Intestinal barrier damage from food additives and pesticides

Intestinal barrier damage from food additives and pesticides/herbicides contributes to autoimmune disease. The intestinal barrier—epithelial cells forming the inner lining of the intestines—is designed for nutrient absorption while protecting the GALT (gut associated lymphoid tissue, the greatest mass of immune system tissue in the body) from compounds that should not gain access. Damage to the tight junctions of the intestinal barrier is a major contributing cause of loss of immune tolerance and autoimmune disease. When the intestinal barrier is breached, the immune system can become sensitized to compounds that either 'mimic' the body's own antigens due to similarity or combine with them to form a hybrid called a hapten. In either case, as the immune system reacts to the compound that has penetrated the intestinal barrier it can cross-react to self-antigens, thus mounting an inflammatory attack on the body's own tissues. This is how diminished intestinal barrier integrity is contributing to the pandemic of diffuse and blatant autoimmune phenomena.

Food additives promote autoimmunity by damaging the intestinal barrier

In a paper published recently in Autoimmunity Reviews, the authors link industrial food additives to intestinal barrier damage that leads to loss of immune tolerance. They note:

"The incidence of autoimmune diseases is increasing along with the expansion of industrial food processing and food additive consumption...The intestinal epithelial barrier, with its intercellular tight junction, controls the equilibrium between tolerance and immunity to non-self-antigens. As a result, particular attention is being placed on the role of tight junction dysfunction in the pathogenesis of AD [autoimmune disease]. Tight junction leakage is enhanced by many luminal components, commonly used industrial food additives being some of them."

 Crucial role of the intestinal barrier

The authors offer a review of the intestinal barrier tight junctions that are crucial for the healthy immune system regulation:

"Only a single layer of epithelial cells separates the luminal contents from effector immune cells in the lamina propria and the internal milieu of the body. Breaching this single layer of epithelium can lead to pathological exposure of the highly immunoreactive subepithelium to the vast number of foreign antigens in the lumen. The permeability of the intestinal epithelium depends on the regulation of the mucosal immune system and intercellular tight junction (TJ)."

Integrity and protection of the intestinal barrier depends on a network of key proteins:

"Zonulins, occludins, claudins and junctional adhesion molecules are a few examples that modulate movement of fluid, macromolecules and leukocytes from intestinal lumen to the blood stream and vice versa. In addition, these TJ proteins are involved in protecting the epithelial cells of the intestine against colonization by microorganisms. It is now apparent that TJs are dynamic structures that are involved in developmental, physiological and pathological processes. They regulate the trafficking of macromolecules between the environment and the host through a barrier mechanism. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular TJs, controls the equilibrium between tolerance and immunity to non-self antigens...in addition to genetic predisposition and exposure to triggering non-self antigens, the loss of protective function of mucosal barriers that interact with the environment is necessary for autoimmunity to develop."

Influences on intestinal barrier tight junctions

Clinicians need to constantly bear in mind factors that commonly have an impact on intestinal barrier integrity. Here the authors note some of the very common ones:

"Pathophysiological regulation of tight junctions is influenced by many factors, including: secretory IgA, enzymes, neuropeptides, neurotransmitters, dietary peptides and lectins, yeast, aerobic and anaerobic bacteria, parasites, proinflammatory cytokines, free radicals and regulatory T-cell dysfunction."

In addition to these 'classics', they list seven food additives whose increase in use has paralleled the sharp increase in autoimmune disease:

1. Sugars: "Glucose is known as an absorption enhancer...found to increase permeability and produce changes in distribution of the main protein of the tight junction in the human cell line Caco-2, indicating intercellular leakage."
2. Salt: besides driving T_H17-associated proinflammatory cytokines (a 'key player' in autoimmune inflammation), "...increased salt consumption is an enhancer of intestinal permeability through the TJ machinery."
3. Emulsifiers and surfactants: "... widely used in the bakery, confectionary, dairy, fat and oil, sauces, butter and margarine, ice cream, cream liqueurs, meat, coffee, gum, beverages, chocolate and convenient food industries...Numerous synthetic surfactant food additives have been shown to increase the intestinal permeability through paracellular and/or transcellular mechanisms." By adversely affecting the hydrophobic intestinal barrier mucus layer, epithelial cell membranes and the transport protein p-glycoprotein, they cause "...destabilization of tight junctions between the GI epithelial cells, thus increasing intestinal leakage." Note for clinicians prescribing essential fatty acids: "Surface active compounds, like oleic and docosahexaenoic acids, compromised the integrity of the intestinal epithelium and enhanced the paracellular absorption of poorly absorbed hydrophilic substances. In general, fatty acids like EPA, DHA, γLA, capric and lauric acids increase TJ permeability."
4. Organic solvents: "Some nutrients like glutamine and polyphenols protect TJ barrier integrity, in contrast, several organic solvents used in the food and beverage industries, like alcohol and its metabolites impair the TJ barriers."
5. Gluten: "Evidence exists that intestinal barrier defects have a role in initiating celiac disease. A number of in vitro studies have confirmed the cytotoxicity of gluten's main antigen, gliadin. Gliadin has agglutinating activity, reduces F-actin content, inhibits cell growth, induces apoptosis, alters redox equilibrium and causes a rearrangement of the cytoskeleton through the zonulin pathway and the loss of TJ competence in the gastrointestinal mucosa...Gliadin causes zonulin release by binding to the CXCR3 receptor in intestinal cells via a MyD88-dependent pathway and subsequent transactivation of EGFR by PAR2, leading to small intestine TJ disassembly." See more on intestinal barrier damage from gluten in non-celiac gluten sensitivity below.
6. Microbial transglutaminase (mTG): used to modify the function of proteins in food products. " There are more than half a dozen ways "...mTG may increase intestinal permeability by cross-linking amino acids or protein."
7. Nanoparticles: "Permeation studies showed that nanoparticles opened the tight junctions of monolayer Caco-2 cells and increased paracellular transportation. The signaling mechanism initiating the cascade of disruption of the TJ, was elucidated recently..."

Eat clean natural foods to preserve the intestinal barrier and calm autoimmunity

The bottom line is that there are several mechanisms by which industrial food additives can damage the intestinal barrier and contribute to loss of immune tolerance. The authors conclude:

"The food and beverage industries are constantly changing and transforming our food composition through new food processing technologies. The result is neo-linked, transformed molecules and delivery systems, representing intestinal mucosal load with altered physicochemical and immunogenic properties...Glucose, salt, emulsifiers, organic solvents, gluten, mTG, and nanoparticles are extensively and increasingly used by these industries to improve the qualities of the food (as claimed by manufacturers and some consumers). However, all these food additives increase intestinal permeability by bringing about TJ paracellular transfer. In fact, TJ dysfunction is common in multiple AD [autoimmune disease] and the central part played by the TJ in AD pathogenesis has been extensively described."

 Glyphosate (Roundup®) promotes celiac disease and gluten intolerance

The herbicide glyphosate (Roundup®) persists in the wheat kernel when used as a 'dessicant' to speed harvesting and causes damage to the intestinal barrier as described in an extensive paper published in Interdisciplinary Toxicology. The authors note:

"Celiac disease is associated with imbalances in gut bacteria that can be fully explained by the known effects of glyphosate on gut bacteria. Characteristics of celiac disease point to impairment in many cytochrome P450 enzymes, which are involved with detoxifying environmental toxins, activating vitamin D3, catabolizing vitamin A, and maintaining bile acid production and sulfate supplies to the gut. Glyphosate is known to inhibit cytochrome P450 enzymes. Deficiencies in iron, cobalt, molybdenum, copper and other rare metals associated with celiac disease can be attributed to glyphosate's strong ability to chelate these elements. Deficiencies in tryptophan, tyrosine, methionine and selenomethionine associated with celiac disease match glyphosate's known depletion of these amino acids."

Glyphosate causes gut dysbiosis

Disruption of the gut microbial ecology is one mechanism by which the intestinal barrier is compromised leading to loss of tolerance to gluten (and other foods).

"...a broad-spectrum herbicide, considered to be nearly nontoxic to humans...Glyphosate suppresses 5-enolpyruvylshikimic acid-3-phosphate synthase (EPSP synthase), the rate-limiting step in the synthesis of the aromatic amino acids, tryptophan, tyrosine, and phenylalanine, in the shikimate pathway of bacteria, archaea and plants...Humans do not possess this pathway, and therefore we depend upon our ingested food and our gut microbes to provide these essential nutrients. Glyphosate...has been shown to disrupt gut bacteria in animals, preferentially killing beneficial forms and causing an overgrowth of pathogens....celiac disease is associated with a reduced presence in the gut of commensal bacteria such as Lactobacilli and Bifidobacteria, which are known to be preferentially killed by glyphosate, and with an overabundance of C. difficile, which is known to be promoted by glyphosate exposure."

 Pesticides and herbicides—it's much worse than it already seems

When the designated active principle (AP) is combined with the other chemicals in a commercial formulation toxicity is greatly increased. Studies done to assess the toxicity of pesticides typically test the main active ingredient, such as glyphosate in Roundup® (hence it's classification as relatively non-toxic to humans). In practice, however, these primary agents are applied as compound formulations. The authors of a study published in BioMed Research International compared the toxicity of the 'active ingredients' of nine major pesticides, herbicides and fungicides with that of the commercial compound formulations actually used in practice. They state:

"Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities."

The results of their investigation are hair-raising:

"Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types...Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone."

Commenting on these principles and the current regulatory practice in general:

"Adjuvants in pesticides are generally declared as inerts, and for this reason they are not tested in long-term regulatory experiments. It is thus very surprising that they amplify up to 1000 times the toxicity of their APs in 100% of the cases where they are indicated to be present by the manufacturer. In fact, the differential toxicity between formulations of pesticides and their APs now appears to be a general feature of pesticides toxicology. As we have seen, the role of adjuvants is to increase AP solubility and to protect it from degradation, increasing its half-life, helping cell penetration, and thus enhancing its pesticidal activity and consequently side effects. They can even add their own toxicity. The definition of adjuvants as “inerts” is thus nonsense; even if the US Environmental Protection Agency has recently changed the appellation for “other ingredients,” pesticide adjuvants should be considered as toxic “active” compounds."

Regarding Roundup® in particular:

"It is commonly believed that Roundup is among the safest pesticides. This idea is spread by manufacturers, mostly in the reviews they promote, which are often cited in toxicological evaluations of glyphosate-based herbicides. However, Roundup was found in this experiment to be 125 times more toxic than glyphosate. Moreover, despite its reputation, Roundup was by far the most toxic among the herbicides and insecticides tested. This inconsistency between scientific fact and industrial claim may be attributed to huge economic interests, which have been found to falsify health risk assessments and delay health policy decisions."

Contributing to the vast increase in autoimmunity

There are multiple environmental factors contributing to the widespread increase in both undifferentiated and full-blown autoimmune disorders in clinical practice. Damage to the intestinal barrier is one of the most important. This data highlights the importance of consuming natural, unprocessed, non-toxic organic food for immune system health, with implications for regulatory and public health policy.