conditions leaky-gut-syndrome


Leaky Gut Syndrome

Condition:Leaky Gut Syndrome
Other:Intestinal Permeability


Top 5 treatemtns for leaky gut syndrome:

1. elimination diet
2. glutamine
3. probiotics
4. digestive enzymes
5. goldenseal (Hydrastis canadensis)

Naturopathic Treatments

Approach to treating leaky gut:

1) Remove cause
• drugs
• infection
• food sensitivities

2a) Stimulate digestion:
bitter herbs
• apple cider vinegar
2b) Supplement digestive juices
• bile salts
• digestive enzymes

3) Repair intestinal integrity
Demulcent herbs - high in mucilage
- marshmallow (Althaea officinalis)
- slippery elm ( Ulmus rubra)
Vulnerary herbs
- chamomile (Matricaria recutita)
- plantain (Plantago spp.)
- marigold (Calendula officinalis)
• Antiinflammatories
- turmeric (Curcuma longa)
• Feed enterocytes (fuel supplies)
- glutamine
- short chain fatty acids (SCFA) - produced from fermentation of fibres by gut flora
• Miscellaneous
- Zinc
- N-Acetyl-L-cysteine (NAC)
- berberine (e.g. goldenseal, barberry, oregon grape)
- zinc carnosine

4) Improve gut flora
• probiotics
- Lactobacillus strains
• prebiotics
- fruits and vegetables (mixed fiber)
- inulin
- glucans

• Specific foods shown to have benefit:
- oatmeal
- green tea
- whey protein
- apples
- ellagic acid (pomegranate, raspberries)

Conventional Treatments

Not an established syndrome so treatment targets symptoms.

Signs & Symptoms

Not established. Symptoms vary depending on how the increased in immune response aggravates the individual:
• low grade fever
• digestive pain
• poor cognition and memory
• skin rashes
muscle pain
• aggravation of other conditions


May contribute to:
• generalized inflammation
• auto-immune diseases
- rheumatoid arthritis
- lupus, multiple sclerosis
- BehÇet's disease
- Crohn's disease
- scleroderma
- psorasis
chronic fatigue syndrome
irritable bowel syndrome (IBS)


• intestinal inflammation causes tight junctions between intestinal cells to widen
• contents of the intestinal lumen, which are normally too large to be absorbed, enters circulation, including:
- endotoxins
- undigested food
- bacteria
- yeast
• the increased absorption of foreign material stimulates the immune system leading to increased antibody complexes, cytokine release and corresponding inflammation

Causes of intestinal inflammation:
• food sensitivities and intolerances
• inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis)
• gastrointestinal surgery
• drugs
- chemotherapy
- alcohol
- castor oil
• Infection (dysbiosis)
- candida
- parasites
- bacteria
- viral (e.g. HIV)
• stress
- heat stroke
- surgery
- burn


• mannitol and lactulose test


"Show references"

"Hide references"

1: Sommansson A, Saudi WS, Nylander O, SjÖblom M. Melatonin inhibits
alcohol-induced increases in duodenal mucosal permeability in rats in vivo. Am J
Physiol Gastrointest Liver Physiol. 2013 Jul 1;305(1):G95-G105. doi:
10.1152/ajpgi.00074.2013. Epub 2013 May 2. PubMed PMID: 23639810.

2: Gecse K, RÓka R, SÉra T, RosztÓczy A, Annah Á zi A, IzbÉki F, Nagy F, Moln Á r T,
Szepes Z, P Á vics L, Bueno L, Wittmann T. Leaky gut in patients with
diarrhea-predominant irritable bowel syndrome and inactive ulcerative colitis.
Digestion. 2012;85(1):40-6. doi: 10.1159/000333083. Epub 2011 Dec 14. PubMed
PMID: 22179430.

3: Rapin JR, Wiernsperger N. Possible links between intestinal permeability and
food processing: A potential therapeutic niche for glutamine. Clinics (Sao
Paulo). 2010 Jun;65(6):635-43. doi: 10.1590/S1807-59322010000600012. Review.
PubMed PMID: 20613941; PubMed Central PMCID: PMC2898551.

4: Li GX, Wang XM, Jiang T, Gong JF, Niu LY, Li N. Berberine Prevents Intestinal
Mucosal Barrier Damage During Early Phase of Sepsis in Rat through the Toll-Like
Receptors Signaling Pathway. Korean J Physiol Pharmacol. 2015 Jan;19(1):1-7. doi:
10.4196/kjpp.2015.19.1.1. Epub 2014 Dec 31. PubMed PMID: 25605990; PubMed Central
PMCID: PMC4297756.

5: Tan S, Yu W, Lin Z, Chen Q, Shi J, Dong Y, Duan K, Bai X, Xu L, Yu Z, Li J, Li
N. Berberine ameliorates intestinal mucosal barrier damage induced by peritoneal
air exposure. Biol Pharm Bull. 2015 Jan 1;38(1):122-6. doi:
10.1248/bpb.b14-00643. Epub 2014 Oct 22. PubMed PMID: 25341882.

6: Liang HY, Chen T, Yan HT, Huang Z, Tang LJ. Berberine ameliorates severe acute
pancreatitis induced intestinal barrier dysfunction via a myosin light chain
phosphorylation dependent pathway. Mol Med Rep. 2014 May;9(5):1827-33. doi:
10.3892/mmr.2014.1996. Epub 2014 Feb 28. PubMed PMID: 24584406.

7: Li GX, Wang XM, Jiang T, Gong JF, Niu LY, Li N. Berberine prevents damage to
the intestinal mucosal barrier during early phase of sepsis in rat through
mechanisms independent of the NOD-like receptors signaling pathway. Eur J
Pharmacol. 2014 May 5;730:1-7. doi: 10.1016/j.ejphar.2014.02.006. Epub 2014 Feb
14. PubMed PMID: 24530556.

8: Gu L, Li N, Yu W, Gong J, Li Q, Zhu W, Li J. Berberine reduces rat intestinal
tight junction injury induced by ischemia-reperfusion associated with the
suppression of inducible nitric oxide synthesis. Am J Chin Med.
2013;41(6):1297-312. doi: 10.1142/S0192415X13500870. PubMed PMID: 24228602.

9: Shan CY, Yang JH, Kong Y, Wang XY, Zheng MY, Xu YG, Wang Y, Ren HZ, Chang BC,
Chen LM. Alteration of the intestinal barrier and GLP2 secretion in
Berberine-treated type 2 diabetic rats. J Endocrinol. 2013 Jul 29;218(3):255-62.
doi: 10.1530/JOE-13-0184. Print 2013 Sep. PubMed PMID: 23757509.

10: Gu L, Li N, Gong J, Li Q, Zhu W, Li J. Berberine ameliorates intestinal
epithelial tight-junction damage and down-regulates myosin light chain kinase
pathways in a mouse model of endotoxinemia. J Infect Dis. 2011 Jun
1;203(11):1602-12. doi: 10.1093/infdis/jir147. PubMed PMID: 21592990.

11: Li N, Gu L, Qu L, Gong J, Li Q, Zhu W, Li J. Berberine attenuates
pro-inflammatory cytokine-induced tight junction disruption in an in vitro model
of intestinal epithelial cells. Eur J Pharm Sci. 2010 Apr 16;40(1):1-8. doi:
10.1016/j.ejps.2010.02.001. Epub 2010 Feb 10. PubMed PMID: 20149867.

12: Gu L, Li N, Li Q, Zhang Q, Wang C, Zhu W, Li J. The effect of berberine in
vitro on tight junctions in human Caco-2 intestinal epithelial cells.
Fitoterapia. 2009 Jun;80(4):241-8. doi: 10.1016/j.fitote.2009.02.005. Epub 2009
Feb 23. PubMed PMID: 19243699.

1: Karaku a-Juchnowicz H, Szachta P, Opolska A, Morylowska-Topolska J, Ga cka M,
Juchnowicz D, Krukow P, Lasik Z. The role of IgG hypersensitivity in the
pathogenesis and therapy of depressive disorders. Nutr Neurosci. 2014 Sep 30.
[Epub ahead of print] PubMed PMID: 25268936.

Newnham ED. Does gluten cause gastrointestinal symptoms in subjects without coeliac disease? J Gastroenterol Hepatol. 2011 Apr;26 Suppl 3:132-4. doi: 10.1111/j.1440-1746.2011.06653.x. Review. PubMed PMID: 21443726.

Rapin JR, Wiernsperger N. Possible links between intestinal permeability and food processing: A potential therapeutic niche for glutamine. Clinics (Sao Paulo). 2010 Jun;65(6):635-43. Review. PubMed PMID: 20613941; PubMed Central PMCID: PMC2898551.

Gecse K, RÓka R, SÉra T, RosztÓczy A, Annah Á zi A, IzbÉki F, Nagy F, Moln Á r T, Szepes Z, P Á vics L, Bueno L, Wittmann T. Leaky gut in patients with diarrhea-predominant irritable bowel syndrome and inactive ulcerative colitis. Digestion. 2012;85(1):40-6. Epub 2011 Dec 14. PubMed PMID: 22179430.

Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10. PubMed PMID: 19112401.

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 Dec;28(6):739-44. PubMed PMID: 18063928.

Liu Z, Li N, Neu J. Tight junctions, leaky intestines, and pediatric diseases. Acta Paediatr. 2005 Apr;94(4):386-93. Review. PubMed PMID: 16092447.

Manahan B. A brief evidence-based review of two gastrointestinal illnesses: irritable bowel and leaky gut syndrome. Altern Ther Health Med. 2004 Jul-Aug;10(4):14. PubMed PMID: 15285270.

Krack A, Sharma R, Figulla HR, Anker SD. The importance of the gastrointestinal system in the pathogenesis of heart failure. Eur Heart J. 2005 Nov;26(22):2368-74. Epub 2005 Jun 24. Review. PubMed PMID: 15980032.

Benjamin J, Makharia G, Ahuja V, Anand Rajan KD, Kalaivani M, Gupta SD, Joshi YK. Glutamine and Whey Protein Improve Intestinal Permeability and Morphology in Patients with Crohn's Disease: A Randomized Controlled Trial. Dig Dis Sci. 2011 Oct 26. [Epub ahead of print] PubMed PMID: 22038507.

Jiang JW, Ren ZG, Chen LY, Jiang L, Xie HY, Zhou L, Zheng SS. Enteral supplementation with glycyl-glutamine improves intestinal barrier function after liver transplantation in rats. Hepatobiliary Pancreat Dis Int. 2011 Aug;10(4):380-5. PubMed PMID: 21813386.

Sevastiadou S, Malamitsi-Puchner A, Costalos C, Skouroliakou M, Briana DD, Antsaklis A, Roma-Giannikou E. The impact of oral glutamine supplementation on the intestinal permeability and incidence of necrotizing enterocolitis/septicemia in premature neonates. J Matern Fetal Neonatal Med. 2011 Oct;24(10):1294-300. Epub 2011 Apr 4. PubMed PMID: 21463215.

dos Santos RG, Viana ML, Generoso SV, Arantes RE, Davisson Correia MI, Cardoso VN. Glutamine supplementation decreases intestinal permeability and preserves gut mucosa integrity in an experimental mouse model. JPEN J Parenter Enteral Nutr. 2010 Jul-Aug;34(4):408-13. PubMed PMID: 20631386.

Song HY, Jiang CH, Yang JR, Chen QH, Huang J, Huang YH, Liang LX. [The change of intestinal mucosa barrier in chronic severe hepatitis B patients and clinical intervention]. Zhonghua Gan Zang Bing Za Zhi. 2009 Oct;17(10):754-8. Chinese. PubMed PMID: 19874691.

Li Y, Ping X, Yu B, Liu F, Ni X, Li J. Clinical trial: prophylactic intravenous alanyl-glutamine reduces the severity of gastrointestinal toxicity induced by chemotherapy--a randomized crossover study. Aliment Pharmacol Ther. 2009 Sep 1;30(5):452-8. Epub 2009 Jun 15. PubMed PMID: 19549287.

Culkin A, Gabe SM, Bjarnason I, Grimble G, Madden AM, Forbes A. A double-blind, randomized, controlled crossover trial of glutamine supplementation in home parenteral nutrition. Eur J Clin Nutr. 2008 May;62(5):575-83. Epub 2007 Apr 18. PubMed PMID: 17440526.

Li Y, Yu Z, Liu F, Tan L, Wu B, Li J. Oral glutamine ameliorates chemotherapy-induced changes of intestinal permeability and does not interfere with the antitumor effect of chemotherapy in patients with breast cancer: a prospective randomized trial. Tumori. 2006 Sep-Oct;92(5):396-401. PubMed PMID: 17168431.

Choi K, Lee SS, Oh SJ, Lim SY, Lim SY, Jeon WK, Oh TY, Kim JW. The effect of oral glutamine on 5-fluorouracil/leucovorin-induced mucositis/stomatitis assessed by intestinal permeability test. Clin Nutr. 2007 Feb;26(1):57-62. Epub 2006 Sep 1. PubMed PMID: 16949180.

Singleton KD, Wischmeyer PE. Oral glutamine enhances heat shock protein expression and improves survival following hyperthermia. Shock. 2006 Mar;25(3):295-9. PubMed PMID: 16552363.

Jiang HP, Liu CA. [Protective effect of glutamine on intestinal barrier function in patients receiving chemotherapy]. Zhonghua Wei Chang Wai Ke Za Zhi. 2006 Jan;9(1):59-61. Chinese. PubMed PMID: 16437375.

De-Souza DA, Greene LJ. Intestinal permeability and systemic infections in critically ill patients: effect of glutamine. Crit Care Med. 2005 May;33(5):1125-35. Review. PubMed PMID: 15891348.

Clark EC, Patel SD, Chadwick PR, Warhurst G, Curry A, Carlson GL. Glutamine deprivation facilitates tumour necrosis factor induced bacterial translocation in Caco-2 cells by depletion of enterocyte fuel substrate. Gut. 2003 Feb;52(2):224-30. PubMed PMID: 12524404; PubMed Central PMCID: PMC1774948.

Chen G, Xie W, Jiang H. [Clinical observation of the protective effect of oral feeding of glutamine granules on intestinal mucous membrane]. Zhonghua Shao Shang Za Zhi. 2001 Aug;17(4):210-1. Chinese. PubMed PMID: 11876941.

Zhou Y, Jiang Z, Sun Y. [Glutamine dipeptide enriched enteral nutrition improving gut permeability in sever burns]. Zhonghua Yi Xue Za Zhi. 1999 Nov;79(11):825-7. Chinese. PubMed PMID: 11715489.

Daniele B, Perrone F, Gallo C, Pignata S, De Martino S, De Vivo R, Barletta E, Tambaro R, Abbiati R, D'Agostino L. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial. Gut. 2001 Jan;48(1):28-33. PubMed PMID: 11115819; PubMed Central PMCID: PMC1728161.

Buchman AL. Glutamine for the gut: mystical properties or an ordinary amino acid? Curr Gastroenterol Rep. 1999 Oct;1(5):417-23. Review. PubMed PMID: 10980981.

Akobeng AK, Miller V, Stanton J, Elbadri AM, Thomas AG. Double-blind randomized controlled trial of glutamine-enriched polymeric diet in the treatment of active Crohn's disease. J Pediatr Gastroenterol Nutr. 2000 Jan;30(1):78-84. PubMed PMID: 10630444.

Jian ZM, Cao JD, Zhu XG, Zhao WX, Yu JC, Ma EL, Wang XR, Zhu MW, Shu H, Liu YW. The impact of alanyl-glutamine on clinical safety, nitrogen balance, intestinal permeability, and clinical outcome in postoperative patients: a randomized, double-blind, controlled study of 120 patients. JPEN J Parenter Enteral Nutr. 1999 Sep-Oct;23(5 Suppl):S62-6. PubMed PMID: 10483898.

Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999 Aug;4(4):239-48. Review. PubMed PMID: 10468648.

Hond ED, Peeters M, Hiele M, Bulteel V, Ghoos Y, Rutgeerts P. Effect of glutamine on the intestinal permeability changes induced by indomethacin in humans. Aliment Pharmacol Ther. 1999 May;13(5):679-85. PubMed PMID: 10233193.

Den Hond E, Hiele M, Peeters M, Ghoos Y, Rutgeerts P. Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn's disease. JPEN J Parenter Enteral Nutr. 1999 Jan-Feb;23(1):7-11. PubMed PMID: 9888411.

Noyer CM, Simon D, Borczuk A, Brandt LJ, Lee MJ, Nehra V. A double-blind placebo-controlled pilot study of glutamine therapy for abnormal intestinal permeability in patients with AIDS. Am J Gastroenterol. 1998 Jun;93(6):972-5. PubMed PMID: 9647031.

Song WB, Zhang ZS, Xiao B. [Protective effect of curcumin against methotrexate-induced small intestinal damage in rats]. Nan Fang Yi Ke Da Xue Xue Bao. 2008 Jan;28(1):119-21. Chinese. PubMed PMID: 18227041.

Ye D, Ma I, Ma TY. Molecular mechanism of tumor necrosis factor-alpha modulation of intestinal epithelial tight junction barrier. Am J Physiol Gastrointest Liver Physiol. 2006 Mar;290(3):G496-504. PubMed PMID: 16474009.

Ma TY, Iwamoto GK, Hoa NT, Akotia V, Pedram A, Boivin MA, Said HM. TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. Am J Physiol Gastrointest Liver Physiol. 2004 Mar;286(3):G367-76. PubMed PMID: 14766535.

Taylor RA, Leonard MC. Curcumin for inflammatory bowel disease: a review of human studies. Altern Med Rev. 2011 Jun;16(2):152-6. Review. PubMed PMID: 21649456.

Ukil A, Maity S, Karmakar S, Datta N, Vedasiromoni JR, Das PK. Curcumin, the major component of food flavour turmeric, reduces mucosal injury in trinitrobenzene sulphonic acid-induced colitis. Br J Pharmacol. 2003 May;139(2):209-18. PubMed PMID: 12770926; PubMed Central PMCID: PMC1573841.

Arafa HM, Hemeida RA, El-Bahrawy AI, Hamada FM. Prophylactic role of curcumin in dextran sulfate sodium (DSS)-induced ulcerative colitis murine model. Food Chem Toxicol. 2009 Jun;47(6):1311-7. Epub 2009 Mar 12. PubMed PMID: 19285535.

Feng D, Ohlsson L, Duan RD. Curcumin inhibits cholesterol uptake in Caco-2 cells by down-regulation of NPC1L1 expression. Lipids Health Dis. 2010 Apr 19;9:40. PubMed PMID: 20403165; PubMed Central PMCID: PMC2865464.

Volman JJ, Mensink RP, Buurman WA, Plat J. In vivo effects of dietary (1 3), (1 4)- β -D-glucans from oat on mucosal immune responses in man and mice. Scand J Gastroenterol. 2011 May;46(5):603-10. Epub 2010 Dec 17. PubMed PMID: 21162692.

Kennedy RJ, Hoper M, Deodhar K, Kirk SJ, Gardiner KR. Probiotic therapy fails to improve gut permeability in a hapten model of colitis. Scand J Gastroenterol. 2000 Dec;35(12):1266-71. PubMed PMID: 11199365.

Mao Y, Nobaek S, Kasravi B, Adawi D, Stenram U, Molin G, Jeppsson B. The effects of Lactobacillus strains and oat fiber on methotrexate-induced enterocolitis in rats. Gastroenterology. 1996 Aug;111(2):334-44. PubMed PMID: 8690198.

Tang Y, Forsyth CB, Banan A, Fields JZ, Keshavarzian A. Oats supplementation prevents alcohol-induced gut leakiness in rats by preventing alcohol-induced oxidative tissue damage. J Pharmacol Exp Ther. 2009 Jun;329(3):952-8. Epub 2009 Mar 10. PubMed PMID: 19276402; PubMed Central PMCID: PMC2683774.

Keshavarzian A, Choudhary S, Holmes EW, Yong S, Banan A, Jakate S, Fields JZ. Preventing gut leakiness by oats supplementation ameliorates alcohol-induced liver damage in rats. J Pharmacol Exp Ther. 2001 Nov;299(2):442-8. PubMed PMID: 11602653.

Forsyth CB, Farhadi A, Jakate SM, Tang Y, Shaikh M, Keshavarzian A. Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitis. Alcohol. 2009 Mar;43(2):163-72. PubMed PMID: 19251117; PubMed Central PMCID: PMC2675276.

Soler AP, Marano CW, Bryans M, Miller RD, Garulacan LA, Mauldin SK, Stamato TD, Mullin JM. Activation of NF-kappaB is necessary for the restoration of the barrier function of an epithelium undergoing TNF-alpha-induced apoptosis. Eur J Cell Biol. 1999 Jan;78(1):56-66. PubMed PMID: 10082424.

Watson JL, Ansari S, Cameron H, Wang A, Akhtar M, McKay DM. Green tea polyphenol (-)-epigallocatechin gallate blocks epithelial barrier dysfunction provoked by IFN-gamma but not by IL-4. Am J Physiol Gastrointest Liver Physiol. 2004 Nov;287(5):G954-61. Epub 2004 Jul 1. PubMed PMID: 15231486.

Vreeburg RA, van Wezel EE, OcaÑa-Calahorro F, Mes JJ. Apple extract induces increased epithelial resistance and claudin 4 expression in Caco-2 cells. J Sci Food Agric. 2012 Jan 30;92(2):439-44. doi: 10.1002/jsfa.4598. Epub 2011 Oct 3. PubMed PMID: 21968969.

Mahmood A, FitzGerald AJ, Marchbank T, Ntatsaki E, Murray D, Ghosh S, Playford RJ. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut. 2007 Feb;56(2):168-75. Epub 2006 Jun 15. PubMed PMID: 16777920; PubMed Central PMCID: PMC1856764.

Disclaimer: This content is subject to change. The information is intended to inform and educate; it does not replace the medical evaluation, advice, diagnosis or treatment by a healthcare professional. © 2015 NDAssist Inc. and/or its affiliates. All rights reserved.