Leaky gut has gaining attention mostly in recent as the condition is claimed to be associated with a wide range of chronic diseases. On the other hand some are saying leaky gut is not real. So, what is leaky gut, how it occurs, leaky gut-myth or real: what is the evidence? Let’s find.
What is leaky gut?
When you eat food you also ingest other micro substances like bacteria, toxins, dirt from the outside world. Apart from that you body also doesn’t usually utilize the complete portion of food item. Hence your intestinal barrier is designed to allow beneficial nutrients, water, and electrolytes from foods into the blood stream. At the same time, it restricts entry of unwanted microorganisms/bacteria, toxins, large substances and other pathogenic substance.
Under some condition this intestinal barrier is damaged and not functioning properly. And such impaired intestinal barrier allows some of those restricted substances to pass though it . If such unwanted substances can penetrate the tissues beneath the intestinal epithelial lining, diffuse into the blood circulation, immune system becomes high alert as those substances are foreigner to the circulatory system as well as to the other tissues/organs where those travels through blood. A war begins in tissues/organs where those substances travels. This phenomenon is termed as leaky gut.
This intestinal barrier system is controlled by physical, biochemical as well as immunological components in entry of most pathogen substance. These components coordinate with each other to maintain barrier integrity as well as prevention such pathogenic entry.
Leaky gut-myth or real: what is the evidence?
Intestinal barrier contains intestinal epithelial cells as mainstay of the intestinal barrier with continuous lining of intestinal epithelial cells (IECs). And the contact between two IECs is sealed by tight junctions (TJs). In normal condition the barrier allows required material to pass through intercellular space as well as though cells in normal condition and on the other hand restricts entry of pathogens and large substances. Tight junction (TJ) proteins regulate the intercellular space and so the paracellular permeability. A large variety of molecules, mainly proteins, control the plasticity of tight junction in physical barrier. Under various condition this permeability of the barrier increases and thus resulting to entry of unwanted substances.
Gut microbiota or gut commensal bacteria one component of the intestinal physical barrier and primarily perform two major functions. Firstly they promote resistance to the colonization of harmful or pathogenic bacteria by competing for nutrients, occupying attachment sites, and releasing antimicrobial substances. Secondly the gut microbiota regulates the digestion and absorption of nutrients to supply energy such as short chain fatty acids to epithelial cells, a major component of the physical barrier.
They also play role in synthesizing of some important nutrients.
However overgrowth of bacteria in small intestine negatively affects to the health.
Together, intestinal epithelial cells or IECs, the mucus layers i.e. the inner and outer layers of intestinal lining, and gut microbial residents serve as the physical barrier to limit the entry of unfriendly contents into blood stream as well as tissues/organs. (1)
Biochemical Barrier (1)
Biochemical barrier includes bile acid and antimicrobial protein exists in the mucus as well as gut lumen form a complicated network to reduce the load of colonized bacteria and decrease the chance of entry of antigens through the barrier. Apart from that they also supplement the physical barrier.
As the distance from the stomach increases, ph rises and the number of colonized bacteria increases. To control overgrowth and fight invaders, Paneth cells in the intestine produces antimicrobial proteins for mucosal defense and also support barrier function. And thus paneth cells play a major role to support and mediate the biochemical barrier function.
Immunological Barrier (1)
Below the intestinal epithelium, a variety of immune cells, including B cells, T cells, dendritic cells (DCs), and neutrophils exits in lymphoid follicles. They arrange their immune response through variety of ways by presenting antigens, secreting cytokines for cell signaling, as well as producing antigen-binding antibodies. M cells present in lymphoid follicles involves in transportation of antigens across the intestinal epithelium. Additionally goblet cells present there acquired luminal antigens by forming goblet cell-associated antigen passages (GAPs). Goblet cells and GAPs can sense invasive pathogens and also inhibit the translocation of pathogenic bacteria into the body’s immune system. On the other hand colonic microbiota involves in regulation of antigen uptake process and formation of GAPs.
Another component IgA an antibody (sIgA in its secretory form) interacts with commensal bacteria to provide protection against invasive pathogens.
We mentioned that under some condition, the integrity of intestinal barrier is compromised and thus allow entry of substances/pathogen which are foreigner to the tissues/cells. And thus this condition leads to a numbers of chronic diseases. But, what are the evidences?
Where are the researches?
Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin a protein that modulates the permeability of tight junctions discovered by Alessio Fasano and his team at the University of Maryland School of Medicine is the only known factor of regulation of intestinal permeability. Zonulin reversibly regulate intestinal permeability and also increases the intestinal permeability. When the finely tuned zonulin pathway is deregulated in genetically susceptible individuals, both intestinal and extra intestinal autoimmune, inflammatory, and abnormal cell growth can occur. (2)
Experts do agree and numbers of studies have found existence of increased intestinal permeability as well as higher serum zonulin level with certain chronic diseases. (3, 4, 5)
In a study conducted on 24 patients of autoimmune hepatitis, a chronic, progressive, and immunologically mediated inflammatory liver disorder, researchers found increased intestinal permeability, derangement of the microbiome and change of bacterial location in those patients. Finally they concluded that intestinal barrier may play an important role in development of autoimmune hepatitis. And autoimmune hepatitis is associated with leaky gut and imbalance of intestinal bacteria.(6)
In an another study, conducted on Thirty-three patients, researcher concluded that abnormal small intestinal permeability in children with ulcerative colitis could predict for more deteriorating condition. (7)
Also many more studies have established link of wide range of chronic diseases with intestinal permeability.
Factors that contribute to leaky gut
Zonulin the only known regulator reversibly regulate intestinal permeability. Among the several stimuli that can trigger zonulin release, two identified powerful factors that triggers zonulin release include intestinal bacteria and gluten a protein found in wheat, barley and rye usually. (5)
Few factors are likely to contribute to leaky gut that includes
Do you know millions of bacteria are living with you, number of which is much bigger than your total number cells in the human body. All are living like a ecosystem. And major percentage of those bacteria resides in the gut. Some promote health and some affect negatively, release toxins. We all need a balance between them. When disruption or imbalance between them occurs, as well as pathogenic bacteria increases, it can affect the intestinal barrier function as well as permeability. (3)
Alcohol can create inflammation and upset the gastrointestinal tract and the liver as well as can lead damage to the both specially with excessive intake. Consumption of alcohol promotes both bacterial overgrowth and bacterial imbalance. Which further increase toxins inside as produced by some gram negative bacteria. (9) Also study found increased intestinal permeability and extra intestinal tissue damage in people consuming alcohol. (10) Hence better to limit your consumption if your seeking your gut health.
Added sugar or refined sugar can harm your health by many ways. Also sugar creates addiction for it. Unhealthy sugar, refined sugar, fructose, added sugar in food has many adverse effects to the health and also in intestinal barrier. (11)So limit your sugar intake and check your food nutrition label of packaged food as sugar hides in package food by many names.
Nutrition deficiency always play role in developing modern lifestyle diseases. Like many other diseases deficiency also plays role here. Among them specially vitamin A, vitamin D seems to play a role for the intestinal barrier with roles in activities like gut commensal bacteria and also Inflammatory bowl disease(Vitamin D). (12, 13) Mineral Zinc also plays roles wide range of gastro intestinal diseases. (14) However don’t concentrate on a single nutrition, rather try for optimal nutrition in your menu.
Non-steroidal anti-inflammatory drugs (NSAIDs):
Non-steroidal anti-inflammatory drugs in some way negatively affects to the health. Also here long-term use of NSAIDs like ibuprofen, indomethacin, naproxen etc can increase intestinal permeability and risk of leaky gut. (15, 16)
Although many people don’t feel stress is becoming a major risk factor of various diseases including heart disease in modern lifestyle. It can also contribute to gastrointestinal problems including intestinal barrier function. (17)Study over 23 healthy people concluded that acute psychological stress increases small intestinal permeability in humans.(18) Not only these stress is also a well established risk factor for many modern diseases. So, try take control over stress. Moderate physical exercises also helps to drain stress, improves daytime activeness as well as night time sleep.
Radiation and Chemotherapy
Radiation and chemotherapy had also shown to increase intestinal permeability along with other effects. (19, 20)
Few years ago people who talked about intestinal permeability or leaky gut was labelled as quack. With present situation as well as growing evidences with a wide numbers of chronic diseases, leaky gut syndrome or intestinal permeability may provide answer to many unanswered questions in future. Research evidenced-many chronic diseases begin with gut. Also even a healthy diet will work if you have unhealthy gut. Thus your gut can be a reason why the same food can have different reaction to different people. This area of research is rapidly developing. In our coming article we will come with diseases associated with leaky gut, leaky gut test, symptoms as well as healing and restore gut. Which will help you identify your gut condition and also restore your gut health.
Disclaimer:This article is for informational purpose only.
1.Leaky Gut As a Danger Signal for Autoimmune Diseases,
Qinghui Mu, Jay Kirby, Christopher M. Reilly, and Xin M. Luo,
Front Immunol. 2017; 8: 598
2.Zonulin and its regulation of intestinal barrier function: the biological
door to inflammation, autoimmunity, and cancer,Fasano A,
Physiol Rev. 2011 Jan;91(1):151-75
3.Alterations in intestinal permeability,
M C Arrieta, L Bistritz, and J B Meddings, Gut. 2006 Oct; 55(10): 1512–1520
4.Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease
and Type 1 Diabetes Paradigms, Jeroen Visser, Jan Rozing, Anna Sapone,
Karen Lammers, and Alessio Fasano, Ann N Y Acad Sci. 2009 May; 1165: 195–205.
5.Intestinal Permeability and its Regulation by Zonulin: Diagnostic and
Therapeutic Implications,Alessio Fasano, M.D,
Clin Gastroenterol Hepatol. 2012 Oct; 10(10): 1096–1100.
6. Abnormal intestinal permeability and microbiota in patients with
autoimmune hepatitis, Rui Lin, Lu Zhou, Jie Zhang, Bangmao Wang,
Int J Clin Exp Pathol. 2015; 8(5): 5153–5160
7. Altered intestinal permeability is predictive of early relapse in
children with steroid‐responsive ulcerative colitis, E. MIELE, F.
PASCARELLA, L. QUAGLIETTA, E. GIANNETTI,L. GRECO, R. TRONCONE, A. STAIANO,
Alimentary Pharmacology and Therapeutics, Vol. 25, Issue 8, Apr. 2007
8. Systemic inflammation increases intestinal permeability during
experimental human endotoxemia,Hietbrink F, Besselink MG, Renooij W, de
Smet MB, Draisma A, van der Hoeven H, Pickkers P., Shock. 2009
9.Alcohol and Gut-Derived Inflammation, Faraz Bishehsari, M.D., Ph.D.;
Emmeline Magno, M.D.; Garth Swanson, M.D.; Vishal Desai, M.D.; Robin M.
Voigt, Ph.D.; Christopher B. Forsyth, Ph.D.; and Ali Keshavarzian, M.D,
The Journal of The National Institute on Alcohol Abuse and Alcoholism
10.THE LEAKY GUT OF ALCOHOLISM: POSSIBLE ROUTE OF ENTRY FOR TOXIC
COMPOUNDS,Ingvar Bjarnason, Kevin Ward, TimothyJ Peters, The Lancet,
Volume 323, ISSUE 8370, P179-182, January 28, 1984
11. Dietary fructose and intestinal barrier: potential risk factor in the
pathogenesis of nonalcoholic fatty liver disease, Spruss A, Bergheim I.,
J Nutr Biochem. 2009 Sep;20(9):657-62
12.Intestinal permeability – a new target for disease prevention and
therapy,Stephan C Bischoff, Giovanni Barbara, Wim Buurman, Theo Ockhuizen,
Jörg-Dieter Schulzke, Matteo Serino, Herbert Tilg, Alastair Watson, and
Jerry M Wells,BMC Gastroenterol. 2014; 14: 189
13.Effects of vitamin A supplementation on intestinal barrier function,
growth, total parasitic, and specific Giardia spp infections in Brazilian
children: a prospective randomized, double-blind, placebo-controlled
trial,Lima AA, Soares AM, Lima NL, Mota RM, Maciel BL, Kvalsund MP, Barrett
LJ, Fitzgerald RP, Blaner WS, Guerrant RL.,J Pediatr Gastroenterol Nutr.
14. Zinc and gastrointestinal disease, Sonja Skrovanek, Katherine DiGuilio,
Robert Bailey, William Huntington, Ryan Urbas, Barani Mayilvaganan,
Giancarlo Mercogliano, and James M Mullin, World J Gastrointest
Pathophysiol. 2014 Nov 15; 5(4): 496–513
15.Increased intestinal permeability in patients with rheumatoid
arthritis: a side-effect of oral nonsteroidal anti-inflammatory drug
therapy?,Jenkins RT, Rooney PJ, Jones DB, Bienenstock J, Goodacre RL.
Br. J Rheumatol,1987 Apr;26(2):103-7.
16.Intestinal permeability and inflammation in patients on NSAIDs,
G Sigthorsson, J Tibble, J Hayllar, I Menzies, A Macpherson, R Moots, D
Scott, M Gumpel, and I Bjarnason, Gut, 1998 Oct; 43(4): 506–511
17.Stress and the gut: pathophysiology, clinical consequences, diagnostic
approach and treatment options,Konturek PC, Brzozowski T, Konturek SJ.,
J. Physiol Pharmacol, 2011 Dec;62(6):591-9
18.Psychological stress and corticotropin-releasing hormone increase
intestinal permeability in humans by a mast cell-dependent mechanism.
Vanuytsel T, van Wanrooy S, Vanheel H, et al. Gut. 2014;63(8):1293-1299
19.Intestinal permeability in humans is increased after radiation therapy.
Nejdfors P, Ekelund M, Weström BR, et al., Dis Colon Rectum.
20.Intestinal permeability in patients with chemotherapy-induced
stomatitis, Melichar B, Kohout P, Brátová, M, Solichová D, Králícková P,
Zadák Z. . J Cancer Res Oncol. 2001;127:314-318