What is causing leaky gut?
Your gut does a lot more than digest food- it plays a powerful role in your immune system, inflammation levels, and overall health. One of the most important features of your gut is the intestinal barrier.
The intestinal barrier is more than just a lining- it’s a complex, dynamic system made up of physical, chemical, immune and microbial components. Together, they form a protective shield between the external world (everything you eat, drink, and are exposed to) and your internal body systems.
Components of the intestinal barrier:
The Physical Barrier: epithelial cells & tight junctions- these cells are packed closely together and sealed by tight junction proteins that regulate what passes through. They function as a selective filter, allowing nutrients, water, and electrolytes in, while blocking toxins, pathogens, and large undigested food molecules. When tight junctions become “leaky”, the barrier is compromised, which can trigger inflammation & immune reactions.
The Chemical Barrier: a sticky mucus layer coats the intestinal lining. This provides a buffer between microbes and the epithelial cells. The mucus traps pathogens and hosts good bacteria that help modulate immune function.
The Immune Barrier: majority of your immune system lives in the gut, as gut-associated lymphoid tissue (GALT). This immune tissue contains specialized immune cells that monitor and respond to what’s passing through the gut.
The Microbial Barrier: millions of bacteria, fungi, and other microbes live in your gut. When in balance, these microbes help support the health of the other barriers, and your overall health. They ferment fibres into short-chain fatty acids, that nourish the gut lining and reduce inflammation.
When all parts of the intestinal barrier are working together, your gut acts as a smart filter-letting in what you need and keeping harmful substances out. But when that system is compromised, it can lead to increased intestinal permeability, aka leaky gut, which contributes to:
Chronic inflammation
Autoimmune conditions
Digestive issues (like IBS, bloating, or food sensitivities)
Skin problems (like eczema or acne)
Brain fog and fatigue
So, what is causing your leaky gut? It could be one culprit, or multiple things. What do they have in common? They all negatively impact one or more components of the intestinal barrier. Let’s break down some of the more common triggers:
Processed foods
Have you noticed that food labels are getting longer and harder to read? Many processed foods now contain dozens of unfamiliar ingredients- and science is starting to uncover how some of them harm gut health:
Emulsifiers (like polysorbate-80) – Added to processed foods to improve texture, but studies show they disrupt the gut barrier, allowing harmful substances to pass through (PMID: 39778648).
Carrageenan – A thickener in dairy alternatives and processed foods, recently was linked to increased intestinal permeability (PMID: 39593091).
Artificial sweeteners- Stay tuned for a deeper dive on this topic, but here’s a quick overview:
Common sweeteners like sucralose and aspartame have been shown in rodent studies to alter the composition of gut bacteria. Some human studies suggest similar effects, though the findings are still inconsistent and evolving. (PMID: 25440050)
Low fibre diet
A diet low in dietary fibre can contribute to increased intestinal permeability, which is commonly referred to as “leaky gut”. Dietary fibres are essential for maintaining gut health through several mechanisms:
Production of Short-Chain Fatty Acids (SCFAs): Fermentation of dietary fibres by gut microbiota produces SCFAs, such as butyrate, which serve as energy sources for intestinal cells and help strengthen the intestinal barrier. A low-fibre diet reduces SCFA production, potentially compromising barrier integrity (PMID: 32238208, PMID: 37432351)
Modulation of gut microbiota: Certain types of fibre (prebiotics) feed the beneficial bacteria in our gut, resulting in increased diversity and abundance of beneficial microbes. A low-fibre diet can lead to dysbiosis, an imbalance in gut bacteria, which is associated with increased intestinal permeability (PMID: 30322146)
Certain medications
NSAID use
Non-Steroidal Anti-Inflammatory (NSAIDs) drugs can contribute to leaky gut through several mechanisms, primarily related to their effects on the intestinal lining. Here’s how:
Disruption of Gut Barrier Function: NSAIDs, such as ibuprofen and aspirin, inhibit cyclooxygenase enzymes (COX-1 and COX-2) that help reduce pain and inflammation- but those same enzymes also help protect the gut lining. When these enzymes are blocked, the production of protective prostaglandins is reduced, leading to weakened mucosal defence and potentially increased intestinal permeability (PMID: 19148789, PMID: 34234675)
Altered Gut Microbiome: NSAIDs may also alter the balance of gut bacteria, leading to dysbiosis (an imbalance of gut microbes). This dysbiosis can promote inflammation and impair the gut's protective functions, potentially exacerbating leaky gut (PMID: 26482265)
Antibiotics:
Antibiotics are essential tools in modern medicine, effectively treating bacterial infections and preventing life-threatening complications. When used appropriately, they save lives, control infections, and support overall health. However, the overuse or unnecessary use of antibiotics can lead to significant unintended consequences, particularly in the gut.
Disruption of the Gut Microbiota: Antibiotics indiscriminately target both pathogenic and beneficial bacteria in the gut, leading to dysbiosis. This disruption can impair the gut barrier function, making it more susceptible to increased permeability (PMID: 26793178)
Overgrowth of Opportunistic Pathogens: By altering the balance of gut microorganisms, antibiotics can allow opportunistic pathogens, such as certain fungi, to overgrow. This overgrowth can compromise the intestinal lining, contributing to increased intestinal permeability (PMID: 26793178).
PPIs
Proton pump inhibitors (PPIs) are commonly prescribed medications for reducing stomach acid production and treating conditions such as gastroesophageal reflux disease (GERD), ulcers, and acid reflux. While they are effective in managing these conditions, long-term use or overuse of PPIs can negatively impact gut health in several ways:
Alteration of gut micriobiota: PPIs can lead to an imbalance in the gut microbiota. A meta-analysis combining data from four studies revealed that PPI users exhibited distinct microbial profiles compared to non-users, suggesting that PPIs can disrupt the natural balance of gut bacteria (PMID: 37337143).
Increased risk of GI infections: Stomach acid plays a crucial role in maintaining a balanced microbiome by inhibiting the growth of harmful bacteria. When acid production is suppressed, the environment in the stomach and intestines becomes more hospitable to harmful bacteria, fungi, and pathogens. This alteration can lead to conditions like Small Intestinal Bacterial Overgrowth (SIBO) and C. difficile infections (PMID: 37337143)
Chronic Stress
Chronic stress profoundly affects gastrointestinal (GI) health through various mechanisms, leading to alterations in brain-gut interactions. These alterations emphasize the importance of stress management to support gut health. These changes can manifest as:
Increase in intestinal permeability: Stress stimulates the release of pro-inflammatory cytokines, which are signalling molecules that promote inflammation. These cytokines can disrupt the integrity of the gut barrier (PMID: 31068783)
Negative effects on the gut microbiota: our stress-response hormones, catecholamines, can elevate certain pathogenic bacteria, which may crowd out the beneficial species. (PMID: 32395568, PMID: 30981718)
Sleep Deprivation
Sleep is a pillar of our health that takes up almost 1/3 of our day. Sleep deprivation (SD) is defined as the body’s incapacity to get enough sleep. SD has become commonplace in our society- due to busy lifestyles, stress, technology and cultural norms. The exact mechanisms by which sleep deprivation affects the gut microbiota are not fully understood. However, it is believed that changes in the host's circadian rhythm, hormonal fluctuations, and immune responses during periods of inadequate sleep may influence the microbial environment of the gut (PMID: 37298553)
Sedentary Lifestyle
A sedentary lifestyle reduces the diversity of the gut microbiome. Microbial communities with higher diversity are more stable and more resistant to pathogenic invasions- which is beneficial for host health. Physical exercise improves intestinal barrier function. Myokines (signalling molecules) released by your muscles during exercise directly talk to your gut microbiome, leading to increased bacterial diversity and stronger intestinal barrier function (PMID: 37831112, PMID: 39978410).
Alcohol
When you consume alcohol (ethanol), your liver breaks it down into acetaldehyde. Acetaldehyde is a toxic product of ethanol metabolism in the body, and is responsible for many of the negative effects associated with alcohol consumption. Even though it is eventually converted to acetate (less toxic), it is highly reactive and can cause cellular damage before it is metabolized. Excessive alcohol consumption likely causes significant pathological changes in the intestines, including leaky gut, gut immune dysfunctions and intestinal dysbiosis (PMID: 37662449).
Pesticides
Pesticides are widely used across the globe to boost crop yields and improve the appearance of agricultural products, providing significant economic advantages. However, their use doesn't come without consequences-these chemicals can seep into the soil, water, and air, and they don’t just stay on the crops. Pesticides can also impact non-target organisms, including humans. There are many pesticides we can cover, but today we will discuss two common ones.
Glyphosate is a broad-spectrum pesticide that has been widely used globally as an herbicide. Concerns have been risen regarding it’s potential health impact due to food contamination. has been shown to induce intestinal dysbiosis by altering gut bacteria, intestinal permeability and mucus secretion (PMID: 38994673). Food sources likely to contain glyphosate are grains (wheat, oats, barely, corn & rice), fruits and vegetables (PMID: 38890925).
Organophosphates (OP) are commonly used as insecticides- and animal research has found that exposure to OP is associated with changes in the gut. These changes included decreased tight junction proteins (aka leakier gut), increased intestinal permeability and gut microbiome dysbiosis (PMID: 38627687). To date, human research is lacking (likely due to the ethics of exposing subjects to OP).
