January 1984. From a pop culture perspective, it is probably best known for the public release of the The Apple Macintosh personal computer. Yet it also when an obscure term – Leaky Gut – was introduced into one of the world’s most prestigious medical journals, The Lancet. The article with the strange name was entitled “The leaky gut of alcoholism: possible route of entry for toxic compounds”; given the stature of the journal, the term immediately stuck and leaky gut began its reign as one of the most controversial terms within integrative medicine.
The intestinal lining, or barrier, is tasked with an enormous responsibility – to be the dividing line between the inner and outer world and decide what it safe and what should be excluded. The researchers who published the study in 1984 suspected that some of the immune system hypersensitivities and intolerances reported by consumers of excess alcohol might be a result of a breakdown in the normal functioning of the intestinal barrier (lining). In other words, if material that would normally be excluded from absorption across the intestinal lining were to be inappropriately “granted” access into the blood, it could provoke a hodge-podge of symptoms that would only compound the problems of chronic alcohol abuse. In their ‘leaky gut’ study they did indeed show that adults with alcohol addiction had increased intestinal absorption of supposedly “non-absorbable” compounds.
Barely a year after the Lancet study, the term leaky gut found its way into health books; a sort of telephone-game emerged in popular writing and before long leaky gut was being described as a bona fide ‘syndrome’ and the cause of many, if not most, chronic ailments. But chronic alcohol abuse represents a special case of extreme irritation of the gut lining, and it was a major leap to suggest that leaky gut was a near-universal problem. Plus, the Lancet study may have shown that intestinal permeability to unwanted material can occur, but it didn’t investigate what the consequences might be – that was still theoretical.
Mostly, leaky gut was a controversial term and the notion that intestinal permeability was a factor in anything but the most serious of gastrointestinal diseases was considered the stuff of faddish nonsense. However, a landmark study published in 2001 in the Archives of General Psychiatry showed precisely what the consequences of intestinal permeability might be if tiny bits of microbes (specifically, parts of the microbial membrane called endotoxin) gained inappropriate access from the gut into the bloodstream. Administering very small amounts of endotoxin directly into the bloodstream of healthy adults caused an immune response and associated fatigue, anxiety, lowered mood and cognitive dysfunction.
The 2001 study has been replicated dozens of times with small amounts of endotoxin (most notably lipopolysacharide endotoxin or LPS) and the symptoms of low-grade body-wide pain have also been added to the list. In addition, volumes of animal studies have shown the detrimental effects of LPS on behavior and metabolism. For example, researchers have demonstrated that when LPS enters the blood at levels slightly, but consistently higher than normal, blood glucose and insulin balance is disturbed and fat storage increases.
At the same time, the microbiome scientific revolution was about to change our entire worldview of the gastrointestinal tract and its living microbes. Studies began to show that intestinal microbes and the mucus covering the gut lining played an important role in maintaining the barrier. For example, when researchers induce dysbiosis (loss of beneficial bacteria and/or diversity of microbes and/or an encroachment of harmful bacteria), intestinal permeability of endotoxin is increased. Stress, sleep loss and circadian disruptions, westernized diets high in sugar and refined fats, inadequate nutrients (such as zinc, vitamins A, C, D), environmental toxins and too much alcohol have also been shown to cause an increase in intestinal permeability. Unsurprisingly, LPS entrance into the blood accompanies intestinal permeability.
Emerging studies are also showing that intestinal permeability isn’t restricted to serious inflammatory conditions of the gastrointestinal tract. The tandem of dysbiosis and intestinal permeability have been observed in allergic diseases, obesity, type 2 diabetes, cardiovascular disease, depression and neurobehavioral disorders, chronic fatigue syndrome and fibromyalgia. But it is important to point out that this may simply be a result of the low-grade inflammation associated with chronic illness. As much as dysbiosis and intestinal permeability might increase low-grade inflammation and oxidative stress, the reverse is also true.
This takes us to the central issue. What can we do, today, about the interrelated issues of gut dysbiosis, intestinal permeability, low-grade inflammation and oxidative stress? There are very few agents, natural or otherwise, that have been shown to specifically “fix” intestinal permeability. Some studies have shown that probiotics hold great potential, particularly by their ability to “tighten” the proteins responsible for controlling transport of material between the intestinal cells. But it’s a tall order to expect probiotics to be the sole defenders of the intestinal lining when lifestyle remains unchanged. We will probably need much more support in the form of whole foods, prebiotic fibre, colourful phytonutrients (e.g. polyphenols), essential fats (e.g. omega-3 fatty acids have been shown to benefit the intestinal lining) and fermented foods. For many, the road to intestinal permeability might be paved by complex factors involving lifestyle, so the way to remediation is an entire lifestyle approach. Love your gut.
It’s probably past time to retire the term leaky gut and leaky gut syndrome. The proper terminology is intestinal permeability, and that will do lovely. In medicine a syndrome is typically described a set of signs and symptoms associated with a disease or disorder. But leaky gut syndrome isn’t a diagnosis, nor is it a disease per se; when present, intestinal permeability is likely to be a product of the way we live, our dietary habits, stressors, low-grade inflammation, dysbiosis, sleep disruptions, and/or the consequence of diagnosable illnesses.
Alan C. Logan is the co-author of The Secret Life of Your Microbiome: Why Nature and Biodiversity are Essential to Health and Happiness (New Society Publishers, 2017)
Bjarnason I, et al. The leaky gut of alcoholism: possible route of entry for toxic compounds. Lancet. 1984 Jan 28;1(8370):179-82.
Reichenberg A, et al. Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry. 2001 May;58(5):445-52.
Konig J, et al. Human Intestinal Barrier Function in Health and Disease. Clin Transl Gastroenterol. 2016 Oct 20;7(10):e196.
Yarandi SS, et al. Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases. J Neurogastroenterol Motil. 2016 Apr 30;22(2):201-12.
Mu Q, et al. Leaky Gut As a Danger Signal for Autoimmune Diseases. Front Immunol. 2017 May 23;8:598.