A Comprehensive Guide to Leaky Gut and What You Can Do to Prevent It

February 02, 2023 14 min read

A Comprehensive Guide to Leaky Gut and What You Can Do to Prevent It

Introduction

In the world of science, there are many fantastic, though at times, difficult to pronounce names that are bestowed on illnesses and conditions, be it the name of the person who discovered it, or maybe just a Latin interpretation. However, we have one that could end up as an outlier if, in the medical world, it is accepted as a condition. Currently, it is known as increased intestinal permeability, but if you look it up, in most blogs and studies, it could almost be a job you’d find on a plumber’s repair list because it also goes by the name of, leaky gut syndrome.

What is it? Well, it’s exactly what it describes. A gut that leaks, allowing toxins and bacteria to freely transfer through the gut membrane, causing illness and pain to boot. In this article, we will look at the current research surrounding the condition, looking into the what’s, the whys, and what HMOs can do about it. 

What is leaky gut syndrome?

Before reading this blog, you may have already heard of the terms leaky gut, leaky gut syndrome, or increased intestinal permeability but if you were to mention this to your doctor, don’t be surprised if they give you a funny look. That’s because leaky gut isn’t an officially recognised medical term, yet.

The lining of your gut serves as a barrier with two primary functions:

  • Allow entry into the body for beneficial components like nutrients.
  • Prevent nasty things from entering the body and wreaking havoc, such as pathogens, toxins, and undigested food particles.

In effect, your gut lining is like your digestive system’s security force, checking the ID of the components that want to gain entry and selectively deciding who can and can’t enter the party.

The gastrointestinal barrier is semi-permeable because it allows nutrients to be absorbed but limits the entry of more harmful components[i]. In that sense, we all have a leaky gut to some extent, but some of us have a leakier one than others, often driven by factors such as poor diet, alcoholism, stress and even genetics.

The internal lining of the barrier is just one cell thick. These epithelial cells function as a physical barrier controlled by tight junction proteins. On top of that is the mucosal layer, a thick layer of mucus that keeps the gut microbiome separate from the epithelial cells. Without mucin, the protein responsible for making up mucus, you’re vulnerable to gut inflammation, increasing the risk of gastrointestinal disorders such as colitis and even colorectal cancer[ii].

Now is probably a good time to introduce Akkermansia muciniphila, a gut microbe we love at Layer Origin.

This microscopic friend of ours makes up around 1 to 3% of our overall gut microbiota, and it loves the mucins in our gut lining. Widely considered a next-generation beneficial microbe[iii], Akkermansia thrives off the mucins in your gut, using them for energy. It may sound counterproductive, but it’s not.

By chomping on the mucins in your gut lining, your cells are stimulated to make more, increasing the barrier’s strength. Plus, Akkermansia also transforms the mucins into short-chain fatty acids (SCFAs) that you (and other gut bacteria) can use.

If your gut lining is compromised, it can cause large holes to appear, meaning your tight junction proteins are no longer tight. An unhealthy gut lining means toxins, pathogens, and undigested food can breach the barrier.

As research progresses, scientists are finding out more about the impact of increased intestinal permeability on human health. It’s already clear that a leaky gut influences some gastrointestinal conditions, but it could also have consequences elsewhere in the body.

What causes a leaky gut?

Because a leaky gut is a bit of a medical phenomenon, the exact causes are still a bit of a mystery. However, current research demonstrates that a leaky gut may play a part in developing some intestinal conditions. For example, Sander et al. (2005) found that intestinal barrier function may be compromised by consuming gliadin in wheat, contributing to the onset of coeliac disease[iv].

A further study by Zhou et al. (2009) showed that some people with irritable bowel syndrome (IBS) displayed evidence of increased intestinal permeability[v]. As the research continues, some of the other factors that may play a role in the development of a leaky gut, include:

  • poor diet
  • increased sugar consumption
  • stress
  • excessive alcohol intake
  • vitamin and mineral deficiencies
  • non-steroidal anti-inflammatory drug (NSAIDs) use
  • dysbiosis

Where did the terms increased intestinal permeability or leaky gut syndrome come from?

Before the term increased intestinal permeability, or let’s call it its street name, leaky gut syndrome was bestowed, the condition was called hypochondriasis, a state believed to come from imbalances present in the stomach. This comes from the ancient Greek term hypochondrium and refers to the upper abdomen.

However, this term was abandoned once science could observe all things parasitic and bacterial through the creation of the microscope. Instead, the original meaning changed, and the word hypochondriac began to describe a person constantly fearing serious chronic disease[vi].

What does a leaky gut mean for you?

Potentially a leaky gut can have some nasty consequences, which in many cases could be avoidable. However, emerging research shows associations between increased intestinal permeability and some chronic conditions.

Leaky gut and chronic illness: What does the research say?

From 1970 through to 1990, many studies were conducted investigating the cause of several inflammatory diseases associated with the gut, like Crohn’s and coeliac disease. Scientists also researched other abnormalities, such as ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs)[vii].

But there is a big conundrum regarding leaky gut and inflammation; is leaky gut an underlying cause or a disease symptom?

It’s true that many studies have shown that leaky gut can be found in several chronic diseases but proving that it is the overall cause is difficult. Because of this, some researchers believe that increased intestinal permeability on its own isn’t enough to cause disease but is a symptom. Odenwald and Turner (2013) state that supporters of the leaky gut as a cause hypothesis believe that “barrier restoration will cure underlying disease, but this has not been demonstrated in clinical trials.”[viii]

Even though there is, as yet, no conclusive evidence that leaky gut syndrome causes disease, research has shown that it is present in several chronic illnesses, including some autoimmune conditions.

Irritable bowel disease (IBD) and irritable bowel syndrome (IBS)

There are distinct differences between IBS and IBD, making them two separate gastrointestinal conditions. In other words, they are not the same, even though the terms are often incorrectly used interchangeably.

IBS is a group of symptoms that tend to come and go, affecting the digestive system. There is no cure and no exact cause. Usually, if your doctor runs investigative tests, the results are likely to be normal if you are suspected of having IBS.

On the other hand, IBD is a condition that stops the digestive tract from functioning as it should. Unlike, IBS, test results should clearly confirm gut inflammation. There are two predominant types of IBD: Crohn’s Disease and ulcerative colitis.

A systematic review by Hanning et al. (2021) found that increased intestinal permeability is apparent in many IBS cases in adults and children, particularly in the diarrhoea and post-infectious subtypes. They found that many of the studies included in their review found a link between loss of gut barrier function and IBS symptoms such as abdominal cramps and changes in bowel movements[ix].

In a review article by Michielan and D’Inca (2015), it was concluded that increased intestinal permeability is implicated in the development of IBD, potentially through the increased leakage of toxins and pathogens into the external environment. This results in increased gut mucosal inflammation, a key characteristic of IBD.

bread cut perfectly in half

Coeliac disease

Coeliac disease is an autoimmune disorder caused by gluten consumption in people with a genetic predisposition to the condition[x]. A study by Sander et al. (2005) showed that ingestion of gluten, in the form of gliadin-derived peptides, had an almost immediate effect on gut barrier function in Caco-2 intestinal epithelial cells[xi].

Type II Diabetes

People with type 2 diabetes have an imbalanced gut microbiome, with mucus-degrading and pathogenic bacteria dominating the precious ecosystem. Because type ii diabetes can be induced through the consumption of a high-fat/low-fibre diet, the lack of fibre can cause pathogenic and mucus-degrading bacteria to become dominant in the gut.

Therefore, the bacteria degrade the intestinal barrier and enable pathogens to breach it, resulting in increased metabolic inflammation[xii].

A further study by Anhê et al. (2021) also found that there is a difference in the bacteria residing in abdominal fat and liver deposits in obese patients, half of whom had type 2 diabetes and half who were prediabetic but had signs of insulin resistance.

Their study concluded that living bacteria and bacterial fragments could cross the gut barrier and initiate an immune response, resulting in insulin becoming defective. The researchers believe that in obese people, gut bacteria crossing the intestinal barrier and infiltrating other tissues in the body are linked to the development of type 2 diabetes[xiii].

Food allergies

Food allergies are caused when your immune system reacts abnormally to certain foods[xiv]. In many cases, allergic reactions are mild, but they can be serious and result in death in the most severe cases.

In a study by Ventura et al. (2006), 21 patients with a food allergy and 20 with food hypersensitivity on an allergen-free diet had their intestinal permeability measured by Lactulose/Mannitol ratio urinary detection.

The data collected from the study found that all participants who experienced an adverse reaction to food presented with increased intestinal permeability[xv]. The study hypothesised that a leaky gut in these individuals may not be wholly dependent on immune-related processes but could be related to other mechanisms related to early life, including breastfeeding and early food sensitisation.

Human milk oligosaccharides can improve a leaky gut, can’t they?

Human milk oligosaccharides are a key component of human breast milk and help shape the infant’s gut microbiota in the early stages of life. HMOs are so powerful that they are now included in infant formula milk, so formula-fed babies can also take advantage of their potent benefits.

Yet, research is coming to light demonstrating that HMOs are beneficial for babies and could also improve adults' digestive health. As adults, we can put our gut through its paces. Some of these factors will be in our control, such as lifestyle or environment, while others, like our genetic risk factors or predispositions, are not. However, there are still steps we can take to help promote the health of our gut microbiota, like eating a healthy diet, getting regular exercise, quitting smoking, and so on, but could HMOs also hold the key to keeping the gut secure?

What are human milk oligosaccharides?

Human milk oligosaccharides are a crucial component of human milk and help to modulate the infant immune system, prevent pathogenic invasion, and develop the early gut microbiome. After lactose and fats (lipids), HMOs are human milk's third most abundant constituent[xvi].

In short, HMOs are prebiotics; they help to feed certain bacterial species in your gut, enabling them to thrive. HMOs are indigestible carbohydrates to humans, but to your gut microbial pals, they’re sustenance. Currently, more than 200 types of HMOs help boost the abundance of Bifidobacteria (as well as others) in your gut[xvii].

How do HMOs help to heal a leaky gut?

Of the 200 characters identified, two are of particular interest and are known to be responsible for feeding your essential good bacteria and protecting the mucosal and epithelial cells.

These two are 2’-fucosyllactose (2’FL), and lacto-N-neotetraose (LNnT. As well as supplying the all-important food, these two HMOs protect the cells in your gut. When it comes to digestive health, balance is key. Let’s face it, no one wants an imbalanced gut microbiome. So, HMOs can help to restore balance.

A 2016 parallel, double-blind, randomised, placebo-controlled study by Elison et al. demonstrated that supplementation with a 4:1 ratio mix of 2’FL & LNnT could help restore gut balance.

Not only did the study show that daily supplementation of HMOs up to a whopping 20g was safe, but it also found that these potent prebiotics increased the abundance of Bifidobacteria and reduced the presence of Firmicutes and proteobacteria[xviii].

That’s the balance bit taken care of, but what about a leaky gut?

HMOs increase the abundance of Bifidobacteria

As we just saw in the previous section, HMOs stimulate the growth of the health-promoting bacteria species Bifidobacteria. These mighty microbes have some powerful health benefits, and in mice, studies have been shown to reduce intestinal permeability in mouse models of colitis[xix].

Other studies have shown that Bifidobacterium species can restore gut barrier function and reduce the chances of pathogens from entering the body via the gut lining[xx]. This demonstrates that probiotics, particularly Bifidobacteria, help maintain the integrity of the tight junction proteins in the intestinal barrier.

HMOs increase the production of SCFAs

With the increased abundance of Bifidobacteria, comes an increased production of SCFAs. This action helps with the repairing of the gut barrier because SCFAs are integral in the maintenance of the barrier’s integrity. In turn, this positively affects the regulation of the immune system, glucose and lipid metabolism, inflammatory response and blood pressure[xxi].

Bifidobacteria are known for producing the short-chain fatty acids acetate and lactate, which regulate the pH of your gut and deter pathogens from taking up residency. Acetate has other roles, too. When the Bifidobacteria in your gut produce acetate, this abundant SCFA is used by other good bacteria as a source of nourishment, namely butyrate producers.

Regarding the integrity of your gut barrier, butyrate is super important. A study by Peng et al. (2009) looked to identify the mechanisms that underpinned butyrate’s’ regulation of the intestinal barrier. The researchers found that butyrate strengthens the gut barrier through the assembly of tight junction proteins[xxii], the regulators between the intestinal environment and the rest of the body.

Butyrate is also the main energy source for the cells that line the colon, called colonocytes. Without butyrate, these cells can’t function like a car without fuel. So, if the colonocytes are well nourished, they can help to maintain the integrity of the gut lining.

HMOs support your immune system

Your gut and immune system have a close relationship, and HMOs can help to support and strengthen it. That’s because HMOs may be able to regulate the immune system's response by preventing opportunistic and pathogenic bacteria from adhering to the gut lining and causing you harm. Doing so, actually helps to strengthen the integrity of your gut barrier.

A recent study investigated the effects of HMOs on the adult gut microbiota and, importantly, gut barrier function. The study results found that using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®), Caco2 cell lines and human intestinal gut organoid-on-chips that 2’FL, LNnT combinations of both (MIX) increased the abundance of Bifidobacteria. Not only this but both the MIX and 2’FL reduced the permeability in the Caco2 cells and the expression of IL-6. This demonstrates that HMOs can regulate immune function and can potentially strengthen the gut barrier[xxiii].

Strengthen your gut with PureHMO®

Suppose you’re looking for a powerful prebiotic to help support the health of your gut, including strengthening that all-important barrier. In that case, you needn’t look any further than PureHMO® human milk oligosaccharide from Layer Origin Nutrition.

In breastfed babies (and now babies fed with HMO-supplemented formula milk), HMOs help promote the development of the gut microbiota by stimulating the growth of Bifidobacteria[xxiv]. But as research continues to grow, scientists are discovering more about how HMOs can support the adult microbiome.

For example, through the increased production of SCFAs by beneficial bacteria, HMOs can help lower intestinal pH and strengthen the mucosal barrier. But as an adult, how exactly can you acquire HMOs?

It’s simple. At Layer Origin Nutrition, we have developed PureHMO®, high-purity HMOs, including 2’-FL, produced by lactose fermentation from cow’s milk and not human breast milk.

Research has shown that HMOs can help to reduce intestinal inflammation[xxv] and boosts the abundance of Bifidobacteria, which, in turn, stimulates the increased production of potent SCFAs, including butyrate. We have already demonstrated this with our own data. You can read more about that here.

So, if you’re looking to boost and maintain the health of your gut, you’ll need to think about supplementing your diet with HMOs. These powerful prebiotics can help to promote the diversity and activity of your microbiota as well as help to reduce digestive symptoms. Take a look at our range of products in our shop.

Summary

Leaky gut syndrome, also known as increased intestinal permeability, is a condition where the integrity of your gut barrier is compromised. This results in the tight junction proteins that regulate what can pass through the barrier becoming loose and increasing the likelihood of toxins and pathogens passing from the gut into the body.

As a result, leaky gut syndrome has been identified in many chronic conditions, including type 2 diabetes and coeliac disease. However, it is not clear if leaky gut is a cause or a symptom of these illnesses.

But what is clear, is the protective role HMOs may play in strengthening and maintaining the integrity of the intestinal barrier through the stimulation of Bifidobacteria, increased SCFA production, and modulation of the immune system.

Taking an HMO supplement as part of your diet is a fast track to better gut health!

 

Written by: Leanne Edermaniger

 

References: 

[i] Vancamelbeke M, Vermeire S. The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol. 2017 Sep;11(9):821-834. doi: 10.1080/17474124.2017.1343143. Epub 2017 Jun 26. PMID: 28650209; PMCID: PMC6104804.

[ii] Chelakkot C, Ghim J, Ryu SH. Mechanisms regulating intestinal barrier integrity and its pathological implications. Experimental & Molecular Medicine. 2018;50(8):1–9. 

[iii] Shin J, Noh J-R, Chang D-H, Kim Y-H, Kim MH, Lee ES, et al. Elucidation of akkermansia muciniphila probiotic traits driven by mucin depletion. Frontiers in Microbiology. 2019;10. 

[iv] Sander GR, Cummins AG, Henshall T, Powell BC. Rapid disruption of intestinal barrier function by gliadin involves altered expression of apical junctional proteins. FEBS Lett. 2005 Aug 29;579(21):4851-5. doi: 10.1016/j.febslet.2005.07.066. PMID: 16099460.

[v] Zhou Q, Zhang B, Verne GN. Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome. Pain. 2009 Nov;146(1-2):41-6. doi: 10.1016/j.pain.2009.06.017. PMID: 19595511; PMCID: PMC2763174.

[vi] Marcelo Campos MD. Leaky gut: What is it, and what does it mean for you? [Internet]. Harvard Health. 2021 [cited 2023Jan5]. Available from: https://www.health.harvard.edu/blog/leaky-gut-what-is-it-and-what-does-it-mean-for-you-2017092212451

[vii] Camilleri M. Leaky gut: mechanisms, measurement and clinical implications in humans. Gut. 2019 Aug;68(8):1516-1526. doi: 10.1136/gutjnl-2019-318427. Epub 2019 May 10. PMID: 31076401; PMCID: PMC6790068.

[viii] Odenwald MA, Turner JR. Intestinal permeability defects: is it time to treat? Clin Gastroenterol Hepatol. 2013 Sep;11(9):1075-83. doi: 10.1016/j.cgh.2013.07.001. Epub 2013 Jul 12. PMID: 23851019; PMCID: PMC3758766.

[ix] Hanning N, Edwinson AL, Ceuleers H, Peters SA, De Man JG, Hassett LC, De Winter BY, Grover M. Intestinal barrier dysfunction in irritable bowel syndrome: a systematic review. Therap Adv Gastroenterol. 2021 Feb 24;14:1756284821993586. doi: 10.1177/1756284821993586. PMID: 33717210; PMCID: PMC7925957.

[x] Akobeng AK, Singh P, Kumar M, Al Khodor S. Role of the gut microbiota in the pathogenesis of coeliac disease and potential therapeutic implications. European Journal of Nutrition. 2020;59(8):3369–90. 

[xi] Sander GR, Cummins AG, Henshall T, Powell BC. Rapid disruption of intestinal barrier function by gliadin involves altered expression of apical junctional proteins. FEBS Lett. 2005 Aug 29;579(21):4851-5. doi: 10.1016/j.febslet.2005.07.066. PMID: 16099460.

[xii] Hu R, Yuan Y, Liu C, Zhou J, Ji L, Jiang G. New insights into the links between anti-diabetes drugs and gut microbiota. Endocr Connect. 2021 Jan;10(1):R36-R42. doi: 10.1530/EC-20-0431. PMID: 33338029; PMCID: PMC7923145.

[xiii] Anhê FF, Jensen BA, Varin TV, Servant F, Van Blerk S, Richard D, et al. Type 2 diabetes influences bacterial tissue compartmentalisation in human obesity. Nature Metabolism. 2020;2(3):233–42. 

[xiv] Food allergy [Internet]. NHS choices. NHS; [cited 2023Jan8]. Available from: https://www.nhs.uk/conditions/food-allergy/

[xv] Ventura MT, Polimeno L, Amoruso AC, Gatti F, Annoscia E, Marinaro M, Di Leo E, Matino MG, Buquicchio R, Bonini S, Tursi A, Francavilla A. Intestinal permeability in patients with adverse reactions to food. Dig Liver Dis. 2006 Oct;38(10):732-6. doi: 10.1016/j.dld.2006.06.012. Epub 2006 Jul 31. PMID: 16880015.

[xvi] Wiciński M, Sawicka E, Gębalski J, Kubiak K, Malinowski B. Human milk oligosaccharides: Health benefits, potential applications in infant formulas, and pharmacology. Nutrients. 2020;12(1):266. 

[xvii] Cheng L, Kiewiet MB, Logtenberg MJ, Groeneveld A, Nauta A, Schols HA, et al. Effects of different human milk oligosaccharides on growth of bifidobacteria in monoculture and co-culture with faecalibacterium prausnitzii. Frontiers in Microbiology. 2020;11. 

[xviii]  Elison, E., Vigsnaes, L. K., Rindom Krogsgaard, L., Rasmussen, J., Sørensen, N., McConnell, B., Hennet, T., Sommer, M. O., & Bytzer, P. (2016). Oral supplementation of healthy adults with 2'-O-fucosyllactose and lacto-N-neotetraose is well tolerated and shifts the intestinal microbiota. The British journal of nutrition, 116(8), 1356–1368. https://doi.org/10.1017/S0007114516003354

[xix] Rao RK, Samak G. Protection and Restitution of Gut Barrier by Probiotics: Nutritional and Clinical Implications. Curr Nutr Food Sci. 2013 May 1;9(2):99-107. doi: 10.2174/1573401311309020004. PMID: 24353483; PMCID: PMC3864899.

[xx] Wang Z, Xiao G, Yao Y, Guo S, Lu K, Sheng Z. The role of bifidobacteria in gut barrier function after thermal injury in rats. The Journal of Trauma: Injury, Infection, and Critical Care. 2006;61(3):650–7. 

[xxi] Nogal, A., Valdes, A. M., & Menni, C. (2021). The role of short-chain fatty acids in the interplay between gut microbiota and diet in cardio-metabolic health. Gut microbes, 13(1), 1–24. https://doi.org/10.1080/19490976.2021.1897212

[xxii] Peng L, Li ZR, Green RS, Holzman IR, Lin J. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr. 2009 Sep;139(9):1619-25. doi: 10.3945/jn.109.104638. Epub 2009 Jul 22. PMID: 19625695; PMCID: PMC2728689.

[xxiii] Šuligoj T, Vigsnæs LK, Abbeele PV, Apostolou A, Karalis K, Savva GM, et al. Effects of human milk oligosaccharides on the adult gut microbiota and barrier function. Nutrients. 2020;12(9):2808. 

[xxiv] Šuligoj T, Vigsnæs LK, Abbeele PVD, Apostolou A, Karalis K, Savva GM, McConnell B, Juge N. Effects of Human Milk Oligosaccharides on the Adult Gut Microbiota and Barrier Function. Nutrients. 2020 Sep 13;12(9):2808. doi: 10.3390/nu12092808. PMID: 32933181; PMCID: PMC7551690.

[xxv]  Grabinger, T., Glaus Garzon, J., Hausmann, M., Geirnaert, A., Lacroix, C. and Hennet, T., 2019. Alleviation of Intestinal Inflammation by Oral Supplementation With 2-Fucosyllactose in Mice. Frontiers in Microbiology, 10.


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