‘Leaky Gut’ & The Stress Matrix.


If you believed what you read on Wikipedia, you’d probably think ‘Leaky Gut Syndrome’ was a bunch of pseudo-science woo woo, promoted by alternative health zealots with silver foil wrapped around their heads. And to some degree, you’d be right.

In reality, intestinal barrier dysfunction is an experimentally verified biological phenomenon – relevant to the development of many disease symptoms – often arising as a result of interference with proper metabolic function.

Instead of looking for a new ‘syndrome’, it makes much more sense to examine the factors which actually promote intestinal barrier dysfunction – or permeability – and to look at the different ways to potentially reduce the impact this can have upon health.

The intestinal barrier isn’t a wall that one day ‘springs a leak’. It exists as an important part of organismic survival, and functions in fluctuating degrees of effectiveness, depending on a variety of external and internal circumstances.

“The gastrointestinal tract constitutes one of the largest sites of exposure to the outside environment. The function of the gastrointestinal tract in monitoring and sealing the host interior from intruders is called the gut barrier…evidence for the role of gut barrier dysfunction in disorders such as Crohn’s disease, celiac disease, food allergy, acute pancreatitis, non-alcoholic fatty liver disease, and alcoholic liver disease…”

From a general viewpoint, anything which inhibits cellular energy metabolism will likely effect intestinal barrier capability, potentially allowing toxic and harmful substances to pass through to the liver, and into the main system.

“Military training, a unique model for studying temporal dynamics of intestinal barrier and intestinal microbiota responses to stress, resulted in increased intestinal permeability concomitant with changes in intestinal microbiota composition and metabolism.”

Stress of any kind can suppress thyroid systems and inhibit digestive function, increasing ‘leaky gut’ potential.

“…stress-induced increases in intestinal permeability, in combination with modern life-style factors, raise the possibility of translocation of bacteria and/or their toxins across the more permeable gut barrier.”

When digestion is sluggish, bacteria tend to grow in number, moving further up into the small intestine where they are not intended to be.

“In healthy individuals normal small GI motility prevents the overgrowth of bacterial microorganisms….It has been reported that SIBO (small intestinal bacterial overgrowth) may be present in more than half of patients with hypothyroidism…”

The overgrowth of bacteria in the intestine can cause a rise in toxic substances – such as endotoxin, nitric oxide, serotonin, histamine and estrogen – involved in the process which reduces intestinal barrier capability.

“…demonstrated that estriol indeed increased permeability of the isolated small intestine…This led to increases in plasma endotoxin, a phenomenon that was prevented by treatment with antibiotics…”

“…changes in gut microbiota controls metabolic endotoxemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability…”

Higher than optimal levels of these inflammatory things are then able to pass into the main system and promote the development of many different disease conditions effecting a variety of organ systems.

“…a brief exposure to circulating endotoxin increases the permeability of the normal gut…during critical illness, prolonged or repeated exposure to systemic endotoxins or associated cytokines may significantly compromise the integrity of the gastrointestinal mucosal barrier.”

Stress redirects energy away from digestion, immediately interfering with intestinal barrier function, allowing for greater amounts of endotoxin and other metabolism interfering substances to pass through into circulation.

“During exertional heat stress, blood flow is preferentially distributed away from the intestinal area to supply the muscles and brain with oxygen….the gastrointestinal barrier becomes increasingly permeable, resulting in the release of lipopolysaccharides (LPS, endotoxin) into the circulation. LPS leakage stimulates an acute-phase inflammatory response…”

When the environment of the intestine is overburdened with bacteria – and the intestinal lining is more permeable – it becomes harder for the liver to properly carry out detoxification and prevent an increase in flow throughout the system, of the stress substances which worsen conditions and promote inflammation and degeneration.

“Increased intestinal permeability to endotoxin leads to increased transfer of endotoxin from the intestine to…the liver where it…initiates a cascade of events leading to…liver injury. Endotoxin that escapes to general circulation may induce injury to other organs.”

The consumption – and storage in the tissue over time – of the polyunsaturated fats (PUFA), can influence whether or not the intestinal barrier functions normally, or whether it becomes something fueling a larger problem.

“…we investigated the effects of saturated fat (MCT enriched) and unsaturated fat (corn oil/linoleic acid enriched) diets on intestinal tight junction (TJ) integrity and permeability…We demonstrate the protective effect of SF (saturated fat)…USF (unsaturated fat) by itself induces dysregulation of intestinal TJ integrity…”

When stress is high – and the supply of sugar, protein and nutrients is inadequate – cortisol and adrenalin (alongside other stress substances) rise, and PUFA is released out of storage, interfering with thyroid activity and exacerbating inflammation.

Chronic stress leading to continuously high cortisol levels suppresses intestinal barrier capability.

“Intestinal permeability and psychological stress have been implicated in the pathophysiology of IBD and IBS…the effect of public speech on permeability was only present in subjects with a significant elevation of cortisol.”

“…elevation in serum corticosterone mediates chronic stress induced decrease in specific intestinal epithelial tight junction proteins…associated with an increase in epithelial paracellular permeability…”

Exposure to fatty acids can directly increase the permeability of the ‘intestinal wall’, and encourage a vicious circle of inflammation – resulting from interactions between PUFA and other stress substances – becoming increasingly difficult to deal with, eventually leading to a variety of metabolically degenerative conditions.

“We…demonstrated that the mechanisms of high-fat diet–induced inflammation and metabolic disorders were clearly linked to LPS(endotoxin)…the intestinal epithelium acts as a continuous barrier to avoid LPS translocation…high-fat feeding strongly increased intestinal permeability…”

PUFA consumed or released from storage under conditions of stress interferes with proper blood sugar regulation and this has been shown to increase the ‘leakiness’ of the intestine.

“Recently it was shown that DM2 (Type 2 diabetes) is accompanied by significant alterations in…intestinal permeability…promoting endotoxin-induced low-grade inflammation…”

“Intestinal permeability was positively correlated with intestinal mitochondrial injury indicated as the level of malondialdehyde (breakdown product of PUFA) in ileum mitochondria…”

The biggest problem with many popular approaches attempting to deal with ‘leaky gut syndrome’, arises from the dietary (as well as other) treatment recommendations commonly made to try to fix it.

It has become customary to suggest the removal of grains (whichever happen to be considered the bad ones at the time), the restriction of dairy products and of course the avoidance of white sugar.

The list of ‘healing’ things being promoted have included sprouted grains and seeds, fermented vegetables, probiotics to support ‘beneficial’ bacteria, and plenty of omega-3 PUFA for their ‘anti-inflammatory’ effects.

Unfortunately there is good evidence indicating that this kind of approach is more likely to be a recipe for the worsening of intestinal barrier related issues, rather than helping to resolve what is causing it.

“Loss of intestinal barrier function…remains a serious clinical problem leading to hypoperfusion, anastomotic leakage, bacterial translocation, and inflammatory mediator liberation…Our data suggest that augmented intestinal barrier permeability…is a possible side effect of (n-3) FA-rich diet supplementation.”

Difficult to digest grains, beans and too many under cooked and overly fibrous foods have been shown to promote bacterial overgrowth, increasing the release of endotoxin and stress substances like nitric oxide and serotonin, further interfering with metabolism and digestive function.

“…studies have confirmed the importance of NO (nitric oxide) homeostasis in liver injury..Increased NO production has been described in intestinal inflammation associated with hyperpermeability…strategies designed to target iNOS could lead to therapeutic agents for the treatment and prevention of…diseases associated with NO overproduction and intestinal hyperpermeability.”

There isn’t anything terribly new about the idea of intestinal leakiness – apart from perhaps the name ‘leaky gut syndrome’, spawning a whole range of new treatments, and products to go with them.

The intestine is always going to be permeable to some degree. It’s intended to be that way. But when energy systems are impaired and nutritional deficiencies exist, the syndrome which is real is the ‘stress matrix syndrome’.

“Chronic non-communicable diseases (NCDs) are the leading causes of work absence, disability, and mortality worldwide…One way of triggering low-grade inflammation is by increasing intestinal barrier permeability through activation of various components of the stress system. Although beneficial to meet the demands necessary during stress, increased intestinal barrier permeability also raises the possibility of the translocation of bacteria and their toxins across the intestinal lumen into the blood circulation.”

One approach to improving gut barrier performance involves play, rest and sleep, exposure to daylight, as well as stress reduction techniques of any kind.  It might also include a diet avoiding PUFA, reducing intake of grains, seeds, nuts, legumes, under cooked vegetables and too many difficult to digest starchy and fibrous foods, but getting enough protein and nutrients from milk, cheese and gelatin, and plenty of sugar from sweet ripe fruits and juices, white sugar and honey.

Suppression of intestinal barrier capability – and the things which are then able to pass through – can probably be associated with every disease or condition. Obesity, diabetes type 1 and 2, cirrhosis of the liver, IBS, Parkinson’s, fibromyalgia, malaria, chronic fatigue, immunodeficiency and fatty liver disease have all been connected to ‘leaky gut’.

“It is more compelling to consider that increased intestinal permeability (leaky gut) and translocation of these substances is the critical factor for intestinal neuronal oxidative injury. Several lines of evidence strongly suggest that endotoxins are plausible neuroinflammatory triggers in PD (Parkinson’s)…”

“Multiple studies suggest that aberrant functional integrity of the gut…in settings of T1D (type 1 diabetes) may indeed contribute to the development of this disease.”

“The pain intensity of patients with FM (fibromyalgia) has recently been reported to be correlated with the degree of small intestinal bacterial overgrowth (SIBO). SIBO is often associated with an increased intestinal permeability…”

Excessive exercise, sugar restriction, radiation exposure, fish oil and other PUFA, and alcohol can impede barrier function. Red light, activated charcoal, methylene blue, penicillin, niacinamide, taurine, coconut oil, certain antihistamines and coffee can all be protective.

The body responds to stress in a variety of ways for the sake of protection and survival. Unfortunately there is a cost associated with this, and the longer it goes on the more expensive it can be. Environmental poisons and toxins – many of which have only become common in more recent times – can make the stress response dysfunctional.

See More Here

The Type of Dietary Fat Modulates Intestinal Tight Junction Integrity, Gut Permeability, and Hepatic Toll-Like Receptor Expression in a Mouse Model of Alcoholic Liver Disease

Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet–Induced Obesity and Diabetes in Mice

Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium.

A Single Dose of Endotoxin Increases Intestinal Permeability in Healthy Humans

Intestinal permeability in liver cirrhosis.

Intestinal permeability in patients with viral and alcoholic liver disease.

Intestinal permeability in liver cirrhosis: relationship with severe septic complications.

Hepatoprotective, antinociceptive and antioxidant activities of cimetidine, ranitidine and famotidine as histamine H2 receptor antagonists.

Methylene Blue inhibits the inflammatory process of the acetic acid-induced colitis in the rat colonic mucosa.

Serotonin reuptake transporter (SERT) plays a critical role in the onset of fructose-induced hepatic steatosis in mice.

Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism.

Chlorogenic acid decreased intestinal permeability and ameliorated intestinal injury in rats via amelioration of mitochondrial respiratory chain dysfunction

Ingestion of (n-3) fatty acids augments basal and platelet activating factor-induced permeability to dextran in the rat mesenteric vascular bed.

Lipid peroxidation induced by DHA enrichment modifies paracellular permeability in Caco-2 cells: protective role of taurine.

Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress.

Intestinal permeation and gastrointestinal disease.

Endotoxin in the gut and chylomicrons: translocation or transportation?

Stress Induces Endotoxemia and Low-Grade Inflammation by Increasing Barrier Permeability

Acute induction of anomalous and amyloidogenic blood clotting by molecular amplification of highly substoichiometric levels of bacterial lipopolysaccharide

Estriol sensitizes rat Kupffer cells via gut-derived endotoxin.

Dietary niacin supplementation ameliorates ethanol-induced liver injury in rats through sealing the leaky gut

Effects of histamine and histamine antagonists on intestinal capillary permeability.

The Impact of a 24-h Ultra-Marathon on Circulatory Endotoxin and Cytokine Profile.

Isolated ascites revealing a hypothyroidism. Study of 2 cases.

Nitric oxide mediated intestinal injury is required for alcohol-induced gut leakiness and liver damage

Protective effects of medium-chain triglycerides on the liver and gut in rats administered endotoxin.

Mast cells and histamine alter intestinal permeability during malaria parasite infection

Increased Intestinal Permeability Correlates with Sigmoid Mucosa alpha-Synuclein Staining and Endotoxin Exposure Markers in Early Parkinson’s Disease

Intestinal Serotonin Transporter Inhibition by Toll-Like Receptor 2 Activation. A Feedback Modulation

Altered intestinal permeability in patients with primary fibromyalgia and in patients with complex regional pain syndrome.

Dietary saturated and monounsaturated fats protect against acute acetaminophen hepatotoxicity by altering fatty acid composition of liver microsomal membrane in rats

Gut inflammation in chronic fatigue syndrome

Jejunal bacterial overgrowth and intestinal permeability in children with immunodeficiency syndromes.

Progression of Intestinal Permeability Changes and Alpha-Synuclein Expression in a Mouse Model of Parkinson’s Disease


The Gut Microbiota, Intestinal Permeability, Bacterial Translocation, and Nonalcoholic Fatty Liver Disease: What Comes First?

Link between hypothyroidism and small intestinal bacterial overgrowth

Intestinal permeability in humans is increased after radiation therapy.

Inflammation and Immunity in Radiation Damage to the Gut Mucosa

Chronic stress and intestinal barrier dysfunction: Glucocorticoid receptor and transcription repressor HES1 regulate tight junction protein Claudin-1 promoter

Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat

Alterations in intestinal permeability

Role of Corticotropin-releasing Factor in Gastrointestinal Permeability

The Role for Gut Permeability in the Pathogenesis of Type 1 Diabetes – A Solid or Leaky Concept?

Heat stress, gastrointestinal permeability and interleukin-6 signaling — Implications for exercise performance and fatigue

Small Intestinal Alterations in Severely Obese Hyperglycemic Subjects


Image: Neo Stops Bullets, The Matrix

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