Leaky Gut, Endotoxins and Holistic Solutions

In this analysis, I will first examine the role of endotoxins in leaky gut (Section A) and follow up with a look at holistic solutions. (Section B)

Section A

Intestinal permeability

Leaky gut, or intestinal permeability, is a condition in which bacteria, endotoxins and undigested nutrients are able to leak through physical holes in the intestinal wall and translocate directly into the bloodstream. In 2015, a review article in Frontiers of Immunology found that increased intestinal permeability, in addition to modern lifestyle factors, was capable of triggering a low-grade inflammatory state through the translocation of bacterial endotoxins. (1)


The most common endotoxin is lipopolysaccharide (LPS), a major component of the outer cell membrane of gram-negative bacteria. When found in the intestinal lumen, this compound is mostly harmless. However, once released into the bloodstream, LPS can trigger an acute inflammatory reaction. (2) While it receives little recognition for the damage that it causes, LPS has been used extensively in the lab to induce a number of chronic diseases, including Alzheimer’s, multiple sclerosis, inflammatory bowel disease, cardiovascular disease, diabetes, obesity, hypogonadism, autoimmunity, and mood disorders like autism, anxiety, and depression. (3)

The findings of this 2015 study suggest that leaky gut plays a “pivotal and perhaps even causal role in the development of low-grade inflammation and its related diseases.” (1)

Causes of Leaky Gut

Some of the basic lifestyle factors that contribute to leaky gut include chronic hard alcohol consumption, chronic smoking, intense exercise, lack of sleep, and overuse of medications like antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), and proton-pump inhibitors (PPIs). (4) Stress is also causative (5) as are toxins like glyphosate.

In 2011, researchers in Germany found that exposure to stress was responsible for alterations in gut motility, an increase in intestinal permeability, and negative effects on the intestinal microbiota, as well as the regenerative capacity of the gut mucosa. Additionally, researchers concluded that “probiotics may profoundly affect the gut-brain axis and attenuate the development of stress-induced disorders in the upper and lower GI tract.” (6)

Section B

Holistic Solutions

Some basic lifestyle choices, like managing stress, limiting alcohol, and getting adequate sleep, can all significantly reduce the risk for developing leaky gut. However, since most people already have leaky gut to some degree,  the following holistic interventions can be useful.

Nutrients that promote secretory IgA levels

One way to prevent LPS from seeping into the bloodstream is to increase secretory IgA levels. Secretory immunoglobulin A (sIgA) is the first line of defense against liberated LPS in the lumen of the intestines because it has the unique capability of binding and neutralizing LPS directly in the lumen. Nutrients that can increase sIgA levels include omega fatty acids, glutathione, glutamine, glycine, vitamin C, zinc, and colostrum from mother’s milk.

Increase mucin production via specific nutrients

Another way to strengthen the intestinal lining is to thicken the protective mucosal barrier known as the mucous layer. This layer creates a thick physical buffer between the intestinal lumen and the inner epithelial cells. Nutrients that can increase mucin production include threonine, serine, protein, and cysteine.

Modulate the microbiome via Bacillus Spore Probiotics

An all-encompassing approach would be to utilize spore-based probiotics that are capable of modulating the intestinal microbiome, up-regulating sIgA levels, and thickening the intestinal mucosa. The major concern with most probiotics is the issue of survivability. Most probiotic strains are not designed to withstand stomach acid, bile salts, the lack of oxygen, or the competitive environment in the large intestine. For this reason, most probiotics fail to make any lasting changes to the gut microbiome or have any protective effects on the host. However, spore-based probiotics are uniquely designed to survive digestion and compete in the large intestine with ease.

In this persepctive, a recent study at the University of North Texas found that just 30 days of supplementation with MegaSporeBiotic demonstrated a 45% reduction in serum LPS levels following a high-fat meal. The placebo treatment group showed a 28% increase in serum LPS levels after 30 days of no treatment, suggesting that leaky gut may be a progressive condition that requires continuous intervention. (7)

UNder contraction

To date, bacterial spores are the only probiotic strains that have been shown to reduce leaky gut. And as a result, MegaSporeBiotic™ is one of the most effective probiotics for the treatment of leaky gut and its associated chronic disease.

References and Precision Notes

1 De Punder K, Pruimboom L. Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability. Front Immunol. 2015;15(6):223.

2 Nakarai H, Yamashita A, Nagayasu S, et al. Adipocyte-macrophage interaction may mediate LPS-induced low-grade inflammation: potential link with metabolic complications. Innate Immunity. 2012;18:164-70.

3 Qin L, Wu X, Block ML, et al. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia. 2007;55:453-62.

4 Yoshikawa K, Kurihara C, Furuhashi H, et al. Psychological stress exacerbates NSAID-induced small bowel injury by inducing changes in intestinal microbiota and permeability via glucocorticoid receptor signaling. J Gastroenterol. 2017;52(1):61-71

5 Karl JP, Margolis LM, Madslien EH, et al. Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiologic stress. Am J Physiol Gastrointest Liver Physiol. 2017;312(6):G559-571.

6 Konturek PC, Brzozowski T, Konturek SJ. Stress and The Gut: Pathophysiology, Clinical Consequences, Diagnostic Approach and Treatment Options. J Physiol Pharm. 2011;62(6):591-599.

7 McKarlin BK, Henning AL, Bowman EM, et al. Oral spore-based probiotic supplementation was associated with reduced incidence of post-prandial dietary endotoxin, triglycerides, and disease risk biomarkers. 2017. Manuscript submitted for publication.

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