Can someone have “leaky gut”? We asked our own Dr Miguel that very question. With a doctorate in gut microbiome and mental health and years of expertise in the field, he is just the person to provide us with a legitimate answer. He also shared a few other gems with us. The references are linked to the full text of the articles so they can be used as further reading.
What exactly is “leaky gut”?
“Leaky gut” or “leaky gut syndrome” is a made-up condition based on the actual fact that the gut lining is permeable by nature. Contrary to popular belief, the permeability of the gut is not a bad thing at all. As a matter of fact, a relatively permeable mucous lining is needed so that the nutrients we get from food can make it into the bloodstream. This would not happen if the gut was just a tightly sealed tube.
The more scientifically sound name for leaky gut is “intestinal permeability”, a completely natural process that is happening and changing in intensity 24 hours a day, every day of your life. That means that permeability will continuously increase and decrease as a result of a number of factors, including:
- What you eat.1Rohr MW, Narasimhulu CA, Rudeski-Rohr TA, Parthasarathy S. Negative Effects of a High-Fat Diet on Intestinal Permeability: A Review. Adv Nutr. 2020 Jan 1;11(1):77-91. doi: 10.1093/advances/nmz061. For example, if your diet is based on high-fat, high-sugar, ultra-processed foods, your gut lining is likely to be more permeable than if the bulk of your food intake is from fresh produce.2Malesza IJ, Malesza M, Walkowiak J, Mussin N, Walkowiak D, Aringazina R, Bartkowiak-Wieczorek J, Mądry E. High-Fat, Western-Style Diet, Systemic Inflammation, and Gut Microbiota: A Narrative Review. Cells. 2021 Nov 14;10(11):3164. doi: 10.3390/cells10113164.. Emerging evidence points to food additives as dietary factors that increase intestinal permeability by damaging the integrity of the mucous layer that protects “the skin of the gut”. These include emulsifiers, typically used in foods that last a long time on a supermarket shelf, like ready meals, sauces, biscuits and confectionery. 3Bancil AS, Sandall AM, Rossi M, Chassaing B, Lindsay JO, Whelan K. Food Additive Emulsifiers and Their Impact on Gut Microbiome, Permeability, and Inflammation: Mechanistic Insights in Inflammatory Bowel Disease. J Crohns Colitis. 2021 Jun 22;15(6):1068-1079. doi: 10.1093/ecco-jcc/jjaa254. Artificial sweeteners like aspartame, sucralose, or saccharin seem to have similar detrimental effects on the gut lining.4Shil A, Olusanya O, Ghufoor Z, Forson B, Marks J, Chichger H. Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. Nutrients. 2020 Jun 22;12(6):1862. doi: 10.3390/nu12061862.
- Whether you drink alcohol or not. Drinking alcohol leads to an increase in permeability,5Swanson G, Forsyth CB, Tang Y, Shaikh M, Zhang L, Turek FW, Keshavarzian A. Role of intestinal circadian genes in alcohol-induced gut leakiness. Alcohol Clin Exp Res. 2011 Jul;35(7):1305-14. doi: 10.1111/j.1530-0277.2011.01466.x., but this is rapidly improved when you stop drinking, even in clinical situations like alcohol-related liver disease.6Jung F, Burger K, Staltner R, Brandt A, Mueller S, Bergheim I. Markers of Intestinal Permeability Are Rapidly Improved by Alcohol Withdrawal in Patients with Alcohol-Related Liver Disease. Nutrients. 2021 May 14;13(5):1659. doi: 10.3390/nu13051659.
- How much exercise you do.7Interplay Between Exercise and Gut Microbiome in the Clauss M, Gérard P, Mosca A, Leclerc M. Interplay Between Exercise and Gut Microbiome in the Context of Human Health and Performance. Front Nutr. 2021 Jun 10;8:637010. doi: 10.3389/fnut.2021.637010. of Human Health and Performance Intense exercise may contribute to a temporary increase in intestinal permeability.8Karl JP, Margolis LM, Madslien EH, Murphy NE, Castellani JW, Gundersen Y, Hoke AV, Levangie MW, Kumar R, Chakraborty N, Gautam A, Hammamieh R, Martini S, Montain SJ, Pasiakos SM. Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress. Am J Physiol Gastrointest Liver Physiol. 2017 Jun 1;312(6):G559-G571. doi: 10.1152/ajpgi.00066.2017. But here’s an interesting thing: a growing body of evidence suggests that committing to a regular exercise regimen lasting weeks to months improves indicators of intestinal permeability.9Keirns BH, Koemel NA, Sciarrillo CM, Anderson KL, Emerson SR. Exercise and intestinal permeability: another form of exercise-induced hormesis? Am J Physiol Gastrointest Liver Physiol. 2020 Oct 1;319(4):G512-G518. doi: 10.1152/ajpgi.00232.2020.
- How well you sleep.10Voigt RM, Forsyth CB, Keshavarzian A. Circadian rhythms: a regulator of gastrointestinal health and dysfunction. Expert Rev Gastroenterol Hepatol. 2019 May;13(5):411-424. doi: 10.1080/17474124.2019.1595588. As an example, people with sleep apnea tend to have a more permeable compared to those without the condition.11Barceló A, Esquinas C, Robles J, Piérola J, De la Peña M, Aguilar I, Morell-Garcia D, Alonso A, Toledo N, Sánchez-de la Torre M, Barbé F. Gut epithelial barrier markers in patients with obstructive sleep apnea. Sleep Med. 2016 Oct;26:12-15. doi: 10.1016/j.sleep.2016.01.019.
- Whether you take aspirin or ibuprofen.12Lambert GP, Schmidt A, Schwarzkopf K, Lanspa S. Effect of aspirin dose on gastrointestinal permeability. Int J Sports Med. 2012 Jun;33(6):421-5. doi: 10.1055/s-0032-1301892.13Bjarnason I, Williams P, Smethurst P, Peters TJ, Levi AJ. Effect of non-steroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine. Gut. 1986 Nov;27(11):1292-7. doi: 10.1136/gut.27.11.1292. And here’s an oddity: taking aspirin and a vitamin C supplement at the same time makes the gut lining more permeable than takin aspirin alone.14Sequeira IR, Kruger MC, Hurst RD, Lentle RG. Ascorbic Acid may Exacerbate Aspirin-Induced Increase in Intestinal Permeability. Basic Clin Pharmacol Toxicol. 2015 Sep;117(3):195-203. doi: 10.1111/bcpt.12388.
- How stressed you feel. Stress is a leading trigger of gastrointestinal symptoms, some of which may happy alongside an increase in intestinal permeability.15Konturek PC, Brzozowski T, Konturek SJ. Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. J Physiol Pharmacol. 2011 Dec;62(6):591-9. All types of stress are likely to have similar effects. For example, it is known that marital stress also makes the gut lining more leaky, i.e. couples who argue regularly have more a permeable gut. 16Kiecolt-Glaser JK, Wilson SJ, Madison A. Marriage and Gut (Microbiome) Feelings: Tracing Novel Dyadic Pathways to Accelerated Aging. Psychosom Med. 2019 Oct;81(8):704-710. doi: 10.1097/PSY.0000000000000647.
- A combination of factors. We now have evidence to show that combining two or more of the above factors can have a cumulative effect that makes the gut lining even more permeable. For example drinking alcohol into the early hours and sleeping during the day disrupts your natural day/night or circadian rhythm and leads to increased permeability beyond of that caused by either circadian disruption or alcohol drinking alone. 17Swanson GR, Gorenz A, Shaikh M, Desai V, Kaminsky T, Van Den Berg J, Murphy T, Raeisi S, Fogg L, Vitaterna MH, Forsyth C, Turek F, Burgess HJ, Keshavarzian A. Night workers with circadian misalignment are susceptible to alcohol-induced intestinal hyperpermeability with social drinking. Am J Physiol Gastrointest Liver Physiol. 2016 Jul 1;311(1):G192-201. doi: 10.1152/ajpgi.00087.2016.18Swanson GR, Gorenz A, Shaikh M, Desai V, Forsyth C, Fogg L, Burgess HJ, Keshavarzian A. Decreased melatonin secretion is associated with increased intestinal permeability and marker of endotoxemia in alcoholics. Am J Physiol Gastrointest Liver Physiol. 2015 Jun 15;308(12):G1004-11. doi: 10.1152/ajpgi.00002.2015. Also, taking aspirin or ibuprofen before exercise also makes your gut more leaky than either the exercise or the drugs alone.19Lambert GP, Boylan M, Laventure JP, Bull A, Lanspa S. Effect of aspirin and ibuprofen on GI permeability during exercise. Int J Sports Med. 2007 Sep;28(9):722-6. doi: 10.1055/s-2007-964891.20Van Wijck K, Lenaerts K, Van Bijnen AA, Boonen B, Van Loon LJ, Dejong CH, Buurman WA. Aggravation of exercise-induced intestinal injury by Ibuprofen in athletes. Med Sci Sports Exerc. 2012 Dec;44(12):2257-62. doi: 10.1249/MSS.0b013e318265dd3d.
Is “leaky gut” a medical condition?
Some people claim to have been “diagnosed with leaky gut”. This is a way of saying that their intestinal permeability was high. Typically they will have had a test that looks for molecules used as indicators of intestinal permeability. The main molecule used for this purpose is called zonulin. It’s a protein that regulates the opening and closing of the spaces between the cells lining the gut epithelium, known as “tight junctions”.21Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011 Jan;91(1):151-75. doi: 10.1152/physrev.00003.2008.
Studies have shown that more zonulin is produced when the mucous layer that coats the gut lining loses its integrity as a result of a derangement in the composition of the gut microbes that inhabit the colon, referred to as dysbiosis.22Safadi JM, Quinton AMG, Lennox BR, Burnet PWJ, Minichino A. Gut dysbiosis in severe mental illness and chronic fatigue: a novel trans-diagnostic construct? A systematic review and meta-analysis. Mol Psychiatry. 2022 Jan;27(1):141-153. doi: 10.1038/s41380-021-01032-1.23Di Tommaso N, Gasbarrini A, Ponziani FR. Intestinal Barrier in Human Health and Disease. Int J Environ Res Public Health. 2021 Dec 6;18(23):12836. doi: 10.3390/ijerph182312836. When the balance between health giving (probiotic) and disease carrying (pathogenic) bacteria is lost, the delicate balance between tolerance and immune response is lost with it, leading to inflammation that contributes to further loss of barrier function. This is when zonulin kicks in, enabling the opening of the tight junctions, and allowing an influx of molecules into the bloodstream, including part-digested food molecules and bacterial cell fragments that can trigger a response by the immune system.24Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016 Oct 21;4(4):e1251384. doi: 10.1080/21688370.2016.1251384.25Fasano A. All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000Res. 2020 Jan 31;9:F1000 Faculty Rev-69. doi: 10.12688/f1000research.20510.1.
All of this is hard science. But the flaw with this approach is that zonulin is not a diagnostic molecule. It is known to go up and down dramatically depending on the same factors we’ve covered above, i.e. food, exercise, stress, etc. Additionally, commercially available zonulin tests have been discredited for their inability to accurately identify zolunin. It has become apparent that they identify a whole group of molecules, some of which have opposite roles to that of zonulin.26Massier L, Chakaroun R, Kovacs P, Heiker JT. Blurring the picture in leaky gut research: how shortcomings of zonulin as a biomarker mislead the field of intestinal permeability. Gut. 2021 Sep;70(9):1801-1802. doi: 10.1136/gutjnl-2020-323026. To make things even more complicated, there are many other molecules that can be measured to assess intestinal permeability. One you’re likely to come across is called lipopolysaccharide, or LPS for short. LPS is produced by certain types of bacteria, mostly pathogens, i.e. those that contribute to disease. It is known to damage the integrity of the protective mucous layer and to contribute to chronic inflammation in the gut.27Page MJ, Kell DB, Pretorius E. The Role of Lipopolysaccharide-Induced Cell Signalling in Chronic Inflammation. Chronic Stress (Thousand Oaks). 2022 Feb 8;6:24705470221076390. doi: 10.1177/24705470221076390.28Candelli M, Franza L, Pignataro G, Ojetti V, Covino M, Piccioni A, Gasbarrini A, Franceschi F. Interaction between Lipopolysaccharide and Gut Microbiota in Inflammatory Bowel Diseases. Int J Mol Sci. 2021 Jun 10;22(12):6242. doi: 10.3390/ijms22126242.
Can intestinal permeability be managed?
Intestinal permeability is self-regulating, so you shouldn’t need to preoccupy yourself with it. However, you could potentially minimise huge spikes in permeability by eating a healthy balanced diet, leading an active life with regular physical activity, and limiting sources of stress. It’s all about being constant and taking a gentle, nurturing, and progressive approach to any changes you make to your diet and lifestyle.
More specifically, drinking kefir has been shown to protect the integrity of the intestinal barrier, helping with the regulation of zonulin.29Peluzio MDCG, Dias MME, Martinez JA, Milagro FI. Kefir and Intestinal Microbiota Modulation: Implications in Human Health. Front Nutr. 2021 Feb 22;8:638740. doi: 10.3389/fnut.2021.638740.30Pražnikar ZJ, Kenig S, Vardjan T, Bizjak MČ, Petelin A. Effects of kefir or milk supplementation on zonulin in overweight subjects. J Dairy Sci. 2020 May;103(5):3961-3970. doi: 10.3168/jds.2019-17696. Additionally, foods that provide prebiotic fibres feed health-giving bacteria that, in turn, produce short-chain fatty acids (SCFAs) like butyrate and acetate. SCFAs are well documented for their ability to keep the intestinal barrier functioning smoothly.31van de Wouw M, Boehme M, Lyte JM, Wiley N, Strain C, O’Sullivan O, Clarke G, Stanton C, Dinan TG, Cryan JF. Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterations. J Physiol. 2018 Oct;596(20):4923-4944. doi: 10.1113/JP276431.32Martin-Gallausiaux C, Marinelli L, Blottière HM, Larraufie P, Lapaque N. SCFA: mechanisms and functional importance in the gut. Proc Nutr Soc. 2021 Feb;80(1):37-49. doi: 10.1017/S0029665120006916.
“Leaky gut” is just an informal way to refer to the natural permeability of the gut, which is always changing in response to the conditions that it needs to tackle at any given time. The gut’s relative permeability makes it possible for us to benefit from the nutrients we extract from food, with the help of our gut bacteria. When permeability increases, it almost always manages to find its way back to balance or, a scientists like to call it, “homeostasis”. Think of intestinal permeability as a tidal river, like the Thames. Its natural ebb and flow helps sustain wildlife on its banks. At times of heavy rain it may overflow slightly, and at times of drought it may run a little lower than usual. In any event, that river will always manage to run at the right level for the circumstances.
Scientists have seen increased intestinal permeability in people with conditions ranging from inflammatory bowel disease and to mental health disorders. 33Massier L, Chakaroun R, Kovacs P, Heiker JT. Blurring the picture in leaky gut research: how shortcomings of zonulin as a biomarker mislead the field of intestinal permeability. Gut. 2021 Sep;70(9):1801-1802. doi: 10.1136/gutjnl-2020-323026.34Toribio-Mateas M. Harnessing the Power of Microbiome Assessment Tools as Part of Neuroprotective Nutrition and Lifestyle Medicine Interventions. Microorganisms. 2018 Apr 25;6(2):35. doi: 10.3390/microorganisms6020035. However, that does not mean that “leaky gut” is the cause of these conditions. A much more likely scenario is that there is a complex relationship between lifestyle factors such as diet, exercise, sleep, alcohol, stress, etc., genetics and bacterial composition. Additionally, the presence of gut dysbiosis is a key factor contributing to the development of various conditions in different people.
No test can diagnose anyone with “leaky gut”, even if their gut happens to be slightly more permeable at the time that the test was performed. The truth is that the same test performed 24 hours later may give a completely different result. Following a “leaky gut diet” that excludes whole food groups, or taking a whole bunch of supplements prescribed to heal your gut’s “leakiness” are faddy approaches that are likely to give you health anxiety. You already know that stress contributes to intestinal permeability, so that’s a vicious circle you don’t want to be trapped in! Embrace the fact that it is natural for the gut lining to have varying degrees of permeability depending on what’s going on for you today, and trust it to do its job properly without worrying about it.
Dr Miguel & The Goats
- 8Karl JP, Margolis LM, Madslien EH, Murphy NE, Castellani JW, Gundersen Y, Hoke AV, Levangie MW, Kumar R, Chakraborty N, Gautam A, Hammamieh R, Martini S, Montain SJ, Pasiakos SM. Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress. Am J Physiol Gastrointest Liver Physiol. 2017 Jun 1;312(6):G559-G571. doi: 10.1152/ajpgi.00066.2017.
- 17Swanson GR, Gorenz A, Shaikh M, Desai V, Kaminsky T, Van Den Berg J, Murphy T, Raeisi S, Fogg L, Vitaterna MH, Forsyth C, Turek F, Burgess HJ, Keshavarzian A. Night workers with circadian misalignment are susceptible to alcohol-induced intestinal hyperpermeability with social drinking. Am J Physiol Gastrointest Liver Physiol. 2016 Jul 1;311(1):G192-201. doi: 10.1152/ajpgi.00087.2016.
- 18Swanson GR, Gorenz A, Shaikh M, Desai V, Forsyth C, Fogg L, Burgess HJ, Keshavarzian A. Decreased melatonin secretion is associated with increased intestinal permeability and marker of endotoxemia in alcoholics. Am J Physiol Gastrointest Liver Physiol. 2015 Jun 15;308(12):G1004-11. doi: 10.1152/ajpgi.00002.2015.