What If Gluten Isn’t the Culprit?

In many older detective stories, the punch line famously is, "the butler did it." In the minds of many contemporary Americans, gluten is the "butler." Increasingly, when individuals experience symptoms such as fatigue, headaches and gastrointestinal distress, including gas, bloating and diarrhea, gluten is called out as the culprit. The passage of partially digested or undigested gluten through the intestines and the gut barrier may also contribute to additional symptoms not limited to those involving the development of food sensitivities and intolerances. The answer in this paradigm is to avoid all gluten-containing foods, such as wheat, oats, rye, barley and spelt. The problem with this paradigm is that other than for a quite small percentage of the populace, there is little evidence that gluten per se is the culprit or that gluten avoidance will solve all or even most gluten-associated issues. This topic often leads to heated debates. Readers should be aware that the gluten-as-villain story has quite serious skeptics.^1,2

Who Reacts to Gluten?
Gluten, a protein, is a large, complex molecule that contains thousands of folded amino acid sequences composed of globulans, albumins, glutenin and gliadin, with the gliadin fraction believed to cause most of the symptoms associated with gluten sensitivity. Gluten's exceptionally rich proline content contributes to resistance to digestion. When this big ball of peptides is insufficiently broken down, amino acid bonds within each molecule remain resulting in a partially-degraded protein that can lead to an array of symptoms. Some authorities suggest that if gluten is a sufficiently rich component of the diet (a rare situation), it will lead to reactions even in those otherwise tolerant as a result of these difficulties in digestion.

There is a spectrum of gluten-related disorders, including celiac disease, gluten sensitivity, and wheat allergy, the latter affecting only on the order of 0.1 percent of individuals in Westernized countries.^3,4 Non-celiac gluten intolerance involves heightened immunologic reaction to gluten in genetically susceptible people whereas celiac disease involves a complex autoimmune response in the small intestine to gluten ingestion.^5,6 The estimated prevalence of celiac disease is approximately one percent of the populace.⁷

This is where things start to become very interesting in ways that suggest that the "gluten did it" scenario may be a bit misleading. As summarized in a fine article a few years back in the New York Times, "roughly 30 percent of people with European ancestry carry predisposing genes, for example. Yet more than 95 percent of the carriers tolerate gluten just fine. So while these genes (plus gluten) are necessary to produce the disease, they're evidently insufficient to cause it."⁸

This observation becomes more intriguing in light of recent blood serum studies. In one, an examination of 9,133 frozen blood samples taken from US Air Force recruits between 1948 and 1954 for the antibody that people with celiac disease produce in reaction to gluten found that only about one in seven hundred tested positive, or 0.2 percent. This was compared to rates of celiac disease among 12,768 people who either had similar years of birth (i.e. were born around 1930) or who were of a similar age to the original donors at the time of sampling (i.e. young adults today). The rates of celiac disease were 0.8 percent and 0.9 percent respectively, or a 4 to 4.5-fold increase. In other words, in populations that genetically were virtually identical, celiac rates had increased more than 400 percent in a mere 50 years.⁹ Another study that analyzed blood serum from more than 3,500 Americans who had been followed since 1974 found that by 1989 the prevalence of celiac disease in this cohort had doubled.¹⁰

More recent studies have confirmed the rising risk of developing celiac among otherwise similar groups in the past. So have cross-national comparative studies. The populations in adjacent Russian Karelia and Finland are equally exposed to grain products and share partly the same ancestry, but live in completely different socioeconomic environments. The two study populations are culturally, linguistically and genetically related with predisposing gene variants are similarly prevalent in both groups. Examination of 5,500 subjects yielded a prevalence of roughly one in 100 among Finnish children whereas the same diagnostic methods indicated only one in 500 among their Russian counterparts.¹¹

More Intrigue
In line with a number of studies looking at the prevalence of asthma and other forms of autoimmune disease, the Finnish/ Russian data suggest modern sanitary and dietary practices are leading to poorer health in unexpected ways. For instance, three of four Russian Karelian children harbored Helicobacter pylori in comparison with one in 20 Finnish children. H. pylori can cause ulcers and stomach cancer, but mounting evidence suggests that exposure also reduces the incidence of asthma. The author of the New York Times article mentioned above notes that one author of the Finnish study suspects that Russian Karelians' microbial wealth (exposure to a much larger variety of microbes compared to more Westernized and metropolitan populations) protects them from autoimmune and allergic diseases by strengthening the arm of the immune system that guards against such illnesses. Similarly, Yolanda Sanz, a researcher at the Institute of Agrochemistry and Food Technology in Valencia, Spain, makes a compelling case for the importance of intestinal microbes. "Years ago, Dr. Sanz noted that a group of bacteria native to the intestine known as bifidobacteria were relatively depleted in children with celiac disease compared with healthy controls. Other microbes, including native E. coli strains, were overly abundant and oddly virulent."

Quite a number of authors have noted a possible role for longer breast-feeding of infants in helping to confirm bifidobacteria in a more dominant role in the large intestine in children and later life as well as controlling E. coli growth. Other changes in Western practices similarly may influence the role of foodstuffs. For example, a study published in 2011 found that a specially fermented wheat flour-derived product did not lead to any sort of toxic reaction after being given to celiac patients for 60 days. This is in line with research indicating that the manufacture of wheat and rye breads or pasta with durum flours by using selected sourdough lactobacilli markedly decreases the toxicity of gluten. In Western countries, cereal baked goods typically are manufactured by fast processes. As noted by researchers, this avoids the traditional long fermentation by sourdough—a cocktail of acidifying and proteolytic lactic acid bacteria—and has replaced fermentation with chemical and baker's yeast leavening agents. Under these conditions, cereal components are not degraded during manufacture.¹²

Again, a number of researchers have uncovered evidence that keeping bifidobacteria and lactobacilli at sufficiently high levels in the appropriate areas of the intestines strongly influences tendencies toward autoimmune diseases.

Other Contributors to the Modern Gluten Intolerance

Gluten has been in the human food chain for thousands of years, yet gluten intolerance has become widespread in recent decades. Along with some items already mentioned, here is an extended list of possible culprits:

• Changes in baking techniques; to speed processing and reduce costs, modern breads almost never are fully yeast-raised as in the past, a process that makes gluten more digestible; similarly, the long steaming of wheat and rye breads typical of Central and Eastern Europe makes breads more digestible
• Changes in the gluten content of wheat—since the 1950s the USDA, without public notice, has been involved in wheat breeding to increase gluten content
• Novel processing techniques when using gluten-derived compounds in foodstuffs, such as deamidation involving removing an amino group (NH2); this makes the peptides more soluble and smaller, but also increases their chances of breaching the gut lumen and activating immune responses
• Changes in refrigeration and storage, which, in turn, change our gut bacteria and lead to novel intolerance reactions to foods
• Reduced breast-feeding and altered feeding and weaning practices; changes in infant formulas; suspected changes in mother's milk itself at the populace at large becomes more prone to overweight and obesity plus the foods consumed by mothers change
• C-sections becoming more common, which tends to alter the bacteria babies inherit (or do not inherit) from the mother via the birth canal
• Reduced exposure to various dusts and other challenges from the natural world that help train the developing immune system and reduce autoimmune overreactions
• GMOs and the chemicals linked to these are ubiquitous in the food supply

Although, as indicated above, heightened sensitivity to gluten extends back several decades, GMOs may be true game-changers for future generations. According to Jeffrey Smith and the Institute for Responsible Technology (IRT), a "possible environmental trigger [for gluten intolerance] may be the introduction of genetically modified organisms (GMOs) to the American food supply, which occurred in the mid-1990s," describing the nine GM crops currently on the market. In soy, corn, cotton (oil), canola (oil), sugar from sugar beets, zucchini, yellow squash, Hawaiian papaya, and alfalfa, "Bt-toxin, glyphosate, and other components of GMOs, are linked to five conditions that may either initiate or exacerbate gluten-related disorders." It's the Bt-toxin in genetically modified foods that kills insects by "puncturing holes in their cells." The toxin is present in ‘every kernel' of Bt-corn and survives human digestion, with a 2012 study confirming that it punctures holes in human cells as well.

According to an IRT report, GMO-related damage is linked to five different areas: intestinal permeability, imbalanced gut bacteria, immune activation and allergic response, impaired digestion, and damage to the intestinal wall. The IRT release also indicated that glyphosate, a weed killer sold under the brand name 'Roundup,' was found to have a negative effect on intestinal bacteria. GMO crops contain high levels of this toxin at harvest. "Even with minimal exposure, glyphosate can significantly reduce the population of beneficial gut bacteria and promote the overgrowth of harmful strains."^13,14

Sometimes the Villains Aren't Bad Guys and How To Promote the Good Guys
A word of caution is in order regarding gut bacteria. Just as gluten may not be the primary actor in its own drama, so, too, are some "bad" bacteria not so bad after all. Above, the case of H. pylori was presented as perhaps not quite as black-and-white as normally argued. Another example is E. coli. Which E. coli? Recent research has uncovered that small molecules produced by the microbiota and related to indole extend healthspan in geriatric worms, flies, and mice.¹⁵ According to the authors of this research, the term "healthspan" describes the length of time a human or animal, while aging, can stay active and resist stress. In this research, the focus is on whether the animals live healthier, but not necessarily longer. The study identified indole and related molecules as compounds released by E. coli bacteria. Indoles may be keeping the intestinal barrier intact and/or limiting systemic inflammatory effects. Moreover, there are specialty E. coli strains that are well-researched as excellent probiotics useful in treating a number of gastro-intestinal disorders and even helping to maintain remission in patients with ulcerative colitis.^16,17 The trick is to encourage the presence of the right E. coli to limit the growth of the wrong E. coli.

What about daily foods that boost good gut microbiome, including diversity in the gut? It is important to be able to promote gut health via daily food habits rather than relying on prebiotic supplements alone. Here are some everyday choices according to a 2016 survey conducted in Europe:¹⁸

Good foods for boosting the gut microbiome

• Fruit and vegetables
• Yogurt
• Coffee
• Tea
• Red wine

Bad habits that hurt the microbial ecosystem

• A high-calorie diet
• A high-carbohydrate diet
• Sugar-sweetened beverages
• Frequent snacks

Medications have the biggest influence on gut microbiome diversity. Antibiotics, proton-pump inhibitors and metformin (a common diabetes drug) all are linked to lower microbiome diversity.

Conclusion
Blaming gluten for GI-tract issues, allergies and even weight gain is akin to the pharmaceutical world's "magic bullet" approach once encapsulated as "one disease, one drug." In reality, in the modern Western world a host of changes have taken place in food growing and processing along with changes in personal habits and some of these changes have led to an otherwise and previously relatively innocuous protein, gluten, becoming a source of health issues. Eliminating gluten from the diet (along with wheat, oats, rye, barley and spelt) is not the answer to environmental mistakes, such as the growing prevalence of poor bread-making practices and the use of GMOs. A better approach is to learn the nature of the non-health- promoting practices and then to find alternatives.

References:

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2. Shewry PR, Hey SJ. Do we need to worry about eating wheat? Nutr Bull. 2016 Mar;41(1):6–13.
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4. Sapone A, Bai JC, Ciacci C, et al. Spectrum of gluten-related disorders: Consensus on new nomenclature and classification. BMC Med. 2012; 10:13.
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8. Moises Velasquez-Manoff. Who Has the Guts for Gluten? New York Times. February 23, 2013.
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11. Catassi C, Kryszak D, Bhatti B, Sturgeon C, Helzlsouer K, Clipp SL, Gelfond D, Puppa E, Sferruzza A, Fasano A. Natural history of celiac disease autoimmunity in a USA cohort followed since 1974. Ann Med. 2010 Oct;42(7):530–8.
12. Kondrashova A, Mustalahti K, Kaukinen K, Viskari H, Volodicheva V, Haapala AM, Ilonen J, Knip M, Mäki M, Hyöty H; Epivir Study Group. Lower economic status and inferior hygienic environment may protect against celiac disease. Ann Med. 2008;40(3):223–31.
13. Francavilla R, De Angelis M, Rizzello CG, Cavallo N, Dal Bello F, Gobbetti M. Selected Probiotic Lactobacilli Have the Capacity To Hydrolyze Gluten Peptides during Simulated Gastrointestinal Digestion. Appl Environ Microbiol. 2017 Jun 30;83(14).
14. GMOs linked to gluten disorders plaguing 18 million Americans https://www.rt.com/usa/gmo-gluten-sensitivitytrigger-343/
15. Are Genetically Modified Foods a Gut-Wrenching Combination? http://responsibletechnology.org/glutenintroduction/
16. "Chemicals from gut bacteria maintain vitality in aging animals: Indoles help worms/flies/mice live stronger for longer." ScienceDaily. ScienceDaily, 21 August 2017. www.sciencedaily.com/releases/2017/08/170821151052.htm.
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18. Zhernakova A, Kurilshikov A, Bonder MJ, Tigchelaar EF, Schirmer M, Vatanen T, Mujagic Z, Vila AV, Falony G, Vieira-Silva S, Wang J, Imhann F, Brandsma E, Jankipersadsing SA, Joossens M, Cenit MC, Deelen P, Swertz MA; LifeLines cohort study, Weersma RK, Feskens EJ, Netea MG, Gevers D, Jonkers D, Franke L, Aulchenko YS, Huttenhower C, Raes J, Hofker MH, Xavier RJ, Wijmenga C, Fu J. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. - Science. 2016 Apr 29;352(6285):565–9.

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