Category Archives: Disease - Page 23

Thinking With Your Gut Bacteria

Posted by on November 2, 2010 18 comments

Is your personality really yours – or is it your bacteria’s?

What prompts this thought is a new paper that studied mate preference in fruit flies. It turns out that the gut bacteria in fruit flies influence their mate preference. [1]

Image source: Wikimedia commons.

It’s been known for 20 years that fruit flies raised on one type of food prefer to mate with fruit flies raised on that same food. Now, researchers have proven that the preference is dictated by gut bacteria. When fruit flies are given antibiotics, they forget their mate preference and will mate with fruit flies that eat different diets. [2]

Mating preference seems to be dominated by a single species:  Lactobacillus plantarum. This species is common in probiotic supplements and in fermented vegetables. So if you find yourself developing an attraction to starch-fed fruit flies, your probiotic could be to blame.

Personality-Altering Pathogens

Personality-altering pathogens may not be that rare. In the book we mention that Toxoplasma gondii, a protozoal parasite, infects 20% to 60% of the population in most countries, forms cysts throughout the body including the brain, and makes its victims behave recklessly:

  • Rats infected with T. gondii lose their fear of cats. [3]
  • Humans infected with T. gondii are 6 times more likely to get in traffic accidents. [4]

Conclusion

If people seem to be behaving increasingly oddly lately, perhaps it’s not your misanthropism. It might be a bug going around.

References

[1] “Gut Bugs Affect Mating,” The Scientist, Nov 2, 2010, http://www.the-scientist.com/news/display/57793/.

[2] Sharon G et al. Commensal bacteria play a role in mating preference of Drosophila melanogaster. PNAS, www.pnas.org/cgi/doi/10.1073/pnas.1009906107, 2010. http://pmid.us/21041648.

[3] Webster JP et al. Parasites as causative agents of human affective disorders? The impact of anti-psychotic, mood-stabilizer and anti-parasite medication on Toxoplasma gondii’s ability to alter host behaviour. Proc Biol Sci. 2006 Apr 22;273(1589):1023-30. http://pmid.us/16627289.

[4] Flegr J et al. Increased incidence of traffic accidents in Toxoplasma-infected military drivers and protective effect RhD molecule revealed by a large-scale prospective cohort study. BMC Infect Dis. 2009 May 26;9:72. http://pmid.us/19470165.

Why Wheat Is A Concealed Cause of Many Diseases, III: Adjuvant Activity

Posted by on November 1, 2010 34 comments

We’ve been looking into how wheat can cause autoimmune diseases other than the “classic” wheat-associated diseases, celiac disease and Hashimoto’s thyroiditis.

The first post in the series discussed how wheat can cause a leaky, permeable gut that lets toxins and bacteria into the body. The second post discussed how wheat can itself generate a variety of auto-antibodies that attack nerves, brain, connective tissue and joints.

Now, we want to look at how wheat can create diseases by binding to other molecules and causing the body to form antibodies to them. Wheat can thereby cause allergies against foods as well as autoimmune attacks on self molecules.

Adjuvant Activity of Wheat Germ Agglutinin

Immunologically speaking, an “adjuvant” is a molecule that when bound to another molecule makes it much more immunogenic. Adjuvants such as aluminum salts are used in vaccines to make the immune system produce antibodies more readily against the target protein. This lowers the vaccine dose needed for immunity.

Wheat germ agglutinin (WGA) is a wheat lectin. (It is not part of gluten.) WGA can act as an adjuvant, causing the body to generate antibodies against proteins that, in isolation, the body would not form antibodies against. 

For instance, antibodies against the egg protein ovalbumin are not generated if it enters the body alone, but are generated if it is accompanied by WGA. [1]

So don’t eat toast with your eggs! If you have a leaky gut, the wheat might give you an egg allergy.

Haptenization Activity of Wheat Gliadin

A similar process that helps create auto-antibodies is “haptenization.” The immune system forms antibodies more readily against large molecules than small ones. (This helps avoid autoimmunity, since small molecules are more likely to have similar human peers.)

When two small molecules bind together, so they look like one big one, the immune system is more likely to form antibodies against the large complex. These antibodies may then react against one of the molecules individually, even if it is not paired up. If the targeted molecule is human, then the antibody is an auto-antibody.

One reason wheat gliadin is so disruptive to the body is that it binds strongly to sugars. The average molecule of wheat gliadin is bound to 1 to 2 molecules of glucose and 2 molecules of sialic acid, another sugar. [2] Since a lot of human molecules have sialic acid residues, gliadin can bind to them.

One of the sialic acid-containing molecules gliadin binds to is called GM1 ganglioside. This molecule is found on the intestinal brush border, but it is also found in nerves. When wheat binds to GM1 ganglioside on the intestinal surface, it induces the formation of auto-antibodies that attack the ganglioside in nerves. In 65% of patients with gluten sensitivity and peripheral nerve damage, anti-ganglioside antibodies are found. [2]

Conclusion

Wheat could be a concealed cause of many food allergies, through WGA’s adjuvant activity. If so, then many food allergies may gradually disappear after wheat is given up.

Wheat proteins can also bind to an extraordinarily large number of human proteins, in part by binding to sialic acid or other carbohydrate residues of glycoproteins or glycolipids, and has a chance to induce antibody formation against many of those proteins.

The bewildering array of ways in which wheat can trigger attacks on human tissue makes it impossible to identify all the wheat-caused diseases.  The only thing we can say for sure is that if you have a disease, it’s a good idea to give up wheat. You may give up your illness at the same time.

Related Posts

Other posts in this series:

  1. Wheat Is A Cause of Many Diseases, I: Leaky Gut Oct 26, 2010.
  2. Why Wheat Is A Concealed Cause of Many Diseases, II: Auto-Antibody Generation Oct 28, 2010.

References

[1] Lavelle EC et al. The identification of plant lectins with mucosal adjuvant activity. Immunology. 2001 Jan;102(1):77-86. http://pmid.us/11168640

[2] Alaedini A, Latov N. Transglutaminase-independent binding of gliadin to intestinal brush border membrane and GM1 ganglioside. J Neuroimmunol. 2006 Aug;177(1-2):167-72.  http://pmid.us/16766047.

Why Wheat Is A Concealed Cause of Many Diseases, II: Auto-Antibody Generation

Posted by on October 28, 2010 22 comments

This week we’re examining why wheat is the most dangerous food, and focusing on its role in causing autoimmune diseases. In Tuesday’s post, we talked about how wheat induces a leaky gut; today, we’ll look at how wheat generates auto-antibodies that attack self tissue.

Known Wheat-Derived Auto-Antibodies

In the book we talk about the role of gluten in creating auto-antibodies that attack tissue transglutaminase (tTg), a human enzyme that is abundant in the thyroid and gut. This leads to Hashimoto’s thyroiditis and celiac disease.

However, wheat can generate auto-antibodies to other human molecules besides tTg. These include:

  • Collagens I, III, V, and VI. tTG catalyzes the cross linking of gliadin peptides with interstitial collagen types I, III, and VI, leading to formation of antibodies against collagen. Celiac disease patients have been found to have circulating auto-antibodies to collagens I, III, V, and VI. [1]
  • Synapsin I. Synapsins are a family of proteins regulating neurotransmitter release at synapses. By forming antibodies against wheat gliadin in animals, and then immunoprecipitating human proteins with these antibodies, investigators found that antibodies to wheat gliadin bind strongly to synapsin I. Anti-wheat antibodies from celiac disease patients bind to human synapsin I. [2]

Other known targets of wheat-generated auto-antibodies include gangliosides, actin, calreticulin and desmin. [3,4]

More Wheat-Derived Auto-Antibodies Still to be Found

Scientists may have only begun to identify the human proteins that wheat can generate antibodies against.

For instance, auto-antibodies taken from the blood of celiac disease patients bind to an unidentified 55 kiloDalton protein expressed on the nuclear membrane of intestinal cells, endothelial cells and fibroblasts. [5] That nuclear protein remains unidentified today.

Effects of Wheat-Derived Auto-Antibodies

These various wheat-derived auto-antibodies can trigger attacks against a wide range of tissues. Blood vessels are a frequent target. In our book we note that heart transplants are generally precipitated by wheat-derived autoimmune attacks on the heart. [6]

Nerves are another. Wheat-derived antibodies against neuronal tissue, probably targeting synapsin, can produce “neurologic complications such as neuropathy, ataxia, seizures, and neurobehavioral changes.” [2]

Neurologic deficits, including axonal neuropathy and cerebellar ataxia, are among the most common extraintestinal symptoms associated with celiac disease. In addition, elevated levels of anti-gliadin Ab have been associated with idiopathic neuropathy and ataxia, even in the apparent absence of the characteristic mucosal pathology. [2]

I’ve bolded that last part because it shows that you can have neurological damage from wheat even if your intestine is doing fine.

Neuronal synapsin has been reported to be reduced in bipolar disorder and schizophrenia. [7] Both diseases have been tied to wheat consumption. It’s possible that wheat-derived autoimmune attacks on synapsin may be a causal factor in both diseases.

The ability of wheat to induce peculiar autoimmune reactions is perhaps best illustrated in schizophrenia. Schizophrenics frequently have antibodies to wheat, but not the ones that occur in celiac disease:

In contrast to celiac disease patients, an association between the anti-gliadin immune response and anti-TG2 antibody or HLA-DQ2 and -DQ8 markers was not found in individuals with schizophrenia. In addition, the majority of individuals with schizophrenia and anti-gliadin antibody did not exhibit antibody reactivity to deamidated gliadin peptides. Further characterization of the antibody specificity revealed preferential reactivity towards different gluten proteins in the schizophrenia and celiac disease groups. These findings indicate that the anti-gliadin immune response in schizophrenia has a different antigenic specificity from that in celiac disease and is independent of the action of transglutaminase enzyme and HLA-DQ2/DQ8. [8]

There are multiple mechanisms by which wheat consumption contributes to schizophrenia and other mental illnesses – we mentioned opioid peptides last week – and elimination of wheat should be a first step in treating schizophrenia, bipolar disorder, and other mental illnesses.

Conclusion

Wheat is a toxic food which can trigger auto-antibodies against a variety of tissues, precipitating a diverse array of autoimmune conditions. Many of these autoimmune conditions have not yet been characterized.

Other grains and legumes can induce autoimmune damage in similar fashion. In a comment today, John Wilson noted that he had recurring mouth sores until he gave up peanuts, which cured the problem. Peanuts are a legume and, much like wheat, contain a variety of immunogenic toxins.

If you have an odd, unexplained medical condition, try Step Two of our book – removing toxic foods from the diet. Removing immunogenic toxins will cure many pathologies, and make it easier to diagnose whatever is left over.

Related Posts

Other posts in this series:

  1. Wheat Is A Cause of Many Diseases, I: Leaky Gut Oct 26, 2010.
  2. Why Wheat Is A Concealed Cause of Many Diseases, III: Adjuvant Activity Nov 01, 2010.

References

[1] Dieterich W et al. Cross linking to tissue transglutaminase and collagen favours gliadin toxicity in coeliac disease. Gut. 2006 Apr;55(4):478-84. http://pmid.us/16188922.

[2] Alaedini A et al. Immune cross-reactivity in celiac disease: anti-gliadin antibodies bind to neuronal synapsin I. J Immunol. 2007 May 15;178(10):6590-5. http://pmid.us/17475890.

[3] Alaedini A, Green PH. Autoantibodies in celiac disease. Autoimmunity. 2008 Feb;41(1):19-26. http://pmid.us/18176861.

[4] Shaoul R, Lerner A.  Associated autoantibodies in celiac disease. Autoimmun Rev. 2007 Sep;6(8):559-65. http://pmid.us/17854749.

[5] Natter S et al. IgA cross-reactivity between a nuclear autoantigen and wheat proteins suggests molecular mimicry as a possible pathomechanism in celiac disease. Eur J Immunol. 2001 Mar;31(3):918-28. http://pmid.us/11241297.

[6] Sategna-Guidetti C et al. Binding by serum IgA antibodies from patients with coeliac disease to monkey heart tissue. Scand J Gastroenterol. 2004 Jun;39(6):540-3. http://pmid.us/15223677.

[7] Vawter MP et al. Reduction of synapsin in the hippocampus of patients with bipolar disorder and schizophrenia. Mol Psychiatry. 2002;7(6):571-8. http://pmid.us/12140780.

[8] Samaroo D et al. Novel immune response to gluten in individuals with schizophrenia. Schizophr Res. 2010 May;118(1-3):248-55. http://pmid.us/19748229.

Wheat Is A Cause of Many Diseases, I: Leaky Gut

Posted by on October 26, 2010 81 comments

I realized last week that I often call wheat the most toxic food, but I haven’t really explained why on the blog. The book has a detailed explanation, which focuses on toxicity effects and on autoimmune processes attacking the gut and thyroid. Here I would like to add to the book’s argument by showing how wheat causes other autoimmune diseases.

There are about 50 diseases which are thought to have an autoimmune basis. Autoimmune diseases are caused by three processes:

  1. Leaky gut and inflammation. A leaky gut lets bacteria and food toxins enter the body. In the body, these precipitate an immune response which creates inflammation and a chance for antibodies to form.
  2.  “Molecular mimicry.” A bacterial protein or food toxin resembles a human protein sufficiently closely that an antibody to the foreign protein may also recognize human proteins, potentially precipitating attacks on self tissue.
  3. Adjuvant activity. Vaccines are produced by bonding an antigen (the target of the hoped-for antibody) to an adjuvant (a molecule that greatly increases the likelihood antibodies will be made – a sort of catalyst). If a “molecular mimic” can bind to an adjuvant, then autoimmune disease becomes much more likely.

Wheat causes many autoimmune diseases because it promotes all three aspects. I’ll look at each aspect in a separate post this week.

Leaky Gut

In a recent comment – it’s nice to have smart readers! – Rich brought up the links between wheat and leaky gut.

Leaky gut is the first step toward autoimmune disease. As a recent review states:

Susceptibility to at least 50 diseases, including celiac disease (CD) and type 1 diabetes (T1D), has been associated with specific HLA class I or class II alleles. A common denominator of these diseases is the presence of several preexisting conditions that lead to an autoimmune process…. In all cases, increased permeability precedes disease and causes an abnormality in antigen delivery that triggers immune events, eventually leading to a multiorgan process and autoimmunity. [1]

Gluten is a complex of proteins found in wheat, rye, oats (PAJ: see comments), barley, and other grains. One part of gluten is a type of protein called prolamins, which are chiefly responsible for gut damage:

It is the gliadin fraction of wheat gluten and similar alcohol-soluble proteins in other grains (collectively known as prolamins) that are associated with the development of intestinal damage. A common feature of the prolamins of wheat, rye, and barley is a high content of glutamine (>30%) and proline (>15%), whereas the nontoxic prolamins of rice and corn have lower glutamine and proline content. [1]

I’m quoting this because it speaks to the differences among grains. Rice and corn do not contain gluten. Corn contains other dangerous toxins, but is not a primary cause of autoimmune disease. Rice is the only grain we consider safe to eat.

From Cholera to the Cause of Leaky Gut

The mechanisms by which wheat causes leaky gut have been intensively studied by Dr. Alessio Fasano’s group. In 1995 Dr. Fasano and colleagues discovered that a toxin released by Vibrio cholerae, the bacterium that causes cholera http://en.wikipedia.org/wiki/Cholera, causes tight junctions to open for a time. [2] This makes the small intestine leaky.

Dr. Fasano and colleagues suspected that the bacterial protein’s action must mimic some natural human protein which controls intestinal permeability. In 2000, they discovered this human protein and named it “zonulin.” [3]

Wheat and Crohn’s Disease

They subsequently showed that gliadin stimulates zonulin release. Gliadin binds to a receptor called CXCR3, and activation of this receptor triggers zonulin release and increased intestinal permeability.

Interestingly, zonulin release was much higher and longer-lasting in Crohn’s disease patients than in healthy patients. [1] Restriction of gluten restores intestinal integrity in Crohn’s disease patients.

So Crohn’s disease patients should absolutely not eat wheat!

Leaky Gut and Type I Diabetes

A leaky small intestine is a feature of many autoimmune diseases, but Crohn’s disease and Type I diabetes are notable for highly permeable small intestines. Patients with both diseases have high serum levels of zonulin. [1]

In a rat model of Type I diabetes, the BioBreeding diabetes prone or “BBDP” line of rats often develops a leaky gut at age 50 to 75 days when eating a (toxic) diet of rat chow. Zonulin levels increase up to 35-fold at this time, but were reduced if the rats were fed a gluten-free diet. Rats with the highest zonulin levels developed Type I diabetes develops 15 to 25 days later. If a compound that blocks the action of zonulin is given to the rats, Type I diabetes incidence is reduced 70%. [1, 4]

This shows how crucial a leaky gut is to onset of autoimmune diseases like Type I diabetes, and also how quickly diseases can develop once the gut is compromised. The longer the gut is leaky, the greater the likelihood that some autoimmune disease will develop.

In humans, the relationships between these diseases are much the same as in rats. Crohn’s disease and Type I diabetes are co-morbid: the prevalence of Crohn’s among Type I diabetics is 6- to 9-fold higher than in the general population. Meanwhile, newborn children exposed to wheat at 3 months of age or earlier, when the gut is immature, are 4- to 5-fold more likely to develop Type I diabetes. [4]

Conclusion

Leaky gut is a prerequisite for development of autoimmune disease. Wheat seems to create a transient, mild leaky gut in nearly everyone, but in Crohn’s disease the gut becomes chronically and severely leaky in response to wheat consumption.

In rats, this leaky gut can lead to development of autoimmune diseases like Type I diabetes in as little as a few weeks.

If you eat wheat, it’s probably only a matter of time before you develop some disease or other. All of the autoimmune diseases, from rheumatoid arthritis to Hashimoto’s to lupus, are made more likely by wheat consumption. Why not switch to rice or other “safe starches” and save yourself some trouble?

Related Posts

Other posts in this series:

  1. Why Wheat Is A Concealed Cause of Many Diseases, II: Auto-Antibody Generation. Oct 28, 2010.
  2. Why Wheat Is A Concealed Cause of Many Diseases, III: Adjuvant Activity Nov 1, 2010.

References

[1] Visser J et al. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci. 2009 May;1165:195-205. http://pmid.us/19538307.

[2] Fasano A et al. Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro. J Clin Invest. 1995 Aug;96(2):710-20. http://pmid.us/7635964.

[3] Wang W et al. Human zonulin, a potential modulator of intestinal tight junctions. J Cell Sci. 2000 Dec;113 Pt 24:4435-40. http://pmid.us/11082037.

[4] Watts T et al. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2916-21. http://pmid.us/15710870.