3 factors autoimmune disease

Is the growth of autoimmune disorders & allergies related to the increased load of pesticides in staple foods?

In the last 20 years the increasing incidence of non-communicable disease, in particular allergies and autoimmune illness, has extended far beyond better diagnosis and simple genetic predisposition.  And it's not just stress - stress may be a catalyst.

Mammalian health is dependent on a healthy digestive tract and an intact intestinal barrier (gut wall).  Unfortunately the digestive tract can degrade deceptively slowly. Then a stressful experience triggers the descent into autoimmune and/or allergic illness, frequently a debilitating, frustrating lifelong struggle. This is why scientists work to understand the environmental triggers that are present that weren't around 30 years ago.  

People may remember eating white bread all through the 1970's and 1980's and never hearing of (for example) coeliac/celiac disease or gluten intolerance.  Back then gluten intolerance and coeliac disease weren't as common. Neither were the extensive applications of fungicides, pesticides, herbicides and growth promotants on cereals. Coeliac disease has existed for a long time, 'malabsorptive syndrome' was around in the second century.   Twenty years ago people rarely had to plan for someone coming to dinner who was allergic to gluten. Restaurants didn't know gluten intolerance existed. Yet gluten intolerance and coeliac disease are the tip of a modern 'non-communicable illness' epidemic.  Like many allergic and autoimmune diseases this new of intolerance and illness has common themes - (1) intestinal dysfunction and that it involves (2) 'immune mediation' - i.e. an autoimmune response (3) malabsorption where critical nutrients required for biological function are not taken into the body.

A relatively unexamined role is that of 'biocides' - fungicides/bacteriacides, herbicides, insecticides, miticides - and the mechanisms by which these agents act as antimicrobial agents and impact the function of bacteria in the human body at a biological and chemical level. 

Genetic predisposition, miscommunication between innate and adaptive immunity, exposure to environmental triggers, and loss of intestinal barrier function secondary to the activation of the zonulin pathway by food-derived environmental triggers or changes in gut microbiota all seem to be key ingredients involved in the pathogenesis of inflammation, autoimmunity, and cancer.
— Fasano 2008 [1]

Autoimmune and allergic disease development, or pathogenesis involves 3 factors:

  1. Loss of intestinal barrier function - gut permeability (leaky gut).
  2. Genetic predisposition
  3. Exposure to environmental triggers - absence of critical nutrients

1. Intestinal barrier & gut permeability  

Intestinal dysfunction covers a broad range of problems - from a leaky gut, where the gut lining ('intestinal barrier') is damaged enabling improperly digested food molecules to enter the bloodstream and trigger an immune response - to an altered gut microbiome - gut dysbiosis.  Animals require healthy gut microflora (essential micro-organisms) to process food and extract nutrients. When gut flora is balanced it is in 'orthobiosis'; when it is out of balance, and there is an overgrowth of pathogenic bacteria in the digestive tract, the gut is in dysbiosis. 

Human health is inextricably tied to the health of the digestive tract. An enormous range of modern 'non-communicable' illness that has a consistent cofactor - altered (digestive tract) 'intestinal permeability.' (hyperpermeability). 

Intestinal permeability &/or gut dysbiosis (and failure to process and absorb critical nutrients) is correlated with (now) common disorders such as irritable bowel syndrome and leaky gut, Crohn's disease and coeliac disease. But there are many more non-communicable illnesses with a co-factor of a 'sick gut' that aren't commonly realised:  allergies (including hay fever), bronchial asthma, type 1 diabetes, rheumatoid arthritis, fibromyalgia, multiple sclerosis, CFS & ME, atopic eczema, dermatitis and psoriasis, some cancers, metabolic and cardiovascular disturbances.

Frequently economic analysis fails to understand the added stress and expense of co-morbidity. Skin, mental health, arthritic and gut related problems can all co-exist as a function of a permeable gut that is also unable to absorb nutrients.

It's important to understand that a sick gut is observed before the development of these diseases -scientists believe gut permeability is involved in the actual development of these diseases and illnesses.  [1] Perhaps Hippocrates had investigated enough digestive tracts to see this common theme that modern research is rediscovering some 2,300 years later.

Therefore a stressful event places strain (stress) on a body that is physically unable to handle that stress, due to an already degraded digestive tract.   We are not converting food efficiently into the nutrients we need. The immune system isn't strong enough. Vulnerable individuals tip into illness.  

Science is beginning to comprehend the degree of bacteria (and other parasites and microbes) that humans naturally lodge in the body - and - just like healthy body cells, humans need healthy body bacteria in order to function in a healthy way.   The human ecosystem is mutually dependent on many of these 'tenants'.  Bodies have developed to manage, tolerate and even gain benefit from the not-so-good tenants by using the immune system to respond. Surprisingly, a rich array of microbial matter makes the immune system stronger.  When we don't have this diversity, we are more vulnerable to illnesses including allergies, autoimmune disease, depression, some cancers and even simple coughs and colds.

Furthermore, it is becoming increasingly apparent that in some conditions increased permeability is critical to the development of disease as, if it is abrogated, the disease does not develop.
— Arrieta et al 2006. [2]

2. Genetic Predisposition

All of us have a unique set of genes.  This is why we have different responses when the gut 'gets sick'. Genetically, human ancestors had different environmental challenges (for example malaria or the chance of seafood poisoning) - as every continent has a different mix of parasites and bacteria. Human genes evolved differently with nomadic lifestyles to manage the various intruders (which frequently lodged in the gut) with appropriate immune responses.  

When the diversity of the microbiome is reduced  - and change the balance of gut bacteria (and most likely body bacteria as well) - it can have knock on effects and the immune system becomes confused and targets different stuff - influenced greatly by our genetic predisposition.

As Velasquez-Manoff discusses in An Epidemic of Absence.  A New Way of Understanding Allergies and Autoimmune diseases, 'By changing our inner ecology, we've hobbled the critical suppressor arm of our immune system'.

Genetic ancestry can aid to predict the 'susceptible mix' - whether a person is more likely to end up with, for instance, allergies, or multiple sclerosis or Crohn's disease. Even depression and cancer. The gut-brain connection and the field of mental health is a common theme in gut related research.  It's complex and fascinating. In his highly detailed and absorbing book, Velasquez-Manoff writes: 'Asthma in childhood increased the risk of depression in adulthood. Autoimmune diseases such as Crohn's and psoriasis often co-occurred with depression...... scientists began to suspect that the inflammation underlying the disease drove the melancholy directly.'  [3]  

As Velasquez-Manoff puts so lucidly: 'we've gone from immune dysfunction in our youth (allergies and asthma) to immune derangement in adulthood (autoimmune disease) and chronic inflammation in the diseases of middle-age (cancer and heart disease), have explored how we feel about the voyage (depression) and now we arrive at the twilight years: old age.... (ageing is associated with immune senescence...the immune system loses its pizazz.)'. Long dormant viruses can come alive again. 
Science has come a long way - but the intricate world of how genes interplay with the microbial world and respond to the external environment is astoundingly challenging. Research reveals new facts monthly.


3. Exposure to Environmental Triggers: More hygiene & more toxins.

There is a dimension to human evolution—a microbial evolution—that is likely occurring at a very rapid rate as our societies undergo dramatic shifts in socioeconomic status and cultural norms, redistribution of populations from rural to urban areas, changes in patterns of food consumption, and alterations in our exposures to xenobiotics, ranging from antibiotics that we intentionally take to various potentially toxic compounds that we unintentionally or deliberately ingest..... There is a “pressing” need for this field to advance rapidly given the great challenges we humans face..
— A rendezvous with our microbes. Gordon & Klaenhammer [4]

City based populations can never have the wide exposure to microbial activity that traditionally resulted in a diverse gut microbiome.  Ghildren the same variety of stimuli. 

The 'hygiene hypothesis' communicates that children raised on farms and exposed to a wide range of bacteria in infancy tend to have a broader range of microbial activity in their gut. This corresponds to less allergies and autoimmune disease - for the rest of their lives.  Today we have 'microbial impoverishment.' Each off-farm generation has reduced microbial diversity in its digestive system, city lives are naturally more hygienic, and this coincides with increases in allergies and autoimmune disease.

Furthermore, science is beginning to understand the adverse effects of antibiotics (antimicrobials) on the microbial load. Many toxins humans have a choice to expose ourselves to -  for example excess alcohol, smoking cigarettes. However there are other toxins in the food chain that accumulate in our bodies, there is no choice. Chemical residues in drinking water, groundwater pesticides, antibiotics in animal feed and preservatives may be included in this group. [5]  The right to safe food must be addressed.

Less beneficial gut bacteria leads to a decreased ability to breakdown food and absorb valuable nutrients. Does this tie in with the increasing incidence of gluten intolerance?  These beneficial bacteria can help breakdown gluten, a process that is becoming increasingly problematic for many.  Perhaps it is a question worth exploring.

Common sense could dictate that we need to protect what we have. Therefore perhaps it is critical to understand what comprises the third 'environmental factor': exposure to xenobiotics - toxins or antigens, that can degrade the gut wall and damage the natural bacterial load - and create a pathway to illness. We have more hygienic homes but we also have more toxins in the environment. It's about picking the puzzle apart.

At this stage medical research examining how to 'restock the gut'  is surging ahead in leaps and bounds. Researchers are investigating everything from stool samples, to helminths, whipworms, probiotics (with critical lactobaccilli and bifidobacteria).  It's important to realise these single organisms aren't silver bullets - the human system needs diversity - which is why we need to maintain healthy and diverse gut populations rather than think we can pop a pharmaceutical pill. 

The costs of autoimmune and other drug related expenditure by governments for the diseases commonly associated with increased permeability of the gut wall have accelerated exponentially over the last decade.  Is this sustainable? Can we afford the sustained increase in expense and suffering?

Human gut profiles are all different, but like blood types, there are perhaps 3 different 'fecotypes', so one prescription isn't applicable to all.  Humans are a complex superorganism. 

If consumers restock the gut with recommended microbiota - but don't eliminate xenobiotics from diets, these same toxins will simply 'rekill' the new introduced micro-organisms.  An expensive merry-go-round.

Prevention: Tree hugging the gut microbiome?

It's easier to manage and restore a forest than to create a new one. Forests are complex.  And like the digestive system, preserving what we have should be the first step to maintaining what we have.  Food should be safe.  

Most people in the world can't afford organic, let alone access an organic shop. It is critical to legislate and manage food system (food security) to ensure conventional food is safe. In addition, most people can't afford to pay to constantly restock their gut with expensive drugs and medicines.  Prevention is key. Scientists researching gut microbiota are deeply concerned at the variety already lost.

There is little funding looking at how to identify and prevent toxins that deplete microbiota in the first place.

There are no studies researching how the full formulation of pesticides affect gut (or human) health held with the US EPA, WHO or European Commission. 

No assessment agency or government are monitoring the toxin mixtures in the food supply and the subtle implications for gut health.  Governments and industry are researching genes and much research is investigating restoration of barrier function and the medicines that may help with this. However, this research does not link what the actual xenobiotics are, that are contributing to gut dysbiosis and digestive tract permeability.

Is there a solution?

Many scientists are coming to the conclusion that pesticides, (including glyphosate based herbicides (GBH such as Roundup), have increasingly high permitted residues in food that may lead to gut related problems.  Yes, there are many other toxins we are exposed to which need isolating and evaluating, but are pesticides playing an increasingly larger role in overall toxin exposures. 

Is Roundup the worlds 'most significant environmental toxin'

Until independent public domain studies, using the full pesticide formulations, researched over a longer time frame, are accepted as part of the pesticides assessment process, gut related problems will continue to be ignored by the agencies. Gut related problems take time to develop, short term corporate funded studies do not reveal these types of illnesses. We need a different assessment framework - 10 demands that will reconfigure this negligent system.

It comes back to a duty of care for the most vulnerable.

The gut related science - how Roundup/glyphosate may have a detrimental 4 way effect.

Traditionally scientists didn't think GBH affected us, it only affects plants. But the shikimate pathway in the gut microbiome which makes vital amino acids (tryptophan and tyrosine) is plant based. This is a big part of the story that science is unravelling.

1. Roundup can destroy beneficial bacteria in the stomach.  Glyphosate was patented as an antibiotic - it kills bacteria. It is considered a microbiocideResidue levels permitted in food are 40 to 800 times the antibiotic threshold and concentrations shown in clinical studies damage mammalian tissues. [6]  

2. GBHs may destroy or damage epithelial cells in the gut lining or may encourage pathogens that lead to cellular breakdown or other damage of the gut lining.  This can result in increased permeability of the gut wall. 

Therefore the (1) food does not breakdown and instead (2) transfers into the body through a weakened gut wall, creating increased propensity for autoimmune disease and allergies. [7]  

3. Glyphosate is an organic phosphate chelator that immobilizes positively charged minerals such as manganese, cobalt, iron, zinc, copper, etc. that are essential for normal physiological functions in soils, plants and animals. [6]  GBHs may reduce nutrient availability in the gut.

4. Glyphosate inhibits/disrupts the shikimate pathway -  involved with the synthesis of the essential aromatic amino acids, phenylalanine, tyrosine, and tryptophan. [8] 

Scientists have identified the glyphosate in human breast milk and urine at higher levels than permitted drinking water. Most countries do not test drinking water for glyphosate/Roundup contamination.

Scientists are beginning to understand that the most important time for microbial gut colonisation is before and in the months after birth. Breast milk critically boosts the infants immune system with DNA from lactobacilli and bifidobacteria essential to digesting the breast milk in the first place. 

But what if there is an antibiotic - glyphosate -  moving through the breast milk that nursing mothers are feeding their babies?  

Am I exposed to high residues of pesticides?

As an example of the increasing toxin load the permitted residues of Roundup and GBH pesticides were permitted to increase 6 fold on wheat in 2006.  On flour and bread, from 5mg/kg to 30mg/kg  - to allow for direct spraying onto the wheat for desiccation (drying) purposes. 

Many people have wheat based meals from 2 to 3 times a day.

If corn, soybeans, canola, cottonseed come from North or South America they are more likely to be GMO's (with their higher insecticidal and/or herbicidal load). These markets are export oriented. Many vegetable oils are soy, cottonseed or canola based. Poultry and pork are fed a heavy GMO diet (unless specified otherwise, as the cheapest protein based stockfeed is frequently a GMO product).  [8]  It is very difficult to establish the origins of these products in processed food. DNA fragments from transgenic plants are increasingly found in animal tissue such as milk, inner organs and muscles.

Staple food groups carry significant amounts of pesticide residue. 

Higher pesticide residues in cereal producing regions. Full formulations never assessed.

Cereal producing regions throughout the world in temperate but higher rainfall areas (Northern Latitude regions) are exposed to higher quantities of pesticides to combat the increased growth of pests (due to warmth and higher rainfall) - including insects, moulds and weeds. It's also important to understand that governments and regulatory agencies never test the full formulation of the pesticides applied to cereals. For instance, full formulation of fungicides can be 1000x more toxic to cells than the active ingredient, the only part assessed. This is an enormous gap in knowledge and may suggest the gut problems are not limited to gluten. 

Is there a link with increased incidence of autoimmune related disease in northern latitude regions as well as southern Canterbury region of New Zealand? Do these regions carry a higher load of pesticides in their drinking water? 

Scientists understand that GBH impairs important cytochrome P450 enzymes required for detoxifying environmental toxins (xenobiotics) and activating vitamin D3 (in the liver). Simply put, does Roundup further reduce access to vitamin D in these Northern Latitude regions where populations are deficient in the first place - contributing to their higher disease load?  [9]

Many regions now commonly desiccate (dry out) sugar cane with GBH. Do these regions also present with higher rates of gut related disease?

Children are more vulnerable to pesticide exposure than adults. 

Traditionally scientists didn't think GBH affected us, it only affects plants. But the shikimate pathway in the gut microbiome which makes vital amino acids (tryptophan and tyrosine) is plant based.. This is a big part of the story that science is unravelling.

1. Roundup can destroy beneficial bacteria in the stomach.  Glyphosate was patented as an antibiotic - it kills bacteria. It is considered a microbiocideResidue levels permitted in food are 40 to 800 times the antibiotic threshold and concentrations shown in clinical studies damage mammalian tissues. [6]  

2. GBHs may destroy or damage epithelial cells in the gut lining or may encourage pathogens that lead to cellular breakdown or other damage of the gut lining.  This can result in increased permeability of the gut wall. 

Therefore the (1) food does not breakdown and instead (2) transfers into the body through a weakened gut wall, creating increased propensity for autoimmune disease and allergies. [7]  

3. Glyphosate is an organic phosphate chelator that immobilizes positively charged minerals such as manganese, cobalt, iron, zinc, copper, etc. that are essential for normal physiological functions in soils, plants and animals. [6]  GBHs may reduce nutrient availability in the gut.

4. Glyphosate inhibits/disrupts the shikimate pathway -  involved with the synthesis of the essential aromatic amino acids, phenylalanine, tyrosine, and tryptophan. [8] 

Scientists have identified the glyphosate in human breast milk and urine at higher levels than permitted drinking water. Most countries do not test drinking water for glyphosate/Roundup contamination.

Scientists are beginning to understand that the most important time for microbial gut colonisation is before and in the months after birth. Breast milk critically boosts the infants immune system with DNA from lactobacilli and bifidobacteria essential to digesting the breast milk in the first place. 

But what if there is an antibiotic - glyphosate -  moving through the breast milk that nursing mothers are feeding their babies? 

Am I exposed to high residues of pesticides?

As an example of the increasing toxin load the permitted residues of Roundup and GBH pesticides were permitted to increase 6 fold on wheat in 2006 - flour and bread, from 5mg/kg to 30mg/kg  - to allow for direct spraying onto the wheat for desiccation (drying) purposes. 

Many people have wheat based meals from 2 to 3 times a day.

If corn, soybeans, canola, cottonseed comes from North or South America it is more likely to be GMO's (with their higher insecticidal and/or herbicidal load). These markets are export oriented. Many vegetable oils are soy, cottonseed or canola based. Poultry and pork are fed a heavy GMO diet (unless specified otherwise, as the cheapest protein based stockfeed is frequently a GMO product).  [8]  It is very difficult to establish the origins of these products in processed food. DNA fragments from transgenic plants are increasingly found in animal tissue such as milk, inner organs and muscles.

Staple food groups carry significant amounts of pesticide residue. 

Higher pesticide residues in cereal producing regions. Full formulations never assessed.

Cereal producing regions throughout the world in temperate but higher rainfall areas (Northern Latitude regions) are exposed to higher quantities of pesticides to combat the increased growth of pests (due to warmth and higher rainfall) - including insects, moulds and weeds. It's also important to understand that governments and regulatory agencies never test the full formulation of the pesticides applied to cereals. For instance, full formulation of fungicides can be 1000x more toxic to cells than the active ingredient, the only part assessed. This is an enormous gap in knowledge and may suggest the gut problems aren't always due to gluten. How do fungicides, many times more toxic than we understand, interact with the microbiota and gut wall. Data gap.

There may be a link with increased incidence of autoimmune related disease in northern latitude regions as well as southern Canterbury region of New Zealand? These may regions carry a higher load of pesticides in their drinking water.

Scientists understand that GBH impairs important cytochrome P450 enzymes required for detoxifying environmental toxins (xenobiotics) and activating vitamin D3 (in the liver). Roundup may further reduce access to vitamin D in these Northern Latitude regions where populations are deficient in the first place. This may contribute to diseases involving vitamin D deficiencies [9]

Many regions now commonly desiccate (dry out) sugar cane with GBH. Do these regions also present with higher rates of gut related disease?

Children are more vulnerable to pesticide exposure than adults. 

 RITE. It's time to understand the environmental triggers.

Where are the pesticide studies that show us how pesticides affect gut tissues (known as gut histology, and the main target tissue of any food) and measurements on gut and immune system responsiveness? 

There are none.

  • Gut related research on pesticides currently stops at the gates of the assessment agencies. It is not invited in. It is dismissed. 
  • The World Health Organisation, the US Environmental Protection Agency and the European Commission do not require studies of glyphosate's (or pesticides in general) effect on the gut.

There are no independent pesticide studies held with the US EPA, WHO or European Commission researching glyphosate / Roundup's ability to trigger an autoimmune response.

It is time to reframe pesticide safety assessment for a healthier world:

RITE.

PDF copy of this text available here.

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References:

Xenobioticxenobiotic is a foreign chemical substance found within an organism that is not normally naturally produced by or expected to be present within that organism. It can also cover substances which are present in much higher concentrations than are usual. Wikipedia

[1] Intracellular tight junctions:    Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer.  IV. INTESTINAL PERMEABILITY AND DISEASE.  A. Fasano. Physiological ReviewsPublished 1 January 2011Vol. 91no. 151-175 DOI: 10.1152/ physrev. 00003.2008. 

[2] Alterations in intestinal permeability   M C Arrieta, L Bistritz, and J B Meddings. Gut. Oct 2006; 55(10): 1512–1520.doi:  10.1136/gut.2005.085373  PMC1856434

[3]  An Epidemic of Absence.  A New Way of Understanding Allergies and Autoimmune diseases.  Moises Velasquez-Manoff.  ISBN 978-1-4391-9939-8  P. 258.

[4] A rendezvous with our microbes. Gordon & Klaenhammer

[5] Gut Reaction: Environmental Effects on the Human Microbiota.  M.L. Phillips. Environ Health Perspect. May 2009; 117(5): A198–A205. PMCID: PMC2685866

[6] Glyphosate and GMOs impact on crops, soils, animals and man. Dr Don Huber

[7] Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance. Samsel, A. & Seneff S.. Interdisciplinary Toxicology. 2013; Vol. 6(4): 159–184 Gut bacteria: Page 163

[8] GMO corn, soybeans dominate US market. June 4, 2013. V. DuPont. Phys.org

[9]  (a) Glyphosate Is an Inhibitor of Plant Cytochrome P450: Functional Expression of Thlaspiarvensae Cytochrome P45071B1/Reductase Fusion Protein in Escherichia coli.  D.C. Lamb, D.E. Kelly, S.Z. Hanley, Z. Mehmood, S.L. Kelly. http://dx.doi.org/10.1006/bbrc.1997.7988

(b) Cytochrome P450 enzymes in the bioactivation of vitamin D to its hormonal form (review). Wikvall, K.  Int. J. Mol. Med. 2001, 7, 201–209. 

(c) Cytochromes P450 are essential players in the vitamin D signaling system. Schuster, I. Biochim.  Biophys. Acta 2011, 1814, 186–199

 

A well-researched book about gut function, allergies and autoimmune disease: An Epidemic of Absence.  A New Way of Understanding Allergies and Autoimmune diseases.  Moises Velasquez-Manoff.  ISBN 978-1-4391-9939-8

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