrointestinal tract of nursery pigs. Int J Mol Sci. 2019;20:1630.
7. Holman DB, Gzyl KE, Mou KT, Allen HK. Weaning age and its effect on the development of the swine gut microbiome and resistome. mSystems. 2021;6:e0068221.
8. Duarte ME, Kim SW. Intestinal microbiota and its interaction to intestinal health in nursery pigs. Anim Nutr. 2022;8:169-84.
9. Duarte ME, Stahl CH, Kim SW. Intestinal damages by F18+ Escherichia coli and its amelioration with an antibacterial bacitracin fed to nursery pigs. Antioxidants. 2023;12:1040.
10. Nagy B, Whipp SC, Imberechts H, et al. Biological relationship between F18ab and F18ac fimbriae of enterotoxigenic and verotoxigenic Escherichia coli from weaned pigs with oedema disease or diarrhoea. Microb Pathog. 1997;22:1-11.
11. Vangroenweghe F, Luppi A, Thas O. Prevalence of enterotoxigenic Escherichia coli pathotypes and virotypes isolated from piglets suffering from post-weaning diarrhea in Belgium and the Netherlands. Arch Vet Anim Sci. 2020;2:1-8.
12. Duarte ME, Garavito-Duarte Y, Kim SW. Impacts of F18+ Escherichia coli on intestinal health of nursery pigs and dietary interventions. Animals. 2023;13:2791.
13. Paiva RC, Burrough ER, Almeida M. Characterization of hemolytic E. coli and antimicrobial susceptibility from ISU-VDL submitted cases from 2010 to 2022. In: 55th American Association of Swine Veterinarians Annual Meeting 2024. American Association of Swine Veterinarians; 2024.
14. Coddens A, Verdonck F, Tiels P, Rasschaert K, Goddeeris BM, Cox E. The age-dependent expression of the F18+ E. coli receptor on porcine gut epithelial cells is positively correlated with the presence of histo-blood group antigens. Vet Microbiol. 2007;122:332-41.
15. Moonens K, De Kerpel M, Coddens A, et al. Nanobody mediated inhibition of attachment of F18 Fimbriae expressing Escherichia coli. PLoS One. 2014;9:e114691.
16. Yi GF, Carroll JA, Allee GL, et al. Effect of glutamine and spray-dried plasma on growth performance, small intestinal morphology, and immune responses of Escherichia coli K88+-challenged weaned pigs. J Anim Sci. 2005;83:634-43.
17. Khafipour E, Munyaka PM, Nyachoti CM, Krause DO, Rodriguez-Lecompte JC. Effect of crowding stress and Escherichia coli K88+ challenge in nursery pigs supplemented with anti-Escherichia coli K88+ probiotics. J Anim Sci. 2014;92:2017-29.
18. Becker SL, Li Q, Burrough ER, et al. Effects of an F18 enterotoxigenic Escherichia coli challenge on growth performance, immunological status, and gastrointestinal structure of weaned pigs and the potential protective effect of direct-fed microbial blends. J Anim Sci. 2020;98:skaa113.
19. Sun Y, Duarte ME, Kim SW. Dietary inclusion of multispecies probiotics to reduce the severity of post-weaning diarrhea caused by Escherichia coli F18+ in pigs. Anim Nutr. 2021;7:326-33.
20. Chang SY, Lee JH, Oh HJ, et al. Effect of different ratios of phytogenic feed additives on growth performance, nutrient digestibility, intestinal barrier integrity, and immune response in weaned pigs challenged with a pathogenic Escherichia coli. J Anim Sci. 2023;101:skad148.
21. Molist F, Gómez de Segura A, Pérez J, Bhandari S, Krause D, Nyachoti C. Effect of wheat bran on the health and performance of weaned pigs challenged with Escherichia coli K88+. Livest Sci. 2010;133:214-7.
22. Silveira H, Amaral LGM, Garbossa CAP, Rodrigues LM, Silva CCD, Cantarelli VS. Benzoic acid in nursery diets increases the performance from weaning to finishing by reducing diarrhoea and improving the intestinal morphology of piglets inoculated with Escherichia coli K88+. J Anim Physiol Anim Nutr. 2018;102:1675-85.
23. Duarte ME, Kim SW. Significance of mucosa-associated microbiota and its impacts on intestinal health of pigs challenged with F18+ E. coli. Pathogens. 2022;11:589.
24. Heo JM, Kim JC, Hansen CF, Mullan BP, Hampson DJ, Pluske JR. Feeding a diet with decreased protein content reduces indices of protein fermentation and the incidence of postweaning diarrhea in weaned pigs challenged with an enterotoxigenic strain of Escherichia coli. J Anim Sci. 2009;87:2833-43.
25. He Y, Kim K, Kovanda L, et al. Bacillus subtilis: a potential growth promoter in weaned pigs in comparison to carbadox. J Anim Sci. 2020;98:skaa290.
26. Liu Y, Song M, Che TM, et al. Dietary plant extracts alleviate diarrhea and alter immune responses of weaned pigs experimentally infected with a pathogenic Escherichia coli. J Anim Sci. 2013;91:5294-306.
27. Garavito-Duarte Y, Duarte ME, Kim SW. Efficacy of ground herb-based and essential oil-based phytobiotics on the intestinal health and performance of nursery pigs challenged with F18+ Escherichia coli. J Anim Sci. 2025;103:skaf018.
28. Gormley AR, Duarte ME, Deng Z, Kim SW. Saccharomyces yeast postbiotics mitigate mucosal damages from F18+ Escherichia coli challenges by positively balancing the mucosal microbiota in the jejunum of young pigs. Anim Microbiome. 2024;6:73.
29. Jang KB, Moita VHC, Martinez N, Sokale A, Kim SW. Efficacy of zinc glycinate reducing zinc oxide on intestinal health and growth of nursery pigs challenged with F18+ Escherichia coli. J Anim Sci. 2023;101:skad035.
30. Xu X, Duarte ME, Kim SW. Postbiotic effects of Lactobacillus fermentate on intestinal health, mucosa-associated microbiota, and growth efficiency of nursery pigs challenged with F18+ Escherichia coli. J Anim Sci. 2022;100:skac210.
31. Deng Z, Choi H, Kim SW. Impacts of replacing soybean meal with processed soybean meal on intestinal health and growth of nursery pigs challenged with F18+ Escherichia coli. Anim Biosci. 2025;38:728-38.
32. Kim K, Ehrlich A, Perng V, et al. Algae-derived β-glucan enhanced gut health and immune responses of weaned pigs experimentally infected with a pathogenic E. coli. Anim Feed Sci Technol. 2019;248:114-25.
33. Li Q, Burrough ER, Gabler NK, et al. A soluble and highly fermentable dietary fiber with carbohydrases improved gut barrier integrity markers and growth performance in F18 ETEC challenged pigs. J Anim Sci. 2019;97:2139-53.
34. Wong BT, Park S, Kovanda L, et al. Dietary supplementation of botanical blends enhanced performance and disease resistance of weaned pigs experimentally infected with enterotoxigenic Escherichia coli F18. J Anim Sci. 2022;100:skac353.
35. Jinno C, Wong B, Klünemann M, Htoo J, Li X, Liu Y. Effects of supplementation of Bacillus amyloliquefaciens on performance, systemic immunity, and intestinal microbiota of weaned pigs experimentally infected with a pathogenic enterotoxigenic E. coli F18. Front Microbiol. 2023;14:1101457.
36. Duarte ME, Tyus J, Kim SW. Synbiotic effects of enzyme and probiotics on intestinal health and growth of newly weaned pigs challenged with enterotoxigenic F18+ Escherichia coli. Front Vet Sci. 2020;7:573.
37. Duarte ME, Deng Z, Kim SW. Effects of dietary Lactobacillus postbiotics and bacitracin on the modulation of mucosa-associated microbiota and pattern recognition receptors affecting immunocompetence of jejunal mucosa in pigs challenged with enterotoxigenic F18+ Escherichia coli. J Anim Sci Biotechnol. 2024;15:139.
38. Luppi A, Gibellini M, Gin T, et al. Prevalence of virulence factors in enterotoxigenic Escherichia coli isolated from pigs with post-weaning diarrhoea in Europe. Porcine Health Manag. 2016;2:20.
39. Ahn J, Lkhagva E, Jung S, et al. Fecal microbiome does not represent whole gut microbiome. Cell Microbiol. 2023;2023:1-14.
40. Zhao W, Wang Y, Liu S, et al. The dynamic distribution of porcine microbiota across different ages and gastrointestinal tract segments. PLoS One. 2015;10:e0117441.
41. Daniel N, Lécuyer E, Chassaing B. Host/microbiota interactions in health and diseases - time for mucosal microbiology! Mucosal Immunol. 2021;14:1006-16.
42. Chassaing B, Koren O, Goodrich JK, et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015;519:92-6.
43. Chassaing B, Raja SM, Lewis JD, Srinivasan S, Gewirtz AT. Colonic microbiota encroachment correlates with dysglycemia in humans. Cell Mol Gastroenterol Hepatol. 2017;4:205-21.
44. Deng Z, Duarte ME, Jang KB, Kim SW. Soy protein concentrate replacing animal protein supplements and its impacts on intestinal immune status, intestinal oxidative stress status, nutrient digestibility, mucosa-associated microbiota, and growth performance of nursery pigs. J Anim Sci. 2022;100:skac255.
45. Sun Y, Kim SW. Intestinal challenge with enterotoxigenic Escherichia coli in pigs, and nutritional intervention to prevent postweaning diarrhea. Anim Nutr. 2017;3:322-30.
46. Jung C, Hugot JP, Barreau F. Peyer’s Patches: the immune sensors of the intestine. Int J Inflam. 2010;2010:823710.
47. Urmila TS, Ramayya PJ, Lakshmi MS, Kumar AS. Histomorphological studies on gut associated lymphoid tissue of pig (Sus scrofa). Int J Chem Stud. 2019;8:1-3. Available from: https://www.thepharmajournal.com/archives/?year=2019&vol=8&issue=3&ArticleId=3123. [Last accessed on 29 Jul 2025].
48. Ruth MR, Field CJ. The immune modifying effects of amino acids on gut-associated lymphoid tissue. J Anim Sci Biotechnol. 2013;4:27.
49. Kim K, Song M, Liu Y, Ji P. Enterotoxigenic Escherichia coli infection of weaned pigs: intestinal challenges and nutritional intervention to enhance disease resistance. Front Immunol. 2022;13:885253.
50. Gonzales-Siles L, Sjöling Å. The different ecological niches of enterotoxigenic Escherichia coli. Environ Microbiol. 2016;18:741-51.
51. Meijerink E, Neuenschwander S, Fries R, et al. A DNA polymorphism influencing alpha(1,2)fucosyltransferase activity of the pig FUT1 enzyme determines susceptibility of small intestinal epithelium to Escherichia coli F18 adhesion. Immunogenetics. 2000;52:129-36.
52. Imberechts H, Bertschinger H, Nagy B, Deprez P, Pohl P. Fimbrial colonisation factors F18ab and F18ac of Escherichia coli isolated from pigs with postweaning diarrhea and edema disease. In: Paul PS, Francis DH, Benfield DA, Editors. Mechanisms in the pathogenesis of enteric diseases. Boston, MA: Springer; 1997. pp. 175-83.
53. Laarmann S, Schmidt MA. The Escherichia coli AIDA autotransporter adhesin recognizes an integral membrane glycoprotein as receptor. Microbiology. 2003;149:1871-82.
54. Dauphinee SM, Karsan A. Lipopolysaccharide signaling in endothelial cells. Lab Invest. 2006;86:9-22.
55. Zughaier SM, Zimmer SM, Datta A, Carlson RW, Stephens DS. Differential induction of the toll-like receptor 4-MyD88-dependent and -independent signaling pathways by endotoxins. Infect Immun. 2005;73:2940-50.
56. Kumar A, Chatterjee I, Gujral T, et al. Activation of nuclear factor-κB by tumor necrosis factor in intestinal epithelial cells and mouse intestinal epithelia reduces expression of the chloride transporter SLC26A3. Gastroenterology. 2017;153:1338-50.e3.
57. Luo C, Xia B, Zhong R, et al. Early-life nutrition interventions improved growth performance and intestinal health via the gut microbiota in piglets. Front Nutr. 2021;8:783688.
58. Song D, Lee J, Kwak W, et al. Effects of stimbiotic supplementation on gut health, immune response, and intestinal microbiota in weaned piglets challenged with E. coli. Front Vet Sci. 2023;10:1187002.
59. Rhayat L, Maresca M, Nicoletti C, et al. Effect of Bacillus subtilis strains on intestinal barrier function and inflammatory response. Front Immunol. 2019;10:564.
60. Liu Y, Wang X, Wu H, et al. Glycine enhances muscle protein mass associated with maintaining Akt-mTOR-FOXO1 signaling and suppressing TLR4 and NOD2 signaling in piglets challenged with LPS. Am J Physiol Regul Integr Comp Physiol. 2016;311:R365-73.
61. Travassos LH, Girardin SE, Philpott DJ, et al. Toll-like receptor 2-dependent bacterial sensing does not occur via peptidoglycan recognition. EMBO Rep. 2004;5:1000-6.
62. Szentirmai É, Massie AR, Kapás L. Lipoteichoic acid, a cell wall component of Gram-positive bacteria, induces sleep and fever and suppresses feeding. Brain Behav Immun. 2021;92:184-92.
63. Schulz S, Green CK, Yuen PS, Garbers DL. Guanylyl cyclase is a heat-stable enterotoxin receptor. Cell. 1990;63:941-8.
64. Vaandrager AB, Smolenski A, Tilly BC, et al. Membrane targeting of cGMP-dependent protein kinase is required for cystic fibrosis transmembrane conductance regulator Cl- channel activation. Proc Natl Acad Sci U S A. 1998;95:1466-71.
65. Field M, Rao MC, Chang EB. Intestinal electrolyte transport and diarrheal disease (2). N Engl J Med. 1989;321:879-83.
66. Labrie V, Beausoleil HE, Harel J, Dubreuil JD. Binding to sulfatide and enterotoxicity of various Escherichia coli STb mutants. Microbiology. 2001;147:3141-8.
67. Gonçalves C, Berthiaume F, Mourez M, Dubreuil JD.
68. Mellström B, Savignac M, Gomez-Villafuertes R, Naranjo JR. Ca2+-operated transcriptional networks: molecular mechanisms and in vivo models. Physiol Rev. 2008;88:421-49.
69. Hardy SJ, Holmgren J, Johansson S, Sanchez J, Hirst TR. Coordinated assembly of multisubunit proteins: oligomerization of bacterial enterotoxins in vivo and in vitro. Proc Natl Acad Sci U S A. 1988;85:7109-13.
70. Angström J, Bäckström M, Berntsson A, et al. Novel carbohydrate binding site recognizing blood group A and B determinants in a hybrid of cholera toxin and Escherichia coli heat-labile enterotoxin B-subunits. J Biol Chem. 2000;275:3231-8.
71. Gill DM, Richardson SH. Adenosine diphosphate-ribosylation of adenylate cyclase catalyzed by heat-labile enterotoxin of Escherichia coli: comparison with cholera toxin. J Infect Dis. 1980;141:64-70.
72. He Y, Jinno C, Li C, et al. Effects of a blend of essential oils, medium-chain fatty acids, and a toxin-adsorbing mineral on diarrhea and gut microbiome of weanling pigs experimentally infected with a pathogenic Escherichia coli. J Anim Sci. 2022;100:skab365.
73. Kovanda L, Park J, Park S, Kim K, Li X, Liu Y. Dietary butyrate and valerate glycerides impact diarrhea severity and immune response of weaned piglets under ETEC F4-ETEC F18 coinfection conditions. J Anim Sci. 2023;101:skad401.
74. Meijerink E, Fries R, Vögeli P, et al. Two alpha(1,2) fucosyltransferase genes on porcine chromosome 6q11 are closely linked to the blood group inhibitor (S) and Escherichia coli F18 receptor (ECF18R) loci. Mamm Genome. 1997;8:736-41.
75. Welch MW, Cross AJ, Solar Diaz IDP, et al. Maintained growth performance and reduced mortality of genetically resistant nursery pigs after an experimental virulent F18 enterotoxigenic Escherichia coli challenge. Transl Anim Sci. 2025;9:txaf004.
76. Wu Z, Liu Y, Dong W, Zhu GQ, Wu S, Bao W. CD14 in the TLRs signaling pathway is associated with the resistance to E. coli F18 in Chinese domestic weaned piglets. Sci Rep. 2016;6:24611.
77. Sung JY, Deng Z, Kim SW. Antibiotics and opportunities of their alternatives in pig production: mechanisms through modulating intestinal microbiota on intestinal health and growth. Antibiotics. 2025;14:301.
78. Maroilley T, Berri M, Lemonnier G, et al. Immunome differences between porcine ileal and jejunal Peyer’s patches revealed by global transcriptome sequencing of gut-associated lymphoid tissues. Sci Rep. 2018;8:9077.
79. Liu X, Lyu W, Liu L, et al. Comparison of digestive enzyme activities and expression of small intestinal transporter genes in Jinhua and Landrace pigs. Front Physiol. 2021;12:669238.
80. Van den Abbeele P, Van de Wiele T, Verstraete W, Possemiers S. The host selects mucosal and luminal associations of coevolved gut microorganisms: a novel concept. FEMS Microbiol Rev. 2011;35:681-704.
81. McEwan GT, Schousboe B, Skadhauge E. Direct measurement of mucosal surface pH of pig jejunum in vivo. Zentralbl Veterinarmed A. 1990;37:439-44.
82. Schwerdtfeger LA, Nealon NJ, Ryan EP, Tobet SA. Human colon function ex vivo: dependence on oxygen and sensitivity to antibiotic. PLoS One. 2019;14:e0217170.
83. Kelly J, Daly K, Moran AW, Ryan S, Bravo D, Shirazi-Beechey SP. Composition and diversity of mucosa-associated microbiota along the entire length of the pig gastrointestinal tract; dietary influences. Environ Microbiol. 2017;19:1425-38.
84. Mu C, Yang Y, Su Y, Zoetendal EG, Zhu W. Differences in microbiota membership along the gastrointestinal tract of piglets and their differential alterations following an early-life antibiotic intervention. Front Microbiol. 2017;8:797.
85. Majlessi L, Sayes F, Bureau JF, et al. Colonization with Helicobacter is concomitant with modified gut microbiota and drastic failure of the immune control of Mycobacterium tuberculosis. Mucosal Immunol. 2017;10:1178-89.
86. Fink D, Romanowski K, Valuckaite V, et al. Pseudomonas aeruginosa potentiates the lethal effect of intestinal ischemia-reperfusion injury: the role of in vivo virulence activation. J Trauma. 2011;71:1575-82.
87. Xiao Y, Wang Y, Tong B, et al.
88. Lee MR, Huang YT, Liao CH, et al. Clinical and microbiological characteristics of bacteremia caused by Eggerthella, Paraeggerthella, and Eubacterium species at a university hospital in Taiwan from 2001 to 2010. J Clin Microbiol. 2012;50:2053-5.
89. Guo G, Wu Y, Liu Y, et al. Exploring the causal effects of the gut microbiome on serum lipid levels: a two-sample Mendelian randomization analysis. Front Microbiol. 2023;14:1113334.
90. De Vos WM, Nguyen Trung M, Davids M, et al. Phytate metabolism is mediated by microbial cross-feeding in the gut microbiota. Nat Microbiol. 2024;9:1812-27.
91. Kajihara Y, Yoshikawa S, Cho Y, Ito T, Miyamoto H, Kodama H. Preferential isolation of Megasphaera elsdenii from pig feces. Anaerobe. 2017;48:160-4.
92. Stanton TB, Humphrey SB. Persistence of antibiotic resistance: evaluation of a probiotic approach using antibiotic-sensitive Megasphaera elsdenii strains to prevent colonization of swine by antibiotic-resistant strains. Appl Environ Microbiol. 2011;77:7158-66.
93. Ciesielska A, Matyjek M, Kwiatkowska K. TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling. Cell Mol Life Sci. 2021;78:1233-61.
94. Qin Q, Xu X, Wang X, et al. Glutamate alleviates intestinal injury, maintains mTOR and suppresses TLR4 and NOD signaling pathways in weanling pigs challenged with lipopolysaccharide. Sci Rep. 2018;8:15124.
95. Silva JE, Mayordomo AC, Dave MN, Aguilera Merlo C, Eliçabe RJ, Di Genaro MS. Dendritic cells of mesenteric and regional lymph nodes contribute to Yersinia enterocolitica O:3-induced reactive arthritis in TNFRp55-/- mice. J Immunol. 2020;204:1859-68.
96. Anosova NG, Chabot S, Shreedhar V, Borawski JA, Dickinson BL, Neutra MR. Cholera toxin, E. coli heat-labile toxin, and non-toxic derivatives induce dendritic cell migration into the follicle-associated epithelium of Peyer’s patches. Mucosal Immunol. 2008;1:59-67.
97. Qin D, Li Y, Chen X, et al. Secretory IgA-ETEC F5 immune complexes promote dendritic cell differentiation and prime T cell proliferation in the mouse intestine. Life. 2023;13:1936.
98. Wang H, Zhong Z, Luo Y, Cox E, Devriendt B. Heat-stable enterotoxins of enterotoxigenic Escherichia coli and their impact on host immunity. Toxins. 2019;11:24.
99. Butt S, Saleh M, Gagnon J. Impact of the Escherichia coli heat-stable enterotoxin b (STb) on gut health and function. Toxins. 2020;12:760.
100. Papista C, Berthelot L, Monteiro RC. Dysfunctions of the Iga system: a common link between intestinal and renal diseases. Cell Mol Immunol. 2011;8:126-34.
101. Vujkovic-Cvijin I, Welles HC, Ha CWY, et al. The systemic anti-microbiota IgG repertoire can identify gut bacteria that translocate across gut barrier surfaces. Sci Transl Med. 2022;14:eabl3927.
102. Tylicka M, Guszczyn T, Maksimowicz M, et al. The concentration of selected inflammatory cytokines (IL-6, IL-8, CXCL5, IL-33) and damage-associated molecular patterns (HMGB-1, HSP-70) released in an early response to distal forearm fracture and the performed closed reduction with Kirschner wire fixation in children. Front Endocrinol. 2021;12:749667.
103. Georganas C, Liu H, Perlman H, Hoffmann A, Thimmapaya B, Pope RM. Regulation of IL-6 and IL-8 expression in rheumatoid arthritis synovial fibroblasts: the dominant role for NF-kappa B but not C/EBP beta or c-Jun. J Immunol. 2000;165:7199-206.
104. Rosero DS, Odle J, Moeser AJ, Boyd RD, van Heugten E. Peroxidised dietary lipids impair intestinal function and morphology of the small intestine villi of nursery pigs in a dose-dependent manner. Br J Nutr. 2015;114:1985-92.
105. Yang X, Xiao Z, Liu F, et al. Enterotoxigenic Escherichia coli infection alters intestinal immunity in mice. Mol Med Rep. 2016;14:825-30.
106. Daig R, Andus T, Aschenbrenner E, Falk W, Schölmerich J, Gross V. Increased interleukin 8 expression in the colon mucosa of patients with inflammatory bowel disease. Gut. 1996;38:216-22.
107. Cao S, Wu H, Wang C, et al. Diquat-induced oxidative stress increases intestinal permeability, impairs mitochondrial function, and triggers mitophagy in piglets. J Anim Sci. 2018;96:1795-805.
108. Long E, Capuco AV, Wood DL, et al.