What is leaky gut syndrome?

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The term “leaky gut syndrome” gets thrown around quite a bit, but what do we actually know about this condition? Leaky gut relates to intestinal permeability, or more accurately, hyperpermeability.¹ When healthy, the gastrointestinal tract controls what can or cannot pass through the intestinal barrier, preventing toxic elements from entering the blood stream through junctions in the intestinal epithelium. Factors such as stress, unhealthy diet, and excessive alcohol consumption can negatively affect the integrity of the intestinal barrier, allowing harmful agents to pass into the bloodstream and impact organs and other systems.

Leaky gut is associated with gastrointestinal diseases such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), as well as a broader range of healthy conditions such as heart disease, obesity, type 1 diabetes, and celiac disease. It’s important to note that leaky gut syndrome is not a clinically recognized medical diagnosis and most medical professionals view abnormal functioning of the intestinal barrier as a symptom rather than a cause of diseases such as IBD.² More research is necessary to better understand intestinal permeability and how it impacts the body, but it is a factor in diseases characterized by inflammation, and worth exploring.

What We Know

If you look up leaky gut syndrome, you are bound to find articles that aim to debunk the “myth” of leaky gut syndrome. These articles make the case that leaky gut syndrome is being erroneously attributed as the cause for a wide range of diseases and oversimplifies a complex system. Moreover, critics state that leaky gut syndrome lacks clinical validation. In short, leaky gut syndrome is somewhat controversial. That said, intestinal permeability is very real, and can be negatively impacted by a number of factors.

The intestinal epithelium is made up of intercellular junctions that are controlled by tight junction proteins on the interior of the intestinal barrier that regulate what leaves and enters through the epithelium.1 The epithelium is the physical barrier, but there is also a microbiota barrier on the interior of the intestinal barrier that is separated, by the epithelium, from an immune barrier, creating multiple layers of protection. The microbiome plays an essential role in maintaining intestinal barrier integrity. Through fermentation, microbiota release metabolites and short chain fatty acids that impart anti-inflammatory properties, contributing to intestinal homeostasis.

During dysbiosis, hosts experience a negative shift in the microbiome wherein harmful bacteria such as Proteobacteria phylum, Escherichia, Vibrio, Yersinia, Helicobacter, and Salmonella increase while beneficial bacteria such as Bacteroides, Bifidobacterium or Faecalibacterium prausnitzii decrease.¹ For example, Faecalibacterium prausnitzii has been shown in research to be inversely correlated to inflammatory conditions such as Crohn’s disease and ulcerative colitis.³

IBD has been associated with alterations in tight junctions and patients suffering from them have been shown to have higher intestinal permeability than healthy subjects. Similar observations have been made with IBS. Conditions that are associated with higher intestinal permeability such as obesity, non-alcoholic fatty liver disease, and heart disease have a common throughline of chronic inflammation or autoimmune response in the case of celiac disease and type 1 diabetes.

Supporting Healthy Intestinal Barrier Function

Because of the relationship between the microbiome and intestinal permeability, nutritional interventions that modulate the microbiome have been proposed to reduce intestinal permeability. For example, in the case of people with IBS, a low-FODMAP diet have been proposed (See page 42 for more). FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) are short-chain carbohydrates that are poorly absorbed in some people, sometime causing small intestine bacterial overgrowth.This diet has been shown to be effective at improving symptoms, but its overall impact on intestinal permeability is unclear.¹ In addition to the diet, supplement ingredients have emerged that support FODMAP digestion. For example, a preparation of the enzyme fructanase (Optiziome Fructanase from Bio-Cat, based in Troy, VA) has been shown to help break down fructans like inulin in vitro,⁴ and has been shown in a human study to be safe and tolerable.⁵

Alternatively, prebiotic dietary fibers which are fermented by microbiota have the potential to positively change the composition of the microbiome and lead to the release of short chain fatty acids which research has shown to positively impact barrier function.⁶ Highly complex prebiotics such as oligosaccharides, for example, can resist fermentation until they reach the large intestine where they are selectively fermented by bacteria such asAkkermansia and Bifidobacteria.³ A resistant potato starch (marketed as Solnul by MSP Starch Products Inc., based in Carberry, MB, Canada) has been found in research to significantly reduce metabolites associated with high intestinal permeability.⁶

Probiotics are another potential option that may support healthy barrier function through a number of mechanisms. For example, probiotics can support microbial homeostasis, exhibit anti-inflammatory properties, increase levels of immune cells, as well as increase production of short-chain fatty acid by promoting the growth of butyrate-producing bacterial species.¹ One review points to a number of Lactobacillus strains (L. rhamnosus GG, L. plantarum, L. acidophilus) as particularly supportive to healthy intestinal barrier function, as well as Bifidobacteria (Bifidobacterim infantis, Bifidobacterium animalis lactis).

Evidence shows that vitamins may also support intestinal permeability. Specifically, vitamins A and D have been shown in research to indirectly impact gut microbiome, improve tight junctions, and modulate immune health.1 One recent study found a correlation between vitamin D deficiency and inflammation associated with IBD.⁷

Takeaways

While there may be some dispute about the legitimacy of leaky gut syndrome, intestinal permeability is a real thing impacted by lifestyle and diet, and associated with a range of health conditions.A common throughline here is inflammation. Regulations limit brands to making structure function claims. “Anti-inflammatory” is considered a disease claim that should be avoided, but consumers do want to support a healthy inflammatory response. Popular products such as probiotics, prebiotics, and even common vitamins like A and D may be tools for consumers who want to support their overall health through the digestive tract and reduce their risk of leaky gut syndrome.

References

1. Aleman, R.S.; Moncada, M.; Aryana, K.J. Leaky Gut and the Ingredients That Help Treat It: A Review. Molecules. 2023, 28 (2), 619. DOI: 10.3390/molecules28020619 
2. Jarry, J. You Probably Don’t Have a Leaky Gut. McGill Office of Science and Society. February 23, 2024. https://www.mcgill.ca/oss/article/medical-critical-thinking/you-probably-dont-have-leaky-gut (accessed 2024-08-28).
3. Krawiec, S. Digestive health category continues to evolve as we learn more about the microbiome and leaky gut syndrome. Nutritional Outlook. 2019, 22 (2).
4. Guice, J.L.; Hollins, M.D.; Farmar, J.G.; Tinker, K.M.; Garvey, S.M. Microbial Inulinase Promotes Fructan Hydrolysis Under Simulated Gastric Conditions. Front Nutr. 2023, 10. DOI: 10.3389/fnut.2023.1129329 
5. Garvey, S.M.; LeMoire, A.; Wang, J.; Lin, L.; Sharif, B.; Bier, A.; Boyd, R.C.; Baisley, J. Safety and Tolerability of Microbial Inulinase Supplementation in Healthy Adults: A Randomized, Placebo-Controlled Trial. Gastro Hep Advances. Article ASAP. June 20, 2024. DOI: 10.1016/j.gastha.2024.05.013. (accessed 2024-07-11). 
6. Camilleri, M.; Vella, A. What to do about the leaky gut. Gut. 2021, 71 (2), 424-435. DOI: 10.1136/gutjnl-2021-325428 
7. Bush, J.R.; Han, J.; Deehan, E.C.; Harding S.V.; Maiya, M.; Baisely, J.; Schibli, D.; Goodlett, D.R. Resistant Potato Starch Supplementation Reduces Serum Histamine Levels in Healthy Adults with Links to Attenuated Intestinal Permeability. Journal of Functional Foods. 2023, Article ASAP. DOI: https://doi.org/10.1016/j.jff.2023.105740 (accessed 2023-8-29) 
8. Topalova-Dimitrova, A.; Dimitrov, I.V.; Nikolov, R. Lower vitamin D levels are associated with the pathogenesis of inflammatory bowel diseases. Medicine, 2023, 102 (41): e35505. DOI: 10.1097/MD.0000000000035505