Intestinal permeability, often referred to as ‘leaky gut’, is an increasingly studied concept in the field of gastroenterology and integrative medicine. This condition refers to a state in which the intestinal barrier, normally impermeable to certain substances, becomes more permeable. The intestinal barrier includes surface mucus, an epithelial layer and immune defences. Its main function is to control the passage of elements from the intestinal lumen into the bloodstream, thereby regulating the absorption of nutrients and protecting against harmful substances.
Disturbances to this barrier result from increased paracellular transport, apoptosis or transcellular permeability. The functions of the barrier can be tested in vivo by administering probe molecules orally or in vitro using biopsies of the human mucosa. Assessing intestinal barrier function beyond the epithelial layer is essential for a complete understanding.
Recent studies have shown that stress factors such as endurance exercise, administration of non-steroidal anti-inflammatory drugs, pregnancy and surfactants (such as bile acids and certain dietary factors such as emulsifiers) can increase intestinal permeability. These disturbances can be reversed by dietary factors, underlining the importance of diet in managing intestinal permeability. Although inflammatory or ulcerative diseases of the intestine result in increased intestinal permeability, none of these diseases can be cured simply by normalising the function of the intestinal barrier. There is as yet no evidence that restoring barrier function can improve the clinical manifestations of gastrointestinal or systemic disease, but clinicians need to be aware of the potential for barrier dysfunction in gastrointestinal disease and of the barrier as a target for future therapies. (4)
In this article, we dive into the details of this fascinating phenomenon, exploring the causes, consequences and ways to repair the intestinal barrier to maintain optimal health.
Understanding the intestinal barrier
The intestinal barrier plays a crucial role in our overall health, acting as a selective gatekeeper that regulates the absorption of nutrients and protects against harmful substances.
Structure and function of the intestinal barrier
The intestinal barrier is a multilayered structure located on the surface of the intestinal mucosa of the gastrointestinal tract. To perform its main functions as a physical and immunological barrier, several components of this barrier act in concert. It includes the layer of epithelial cells, the tight junctions between these cells, and a layer of mucus that protects against pathogens and facilitates the movement of food. Tight junction proteins, such asoccludin, claudins and zonula occludens, play a crucial role in maintaining the integrity of the epithelial barrier. (1)(2)
Biological mechanisms of intestinal permeability
The mechanisms regulating the integrity of the intestinal barrier are complex and involve a series of intracellular and extracellular signals. These mechanisms dynamically modulate tight junction protein complexes to allow the transport of essential molecules and restrict harmful substances. An imbalance in these regulations leads to a compromise in the integrity of the barrier, which is linked to various pathological conditions such as inflammatory bowel disease, obesity and metabolic disorders.
Factors that can alter the intestinal barrier
Several factors can alter the function of the intestinal barrier. Among these, environmental and physiological stresses, including the use of non-steroidal anti-inflammatory drugs, physical exercise and conditions such as pregnancy, generally reduce the function of the barrier. These effects can be reversed by supplements such as zinc or glutamine, which improve the barrier. Other dietary factors beneficial to the barrier include vitamins A and D, tryptophan, cysteine and fibre. Conversely, ethanol, fructose and food emulsifiers increase permeability. The effects of prebiotics on barrier function are modest, while probiotics exert direct and indirect antagonism against pathogens. Various studies show the effects of probiotics on barrier function, notably in vitro, in vivo in animals, and in randomised clinical trials in humans in response to stress or disease. (3)
Consequences of a damaged intestinal barrier
Recent research highlights the crucial importance of the intestinal barrier and its permeability for health and disease. However, the terms ‘intestinal barrier’ and ‘intestinal permeability’ remain poorly defined, and their assessment and clinical significance are the subject of debate.
Link between intestinal permeability and various pathologies
- Autoimmune and inflammatory diseases: A damaged intestinal barrier is associated with various inflammatory and autoimmune diseases. Translocation of luminal components into the host can trigger inflammatory reactions, contributing to the development and progression of diseases such as Crohn’s disease, coeliac disease, food allergy, irritable bowel syndrome, obesity, metabolic diseases and, more recently, neurodegenerative and cardiovascular diseases. (5)(6)
- Digestive disorders: Increased permeability is observed in most patients with Crohn’s disease and in 10-20% of their clinically healthy relatives. This abnormal permeability may be amplified by the administration of aspirin. Permeability measurements in patients with Crohn’s disease reflect the activity, extent and distribution of the disease, and can predict the likelihood of recurrence after surgery or medical remission. Permeability is also increased in coeliac disease and by factors such as trauma, burns and non-steroidal anti-inflammatory drugs. (7)
Discussion based on recent studies
Current evidence highlights the key role of the intestinal barrier in the prevention and treatment of disease. This barrier represents a vast mucosal surface where billions of bacteria face our body’s largest immune system. On the one hand, an intact intestinal barrier protects the human body against the invasion of micro-organisms and toxins; on the other, it must be open to absorb essential fluids and nutrients. Opposing objectives are achieved by a complex anatomical and functional structure, the functional state of which is described by “intestinal permeability”. The means of assessing intestinal permeability vary enormously and probably evaluate different functional components of the barrier. Assessments of the barrier are further complicated by the natural variability of this functional entity as a function of species and genes as well as diet and other environmental factors. (5)
Diagnosing intestinal permeability problems
Diagnosing intestinal permeability problems requires a careful and precise approach, involving specific tests to identify dysfunctions and determine appropriate treatment measures.
Current diagnostic methods
Methods for diagnosing intestinal permeability vary, but generally focus on assessing the function of the intestinal barrier. These methods include ex vivo and in vivo tests, using various biomarkers and analytical techniques. In France, in vivo testing may involve the use of biomarkers of epithelial injury such as citrulline (in plasma), zonulin (in serum), and claudins 3-4 (in urine). Zonulin, in particular, is known to cause disorganisation of intercellular tight junctions and alter intestinal permeability. An increase in its levels can be observed in the serum of patients suffering from certain pathologies, such as active coeliac disease or type 1 diabetes. (8)
Available biomarkers and tests
Biomarkers such as calprotectin (in stools) are also used to assess intestinal micro-inflammation, although this biomarker is not specific. Zonulin is also used as a biomarker, but it is important to note that its serum level does not necessarily reflect the local concentration in the intestine, and that it is a precursor of haptoglobin 2, a non-specific marker of systemic inflammation. A specific antibody is therefore needed to distinguish these two proteins and make zonulin a reliable biomarker of intestinal permeability.
These methods and biomarkers can be used to assess intestinal permeability, although various factors can influence the results and some methods require further validation before they can be widely used clinically.
Strategies for repairing the intestinal barrier
Repair of the intestinal barrier can be significantly influenced by diet. One study highlights the impact of diet on the gastrointestinal microbiota, particularly in terms of preventing dysbiosis, an imbalance in the microbiota that can lead to inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease. It has been established that the Western diet, high in fat and low in fibre, promotes severe dysbiosis. Conversely, Mediterranean and vegetarian diets, rich in fruit, vegetables, olive oil and oily fish, have anti-inflammatory effects and could prevent dysbiosis and associated inflammatory bowel disease. (9)
Supplements and natural remedies
With regard to supplements and natural remedies, one study has shown that nicotinamide riboside (NR), an NAD booster, can reduce ethanol-induced damage to the intestinal barrier. Ethanol increases intestinal permeability and damages the structure of the intestinal epithelial barrier. NR has been shown to have protective effects on epithelial tight junctions, which are essential for the integrity of the intestinal barrier. It promotes the maintenance of NAD homeostasis and mitochondrial function, thus playing a crucial role in protecting the intestinal barrier. (10)
Stress management and physical exercise
Stress management and physical exercise also play an essential role in intestinal health. Stress, perceived as an acute threat to homeostasis, affects the functions of the gastrointestinal tract in both the short and long term. It alters brain-gut interactionsleading to the development of a variety of gastrointestinal disorders. These effects include alterations in gastrointestinal motility, increased visceral perception, changes in gastrointestinal secretion, increased intestinal permeability, negative effects on the regenerative capacity of the gastrointestinal mucosa and on the intestinal microbiota. At the same time, physical exercise has been shown to independently modify the composition and functional capacity of the intestinal microbiota, underlining its importance in maintaining intestinal health. (11)
These combined approaches, combining a suitable diet, targeted supplements and the management of stress and exercise, offer a holistic strategy for repairing and maintaining the health of the intestinal barrier.
Foods that repair the intestinal barrier
In order to support the repair and maintenance of a healthy intestinal barrier, it is essential to pay attention to our diet. Certain specific foods play a key role in this process. Here is a summary table of foods beneficial to intestinal health, based on recent reliable research. In addition to their nutritional value, these foods offer unique properties to promote optimal intestinal function(12)
| Food | Properties and Benefits |
|---|---|
| Sauerkraut (or fermented cabbage) | Rich in vitamin C, potassium, phosphorus and calcium. Promotes the mobilisation of bacteria essential for the intestine thanks to lacto-fermentation. |
| Honey | Contains fructo-oligosaccharides, which act as a prebiotic to stimulate the growth of bacteria favourable to the intestine. Antioxidant. |
| Miso | Source of zinc and iron. Fermented paste beneficial for digestion and the intestinal tract. |
| Natural yoghurts and probiotics | Rich in calcium, vitamin D and phosphorus. Contains acid-lactic bacteria that help restore intestinal balance. |
| Vegetables and certain fruits | Source of essential dietary fibre, particularly galacto-oligosaccharides and fructo-oligosaccharides. Examples: onion, banana, asparagus, leek, artichoke, chicory. |
| Fibre-rich foods | Vegetables, fruit, wholegrain cereals, pulses. Fibre promotes healing of the intestinal mucosa. |
| Foods rich in omega-3 fatty acids | Oily fish, walnuts, flaxseed. Beneficial for intestinal health. |
| Anti-inflammatory foods | Berries, cruciferous vegetables, avocados, walnuts, linseed. Rich in antioxidants and omega-3s, they reduce inflammation and promote intestinal healing. |
| Fermented foods | Kefir, sauerkraut, kimchi, yoghurt. Contain live cultures and certain probiotics that improve the diversity of the intestinal microbiota. |
| Prebiotics | Dietary fibres in vegetables and fruit that nourish and stimulate the growth of beneficial bacteria, strengthening the intestinal barrier. |
Glutamine and intestinal health
Glutamine, a key amino acid in intestinal health, has been the subject of numerous scientific studies highlighting its essential role in repairing and maintaining the intestinal barrier
- Improving intestinal permeability with glutamine: Several studies have shown that glutamine supplementation can protect the intestine against the harmful effects of stress and reduce intestinal permeability. Glutamine has also been shown to be effective in preventing damage to the intestinal mucosa caused by indomethacin, a drug that increases intestinal permeability. “In addition, it was found to be able to prevent the dysfunction of the intestinal barrier caused by the administration of corticosterone in rats.
- Repair of damaged mucosa and maintenance of intestinal balance: Glutamine helps to strengthen the tight junctions between intestinal epithelial cells, thereby helping to maintain the integrity of the intestinal barrier. It has also been shown to improve the barrier function of human enterocytes and prevent atrophy and dysfunction of the intestinal barrier by increasing the expression of the Hsp70 protein in intestinal epithelial cells.
Dietary diversity for a healthy intestinal microbiota
Adopting a diversified diet is fundamental to enriching the diversity of the intestinal microbiota, which plays a crucial role in protecting and maintaining the health of the intestinal mucosa.
The diversity of the intestinal microbiota
Dietary diversity plays a crucial role in the health of the intestinal microbiota. According to research, including the study“Influence of Foods and Nutrition on the Gut Microbiome and Implications for Intestinal Health“(PMID: 36076980), food components provide substrates for the mutualistic microbial flora in our gastrointestinal tract, modulating its structure, composition and function. This interaction between the microbiota and the intestinal epithelium is vital for maintaining intestinal homeostasis in a healthy state.
The importance of dietary diversity
Dr Will Bulsiewicz, a renowned gastroenterologist, also stresses the importance of diversity in our diet. Each microorganism in our intestine fulfils a different function and offers unique benefits. The more diverse our intestinal microbiota is in terms of species, the better our body functions and the healthier we stay. Reduced diversity, often caused by factors such as antibiotics and stress, can diminish this capacity.
The role of dietary fibre
Dietary fibre is essential for nourishing the microbiota and maintaining its health. They produce compounds called short-chain fatty acids, which are beneficial to health and increase the diversity of the intestinal microbiota. A high fibre intake therefore promotes a diverse and functional microbiota.
The Netflix documentary “Bien dans son assiette, la preuve par 2” (in French only)
The documentary“Bien dans son assiette, la preuve par 2“, also known as “You Are What You Eat: A Twin Experiment“, offers a fascinating exploration of the impact of diet on the human body. This Netflix documentary series, launched in 2024, features identical twins who change their diet and lifestyle for eight weeks as part of a scientific experiment. The study, inspired by research at Stanford University, aims to observe the effects of two distinct diets – a vegan diet and an omnivorous diet– on these genetically identical twins.
This documentary is also particularly relevant to our article on intestinal permeability and repair. It highlights the importance of food choices in intestinal health. By observing the physical and mental differences between twins on different diets, the documentary provides valuable insights into how different diets can influence overall health and, more specifically, gut health. This focus on diets aligns with the section of our article on nutritional approaches to intestinal barrier repair.
What’s more, the documentary, directed by Louie Psihoyos, does not confine itself to nutritional aspects. It also draws a link between eating habits and climate change, highlighting the interconnection between personal health and the health of the planet. This broader perspective is in line with the notion of global well-being discussed in our article, which encompasses not only gut health but also the environmental and social impact of our food choices.
- https://pubmed.ncbi.nlm.nih.gov/37606514/
- https://pubmed.ncbi.nlm.nih.gov/30115904/
- https://pubmed.ncbi.nlm.nih.gov/33492118/
- https://pubmed.ncbi.nlm.nih.gov/31076401/
- https://pubmed.ncbi.nlm.nih.gov/25407511/
- https://pubmed.ncbi.nlm.nih.gov/37505311/
- https://pubmed.ncbi.nlm.nih.gov/10980980/
- https://www.ipubli.inserm.fr/bitstream/handle/10608/8881/
- https://pubmed.ncbi.nlm.nih.gov/27812084/
- https://pubmed.ncbi.nlm.nih.gov/36615829/
- https://pubmed.ncbi.nlm.nih.gov/30883471/
- https://cdhf.ca/fr/comment-lalimentation-peut-elle-favoriser-la-sante-intestinale-et-le-systeme-immunitaire/
- lanutrition.fr
- https://www.biron.com/fr/centre-du-savoir/parole-de-specialiste/stress-gastro-intestinal/
- Fiber Fueled; Will Bulsiewicz, MD.
- https://zoe.com/
