THE BABOON, GLUTEN, GUT PERMEABILITY, AND ZONULIN-GATE
Majid Ali, M.D.
January 18, 2010
At the spring meeting 1992 meeting of the American College of Advancement in Medicine in Dallas, as the program director I had the privilege of hosting Linus Pauling, a two-time winner of the Nobel Prize. I asked him how much vitamin C he took daily.
Author with Linus Pauling
“Eighteen grams,” Dr. Pauling replied.
“Doesn’t it cause loose bowel movements?” I asked.
“What do you have against loose bowel movements?” he asked.
“Nothing. Nothing, really,” I stammered.
“Open bowels are good for health,” he chuckled.
Baboons With Open Bowels
There is a pedigreed colony of baboons with hereditary chronic diarrhea. I do not know if they consider their loose bowel movements a problem. A baboon of that clan might respond to an inquiry about his bowel as Dr. Pauling did: What do you have against loose bowel movements?”
A drug company plans to use the baboons as a primate non-human model of gluten sensitivity and celiac disease. It will drug the baboons to find out the effects of its drugs. Will the baboons consent to this drug experiment? How will their natural bowel rhythms be affected by the drug? Since the bowel ecosystem serves as the roots of the immune defenses of the body, how many baboons will sicken? And in how many ways”? And for how long? Death begins in the colon, the ancients taught. How many baboons will die because their bowel rhythm—including their gut transit time—will be violated?
Gut Permeability and Zonulin Gates
Nature created the blood stream as a remarkable, self-cleansing transit system. It is the primary interface between what the body is and what it is not. The blood has to be protected from contamination by the contents of the bowel. So, evolution knitted the inside lining of the bowel tightly—made it non-leaky, impermeable in the scientific language—so that undigested foods, bugs, and fibers cannot get through. However, absorbing nutrients is a core bowel function. Evolution also created systems of loosening the tight knit—produced bowel “gates” and an “open-close hinge system,” so to speak—that operated at appropriate intervals to make the bowel lining leaky (permeable) to facilitate absorption. One of the many open-close gating systems of the bowel lining involves a protein called zonulin—and the “zonulin-gate” seems an appropriate designation.
Zonulin periodically opens the zonulin-gates to facilitate absorption by loosening the specialized structures that create the tight knit of the bowel lining. When in excess, zonulin over-stretches the tight zones—the gates between the cells get stuck in an open position, so to speak—increasing bowel permeability and allowing the entry of large undigested food particles and microbes in larger numbers. Unless the zonulin spigots are expediently turned off, such loosening of the bowel knit wreaks havoc on the blood. Indeed, this is how many inflammatory and immune disorders begin.
Excess Zonulin In Inflammatory and Immune Disorders
Since zonulin is one part of a large multi-faceted opening-closing system of the bowel lining, one would expect that it would also become dysfunctional when other leakiness (permeability) systems of the bowel lining and bowel vascularity are abnormal. This, indeed, is the case in most, if not all, inflammatory and immune disorders. Indeed, zonulin levels were found to be high in nearly all research studies conducted in inflammatory and immune disorders. Notably, and not unexpectedly, in the context of gluten sensitivity and celiac disease, zonulin levels are high.
Below are brief comments about two drugs that were used to suppress the bowel’s cries for help. Instead, the bowel was silenced. What tormented the bowel was completely ignored. Each story gives an inkling of what to expect from the zonulin-blocking drugs when they become available.
An Anti-Zonulin Drug
Whenever a protein function is abnormal in the body, the pharmaceutical industry is interested in finding a drug to block it. Blocker drugs do offer some benefits in acute illness but cause much harm after chronic use because while they suppress symptoms they do not address the underlying cause. There is intense interest in developing an anti-zonulin drug. It seems probable that the drug will be heavily promoted for many inflammatory and immune disorders, especially for celiac disease and gluten sensitivity. One proposed celiac disease trial will test the safety, tolerance, and efficacy of a drug that blocks the zonulin receptor.
Do Dogs Have Celiac Disease?
I know flatulent dogs. I do not know if they suffer from celiac disease. I suspect that many dogs who are fed the standard American diet develop gluten sensitivity. I foresee a time when dog gastroenterologists will do colonoscopies and dog pathologists will examine the bowel biopsies and issue reports that will read as “shortening and clubbing of villi and inflammatory cell infiltration consistent with but not diagnostic of celiac disease.” This, of course, is how pathologists now report on bowel biopsies done to diagnose celiac disease. They know celiac disease cannot be diagnosed with bowel biopsies, but have to keep gastroenterologists happy. It is not clever to bite the hand that feeds. The diagnosis of celiac disease, of course, is an empty diagnostic label. Later in this article, I outline my reasons for this view with text taken from my three-part essay entitled “Oxygen, Gluten Sensitivity, and Healing” posted on this site.
Here is a proposal: Leave the poor baboons alone. Instead feed dogs peanut butter-jelly sandwiches daily. A good number of them will develop shortening and clubbing of villi and inflammatory cell infiltration in their bowel that will be consistent with—but not diagnostic, of course—of celiac disease. It will be far less expensive and easily approved by the FDA. My proposal need not be derided. Consider this: wheat gluten tainted with melamine imported from China sickened as many as 8,800 pets, including the deaths of up to 2,797 animals, according to recent reports. Wheat gluten and melamine are forbidden in American pet foods. Who knows melamine may also save diarrheal baboons some day.
What Is Celiac Disease?
I began Part One of my three part series entitled “Oxygen, Gluten, and Healing” (see below) about gluten sensitivity and celiac disease with the following summary of my experience with gluten-related clinical problems:
1. The frequency of problems caused by wheat, rye, oats, and barley is increasing among people with chronic health issues.
2. Nearly all my patients with gluten-related symptoms ate bread and other gluten foods freely and without symptoms before they developed gluten sensitivity.
3. Gluten intolerance developed when the bowel became inflamed and “leaky,” leading to entry into the blood of undigested gluten proteins.
4. Gluten-free diet only partially improved health.
5. Gluten-sensitive individuals regained their health only after bowel-liver detox was achieved and other oxygen-related issues—mold allergy, mold toxins, thyroid-adrenal weakness, hormonal imbalance, anger, and deep disappointments that caused the leaky gut state—were addressed.
6. The recovery in some cases with severe stress, mold toxicity, and instability of the autonomic nervous system, and continuing stress was sometimes delayed or incomplete or both.
7. Complete elimination of gluten grains was usually helpful in the short-term but was necessary in the long run only for a small number patients.
The Immune System Planted in the Bowel.
Death begins in the bowel. People dig their graves with their teeth. The deep wisdom of these simple words spoken by the ancients must be duly considered in all deliberations of bowel health. In my monograph Altered States of Bowel Ecology (1980), (see Bowel DVD) I tried to paraphrase the ancient dictum with the following words: Human immune systems are plants rooted in the contents of the bowel. By that time, I estimate that as a hospital pathologist I had examined over 5,000 bowel biopsies and over 1,500 stomach biopsies. I did not think I was taking poetic license. Later, joyfully I read the following words of Dennis Burkitt, the Dutch physician working in Africa, who paraphrased this enduring truth with his famous words:
A society has a choice:
It can keep stools small and build large hospitals.
it can keep its stools large and build small hospital.
Fully recognizing the short-term benefits of drugs for stomach and bowel disorders, my larger point here is: No drugs can ever be considered optimal therapy for these disorders because the disrupted energetic kaleidoscopic mosaics of bowel ecology are far too complex to be restored with drugs that block one or the other of the millions of the faces of this kaleidoscope.
To illustrate this crucial point, below are brief comments about two drugs that were used to suppress the bowel’s cries for help. Instead, the bowel was silenced. What tormented the bowel was completely ignored. Both drugs were withdrawn later. Each story gives an inkling of what to expect from the zonulin-blocking drugs when they become available.
The Zelnorm and Lotronex Stories
Zelnorm is a drug that was claimed to enhance the action of the neurotransmitter serotonin in the intestines—the antidepressants Paxil and Prozac are claimed to increase the action of the serotonin in the brain. Zelnorm was heavily promoted for treating severe, chronic, irritable bowel syndrome (IBS) in women. It was withdrawn from the U.S. market on March 30, 2007 due to serious side effects.
Lotronex is another drug used for irritable bowel syndrome. It blocks receptors for another neurotransmitter called 5-HT3. While helpful for some people on a short-term basis, I have not seen it to be useful over the long haul. That is not unexpected since the drug does not address any of the causes of altered bowel ecology and disruptions of bowel motility.
My microscope and patients have taught me to think ecologically. They have told me that the liver is more intelligent than the brain. And the bowel is more intelligent than the liver. This is the view of a pathologist-turned-molecular biologist who examined more than 14,000 bowel biopsies and more than 5,000 stomach biopsies as a hospital pathologist over a 29-year period. I tell the short story about gluten, celiac disease, zonulin gates, baboons, and zonulin-blocker drugs of the future through the prisms of the bowel and the liver.
Zonulin Gates and Zonulin-gate
Why is zonulin production increased (upregulated) in inflammatory conditions? What comes first, inflammation or excess zonulin production? Does weak digestion in the stomach cause excess zonulin production or it is the cause? What comes first, toxins in the bowel or excess zonulin production? Does overpopulation of fermenting microbes in the small and large bowels cause excess zonulin production or does zonulin feed the fermenters? These should be crucial questions in zonulin interest. However, these questions cut into drug profitability. Drug doctors do not like them.
Drug companies like animal models of disease. They test the drugs on animals who cannot speak in ways that humans can understand. The drugs approved for the voiceless animals are then pushed on people numbed by media ad blizzards. Doctors simply do not have enough ethical energy to fight back. Writing a prescription is so much quicker than educating people. Years later, when the long-term toxicity of drugs become known to people who take them, the drugmakers hire other doctors to deflect the blame—and the responsibility of sickening millions of people worldwide. In a decade or so, I foresee the appearance of a “zolunlin-gate—to continue the great traditions of other great “drug-gates”—Vioxx-gate, Zelnorm-gate, Lotronex-gate, Rezulin-gate (a diabetes drug withdrawn because of liver toxicity), Propulsid-gate (a stomach drug withdrawn in many countries because of cardiac arrhythmias), Baycol0gate (a cholesterol drug withdrawn because of potentially fatal muscle tissue death), and others—in which the health of millions was jeopardized for years for short-term benefits of a few, and enormous enrichment of drug makers.
Will the anti-zonulin drugs be beneficial for some acutely ill individuals? Probably. Will they be a true long-term answer to the problems of gluten sensitivity and celiac disease? Categorically not. Why? Because the drugs will not address any of the elements that cause overproduction of zonulin in the first place. It will be a repeat of the story of the incremental use of blocker drugs for high blood pressure (BP)—nearly all patients who regularly take one drug for BP need two, three, or more years later—because BP drugs do not address problems of toxic foods, toxic environment, and toxic thoughts. This is true of drugs that block acid production in the stomach and those that suppress the immune system. There are limited short-term benefits and enormous long-term adverse effects. That such will be the case with zonulin blocker drugs is safe to predict. Drugmakers will continue to enrich themselves as long as they throw crumbs at the writers and editors of The New Enron Journal of Medicine. All blocker drugs will sell well—and sell big. Long live The New Enron Journal of Medicine