The human gut contains enough endotoxin, inflammatory mediators, and bacteria to kill the host many times over.

Abstract
Introduction
TABLE 1Conditions Caused By Or Seen In Connection With Intestinal Permeability Defects
Multiple organ failure5,6
Chronic fatigue syndrome7,8,9,10
Ulcerative colitis11,12
Crohn’s disease 13,14,15,16,17
Celiac disease18,19
Diarrhea-predominant irritable bowel syndrome20
Inflammatory joint disease 21,22,23,24
Ankylosing spondylitis25,26,27,28
Juvenile onset arthritis29
Psoriatic arthritis30
Food allergy31,32,33,34
Atopic dermatitis, eczema35
Chronic heart failure36,37
Psychological conditions38,39
HIV/AIDS40,41
Chemotherapy42,43
Pelvic radiotherapy44,45
|
Diagnosis
Causative Factors
TABLE 2Causative Factors Associated With Development Of Intestinal Permeability DefectsIntestinal inflammation57,58
Mucosal oxidative stress59,60
Stress61,62
Nonsteroidal inflammatory drugs (NSAIDs)63
Alcohol consumption64,65
Cow’s milk intolerance66,67
Small intestine bacterial overgrowth68,69
Pancreatic insufficiency70
Intestinal infections71
Obstructive jaundice72
|
Nutritional Treatment Protocol
Antioxidants
A number of studies have demonstrated bioavailability of quercetin on oral administration or shown significant benefit in a number of conditions including systolic hypertension, interstitial cystitis, and chronic prostatitis
TABLE 3Antioxidant SupplementationAntioxidant Combination to Provide:
Quercetin 400–800 mg
Ginkgo biloba extract (24% ginkgo flavone glycosides) 40–80 mg
Vitamin C (calcium, magnesium ascorbates) 1,000–2,000 mg
Vitamin E (d-alpha tocopheryl succinate) 200–400 mg
N-acetyl-L-cysteine (NAC) 150–300 mg Zinc (Zinc picolinate) 45–90 mg
(Consider copper supplementation at 0.75–1.5 mg in light of zinc intake.)
|
Mucosal Nutrients
TABLE 4Targeted Mucosal NutrientsMucosal Nutrient Combination to Provide:
L-glutamine 750–1,500 mg
N-acetyl-D-glucosamine (NAG) 375–750 mg
Phosphatidylcholine 75–150 mg
Gamma-linolenic acid (GLA) 200–400 mg
|
Digestive Enzymes and Intestinal Permeability
Acid-Stable Fungal Enzymes
TABLE 5Digestive Plant EnzymesAcid-Stable Enzyme Combination Totaling 613 mg to Provide:
Protease 30,000 USP
Amylase 32,000 USP
Lipase 2,100 FIP
Lactase 1,600 ALU
Sucrase 300 INVU
Maltase 32,100 DPo
Phytase 1.7 PU
Cellulase 350 CU
|
Probiotics
TABLE 6Probiotic Intestinal MicrofloraProbiotic Combination to Provide 1–5 billion CFU:
Lactobacilli: L. acidophilus, L. rhamnosus
Bifidobacteria: B. bifidum, B. lactis, B. longum, B. breve
|
Dietary Fiber
TABLE 7Dietary Fiber SupplementationDietary Fiber Combination to Provide:
Psyllium Seed Husk 1-5g
Flax Seed 1-5g
|
Case Study of Nutritional Intervention in Leaky Gut Syndrome with Joint Pain and Fatigue
Conclusion
Disclosure
References
1 Swank GM, Deitch EA. Role of the gut in multiple organ failure: bacterial translocation and permeability changes. World J Surg. 1996;20:411-417.
2 Ibid.
3 Ibid.
4 Ibid.
5 Ibid.
6 Doig CJ, Sutherland LR, Sandham JD, et al. Increased intestinal permeability is associated with the development of multiple organ dysfunction syndrome in critically ill ICU patients. Am J Respir Crit Care Med. 1998;158(2):444-451.
7 Goldberg PA. Musculoskeletal complaints and intestinal permeability: a discussion and limited case study. Nutritional Perspectives (American Chiropractic Association). 1993;16(2):17-19.
8 Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008;29(1):117-124.
9 Maes M, Coucke F, Leunis JC. Normalization of the increased translocation of endotoxin from gram negative enterobacteria (leaky gut) is accompanied by a remission of chronic fatigue syndrome. Neuro Endocrinol Lett. 2007;28(6):739-744.
10 Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007;99(1-3):237-240.
11 McGuckin MA, Eri R, Simms LA, et al. Intestinal barrier dysfunction in inflammatory bowel diseases. Inflamm Bowel Dis. 2009;15(1):100-113.
12 Mankertz J, Schulzke JD. Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications. Curr Opin Gastroenterol. 2007;23(4):379-383.
13 McGuckin MA, Eri R, Simms LA, et al. Intestinal barrier dysfunction in inflammatory bowel diseases. Inflamm Bowel Dis. 2009;15(1):100-113.
14 Mankertz J, Schulzke JD. Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications. Curr Opin Gastroenterol. 2007;23(4):379-383.
15 Ma TY. Intestinal epithelial barrier dysfunction in Crohn’s disease. Proc Soc Exp Biol Med. 1997;214(4):318-327.
16 O’Mahony S, Anderson N, Nuki G, Ferguson A. Systemic and mucosal antibodies to Klebsiella in patients with ankylosing spondylitis and Crohn’s disease. Ann Rheum Dis. 1992;51(12):1296-1300.
17 Mielants H, De Vos M, Goemaere S, et al. Intestinal mucosal permeability in inflammatory rheumatic diseases. II. Role of disease. J Rheumatol. 1991;18(3):394-400.
18 Visser J, Rozing J, Sapone A, et al. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci. 2009;1165:195-205.
19 Festen EA, Szperl AM, Weersma RK, et al. Inflammatory bowel disease and celiac disease: overlaps in the pathology and genetics, and their potential drug targets. Endocr Metab Immune Disord Drug Targets. 2009;9(2):199-218.
20 Zeng J, Li YQ, Zhen YB, et al. Clinical trial: effect of active lactic acid bacteria on mucosal barrier function in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2008;28(8):994-1002.
21 Goldberg PA. Musculoskeletal complaints and intestinal permeability: a discussion and limited case study. Nutritional Perspectives (American Chiropractic Association). 1993;16(2):17-19.
22 Sartor RB. Review article: Role of the enteric microflora in the pathogenesis of intestinal inflammation and arthritis. Aliment Pharmacol Ther. 1997;11(Suppl 3):17-22; discussion 22-23.
23 Picco P, Gattorno M, Marchese N, et al. Increased gut permeability in juvenile chronic arthritides. A multivariate analysis of the diagnostic parameters. Clin Exp Rheumatol. 2000;18(6):773-778.
24 Hvatum M, Kanerud L, Hallgren R, Brandtzaeg P. The gut-joint axis: cross reactive food antibodies in rheumatoid arthritis. Gut. 2006;55(9):1240-1247.
25 O’Mahony S, Anderson N, Nuki G, Ferguson A. Systemic and mucosal antibodies to Klebsiella in patients with ankylosing spondylitis and Crohn’s disease. Ann Rheum Dis. 1992;51(12):1296-1300.
26 Mielants H, De Vos M, Goemaere S, Schelstraete K, et al. Intestinal mucosal permeability in inflammatory rheumatic diseases. II. Role of disease. J Rheumatol. 1991;18(3):394-400.
27 Mielants H, De Vos M, Cuvelier C, Veys EM. The role of gut inflammation in the pathogenesis of spondyloarthropathies. Acta Clin Belg. 1996;51(5)340-349.
28 Holden W, Orchard T, Wordsworth P. Enteropathic arthritis. Rheum Dis Clin North Am. 2003;29(3):513-530, viii.
29 Picco P, Gattorno M, Marchese N, et al. Increased gut permeability in juvenile chronic arthritides. A multivariate analysis of the diagnostic parameters. Clin Exp Rheumatol. 2000;18(6):773-778.
30 Holden W, Orchard T, Wordsworth P. Enteropathic arthritis. Rheum Dis Clin North Am. 2003;29(3):513-530, viii.
31 Pena AS, Crusius JB. Food allergy, celiac disease and chronic inflammatory bowel disease in man. Vet Q. 1998:20(Suppl 3):S49-52.
32 Heyman M. Gut barrier dysfunction in food allergy. Eur J Gatroenterol Hepatol. 2005;17(12):1279-1285.
33 Ventura MT, Polimeno L, Amoruso AC, et al. Intestinal permeability in patients with adverse reactions to food. Dig Liver Dis. 2006;38(10):732-736.
34 Husby S, Jensenius JC, Svehag SE. Passage of undegraded dietary antigen into the blood of healthy adults. Further characterization of the kinetics of uptake and the size distribution of the antigen. Scand J Immunol. 1986;24(4):447-455.
35 Rosenfeldt V, Benfeldt E, Valerius NH, et al. Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis. J Pediatr. 2004;145(5):612-616.
36 Sandek A, Rauchhaus M, Anker SD, von Haeling S. The emerging role of the gut in heart failure. Curr Opin Clin Nutr Metab Care. 2008;11(5):632-639.
37 Sandek A, Bauditz J, Swidsinski A, et al. Altered intestinal function in patients with chronic heart failure. J Am Coll Cardiol. 2007;50(16):1561-1569.
38 Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008;29(1):117-124.
39 Wei J, Hemmings P. Gene, gut and schizophrenia: the meeting point for the gene-environment interaction in developing schizophrenia. Med Hypotheses. 2005;64(3):547-552.
40 Epple HJ, Schneider T, Troeger H, et al. Impairment of the intestinal barrier is evident in untreated but absent in suppressively treated HIV-infected patients. Gut. 2009;58(2):220-227.
41 Brenchley JM, Douek DC. The mucosal barrier and immune activation in HIV pathogenesis. Curr Opin HIV AIDS. 2008;3(3):356-361.
42 Melichar B, Hyspler R, Dragounova E, et al. Gastrointestinal permeability in ovarian cancer and breast cancer patients treated with paclitaxel and platinum. BMC Cancer. 2007;7:155.
43 Inutsuka S, Takesue F, Yasuda M, et al. Assessment of the intestinal permeability following postoperative chemotherapy for human malignant disease. Eur Surg Res. 2003;35(1):22-25.
44 Carratu R, Secondulfo M, de Magistris L, et al. Assessment of small intestinal damage in patients treated with pelvic radiotherapy. Oncol Rep. 1998;5(3):635-639.
45 Nejdfors P, Ekelund M, Westrom BR, et al. Intestinal permeability in humans is increased after radiation therapy. Dis Colon Rectum. 2000;43(11):1582-1588.
46 Dastych M, Dastych M Jr, Novotna H, Cihalova J. Lactulose/mannitol test and specificity, sensitivity, and area under curve of intestinal permeability parameters in patients with liver cirrhosis and Crohn’s disease. Dig Dis Sci. 2008;53(10):2789-2792.
47 Farhadi A, Keshavarzian A, Fields JZ, et al. Resolution of common dietary sugars from probe sugars for test of intestinal permeability using capillary gas chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2006;836(1-2):63-68.
48 Dastych M, Dastych M Jr, Novotna H, Cihalova J. Lactulose/mannitol test and specificity, sensitivity, and area under curve of intestinal permeability parameters in patients with liver cirrhosis and Crohn’s disease. Dig Dis Sci. 2008;53(10):2789-2792.
49 Vecsei AK, Graf UB, Vogelsang H. Follow-up of adult celiac patients: which non-invasive test reflects mucosal status most reliably? Endoscopy. 2009;41(2):123-128.
50 Vilela EG, de Abreu Ferrari Mde L, de Gama Torres HO, et al. Intestinal permeability and antigliadin antibody test for monitoring adult patients with celiac disease. Dig Dis Sci. 2007;52(5):1304-1309.
51 Di Leo V, D’Inca R, Diaz-Granado N, et al. Lactulose/mannitol test has high efficacy for excluding organic causes of chronic diarrhea. Am J Gastroenterol. 2003;98(10):2245-2252.
52 Farhadi A, Keshavarzian A, Fields JZ, et al. Resolution of common dietary sugars from probe sugars for test of intestinal permeability using capillary gas chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2006;836(1-2):63-68.
53 Pena AS, Crusius JB. Food allergy, celiac disease and chronic inflammatory bowel disease in man. Vet Q. 1998:20(Suppl 3):S49-52.
54 Geboes K. From inflammation to lesion. Acta Gastroenterol Belg. 1994;57(5-6):273-284.
55 Banan A, Choudhary S, Zhang Y, et al. Oxidant-induced intestinal barrier disruption and its prevention by growth factors in a human colonic cell line: role of the microtubule cytoskeleton. Free Radic Biol Med. 2000;28(5):727-738.
56 Forsyth CB, Banan A, Farhadi A, et al. Regulation of oxidant-induced intestinal permeability by metalloprotease-dependent epidermal growth factor receptor signaling. J Pharmacol Exp Ther. 2007;321(1):84-97.
57 Pena AS, Crusius JB. Food allergy, celiac disease and chronic inflammatory bowel disease in man. Vet Q. 1998:20(Suppl 3):S49-52.
58 Geboes K. From inflammation to lesion. Acta Gastroenterol Belg. 1994;57(5-6):273-284.
59 Banan A, Choudhary S, Zhang Y, et al. Oxidant-induced intestinal barrier disruption and its prevention by growth factors in a human colonic cell line: role of the microtubule cytoskeleton. Free Radic Biol Med. 2000;28(5):727-738.
60 Forsyth CB, Banan A, Farhadi A, et al. Regulation of oxidant-induced intestinal permeability by metalloprotease-dependent epidermal growth factor receptor signaling. J Pharmacol Exp Ther. 2007;321(1):84-97.
61 Lambert GP. Stress-induced gastrointestinal barrier dysfunction and its inflammatory effects. J Anim Sci. 2009;87(14 Suppl):E101-108.
62 Caso JR, Leza JC, Menchen L. The effects of physical and psychological stress on the gastrointestinal tract: lessons from animal models. Curr Mol Med. 2008;8(4):299-312.
63 Lanas A, Sopena F. Non-steroidal anti-inflammatory drugs and lower gastrointestinal complications. Gastroenterol Clin North Am. 2009;38(2):333-352.
64 Bode C, Bode JC. Effect of alcohol consumption on the gut. Best Pract Res Clin Gastroenterol. 2003;17(4):575-592.
65 Purohit V, Bode JC, Bode C, et al. Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium. Alcohol. 2008;42(5):349-361.
66 Troncone R, Caputo N, Florio G, Finelli E. Increased intestinal sugar permeability after challenge in children with cow’s milk allergy or intolerance. Allergy. 1994;49(3):142-146.
67 Schrander JJ, Unsalan-Hooyen RW, Forget PP, Jansen J. [51Cr]EDTA intestinal permeability in children with cow’s milk intolerance. J Pediatr Gastroenterol Nutr. 1990;10(2):189-192.
68 Ziegler TR, Cole CR. Small bowel bacterial overgrowth in adults: a potential contributor to intestinal failure. Curr Gastroenterol Rep. 2007;9(6):463-467.
69 Othman M, Aguero R, Lin HC. Alterations in intestinal microbial flora and human disease. Curr Opin Gastroenterol. 2008;24(1):11-16.
70 Mack DR, Flick JA, Durie PR, et al. Correlation of intestinal lactulose permeability with exocrine pancreatic dysfunction. J Pediatr. 1992;120(5):696-701.
71 Muller N, von Allmen N. Recent insights into the mucosal reactions associated with Giardia lamblia infections. Int J Parisitol. 2005;35(13):1339-1347.
72 Welsh FK, Ramsden CW, MacLennan K. Increased intestinal permeability and altered mucosal immunity in cholestatic jaundice. Ann Surg. 1998;227(2):205-212.
73 McGuckin MA, Eri R, Simms LA, et al. Intestinal barrier dysfunction in inflammatory bowel diseases. Inflamm Bowel Dis. 2009;15(1):100-113.
74 Mankertz J, Schulzke JD. Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications. Curr Opin Gastroenterol. 2007;23(4):379-383.
75 Pena AS, Crusius JB. Food allergy, celiac disease and chronic inflammatory bowel disease in man. Vet Q. 1998:20(Suppl 3):S49-52.
76 Geboes K. From inflammation to lesion. Acta Gastroenterol Belg. 1994;57(5-6):273-284.
77 Banan A, Choudhary S, Zhang Y, et al. Oxidant-induced intestinal barrier disruption and its prevention by growth factors in a human colonic cell line: role of the microtubule cytoskeleton. Free Radic Biol Med. 2000;28(5):727-738.
78 Forsyth CB, Banan A, Farhadi A, et al. Regulation of oxidant-induced intestinal permeability by metalloprotease-dependent epidermal growth factor receptor signaling. J Pharmacol Exp Ther. 2007;321(1):84-97.
79 Mankertz J, Schulzke JD. Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications. Curr Opin Gastroenterol. 2007;23(4):379-383.
80 Ibid.
81 McGuckin MA, Eri R, Simms LA, et al. Intestinal barrier dysfunction in inflammatory bowel diseases. Inflamm Bowel Dis. 2009;15(1):100-113.
82 Mankertz J, Schulzke JD. Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications. Curr Opin Gastroenterol. 2007;23(4):379-383.
83 Pena AS, Crusius JB. Food allergy, celiac disease and chronic inflammatory bowel disease in man. Vet Q. 1998:20(Suppl 3):S49-52.
84 Geboes K. From inflammation to lesion. Acta Gastroenterol Belg. 1994;57(5-6):273-284.
85 Banan A, Choudhary S, Zhang Y, et al. Oxidant-induced intestinal barrier disruption and its prevention by growth factors in a human colonic cell line: role of the microtubule cytoskeleton. Free Radic Biol Med. 2000;28(5):727-738.
86 Forsyth CB, Banan A, Farhadi A, et al. Regulation of oxidant-induced intestinal permeability by metalloprotease-dependent epidermal growth factor receptor signaling. J Pharmacol Exp Ther. 2007;321(1):84-97.
87 Shaik YB, Castellani ML, Perrella A, et al. Role of quercetin (a natural herbal compound) in allergy and inflammation. J Biol Regul Homeost Agents. 2006;20(3-4):47-52.
88 Suzuki T, Hara H. Quercetin enhances intestinal barrier function through the assembly of zonula [corrected] occludens-2, occluding, and claudin-1 and the expression of claudin-4 in Caco-2 cells. J Nutr. 2009;139(5):965-974.
89 Farhadi A, Fields JZ, Keshavarzian A. Mucosal mast cells are pivotal elements in inflammatory bowel disease that connect the dots: stress, intestinal hyperpermeability and inflammation. World J Gastroenterol. 2007;13(22):3027-3030.
90 Befus AD, Dyck N, Goodacre R, Bienenstock J. Mast cells from the human intestinal lamina propria. Isolation, histochemical subtypes, and functional characterization. J Immunol. 1987;138(8):2604-2610.
91 Penissi AB, Rudolph MI, Piezzi RS. Role of mast cells in gastrointestinal mucosal defense. Biocell. 2003;27(2):163-172.
92 Park HH, Lee S, Son HY, et al. Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells. Arch Pharm Res. 2008;31(10):1303-1311.
93 Pearce FL, Befus AD, Bienenstock J. Mucosal mast cells. III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells. J Allergy Clin Immunol. 1984;73(6):819-823.
94 Egert S, Bosy-Westphal A, Seiberl J, et al. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blind, placebo controlled cross-over study. Br J Nutr. 2009;102(7):1065-1074.
95 Katske F, Shoskes DA, Sender M, et al. Treatment of interstitial cystitis with a quercetin supplement. Tech Urol. 2001;7(1):44-46.
96 Shoskes DA, Zeitlin SI, Shahed A, Rajfer J. Quercetin in men with category III chronic prostatitis: a preliminary prospective, placebo-controlled trial. Urology. 1999;54(6):960-963.
97 Egert S, Bosy-Westphal A, Seiberl J, et al. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blind, placebo controlled cross-over study. Br J Nutr. 2009;102(7):1065-1074.
98 Chao JC, Hung HC, Chen SH, Fang CL. Effects of Ginkgo biloba extract on cytoprotective factors in rats with duodenal ulcer. World J Gastroenterol. 2004;10(4):560-566.
99 Mustafa A, El-Medany A, Hagar HH, El-Medany G. Ginkgo biloba attenuates mucosal damage in a rat model of ulcerative colitis. Pharmacol Res. 2006;53(4):324-330.
100 Mustafa A, El-Medany A, Hagar HH, El-Medany G. Ginkgo biloba attenuates mucosal damage in a rat model of ulcerative colitis. Pharmacol Res. 2006;53(4):324-330.
101 Otamiri T, Tagesson C. Ginkgo biloba extract prevents mucosal damage associated with small-intestinal ischaemia. Scand J Gastroenterol. 1989;24(6):666-670.
102 Pehlivan M, Dalbeler Y, Hazinedaroglu S, et al. An assessment of the effect of Ginkgo biloba EGb 761 on ischemia reperfusion injury of intestine. Hepatogastroenterology. 2002;49(43):201-204.
103 Beno I, Staruchova M, Volkovova K. Ulcerative colitis: activity of antioxidant enzymes of the colonic mucosa. Presse Med. 1997;26(31):1474-1477.
104 Buffinton GD, Doe WF. Depleted mucosal antioxidant defences in inflammatory bowel disease. Free Radic Biol Med. 1995;19(6):911-918.
105 Schimpl G, Pesendorfer P, Steinwender, et al. The effect of vitamin C and vitamin E supplementation on bacterial translocation in chronic portal hypertensive and common-bile-duct-ligated rats. Eur Surg Res. 1997;29(3):187-194.
106 Sun Z, Lasson A, Olanders K, et al. Gut barrier permeability, reticuloendothelial system function and protease inhibitor levels following intestinal ischaemia and reperfusion—effects of pretreatment with N-acetyl-L-cysteine and indomethacin. Dig Liver Dis. 2002;34(8):560-569.
107 Finamore A, Massimi M, Conti Devirgiliis L, Mengheri E. Zinc may contribute to the host defense by maintaining the membrane barrier. J Nutr. 2008;138(9):1664-1670.
108 Penissi AB, Rudolph MI, Piezzi RS. Role of mast cells in gastrointestinal mucosal defense. Biocell. 2003;27(2):163-172.
109 Yalcin SS, Yurdakok K, Tezcan I, Oner L. Effect of glutamine supplementation on diarrhea, interleukin-8 and secretory immunoglobulin A in children with acute diarrhea. J Pediatr Gastroenterol Nutr. 2004;38(5):494-501.
110 Burke DJ, Alverdy JC, Aoys E, Moss GS. Glutamine-supplemented total parenteral nutrition improves gut immune function. Arch Surg. 1989;124(12):1396-1399.
111 Klein S. Glutamine: and essential nonessential amino acid for the gut. Gastroenterology. 1990;99(1):279-281.
112 Alverdy JC. Effects of glutamine-supplemented diets on immunology of the gut. J Parenter Enteral Nutr. 1990;14(4 Suppl):109S-113S.
113 van der Hulst RR, van Kreel BK, von Meyenfeldt MF, et al. Glutamine and the preservation of gut integrity. Lancet. 1993;341(8857):1363-1365.
114 Kudsk KA, Wu Y, Fukatsu K, et al. Glutamine-enriched total parenteral nutrition maintains intestinal interleukin-4 and mucosal immunoglobulin A levels. J Parenter Enteral Nutr. 2000;24(5):270-274; discussion 274-275.
115 White JS, Hoper M, Parks RW, et al. Glutamine improves intestinal barrier function in experimental biliary obstruction. Eur Surg Res. 2005;37(6):342-347.
116 Petschow BW, Talbott RD. Response of Bifidobacterium species to growth promoters in human and cow milk. Pediatr Res. 1991;29(2):208-213.
117 Ghannoum MA, Abu-Elteen K, Ibrahim A, Stretton R. Protection against Candida albicans gastrointestinal colonization and dissemination by saccharides in experimental animals. Microbios. 1991;67(271):95-105.
118 Burton AF, Anderson FH. Decreased incorporation of 14C-glucosamine relative to 3H-N-acetyl glucosamine in the intestinal mucosa of patients with inflammatory bowel disease. Am J Gastroenterol. 1983;78(1):19-22.
119 Rhodes JM, Black RR, Savage A. Altered lectin binding by colonic epithelial glycoconjugates in ulcerative colitis and Crohn’s disease. Dig Dis Sci. 1988;33(11):1359-1363.
120 Burton AF, Anderson FH. Decreased incorporation of 14C-glucosamine relative to 3H-N-acetyl glucosamine in the intestinal mucosa of patients with inflammatory bowel disease. Am J Gastroenterol. 1983;78(1):19-22.
121 Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000;14(12):1567-1579.
122 Ibid.
123 Dial EJ, Zayat M, Lopez-Storey M, et al. Oral phosphatidylcholine preserves gastrointestinal mucosal barrier during LPS-induced inflammation. Shock. 2008;30(6):729-733.
124 Ibid.
125 Parlesak A, Schaeckeler S, Moser L, Bode C. Conjugated primary bile salts reduce permeability of endotoxin through intestinal epithelial cells and synergize with phosphatidylcholine in suppression of inflammatory cytokine production. Crit Care Med. 2007;35(10):2367-2374.
126 Mitzscherling K, Volynets V, Parlesak A. Phosphatidylcholine reverses ethanol induced increase in transepithelial endotoxin permeability and abolishes transepithelial leukocyte activation. Alcohol Clin Exp Res. 2009;33(3):557-562.
127 Willemsen LE, Koetsier MA, Balvers M, et al. Polyunsaturated fatty acids support epithelial barrier integrity and reduce IL-4 mediated permeability in vitro. Eur J Nutr. 2008;47(4):183-191.
128 Husby S, Jensenius JC, Svehag SE. Passage of undegraded dietary antigen into the blood of healthy adults. Further characterization of the kinetics of uptake and the size distribution of the antigen. Scand J Immunol. 1986;24(4):447-455.
129 Husby S, Foged N, Host A, Svehag SE. Passage of dietary antigens into the blood of children with coeliac disease. Quantification and size distribution of absorbed antigens. Gut. 1987;28(9):1062-1072.
130 Hvatum M, Kanerud L, Hallgren R, Brandtzaeg P. The gut-joint axis: cross reactive food antibodies in rheumatoid arthritis. Gut. 2006;55(9):1240-1247.
131 Mancilla A, Madrid S, Hurtado H, et al. [Small intestine bacterial overgrowth in patients with chronic pancreatitis]. Rev Med Chil. 2008;136(8):976-980.
132 Barillas C, Solomons NW. Effective reduction of lactose maldigestion in preschool children by direct addition of beta-galactosidase to milk at mealtime. Pediatrics. 1987;79(5):766-772.
133 Medow MS, Thek KD, Mewman LJ, et al. Beta-galactosidase tablets in the treatment of lactose intolerance in pediatrics. Am J Dis Child. 1990;144(11);1261-1264.
134 Roberts IM. Enzyme therapy for malabsorption in exocrine pancreatic insufficiency. Pancreas. 1989;4(4):496-503.
135 Mack DR, Flick JA, Durie PR, et al. Correlation of intestinal lactulose permeability with exocrine pancreatic dysfunction. J Pediatr. 1992;120(5):696-701.
136 Roberts IM. Enzyme therapy for malabsorption in exocrine pancreatic insufficiency. Pancreas. 1989;4(4):496-503.
137 Resnick C. Microbial enzyme therapy. In Pizzorno JE, Murray MT, eds. Textbook of Natural Medicine. St. Louis, MO: Churchill Livingstone, 2006:1075-1083.
138 Schneider MU, Knoll-Ruzicka S, Domschke S, et al. Pancreatic enzyme replacement therapy: comparative effects of conventional and enteric-coated microspheric pancreatin and acid-stable fungal enzyme preparations on steatorrhea in chronic pancreatitis. Hepatogastroenterology. 1985;32(2):97-102.
139 Lebenthal E, Rolston DD, Holsclaw DS. Enzyme therapy for pancreatic insufficiency: present status and future needs. Pancreas.1994;9(1):1-12.
140 Nakamura T, Takeuchi T, Tando Y. Pancreatic dysfunction and treatment options. Pancreas. 1998;16(3):329-336.
141 Griffin SM, Alderson D, Farndon DR. Acid resistant lipase as replacement therapy in chronic pancreatic exocrine insufficiency: a study in dogs. Gut. 1989;30(7):1012-1015.
142 Lebenthal E, Rolston DD, Holsclaw DS. Enzyme therapy for pancreatic insufficiency: present status and future needs. Pancreas.1994;9(1):1-12.
143 Roberts IM. Enzyme therapy for malabsorption in exocrine pancreatic insufficiency. Pancreas. 1989;4(4):496-503.
144 Lebenthal E, Rolston DD, Holsclaw DS. Enzyme therapy for pancreatic insufficiency: present status and future needs. Pancreas.1994;9(1):1-12.
145 Roberts IM. Enzyme therapy for malabsorption in exocrine pancreatic insufficiency. Pancreas. 1989;4(4):496-503.
146 Lebenthal E, Rolston DD, Holsclaw DS. Enzyme therapy for pancreatic insufficiency: present status and future needs. Pancreas.1994;9(1):1-12.
147 Roberts IM. Enzyme therapy for malabsorption in exocrine pancreatic insufficiency. Pancreas. 1989;4(4):496-503.
148 Lebenthal E, Rolston DD, Holsclaw DS. Enzyme therapy for pancreatic insufficiency: present status and future needs. Pancreas.1994;9(1):1-12.
149 Sandberg AS, Hulthen LR, Turk M. Dietary Aspergillus niger phytase increases iron absorption in humans. J Nutr. 1996;126(2):476-480.
150 Schneider MU, Knoll-Ruzicka S, Domschke S, et al. Pancreatic enzyme replacement therapy: comparative effects of conventional and enteric-coated microspheric pancreatin and acid-stable fungal enzyme preparations on steatorrhea in chronic pancreatitis. Hepatogastroenterology. 1985;32(2):97-102.
151 Griffin SM, Alderson D, Farndon DR. Acid resistant lipase as replacement therapy in chronic pancreatic exocrine insufficiency: a study in dogs. Gut. 1989;30(7):1012-1015.
152 Schneider MU, Knoll-Ruzicka S, Domschke S, et al. Pancreatic enzyme replacement therapy: comparative effects of conventional and enteric-coated microspheric pancreatin and acid-stable fungal enzyme preparations on steatorrhea in chronic pancreatitis. Hepatogastroenterology. 1985;32(2):97-102.
153 Griffin SM, Alderson D, Farndon DR. Acid resistant lipase as replacement therapy in chronic pancreatic exocrine insufficiency: a study in dogs. Gut. 1989;30(7):1012-1015.
154 O’Grady JG, Stevens FM, Keane R. Intestinal lactase, sucrase, and alkaline phosphatase in 373 patients with celiac disease. J Clin Pathol. 1984;37(3):298-301.
155 Simadibrata M, Wanders RJ, Jan G, et al. Examination of small bowel enzymes in chronic diarrhea. J Gastroenterol Hepatol. 2003;18(1):53-56.
156 Langman JM, Rowland R. Activity of duodenal disaccharidases in relation to normal and abnormal mucosal morphology. J Clin Pathol. 1990;43(7):537-540.
157 Gupta SK, Chong SK, Fitzgerald JF. Disaccharidase activities in children: normal values and comparison based on symptoms and histologic changes. J Pediatr Gastroenterol Nutr. 1999;28(3):246-251.
158 Jarvela I, Torniainen S, Kolho KL. Molecular genetics of human lactase deficiencies. Ann Med. 2009;41(8):568-575.
159 Gupta SK, Chong SK, Fitzgerald JF. Disaccharidase activities in children: normal values and comparison based on symptoms and histologic changes. J Pediatr Gastroenterol Nutr. 1999;28(3):246-251.
160 Barillas C, Solomons NW. Effective reduction of lactose maldigestion in preschool children by direct addition of beta-galactosidase to milk at mealtime. Pediatrics. 1987;79(5):766-772.
161 Medow MS, Thek KD, Mewman LJ, et al. Beta-galactosidase tablets in the treatment of lactose intolerance in pediatrics. Am J Dis Child. 1990;144(11);1261-1264.
162 Montalto M, Nucera G, Santoro L, et al. Effect of exogenous beta-galactosidase in patients with lactose malabsorption and intolerance: a crossover double-blind placebo-controlled study. Eur J Clin Nutr. 2005;59(4):489-493.
163 Corazza GR, Benati G, Sorge M, et al. beta-Galactosidase from Aspergillus niger in adult lactose malabsorption: a double-blind crossover study. Aliment Pharmacol Ther. 1992;6(1):61-66.
164 Pallauf J, Rimbach G. Nutritional significance of phytic acid and phytase. Arch Tierernahr. 1997;50(4):301-319.
165 Sandberg AS, Hulthen LR, Turk M. Dietary Aspergillus niger phytase increases iron absorption in humans. J Nutr. 1996;126(2):476-480.
166 Lei X, Ku PK, Miller ER, et al. Supplemental microbial phytase improves bioavailability of dietary zinc to weanling pigs. J Nutr. 1993;123(6):1117-1123.
167 Venum TL, Ellersieck MR. Effect of low doses of Aspergillus niger phytase on growth performance, bone strength, and nutrient absorption and excretion by growing and finishing swine fed corn-soybean meal diets deficient in available phosphorus and calcium. J Anim Sci. 2008;86(4):858-870.
168 Friesen OD, Guenter W, Rotter BA, Marquardt RR. The effects of enzyme supplementation on the nutritive value of rye grain (Secale cereale) for the young broiler chick. Poult Sci. 1991;70(12):2501-2508.
169 Nahm KH, Carlson CW. Effects of cellulase from Trichoderma viride on nutrient utilization by broilers. Poult Sci. 1985;64(8):1536-1540.
170 Ibid.
171 Omogbenigun FO, Nyachoti CM, Slominski BA. Dietary supplementation with multienzyme preparations improves nutrient utilization and growth performance in weaned pigs. J Anim Sci. 2004;82(4):1053-1061.
172 Cowieson AJ, Acamovic T, Bedford MR. Supplementation of diets containing pea meal with exogenous enzymes: effects on weight gain, feed conversion, nutrient digestibility and gross morphology of the gastrointestinal tract of growing broiler chicks. Br Poult Sci. 2003;44(3):427-437.
173 Blum S, Schiffrin EJ. Intestinal microflora and homeostasis of the mucosal response: implications for probiotic bacteria? Curr Issues Intest Microbiol. 2003;4(2):53-60.
174 Rosenfeldt V, Benfeldt E, Valerius NH, et al. Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis. J Pediatr. 2004;145(5):612-616.
175 Blum S, Schiffrin EJ. Intestinal microflora and homeostasis of the mucosal response: implications for probiotic bacteria? Curr Issues Intest Microbiol. 2003;4(2):53-60.
176 Salvini F, Granieri L, Gemmellaro L, Giovannini M. Probiotics, prebiotics and child health: where are we going? J Int Med Res. 2004;32(2):97-108.
177 Chen CC, Walker WA. Probiotics and prebiotics: role in clinical disease states. Adv Pediatr. 2005;52:77-113.
178 Ramakrishna BS. Probiotic induced changes in the intestinal epithelium: implications in gastrointestinal disease. Trop Gastroenterol. 2009;30(2):76-85.
179 Salminen S, Isolauri E, Salminen E. Clinical uses of probiotics for stabilizing the gut mucosal barrier: successful strains and future challenges. Antonie Van Leeuwenhoek. 1996;70(2-4):347-358.
180 Fujimori S, Gudis K, Mitsui K, et al. A randomized controlled trial on the efficacy of synbiotic versus probiotic and prebiotic treatment to improve the quality of life in patients with ulcerative colitis. Nutrition. 2009;25(5):520-525.
181 Colombel JF, Cortot A, Neut C, et al. Yoghurt with Bifidobacterium longum reduces erythromycin-induced gastrointestinal effects. Lancet. 1987;2(8549):43.
182 Zeng J, Li YQ, Zhen YB, et al. Clinical trial: effect of active lactic acid bacteria on mucosal barrier function in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2008;28(8):994-1002.
183 Wada M, Nagata S, Saito M, et al. Effects of the enteral administration of Bifidobacterium breve on patients undergoing chemotherapy for pediatric malignancies. Support Care Cancer. 2009 Aug 14.
184 Kim JY, Kwon JH, Ahn SH, et al. Effect of probiotic mix Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus in the primary prevention of eczema: a double-blind, randomized, placebo-controlled trial. Pediatr Allergy Immunol. 2009 Oct 14.
185 Fang SB, Lee HC, Hu JJ, et al. Dose-dependent effect of Lactobacillus rhamnosus on quantitative reduction of faecal rotavirus shedding in children. J Trop Pediatr. 2009;55(5):297-301.
186 Salminen S, Isolauri E, Salminen E. Clinical uses of probiotics for stabilizing the gut mucosal barrier: successful strains and future challenges. Antonie Van Leeuwenhoek. 1996;70(2-4):347-358.
187 McGuckin MA, Eri R, Simms LA, et al. Intestinal barrier dysfunction in inflammatory bowel diseases. Inflamm Bowel Dis. 2009;15(1):100-113.
188 Mankertz J, Schulzke JD. Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications. Curr Opin Gastroenterol. 2007;23(4):379-383.
189 Fujimori S, Gudis K, Mitsui K, et al. A randomized controlled trial on the efficacy of synbiotic versus probiotic and prebiotic treatment to improve the quality of life in patients with ulcerative colitis. Nutrition. 2009;25(5):520-525.
190 Colombel JF, Cortot A, Neut C, et al. Yoghurt with Bifidobacterium longum reduces erythromycin-induced gastrointestinal effects. Lancet. 1987;2(8549):43.
191 Zeng J, Li YQ, Zhen YB, et al. Clinical trial: effect of active lactic acid bacteria on mucosal barrier function in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2008;28(8):994-1002.
192 Wada M, Nagata S, Saito M, et al. Effects of the enteral administration of Bifidobacterium breve on patients undergoing chemotherapy for pediatric malignancies. Support Care Cancer. 2009 Aug 14.
193 Kim JY, Kwon JH, Ahn SH, et al. Effect of probiotic mix Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus in the primary prevention of eczema: a double-blind, randomized, placebo-controlled trial. Pediatr Allergy Immunol. 2009 Oct 14.
194 Rosenfeldt V, Benfeldt E, Valerius NH, et al. Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis. J Pediatr. 2004;145(5):612-616.
195 Fang SB, Lee HC, Hu JJ, et al. Dose-dependent effect of Lactobacillus rhamnosus on quantitative reduction of faecal rotavirus shedding in children. J Trop Pediatr. 2009;55(5):297-301.
196 Deitch EA. Bacterial translocation: the influence of dietary variables. Gut. 1994;35(1 Suppl):S23-S-27.
197 Mosenthal AC, Xu D, Deitch EA. Elemental and intravenous total parenteral nutrition diet-induced gut barrier failure is intestinal site specific and can be prevented by feeding nonfermentable fiber. Crit Care Med. 2002;30(2):396-402.
198 Deng G, Jiang Z, Liu Y, Xu Y. [Dietary fiber protects intestinal structure and barrier function]. Zhonghua Wai Ke Za Zhi. 1998;36(12):759-762.
199 Mariadason JM, Catto-Smith A, Gibson PR. Modulation of distal colonic epithelial barrier function by dietary fibre in normal rats. Gut. 1999;44(3):394-399.
200 Koruda MJ. Dietary fiber and gastrointestinal disease. Sug Gynecol Obstet. 1993;177(2):209-214.
201 Hamer HM, Jonkers D, Venema K, et al. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther. 2008;27(2):104-119.
202 Dahl WJ, Lockert EA, Cammer EL, Whiting SJ. Effects of flax fiber on laxation and glycemic response in healthy volunteers. J Med Food. 2005;8(4):508-511.
203 Yu LL, Lutterodt H, Cheng Z. Beneficial health properties of psyllium and approaches to improve its functionalities. Adv Food Nutr Res. 2009;55:193-220.
204 Marlett JA, Kajs TM, Fischer MH. An unfermented gel component of psyllium seed husk promotes laxation as a lubricant in humans. Am J Clin Nutr. 2000;72(3):784-789.
205 Mosenthal AC, Xu D, Deitch EA. Elemental and intravenous total parenteral nutrition diet-induced gut barrier failure is intestinal site specific and can be prevented by feeding nonfermentable fiber. Crit Care Med. 2002;30(2):396-402.
206 Mariadason JM, Catto-Smith A, Gibson PR. Modulation of distal colonic epithelial barrier function by dietary fibre in normal rats. Gut. 1999;44(3):394-399.
207 Mao Y, Kasravi B, Nobaek S, et al. Pectin-supplemented enteral diet reduces the severity of methotrexate incuded enterocolitis in rats. Scand J Gastroenterol. 1996;31(6):558-567.
208 Dahl WJ, Lockert EA, Cammer EL, Whiting SJ. Effects of flax fiber on laxation and glycemic response in healthy volunteers. J Med Food. 2005;8(4):508-511.
209 Bijkerk CJ, de Wit NJ, Muris JW, et al. Soluble or insoluble fibre in irritable bowel syndrome in primary care? Randomised placebo controlled trial. BMJ. 2009;339:b3154.
210 Fujimori S, Tatsuguchi A, Gudis K. High dose probiotic and prebiotic cotherapy for remission induction of active Crohn’s disease. J Gastroenterol Hepatol. 2007;22(8):1199-1204.
211 Goldberg PA. Musculoskeletal complaints and intestinal permeability: a discussion and limited case study. Nutritional Perspectives (American Chiropractic Association). 1993;16(2):17-19.
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