Fecal biomarkers of intestinal health and disease in children

Frontiers in Pediatrics

Volumn 2, Issue JAN, 2014, Pages

  Pang, Tamara ^a   Leach, Steven T ^a,b   Katz, Tamarah ^b   Day, Andrew S ^c   Ooi, Chee Y ^a,b  

^a UNIVERSITY OF NEW SOUTH WALES   (Australia)

^b SYDNEY CHILDREN'S HOSPITAL   (Australia)

^c UNIVERSITY OF OTAGO   (New Zealand)

Author keywords

Calprotectin; Cathelicidins; Defensins; Inflammation; Lactoferrin; M2 pyruvate kinase; Osteoprotegerin; S100A12

Indexed keywords

EID: 85061994955     PISSN: None     EISSN: 22962360     Source Type: Journal    
DOI: 10.3389/fped.2014.00006     Document Type: Review

References (104)

1. Muller CA, Autenrieth IB, Peschel A. Innate defenses of the intestinal epithelial barrier. Cell Mol Life Sci (2005) 62(12):1297-307. doi: 10.1007/s00018-005-5034-2
2. Dommett R, Zilbauer M, George JT, Bajaj-Elliott M. Innate immune defence in the human gastrointestinal tract. Mol Immunol (2005) 42(8):903-12. doi:10.1016/j.molimm.2004.12.004
3. Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev (2001) 81(3):1031-64
4. Yuan Q, Walker WA. Innate immunity of the gut: mucosal defense in health and disease. J Pediatr Gastroenterol Nutr (2004) 38(5):463-73. doi:10.1097/00005176-200405000-00001
5. Ramasundara M, Leach ST, Lemberg DA, Day AS. Defensins and inflammation: the role of defensins in inflammatory bowel disease. J Gastroenterol Hepatol (2009) 24(2):202-8. doi:10.1111/j.1440-1746.2008.05772.x
6. Penders J, Thijs C, van den Brandt PA, Kummeling I, Snijders B, Stelma F, et al. Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. Gut (2007) 56(5):661-7. doi:10.1136/gut.2006.100164
7. Greiner T, Backhed F. Effects of the gut microbiota on obesity and glucose homeostasis. Trends Endocrinol Metab (2011) 22(4):117-23. doi:10.1016/j.tem.2011.01.002
8. Giongo A, Gano KA, Crabb DB, Mukherjee N, Novelo LL, Casella G, et al. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J (2011) 5(1):82-91. doi:10.1038/ismej.2010.92
9. Larsen N, Vogensen FK, van den Berg FW, Nielsen DS, Andreasen AS, Pedersen BK, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One (2010) 5(2):e9085. doi:10.1371/journal.pone.0009085
10. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med (2013) 368(17):1575-84. doi:10.1056/NEJMoa1109400
11. Willing BP, Dicksved J, Halfvarson J, Andersson AF, Lucio M, Zheng Z, et al. A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology (2010) 139(6):1844-54.e1. doi:10.1053/j.gastro.2010.08.049
12. Lee JM, Leach ST, Katz T, Day AS, Jaffe A, Ooi CY. Update of faecal markers of inflammation in children with cystic fibrosis. Mediators Inflamm (2012) 2012:948367. doi:10.1155/2012/948367
13. Zasloff M. Antimicrobial peptides of multicellular organisms. Nature (2002) 415(6870):389-95. doi:10.1038/415389a
14. Wehkamp J, Stange EF, Fellermann K. Defensin-immunology in inflammatory bowel disease. Gastroenterol Clin Biol (2009) 33(Suppl 3):S137-44. doi:10.1016/S0399-8320(09)73149-5
15. Wehkamp J, Schauber J, Stange EF. Defensins and cathelicidins in gastrointestinal infections. Curr Opin Gastroenterol (2007) 23(1):32-8. doi:10.1097/MOG.0b013e32801182c2
16. Chaly YV, Paleolog EM, Kolesnikova TS, Tikhonov II, Petratchenko EV, Voitenok NN. Neutrophil alpha-defensin human neutrophil peptide modulates cytokine production in human monocytes and adhesion molecule expression in endothelial cells. Eur Cytokine Netw (2000) 11(2):257-66
17. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, et al. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science (1999) 286(5439):525-8. doi:10.1126/science.286.5439.525
18. Fahlgren A, Hammarstrom S, Danielsson A, Hammarstrom ML. Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis. Clin Exp Immunol (2003) 131(1):90-101. doi:10.1046/j.1365-2249.2003.02035.x
19. Kapel N, Benahmed N, Morali A, Svahn J, Canioni D, Goulet O, et al. Fecal beta-defensin-2 in children with inflammatory bowel diseases. J Pediatr Gastroenterol Nutr (2009) 48(1):117-20. doi:10.1097/MPG.0b013e318174e872
20. Wehkamp J, Harder J, Weichenthal M, Mueller O, Herrlinger KR, Fellermann K, et al. Inducible and constitutive beta-defensins are differentially expressed in Crohn's disease and ulcerative colitis. Inflamm Bowel Dis (2003) 9(4):215-23. doi:10.1097/00054725-200307000-00001
21. Wehkamp J, Salzman NH, Porter E, Nuding S, Weichenthal M, Petras RE, et al. Reduced Paneth cell alpha-defensins in ileal Crohn's disease. Proc Natl Acad Sci U S A (2005) 102(50):18129-34. doi:10.1073/pnas.0505256102
22. Fellermann K, Stange DE, Schaeffeler E, Schmalzl H, Wehkamp J, Bevins CL, et al. A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am J Hum Genet (2006) 79(3):439-48. doi:10.1086/505915
23. Voss E, Wehkamp J, Wehkamp K, Stange EF, Schroder JM, Harder J. NOD2/CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2. J Biol Chem (2006) 281(4):2005-11. doi:10.1074/jbc.M511044200
24. Langhorst J, Junge A, Rueffer A, Wehkamp J, Foell D, Michalsen A, et al. Elevated human beta-defensin-2 levels indicate an activation of the innate immune system in patients with irritable bowel syndrome. Am J Gastroenterol (2009) 104(2):404-10. doi:10.1038/ajg.2008.86
25. Yao X, Yang YS, Cui LH, Zhao KB, Zhang ZH, Peng LH, et al. Subtypes of irritable bowel syndrome on Rome III criteria: a multicenter study. J Gastroenterol Hepatol (2012) 27(4):760-5. doi:10.1111/j.1440-1746.2011.06930.x
26. Simren M, Barbara G, Flint HJ, Spiegel BM, Spiller RC, Vanner S, et al. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut (2013) 62(1):159-76. doi:10.1136/gutjnl-2012-302167
27. O'Sullivan M, Clayton N, Breslin NP, Harman I, Bountra C, McLaren A, et al. Increased mast cells in the irritable bowel syndrome. Neurogastroenterol Motil (2000) 12(5):449-57. doi:10.1046/j.1365-2982.2000.00221.x
28. Salzmann JL, Peltier-Koch F, Bloch F, Petite JP, Camilleri JP. Morphometric study of colonic biopsies: a new method of estimating inflammatory diseases. Lab Invest (1989) 60(6):847-51
29. Lin PW, Stoll BJ. Necrotising enterocolitis. Lancet (2006) 368(9543):1271-83. doi:10.1016/S0140-6736(06)69525-1
30. Lin PW, Nasr TR, Stoll BJ. Necrotizing enterocolitis: recent scientific advances in pathophysiology and prevention. Semin Perinatol (2008) 32(2):70-82. doi:10.1053/j.semperi.2008.01.004
31. Deshpande G, Rao S, Patole S. Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: a systematic review of randomised controlled trials. Lancet (2007) 369(9573):1614-20. doi:10.1016/S0140-6736(07)60748-X
32. Jenke AC, Zilbauer M, Postberg J, Wirth S. Human beta-defensin 2 expression in ELBW infants with severe necrotizing enterocolitis. Pediatr Res (2012) 72(5):513-20. doi:10.1038/pr.2012.110
33. Schauber J, Rieger D, Weiler F, Wehkamp J, Eck M, Fellermann K, et al. Heterogeneous expression of human cathelicidin hCAP18/LL-37 in inflammatory bowel diseases. Eur J Gastroenterol Hepatol (2006) 8(6):615-21. doi:10.1097/00042737-200606000-00007
34. Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol (2004) 75(1):39-48. doi:10.1189/jlb.0403147
35. De Y, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, et al. LL-37, the neutrophil granule-and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med (2000) 192(7):1069-74. doi:10.1084/jem.192.7.1069
36. Niyonsaba F, Iwabuchi K, Someya A, Hirata M, Matsuda H, Ogawa H, et al. A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology (2002) 106(1):20-6. doi:10.1046/j.1365-2567.2002.01398.x
37. Hase K, Eckmann L, Leopard JD, Varki N, Kagnoff MF. Cell differentiation is a key determinant of cathelicidin LL-37/human cationic antimicrobial protein 18 expression by human colon epithelium. Infect Immun (2002) 70(2):953-63. doi:10.1128/IAI.70.2.953-963.2002
38. Schauber J, Svanholm C, Termen S, Iffland K, Menzel T, Scheppach W, et al. Expression of the cathelicidin LL-37 is modulated by short chain fatty acids in colonocytes: relevance of signalling pathways. Gut (2003) 52(5):735-41. doi:10.1136/gut.52.5.735
39. Raqib R, Sarker P, Bergman P, Ara G, Lindh M, Sack DA, et al. Improved outcome in shigellosis associated with butyrate induction of an endogenous peptide antibiotic. Proc Natl Acad Sci U S A (2006) 103(24):9178-83. doi:10.1073/pnas.0602888103
40. Raqib R, Sarker P, Mily A, Alam NH, Arifuzzaman AS, Rekha RS, et al. Efficacy of sodium butyrate adjunct therapy in shigellosis: a randomized, double-blind, placebo-controlled clinical trial. BMC Infect Dis (2012) 12:111. doi:10.1186/1471-2334-12-111
41. Islam D, Bandholtz L, Nilsson J, Wigzell H, Christensson B, Agerberth B, et al. Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator. Nat Med (2001) 7(2):180-5. doi:10.1038/84627
42. Gonzalez-Chavez SA, Arevalo-Gallegos S, Rascon-Cruz Q. Lactoferrin: structure, function and applications. Int J Antimicrob Agents (2009) 33(4):301.e1-8. doi:10.1016/j.ijantimicag.2008.07.020
43. Farnaud S, Evans RW. Lactoferrin-a multifunctional protein with antimicrobial properties. Mol Immunol (2003) 40(7):395-405. doi:10.1016/S0161-5890(03)00152-4
44. Ellison RT III, Giehl TJ. Killing of Gram-negative bacteria by lactoferrin and lysozyme. J Clin Invest (1991) 88(4):1080-91. doi:10.1172/JCI115407
45. Ward PP, Uribe-Luna S, Conneely OM. Lactoferrin and host defense. Biochem Cell Biol (2002) 80(1):95-102. doi:10.1139/o01-214
46. Kane S. Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation. Am J Gastroenterol (2003) 98(6):1309-14. doi:10.1111/j.1572-0241.2003.07458.x
47. Abraham BP, Kane S. Fecal markers: calprotectin and lactoferrin. Gastroenterol Clin North Am (2012) 41(2):483-95. doi:10.1016/j.gtc.2012.01.007
48. Parsi MA, Shen B, Achkar JP, Remzi FF, Goldblum JR, Boone J, et al. Fecal lactoferrin for diagnosis of symptomatic patients with ileal pouch-anal anastomosis. Gastroenterology (2004) 126(5):1280-6. doi:10.1053/j.gastro.2004.02.012
49. Walker TR, Land ML, Kartashov A, Saslowsky TM, Lyerly DM, Boone JH, et al. Fecal lactoferrin is a sensitive and specific marker of disease activity in children and young adults with inflammatory bowel disease. J Pediatr Gastroenterol Nutr (2007) 44(4):414-22. doi:10.1097/MPG.0b013e3180308d8e
50. Chakravarti A, Marceau AA, Flamand L, Poubelle PE. Normal human primary CD4+ T lymphocytes synthesize and release functional osteoprotegerin in vitro. Lab Invest (2008) 88(2):171-84. doi:10.1038/labinvest.3700701
51. Vidal K, Serrant P, Schlosser B, van den Broek P, Lorget F, Donnet-Hughes A. Osteoprotegerin production by human intestinal epithelial cells: a potential regulator of mucosal immune responses. Am J Physiol Gastrointest Liver Physiol (2004) 287(4):G836-44. doi:10.1152/ajpgi.00428.2003
52. Nahidi L, Leach ST, Sidler MA, Levin A, Lemberg DA, Day AS. Osteoprotegerin in pediatric Crohn's disease and the effects of exclusive enteral nutrition. Inflamm Bowel Dis (2011) 17(2):516-23. doi:10.1002/ibd.21361
53. Ashcroft AJ, Cruickshank SM, Croucher PI, Perry MJ, Rollinson S, Lippitt JM, et al. Colonic dendritic cells, intestinal inflammation, and T cell-mediated bone destruction are modulated by recombinant osteoprotegerin. Immunity (2003) 19:849-61. doi:10.1016/S1074-7613(03)00326-1
54. Sylvester FA, Turner D, Draghi A II, Uuosoe K, McLernon R, Koproske K, et al. Fecal osteoprotegerin may guide the introduction of second-line therapy in hospitalized children with ulcerative colitis. Inflamm Bowel Dis (2011) 17(8):1726-30. doi:10.1002/ibd.21561
55. Nahidi L, Leach ST, Lemberg DA, Day AS. Osteoprotegerin exerts its pro-inflammatory effects through nuclear factor-κB activation. Dig Dis Sci (2013) 58(11):3144-55. doi:10.1007/s10620-013-2851-2
56. Bouzid M, Hunter PR, Chalmers RM, Tyler KM. Cryptosporidium pathogenicity and virulence. Clin Microbiol Rev (2013) 26(1):115-34. doi:10.1128/CMR.00076-12
57. Castellanos-Gonzalez A, Yancey LS, Wang HC, Pantenburg B, Liscum KR, Lewis DE, et al. Cryptosporidium infection of human intestinal epithelial cells increases expression of osteoprotegerin: a novel mechanism for evasion of host defenses. J Infect Dis (2008) 197(6):916-23. doi:10.1086/528374
58. Foell D, Wittkowski H, Roth J. Monitoring disease activity by stool analyses: from occult blood to molecular markers of intestinal inflammation and damage. Gut (2009) 58(6):859-68. doi:10.1136/gut.2008.170019
59. Donato R. Intracellular and extracellular roles of S100 proteins. Microsc Res Tech (2003) 60(6):540-51. doi:10.1002/jemt.10296
60. Foell D, Wittkowski H, Vogl T, Roth J. S100 proteins expressed in phagocytes: a novel group of damage-associated molecular pattern molecules. J Leukoc Biol (2007) 81(1):28-37. doi:10.1189/jlb.0306170
61. Newton RA, Hogg N. The human S100 protein MRP-14 is a novel activator of the beta 2 integrin Mac-1 on neutrophils. J Immunol (1998) 160(3):1427-35
62. Fagerberg UL, Loof L, Merzoug RD, Hansson LO, Finkel Y. Fecal calprotectin levels in healthy children studied with an improved assay. J Pediatr Gastroenterol Nutr (2003) 37(4):468-72. doi:10.1097/00005176-200310000-00013
63. Day AS, Ehn M, Gearry RB, Lemberg DA, Leach ST. Fecal S100A12 in healthy infants and children. Dis Markers (2013) 35(5):295-9. doi:10.1155/2013/873582
64. Leach ST, Yang Z, Messina I, Song C, Geczy CL, Cunningham AM, et al. Serum and mucosal S100 proteins, calprotectin (S100A8/S100A9) and S100A12, are elevated at diagnosis in children with inflammatory bowel disease. Scand J Gastroenterol (2007) 42(11):1321-31. doi:10.1080/00365520701416709
65. Sidler MA, Leach ST, Day AS. Fecal S100A12 and fecal calprotectin as noninvasive markers for inflammatory bowel disease in children. Inflamm Bowel Dis (2008) 14(3):359-66. doi:10.1002/ibd.20336
66. D'Inca R, Dal Pont E, Di Leo V, Ferronato A, Fries W, Vettorato MG, et al. Calprotectin and lactoferrin in the assessment of intestinal inflammation and organic disease. Int J Colorectal Dis (2007) 22(4):429-37. doi:10.1007/s00384-006-0159-9
67. Bunn SK, Bisset WM, Main MJ, Golden BE. Fecal calprotectin as a measure of disease activity in childhood inflammatory bowel disease. J Pediatr Gastroenterol Nutr (2001) 32(2):171-7. doi:10.1097/00005176-200102000-00015
68. Roseth AG, Aadland E, Jahnsen J, Raknerud N. Assessment of disease activity in ulcerative colitis by faecal calprotectin, a novel granulocyte marker protein. Digestion (1997) 58(2):176-80. doi:10.1159/000201441
69. Costa F, Mumolo MG, Bellini M, Romano MR, Ceccarelli L, Arpe P, et al. Role of faecal calprotectin as non-invasive marker of intestinal inflammation. Dig Liver Dis (2003) 35(9):642-7. doi:10.1016/S1590-8658(03)00381-5
70. Langhorst J, Elsenbruch S, Koelzer J, Rueffer A, Michalsen A, Dobos GJ. Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN-elastase, CRP, and clinical indices. Am J Gastroenterol (2008) 103(1):162-9. doi:10.1111/j.1572-0241.2007.01556.x
71. Bunn SK, Bisset WM, Main MJ, Gray ES, Olson S, Golden BE. Fecal calprotectin: validation as a noninvasive measure of bowel inflammation in childhood inflammatory bowel disease. J Pediatr Gastroenterol Nutr (2001) 33(1):14-22. doi:10.1097/00005176-200107000-00003
72. Tibble J, Teahon K, Thjodleifsson B, Roseth A, Sigthorsson G, Bridger S, et al. A simple method for assessing intestinal inflammation in Crohn's disease. Gut (2000) 47(4):506-13. doi:10.1136/gut.47.4.506
73. Sykora J, Siala K, Huml M, Varvarovska J, Schwarz J, Pomahacova R. Evaluation of faecal calprotectin as a valuable non-invasive marker in distinguishing gut pathogens in young children with acute gastroenteritis. Acta Paediatr (2010) 99(9):1389-95. doi:10.1111/j.1651-2227.2010.01843.x
74. Gisbert JP, McNicholl AG. Questions and answers on the role of faecal calprotectin as a biological marker in inflammatory bowel disease. Dig Liver Dis (2009) 41(1):56-66. doi:10.1016/j.dld.2008.05.008
75. Tibble JA, Sigthorsson G, Bridger S, Fagerhol MK, Bjarnason I. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology (2000) 119(1):15-22. doi:10.1053/gast.2000.8523
76. Costa F, Mumolo MG, Ceccarelli L, Bellini M, Romano MR, Sterpi C, et al. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn's disease. Gut (2005) 54(3):364-8. doi:10.1136/gut.2004.043406
77. de Jong NS, Leach ST, Day AS. Fecal S100A12: a novel noninvasive marker in children with Crohn's disease. Inflamm Bowel Dis (2006) 12(7):566-72. doi:10.1097/01.ibd.0000227626.72271.91
78. Werlin SL, Benuri-Silbiger I, Kerem E, Adler SN, Goldin E, Zimmerman J, et al. Evidence of intestinal inflammation in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr (2010) 51(3):304-8. doi:10.1097/MPG.0b013e3181d1b013
79. Bruzzese E, Raia V, Gaudiello G, Polito G, Buccigrossi V, Formicola V, et al. Intestinal inflammation is a frequent feature of cystic fibrosis and is reduced by probiotic administration. Aliment Pharmacol Ther (2004) 20(7):813-9. doi:10.1111/j.1365-2036.2004.02174.x
80. Lisowska A, Madry E, Pogorzelski A, Szydlowski J, Radzikowski A, Walkowiak J. Small intestine bacterial overgrowth does not correspond to intestinal inflammation in cystic fibrosis. Scand J Clin Lab Invest (2010) 70(5):322-6. doi:10.3109/00365513.2010.486869
81. Ooi CY, Lee JM, Leach S, Katz T, Day AS, Jaffe A. Intestinal inflammation in CF: stool markers and correlation with pancreatic enzymes. J Cyst Fibros (2012) 11(S1):S114. doi:10.1016/S1569-1993(12)60395-6
82. Czub E, Herzig KH, Szaflarska-Popawska A, Kiehne K, Socha P, Wos H, et al. Fecal pyruvate kinase: a potential new marker for intestinal inflammation in children with inflammatory bowel disease. Scand J Gastroenterol (2007) 42(10):1147-50. doi:10.1080/00365520701320513
83. Chung-Faye G, Hayee B, Maestranzi S, Donaldson N, Forgacs I, Sherwood R. Fecal M2-pyruvate kinase (M2-PK): a novel marker of intestinal inflammation. Inflamm Bowel Dis (2007) 13(11):1374-8. doi:10.1002/ibd.20214
84. Judd TA, Day AS, Lemberg DA, Turner D, Leach ST. Update of fecal markers of inflammation in inflammatory bowel disease. J Gastroenterol Hepatol (2011) 26(10):1493-9. doi:10.1111/j.1440-1746.2011.06846.x
85. Hardt PD, Mazurek S, Toepler M, Schlierbach P, Bretzel RG, Eigenbrodt E, et al. Faecal tumour M2 pyruvate kinase: a new, sensitive screening tool for colorectal cancer. Br J Cancer (2004) 91(5):980-4. doi:10.1038/sj.bjc.6602033
86. Oehler R, Weingartmann G, Manhart N, Salzer U, Meissner M, Schlegel W, et al. Polytrauma induces increased expression of pyruvate kinase in neutrophils. Blood (2000) 95(3):1086-92
87. McDowell G, Gupta S, Dellerba M, Coppinger T, Levy RD, Keevil BG. Plasma concentrations of tumour dimeric pyruvate kinase are increased in patients with chronic cardiac failure. Ann Clin Biochem (2004) 41(Pt 6):491-3. doi:10.1258/0004563042466712
88. Turner D, Leach ST, Mack D, Uusoue K, McLernon R, Hyams J, et al. Faecal calprotectin, lactoferrin, M2-pyruvate kinase and S100A12 in severe ulcerative colitis: a prospective multicentre comparison of predicting outcomes and monitoring response. Gut (2010) 59(9):1207-12. doi:10.1136/gut.2010.211755
89. Walkowiak J, Banasiewicz T, Krokowicz P, Hansdorfer-Korzon R, Drews M, Herzig KH. Fecal pyruvate kinase (M2-PK): a new predictor for inflammation and severity of pouchitis. Scand J Gastroenterol (2005) 40(12):1493-4. doi:10.1080/00365520500319112
90. Johnson MW, Maestranzi S, Duffy AM, Dewar DH, Ciclitira PJ, Sherwood RA, et al. Faecal M2-pyruvate kinase: a novel, noninvasive marker of ileal pouch inflammation. Eur J Gastroenterol Hepatol (2009) 21(5):544-50. doi:10.1097/MEG.0b013e3283040cb3
91. Roy CC, Kien CL, Bouthillier L, Levy E. Short-chain fatty acids: ready for prime time? Nutr Clin Pract (2006) 21(4):351-66. doi:10.1177/0115426506021004351
92. Forchielli ML, Walker WA. The role of gut-associated lymphoid tissues and mucosal defence. Br J Nutr (2005) 93(Suppl 1):S41-8. doi:10.1079/BJN20041356
93. Canani RB, Costanzo MD, Leone L, Pedata M, Meli R, Calignano A. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol (2011) 17(12):1519-28. doi:10.3748/wjg.v17.i12
94. Luhrs H, Gerke T, Muller JG, Melcher R, Schauber J, Boxberge F, et al. Butyrate inhibits NF-kappaB activation in lamina propria macrophages of patients with ulcerative colitis. Scand J Gastroenterol (2002) 37(4):458-66. doi:10.1080/003655202317316105
95. Segain JP, Raingeard de la Bletiere D, Bourreille A, Leray V, Gervois N, Rosales C, et al. Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. Gut (2000) 47(3):397-403. doi:10.1136/gut.47.3.397
96. Thibault R, Blachier F, Darcy-Vrillon B, de Coppet P, Bourreille A, Segain JP. Butyrate utilization by the colonic mucosa in inflammatory bowel diseases: a transport deficiency. Inflamm Bowel Dis (2010) 16(4):684-95. doi:10.1002/ibd.21108
97. Harig JM, Soergel KH, Komorowski RA, Wood CM. Treatment of diversion colitis with short-chain-fatty acid irrigation. N Engl J Med (1989) 320(1):23-8. doi:10.1056/NEJM198901053200105
98. Monira S, Hoq MM, Chowdhury AK, Suau A, Magne F, Endtz HP, et al. Short-chain fatty acids and commensal microbiota in the faeces of severely malnourished children with cholera rehydrated with three different carbohydrates. Eur J Clin Nutr (2010) 64(10):1116-24. doi:10.1038/ejcn.2010.123
99. Clausen MR, Bonnen H, Tvede M, Mortensen PB. Colonic fermentation to short-chain fatty acids is decreased in antibiotic-associated diarrhea. Gastroenterology (1991) 101(6):1497-504
100. Vaisman N, Tabachnik E, Sklan D. Short-chain fatty acid absorption in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr (1992) 15(2):146-9. doi:10.1097/00005176-199208000-00008
101. Owira PM, Winter TA. Colonic energy salvage in chronic pancreatic exocrine insufficiency. JPEN J Parenter Enteral Nutr (2008) 32(1):63-71. doi:10.1177/014860710803200163
102. Nguyen TD, Kim US, Perrine SP. Novel short chain fatty acids restore chloride secretion in cystic fibrosis. Biochem Biophys Res Commun (2006) 342(1):245-52. doi:10.1016/j.bbrc.2006.01.127
103. Torii T, Kanemitsu K, Wada T, Itoh S, Kinugawa K, Hagiwara A. Measurement of short-chain fatty acids in human faeces using high-performance liquid chromatography: specimen stability. Ann Clin Biochem (2010) 47(Pt 5):447-52. doi:10.1258/acb.2010.010047
104. Pallen MJ, Loman NJ, Penn CW. High-throughput sequencing and clinical microbiology: progress, opportunities and challenges. Curr Opin Microbiol (2010) 13(5):625-31. doi:10.1016/j.mib.2010.08.003