Celiac.com 09/16/2022 - What’s for dinner? Somewhere between soccer practice, business meetings, hobbies, dentist appointments and time for family and friends, that question is always in the background.

People often ask me for quick dinner ideas. In the real world, not every meal––or even week of meals––can be gourmet. Hectic lifestyles warrant easy, affordable meals that are kid-friendly and satisfying for adults.

Everyone’s lifestyles and dietary needs are a little different. Some of the quick meal ideas below start with seasoned or pre-made items. Many people may enjoy this technique while others would prefer to add all the seasonings themselves and start from scratch at each meal.

Whatever your preference, you can add any of these ideas to your meal-making repertoire either as they are shown, or by making your own personal adjustments. Brand names given were gluten-free at the time of writing this article. However, it is always necessary to verify before enjoying.

Order a Meal to Take Home

When dining out at a restaurant, order an extra gluten-free dish to take home to enjoy the next evening. I frequently enjoy this option locally at P.F. Changs Thai Restaurant, Outback Steakhouse and Boston Market. Many of their dishes travel well and are equally as good on the second day. This second meal is not to be considered leftovers. Pitch the take-home box and serve it on dinner plates.

Shop the Grocery Deli

Pick up a gluten-free pre-made rotisserie chicken or two, a pre-washed bag of salad greens, bag of baking potatoes, shredded Mozzarella cheese and pears. Once home, add raisins, pine nuts and mandarin oranges to the salad. Sprinkle Mozzarella cheese on top. Combine the Mandarin orange juice with mayonnaise for a tasty dressing. Bake the potato in the microwave until done. Add toppings of your choice. For dessert, wash and cut the pear in half. Remove the stem and seeds. Top with Mozzarella cheese and warm the pear in the microwave until the cheese melts.

Use a Store Bought Dinner Mix

Thai Kitchen and other brand names offer meal mixes that need very few additional ingredients for a complete meal. You can expand the number of servings for their Pad Thai seasoned noodle mix by adding more of your favorite vegetables to the dish, 1⁄2 teaspoon of their red curry and a can of low fat coconut milk. For a refreshing dessert, a simple scoop of gluten-free lemon sorbet is very satisfying.

Enhance a Premade Item

Amy’s Gluten-free frozen Cheese Pizza provides the base for a quick meal. Bake the pizza for 5 minutes as directed on the package. Top with stewed tomatoes or gluten-free pizza sauce, add gluten-free pepperoni, a layer of onions, chopped bell peppers, chicken from a can or left over rotisserie chicken from a previous meal and top with a layer of Mexican Cheese Mixture and Mozzarella. Bake for an additional 15 minutes. Serve applesauce on the side. Of course leftover pizza makes great snacks and lunches.

Have Fun with Finger Food

Make a Tuna Spread with a can of drained gluten-free tuna or seasoned tuna from a pouch, a half-cup of gluten-free mayonnaise, and a dab of pickle relish, salt and pepper. Serve with crackers and cheese and sliced Boars Head or Hormel luncheon meats. Add a plate of cut vegetables (can be purchased precut from the store) and a tray of beautiful fruit. Gluten-free cottage cheese or a fruit yogurt are an easy dip. For an even hungrier crowd, make Chebe Bread Mix into Pigs in the Blanket with Hillshire Sausages and enjoy a fun finger food dinner with a movie. For dessert, serve apple slices with melted gluten-free chocolate.

Prepare a Pasta Dish

One of the fastest meals is a pasta dish. This recipe for Sarah’s Cheese Lasagna may be changed by using different types of pasta. Serve it in a stylish dish.

• Boil gluten-free lasagna noodles until tender then drain and rinse with warm water
• Slice mozzarella cheese into thick slices
• Open a jar of your favorite gluten-free spaghetti sauce
• Find a pretty baking dish that is suitable for the microwave
• Layer lasagna in the dish as follows: Sauce, noodles, ricotta cheese, mozzarella, sauce, noodles, ricotta cheese, and mozzarella. Top with a layer of noodles and sauce. Cover entirely with mozzarella and parmesan cheese. Microwave on high for 5-7 minutes until the cheese has melted.
• Vary the recipe by including walnuts and a can of spinach. Or while the noodles are boiling, you can fry a pound of ground turkey with a few diced vegetables and onions to add to the lasagna. This dish also makes great leftovers.

Keep it Simple with Salad and Poached Fish Seafood Salad and Apple Rings for Dessert

• Open a package of pre-washed Spring Salad Mix.
• Add sliced almonds, sesame seeds, sunflower or pumpkin seeds to the salad
• Pour 2 cups of gluten-free chicken broth in a fry pan and add 2 teaspoons of berry jelly to the broth. Turn on to medium heat and stir together.
• If desired, add strips of green, yellow and red pepper to the broth.
• Add your choice of cod, monkfish or tilapia fillets and simmer (poach) until the fish turns opaque and flakes, about 7 minutes. Remove from the broth, salt and pepper the fish and serve on top of the salad greens. Be careful of any bones.
• Top with a gluten-free dressing like Annie’s Naturals Low Fat Raspberry Vinaigrette or make your own Ginger Dressing by combining 1 1⁄2 Tablespoon of freshly chopped ginger, 3 Tablespoons of gluten-free soy sauce, 3 Tablespoons of mirin, 1 teaspoon of sugar and 2 teaspoons of rice wine vinegar
• Dessert: Cut a tart apple horizontally into 1⁄2 inch rounds. Remove the core. Baste with butter and sprinkle with brown sugar and then with cinnamon (or ginger). Top with chopped nuts if desired. Placed rings on a lined cookie sheet and broil until soft, about 8 minutes.

Broiling is Fast

• Steak Rolls with Vegetables and Wild Rice. Pistachio Peaches for Dessert.
• Slice 1 pound of flank steak across the grain into 16 strips. They should be less than 1⁄2 inch thick. Pound each strip to 1/8 inch thick and season with salt and pepper
• Place slices of bell pepper and Portobello mushrooms (or any of your favorite vegetables––well, corn probably wouldn’t work) across the short end of a strip of pounded flank steak. Roll the steak around the vegetables and secure with a toothpick. Place on a lined baking pan in a single layer.
• Marinate for 10 minutes using your favorite gluten-free salsa, Lea & Perrins Steak Sauce or your favorite vinegar dressing. Or prepare a marinate of 6 Tablespoons of seasoned rice vinegar, 6 Tablespoons of gluten-free soy sauce, 4 teaspoons of brown sugar and 1 Tablespoon of toasted sesame oil.
• Broil steaks for 5 minutes 10 inches from the broiler. A grill would also work, but be careful of the toothpicks (if you soak the toothpicks prior to using, they will not burn).
• Serve steaks with gluten-free barbeque sauce or Lea & Perrins Steak Sauce and pre-prepared wild rice by Fall River. Simply open the package of rice and reheat. Add as many toasted pecans and sliced grapes as you desire. Or make the rice into small patties by combining 1 cup of the cooked rice with 1⁄4 cup chopped pecans, 1 Tablespoon of cornstarch and 2 eggs. Mix all ingredients together and fry on medium heat for about 3 minutes on each side.
• For dessert, open a can of sliced peaches. Put in a medium size pot on the stove and add 1/3 cup of low fat cream cheese. Cook on low until the cream cheese has melted. Remove from the stove. Pour a package of Pistachio Instant Pudding (or your favorite complimentary pudding) into a clean bowl. Pour the peaches and cream mixture over the pudding. Mix well. Serve warm with a gluten-free cookie or on top of pound cake. Or serve cold by mixing in 1 cup of whipped cream.

Celiac.com 09/10/2022 - Starch––the single word “starch” on a US or Canadian food label is considered the common or usual name for cornstarch. Starches from other sources must be labeled accordingly such as “potato starch”, “tapioca starch” or “wheat starch”. It is very difficult to completely remove all traces of protein during the manufacture of food-grade starch. Wheat starch contains varying amounts of gluten. Some European products labeled “gluten-free” are made from Codex Alimentarius quality wheat starch. North American celiac organizations do not recommend that celiacs consume wheat starch-based products.

Modified Food Starch

There are specific regulations for how food starches can be modified. However, there is no requirement for the identification of the name of the plant sources of the modified food starch on US or Canadian food labels. Corn, tapioca, potato, wheat or other starches can be used by the food industry. Corn is the most common source of North American modified food starch, with potato, tapioca or rice used occasionally. To be 100% certain, it is best to contact the company to determine the source of the modified food starch.

Dextrin

Dextrin is partially hydrolyzed starch by heat alone or by heating in the presence of food-grade acids and buffers. A variety of starches such as corn, milo, potato, arrowroot, rice, tapioca or wheat can be used. In North America, dextrin is almost always derived from corn or tapioca; however, contact the company to confirm the source of dextrin.

Maltodextrin

Corn, waxy maize, potato, rice or wheat can be used in the production of maltodextrin. North American maltodextrin is usually derived from corn or potato; however, wheat is often used in European products, and occasionally in some North American products. The US Code of Federal Regulations for maltodextrin (Sec. 184.1444) state it is derived from corn, potato or rice starch. The FDA also permits the use of other starches including wheat. If wheat is used, it must be labeled “wheat maltodextrin”.

Caramel Color

Caramel color is manufactured by heating carbohydrates, either alone, or in the presence of food-grade acids, alkalis and/or salts, and is produced from fructose, dextrose (glucose), invert sugar, sucrose and/or starch hydrolysates and fractions thereof. Although gluten-containing ingredients [malt syrup (barley) and starch hydrolysates] can be used in the production of caramel color, they are not used according to food processors in North America. Corn is used most often, as it produces a longer shelf life and a much better product.

*Note that food allergen labelling laws passed after this article was written require companies to disclose the top 8 food allergens in the ingredients, including wheat.

Celiac.com 09/03/2022 - Anemia is one of the most common presentations in adults with newly diagnosed celiac disease. In 1996 approximately 3.4 million Americans were diagnosed with anemia, according to the Centers for Disease Control, and out of these 2.1 million were under the age of 45. Celiac disease can present with classic and/or atypical symptoms. Atypical symptoms of celiac disease are associated with malabsorption and can include iron deficiency anemia in both adults and children.

Celiac disease was once thought to be a childhood disease. However the average age at diagnosis today is 40 to 50 years old. It is more commonly seen in women than men. Celiac disease is a disease that can begin in infancy with gastrointestinal symptoms, in childhood, or even late in life. Many persons diagnosed later in life may have no gastrointestinal symptoms. Often, in older adults, routine health checks discover silent celiac disease, because of undefined anemia or bone disease(3).

Anemia can be a symptom of many conditions, including excess blood loss from bleeding or surgery; autoimmune diseases such as celiac disease; chronic infections, or from the use of some medications. There are different types of anemia. Blood studies are used to help determine the type of anemia, its possible cause, and the correct treatment.

Macrocytic anemia is usually caused by a folate or vitamin B12 deficiency. Microcytic anemia is a caused from iron deficiency. Inflammation, either chronic or acute, can alter ferritin levels in persons with iron-deficiency anemia. When inflammation is present, iron levels can appear either normal or elevated in iron deficiency.

Folate deficiency should be considered in persons who have both celiac disease and anemia. Folate is absorbed in the jejunum, the upper part of the small intestine. This is the part of the small intestine that is largely damaged in untreated or undiagnosed celiac disease. Celiac disease is a disease of malabsorption due to inflammation and damage of the microvilli and villi of the small intestine. The microvilli and villi normally increase the absorption capacity of the small intestine by expanding its surface area to nearly 500 times its length. When there is damage to the jejunum and duodenum, the absorption of many nutrients, including iron, is altered. Celiac disease is not often suspected when a person is diagnosed with persistent anemia that does not respond well to traditional therapies, even though iron absorption can be significantly altered by the damage to the intestine.

Studies suggest that persons with celiac disease may present with anemia as a single symptom or one of many symptoms. The incidence of anemia in the patients with newly diagnosed celiac disease ranges from 4% in the United States, to 24% in Romania, and over 66% in East Indian patients. In surveys of members of national celiac support groups in Canada and the U.S., anemia is a common pre-celiac diagnosis. Three recent studies in the United Kingdom screened men and women with anemia for celiac disease and found undiagnosed celiac disease in 2.3 to 6.7 percent of subjects. Another study in the UK screened 1,200 people in the general population and found celiac disease in one percent, a frequency similar to that of the U.S. study.

It is possible to conservatively estimate that 78,000 people with anemia in the US could have celiac disease as the cause of their anemia. Clearly, physicians treating patients with anemia should consider screening them for celiac disease, especially if the anemia is unresponsive to traditional therapy.

Anemias Found in Celiac Disease

Several conditions can contribute to the development of anemia, including blood loss, poor diet, genetic disorders, chronic illnesses, and damage to the bone marrow from radiation or chemotherapy. Gastrointestinal conditions, such as Crohn’s disease or celiac disease, that decrease the absorption of iron, folate, or vitamin B12 can also cause anemia. Iron-deficiency anemia is the most common type of anemia found in women. The most common causes of iron-deficiency anemia are blood loss due to menstruation or pregnancy, and poor absorption of iron from foods(15). Iron deficiency is uncommon in postmenopausal women. If iron-deficiency anemia is discovered in postmenopausal women, it is generally the result of bleeding in the gastrointestinal tract or malabsorption.

Both iron-deficiency anemia and B12 deficiencies are common in celiac disease. Iron-deficiency anemia is the most common type of anemia found with celiac disease. Decreased iron and folate absorption are often seen in untreated celiac disease. Many physicians overlook iron and folate malabsorption as a cause of anemia. As part of the evaluation process for iron-deficiency anemia endoscopic procedures are often performed, generally without taking biopsies of the small intestine. If biopsies are not taken, celiac disease would be overlooked as the causal factor for the anemia.

Anemia generally develops slowly with symptoms worsening over time. Common symptoms of anemia include extreme fatigue, pale skin, weakness, shortness of breath, lightheadedness, and cold hands and feet. Iron-deficiency anemia symptoms may also include with cracks at the sides of the mouth, complaints of inflamed or sore tongue, brittle nails, pica, headaches, decreased appetite, and increased infections. Some people may also experience Restless Leg Syndrome. If not treated, iron-deficiency anemia can lead to other severe health problems, such as heart irregularities; complications with premature and low-birth-weight infants; and delayed growth and development in children. Symptoms of Vitamin B12 deficiency can cause yellowing or darkening of the skin, colorblindness to yellow-blue colors, and confusion or forgetfulness. Signs of vitamin B12 deficiencies such as neurological problems, peripheral neuropathy, mental confusion and forgetfulness can be seen before anemia is diagnosed.

The most likely cause of vitamin B12 deficiency in celiac disease is due to damage in the small intestine, which makes it difficult to adequately absorb B12. Bacterial overgrowth in the small intestine is another possible cause of B12 deficiency. Anemia, as a result of vitamin B12 deficiency is considered to be uncommon in celiac disease that is diagnosed early.

In a small study of 39 patients, Dahele, et al., 16 (41 percent) were found to have vitamin B12 deficiency and 16 were anemic. After four months on a gluten-free diet all patients with B12 deficiency had B12 levels that normalized. Only five patients with combined folate and B12 deficiencies received B12 therapy.

Dickey found in screening celiac patients with low serum vitamin B12 levels that low B12 is common in celiac disease without having pernicious anemia, and may be the only presenting manifestation of celiac disease (14). Studies by Dahele and Dickey suggest that vitamin B12 deficiency is a common condition in untreated celiac disease, however their studies do not support that pernicious anemia is associated with celiac disease. Dahele and Dickey indicate the vitamin B12 deficiency usually resolves on a gluten-free diet, without vitamin B12 replacement.

Treating Anemia in Celiac Disease

The most important issue in anemia as a result of celiac disease is to follow strict gluten-free diet. The small intestine must heal in order to absorb nutrients correctly and adequately. Studies indicate that it can take several months to years to heal the small intestine in persons with celiac disease, and it is imperative that all persons with celiac disease have regular follow-up visits with a dietitian to check the adequacy of their diet.

A gluten-free diet alone has been shown to reverse signs of anemia in most newly diagnosed celiac patients. In otherwise healthy individuals, it takes six to 12 months of diet therapy to correct anemia. Reversing anemia in persons with celiac disease may take several months longer, even with supplementation. Iron replacement therapy may not be necessary in mildly-depleted persons. In these cases a gluten-free diet high in iron-rich foods and a good gluten-free multi-vitamin supplement should be tried for six to 12 months before further therapy options are considered. Persons taking iron supplements should take iron with vitamin C-rich foods, such as citrus juice, which will help increase iron absorption. They should also avoiding calcium and dairy products within an hour of eating iron-rich foods, as calcium binds with iron and neither nutrient is absorbed well. Iron-rich foods including fish, poultry, and red meats should be included at each meal. Use of coffee and tea should be restricted.

Iron supplementation therapy recommendations for persons with celiac disease vary by physician. Recommendations of up to one gram of iron per day, with close monitoring for clinical and blood level improvement are sometimes recommended. In severe situations, blood transfusions are used to boost the patient’s initial iron and hemoglobin levels. As with other medications, all supplements used must be gluten-free.

Foods rich in iron that are naturally gluten-free include: lean red meats, liver, kidney, clams, oysters, shrimp, chicken, haddock, crab, tuna, salmon, turkey, broccoli, parsley, leafy greens, peas, dried beans, lentils, peaches, pears, dates, raisins, dried prunes, and blackstrap molasses. Many of the special seeds and flours used in the gluten-free diet are rich in iron, including amaranth, buckwheat, Montina™, quinoa, and teff. These foods are also high in other nutrients, including calcium, amino acids, magnesium, zinc and fiber. When compared to whole wheat and enriched all-purpose white wheat flours (iron content 4.7 mg and 5.8 mg, respectively), many of the gluten-free flours are nutritionally equal or superior to wheat flour. Amaranth, buckwheat, flax, garfava, millet, Montina™, quinoa, rice bran and soy all have higher iron content than wheat flours. In gluten-free baking, a blend of flours is required for best results.

Many of the flours mentioned above are used as secondary ingredients in the flour blends, in combination with refined starches such as rice flour, potato starch and tapioca or corn starch, all of which are much lower in iron than wheat flour. Using the whole seed or groat of these seeds in cooking can significantly increase the iron content of the gluten-free diet. Many of these products make wonderful side-dishes and starches in casseroles or soups. Teff is used as a staple food in Ethiopia. It is extremely high in iron and it is speculated that it is the extensive use of teff that keeps the incidence of iron-deficiency anemia low in Ethiopia. For persons with celiac disease who are also lactose intolerant or choose to follow a vegetarian diet, inclusion of these seeds helps to assure adequate nutrient intake.

Anemia is common in the general population and even higher in celiac disease. Malabsorption is a common cause of anemia. Persons with anemia are at risk for celiac disease. Patients with anemia from unknown reasons or those who do not respond to traditional treatments require further evaluation which should include screening for celiac disease. If celiac disease is discovered, appropriate treatment with a gluten-free diet that includes foods that are rich in iron is normally all that is necessary to treat anemia in most cases.

The Dietary Reference Index (RDI) for Iron:

• 7 to 10 mg/day for young children
• 8 to 11 mg/day for males
• 15 to 18 mg/day for females of menstrual age
• 8 mg/day for older females
• 27 mg/day during pregnancy

References:

1. Anemia,  Vital and Health Statistics, Series 10, No. 200 , 1996. <http://www.cdc.gov/nchs/fastats/anemia.htm> Accessed 9/10/03
2. Fasano A, Berti I, et al. Prevalence of Celiac Disease in At-Risk and Not-At-Risk Groups in the United States Arch Intern Med. 2003;163:286-292. 
3. Guandalini S. Celiac disease. School Nurse News. 2003 Mar;20(2):24-7. 
4. Sood A, Midha V, et al. Adult celiac disease in northern India. Indian J Gastroenterol. 2003 Jul-Aug;22(4):124-6. 
5. Sachdev A, Srinivasan V, et al. Adult onset celiac disease in north India. Trop Gastroenterol. 2002 Jul-Sep;23(3):117-9. 
6. Dobru D, Pascu O, et al. The prevalence of coeliac disease at endoscopy units in Romania: routine biopsies during gastroscopy are mandatory (a multicentre study). Rom J Gastroenterol. 2003 Jun;12(2):97-100. 
7. Zipser RD, Patel S, et al. Presentations of adult celiac disease in a nationwide patient support group. Dig Dis Sci. 2003 Apr;48(4):761-4. 
8. Cranney A, Zarkadas M, et al. The Canadian celiac health survey – the Ottawa chapter pilot. BMC Gastroenterol. 2003; 3 (1): 8. 
9. Ransford RA, Hayes M, et al. A controlled, prospective screening study of celiac disease presenting as iron deficiency anemia. J Clin Gastroenterol. 2002 Sep;35(3):228-33. 
10. Howard MR, Turnbull AJ, et al. A prospective study of the prevalence of undiagnosed coeliac disease in laboratory defined iron and folate deficiency. J Clin Pathol. 2002 Oct;55(10):754-7. 
11. Brooklyn TN, Di Mambro AJ, et al. Patients over 45 years with iron deficiency require investigation. Eur J Gastroenterol Hepatol. 2003 May;15(5):535-8. 
12. Sanders DS, Patel D, et al. A primary care cross-sectional study of undiagnosed adult coeliac disease. Eur J Gastroenterol Hepatol. 2003 Apr;15(4):407-13. 
13. Dahele A, Ghosh S. Vitamin B12 deficiency in untreated celiac disease. Am J Gastroenterol. 2001 Mar;96(3):745-50. 
14. Dickey W. Low serum vitamin B12 is common in coeliac disease and is not due to autoimmune gastritis. Eur J Gastroenterol Hepatol. 2002 Apr;14(4):425-7. 
15. Iron-deficiency anemia in women. Harvard Women's Health Watch, Nov 2002, Vol. 10 Issue 3, p3 
16. Anemia Patient Education Sheets. Mayo Clinic website. www.mayoclinic.org. Accessed 9-5-03. 
17. Annibale B, Severi C, et al. Efficacy of gluten-free diet alone on recovery from iron deficiency anemia in adult celiac patients. Am J Gastroenterol. 2001 Jan;96(1):132-7.

Celiac.com 08/27/2022 - Just as “bovine spongiform encephalopathy,” better known as mad cow disease, is thought to be the result of feeding infected animal parts to cattle, gluten sensitivity, dermatitis herpetiformis, celiac disease, and a host of autoimmune diseases are the result of feeding grains to humans. Cattle are better equipped to eat grains and we are better equipped to eat meats. And when we step outside the food sources that shaped our evolution, we can expect some problems––sometimes very serious problems.

Let’s start by comparing human and ruminant digestive processes. Cows, for instance, have a stomach that is divided into four chambers. When grazing, cattle eat large quantities of food. They mix it with saliva and form it into boluses that they can swallow. After these boluses have been “worked on” by the micro-organisms in the first and second chambers of their four-part stomach, cattle regurgitate and chew them further, preparing them for return to the cow’s stomach where much of this feed may remain for up to 5 days of further digestion. In the final chamber of the stomach acids are secreted to aid further digestion.

Cattle spend more than 12 hours a day chewing their food. They produce more than five gallons of saliva every day, and they even utilize fermentation as part of their digestive process. The size of their digestive tracts is disproportionately large compared to that of a human. Although many infectious agents can gain entry with feed, the cow relies on the competitive advantage enjoyed by the friendly bacteria in their intestines. By comparison, humans process food very rapidly, typically taking less than 24 hours of transit time, from mouth to anus. We have only one chamber in the stomach and a comparatively short digestive tract. Our digestive tract is the site of a large number and variety of immune processes aimed at protecting us from invading microbes.

About 10,000 years ago, humans began a dietary experiment. They started eating grains in enough quantity to warrant cultivation. Nobody knew, back then, what caused sickness or dental cavities, or even what caused people to be shorter or taller. It was not until Twentieth Century that archaeologists made the connection that we began to realize that wherever grains were cultivated, within a generation or two, people became shorter by 5 or 6 inches, they also developed considerable dental cavities and bone disease.

Because the remains are only skeletal, we can’t really tell what other diseases most early farmers suffered. However, archaeologists and other scientists have reported a host of evidence from Egyptian mummies indicating that this grain-dominated culture experienced considerable cardio-vascular and autoimmune disease. We also know that hunter-gatherers who consume no grains show little or no signs of such diseases.

At the October, 2003 CSA/USA conference in Buffalo, Dr. Martin Kagnoff mentioned that we humans simply do not make the digestive enzymes necessary to fully digest some of the proteins found in gluten-containing grains. Just as we have been coming to realize the fallacy of dietary recommendations that encourage humans to eat grains, we have developed some other problematic economies in our food supply. For a variety of reasons, we started feeding cattle dietary protein that was largely made from the waste products of butchering other cattle. It is difficult to imagine a more effective means of communicating disease from one animal to the next.

Recently outlawed, this practice has been altered. Now, it is perfectly acceptable to feed animal parts from poultry and other species of slaughtered animals, but we are no longer allowed to feed cattle animal proteins from other cattle because it might contain the toxic prions that are implicated in Mad Cow disease.

As a consumer of beef, I am appalled at the foolishness of these “adjustments” in feeding practices for cattle. As a celiac, I am equally appalled by the continued practice of advising humans to eat enormous quantities of grains. Look at any of the food guides published by various governments of industrialized nations. No part that I can see is of, by, and for the people. Just as humans are not well equipped to eat grains, cows are ill equipped to eat meats. The first priority of our food scientists, producers, and our government eating guides, should be the good health of the general population.

Celiac.com 10/08/2014 - The one condition that accounts for almost half of the patients who seek out gastroenterologists is IBS (Irritable Bowel Syndrome).  Many celiacs suffer from this ailment.  IBS is a ‘functional’ disorder, meaning that there is no damage to the digestive tract.  Only the bowel’s function, not its structure, is disturbed.   

Here is Where the Irony Begins

Patients suffering from constipation are encouraged to consume a lot of dietary fiber (non-digestible carbohydrates and lignin from plants) because it acts as a mild laxative and promotes bowel evacuation.  A ‘mild laxative’ is the last thing someone with diarrhea needs, right?  Wrong!  It is recommended that IBS patients go on a high-fiber diet.  

Studies show that IBS patients on a high fiber diet report a reduction in pain; those on a low fiber diet do not.  Bowel habits improve in about half of IBS patients on the high fiber diet.  Even for people who do not have IBS, doctors recommend that we all include more fiber in our diets.

So How Much is ‘Enough’ Fiber?

The daily recommendation is 25 to 35 grams of combined soluble fiber (dissolves in water) and insoluble fiber (‘roughage’ that does not dissolve in water).   Peas, beans and apples contain soluble fiber, which slows digestion and helps the body absorb nutrients from food.  Flax seeds and nuts provide insoluble fiber, which helps foods pass through the stomach and intestines and adds bulk to the stool.  Fiber is found in plant foods and cannot be digested by humans.  It may also help control weight because it makes you feel full sooner.  The total grams of fiber you should ingest depends on your digestive system’s sensitivity.  

Just a warning:  A high-fiber diet causes gas because the carbohydrates in high-fiber foods cannot be completely digested in the stomach and small intestine.  It is best to increase the amount of consumed fiber slowly to allow your body to get used to it gradually.  Additionally, it is vital to increase water consumption in proportion to the increased intake of fiber.

Where Do You Find Fiber?

Fiber is found in vegetable gums (konjac gum, gum Arabic, carrageenan, guar gum, locust bean gum, petin vegetable gums, xanthan gum).  It is also found in nature, in the foods we harvest from the ground.  The following list shows some of the foods that are high in fiber:

• 1 oz. dry almonds (3g)
• 1 oz. roasted pumpkin seeds (10.2g)
• 1 oz. sunflower seeds (4g)
• 1 unpeeled medium apple (3.7g)
• 1 unpeeled pear (4.5g)
• 1 kiwi (5g)
• 4 oz. dried, sulfured apricots (8.8g)
• 4 oz. dried figs (10.5g)
• 10 dried prunes (6.1g)
• 1 cup raspberries (9g)
• ¾ cup blackberries (7g)
• ½ cup baked beans (7g)
• ½ cup chick peas (7g)
• 1 cup boiled lentils (15.6g)
• ½ cup canned lima beans (5.8g)
• ½ cup navy beans (6.7g)
• ½ cup pinto refried beans (11g)
• 1 corn on the cob (5.9g)
• 1 cup white corn (11.2g)
• 3 ½ cups air-popped popcorn (4.5g)
• 2 oz. corn pasta, cooked (7.9g)
• ½ cup frozen peas, cooked (4.2g)
• 1 cup spinach (4g)

You may have to eat 50 stalks of celery each day to get your recommended amount of fiber, or you may prefer to incorporate the suggestions below: 

1. Add nuts and seeds (sesame seeds, pumpkin seeds, sunflower seeds) to salads and casseroles, sprinkle them over vegetables, or add them to a stir-fry.  You can also sprinkle them with seasonings and roast them slowly in the oven for a healthy snack.
2. Add cooked dried beans and shredded carrots to everything from salads to soups, stews, casseroles, meatloaf, or even rice (Note that cooking vegetables does not change their fiber content).
3. Eat plenty of fruits (especially citrus fruits), berries, prunes, figs or apricots.  Keeping the skins on fruits (and vegetables) will add a small amount of extra fiber, but the skins are the part that are most exposed to pesticides, so unless you are buying organic fruits and vegetables, you may be better off peeling them first.
4. Snack on popcorn (Air-popped is the healthiest).
5. Sprinkle raisins on salads, puddings, canned fruit, baked apples, sweet potatoes, cereal, or just eat them plain as a snack.
6. Add shredded cabbage and peas to salads, soups, wraps, stir-fries, and stews.
7. Use brown rice or quinoa in place white rice.  
8. Add shredded apples to pancake batters, quick breads, and yam dishes.  Serve a baked apple for dessert instead of cookies.
9. Eat a fresh apples, apricots, prunes or oranges instead of drinking their juice.
10. Add dried cranberries to cereal, quick breads, muffins, cookie batter, yam dishes, and salads.  Make up a bowl of nuts, raisins and dried cranberries for a snack.

Celiac.com 04/05/2010 - In the 13 years I’ve been involved in the wonderful world of “gluten freedom,” one of the questions I’ve been asked most frequently is whether or not the entire family should be gluten-free.  For parents who have kids on the gluten-free diet, this seems to be a natural instinct––if Johnny can’t eat gluten, none of us will.  But I’m not sure that having the entire family go gluten-free is the best thing––unless, of course, it’s for health reasons (I, for example, choose a gluten-free diet because I believe it’s healthier).  This is one of those questions that has no correct or incorrect answer, so I’ll share with you, for what it’s worth, my personal perspective on the issue.

Pros: It’s easier when the whole family is gluten-free, because you’re making only one version of every meal, as opposed to two or three.  There is less risk of contaminating safe foods because there aren’t any “unsafe” foods in the house.  Preparation is easier, and there’s no need for the gob drop or any other tricky food-preparation maneuvers.  Finally, from a psychological standpoint, you avoid having some people feel ostracized when their food is made separately and they’re eating different foods from the rest of the family.

Cons: It’s more expensive and sometimes more labor-intensive for everyone to eat specialty foods (Try not to be a “saver.”  Sometimes, after spending $3 each for sugar ice cream cones, I’ll find myself guarding them like a hawk.  I’ve accumulated several boxes of untouched stale cones now).  Feeding the whole family home-made gluten-free bread at nearly five dollars per loaf, when three out of four family members could be eating a commercial brand, has an impact on the family’s time and finances.

More important, especially if children are involved, forcing the entire family to be gluten-free because of one person’s dietary restrictions can put a strain on relationships.  Sometimes this works in both directions.  In my family, for instance, my daughter would resent being forced to be on a 100 percent gluten-free diet (we’re pretty close to that anyway) just because that’s how her brother Tyler eats.  Interestingly, though, it works the other way too.  Tyler doesn’t want his sister to be deprived of a bagel, nor does he resent her for being able to eat one (especially because the gluten-free bagels we buy over the Internet are so good these days!).  Resentment is almost inevitable at some level if family members are forced to give up their favorite foods for one member of the family––at least when kids are involved.

The last reason against a gluten-free family is probably the most compelling one, and is the primary reason I haven’t forced my whole family to be gluten-free: it’s not reality.  Again, this is more important when a child in the family has the restricted diet, because the reality is that this world is filled with gluten, and most people on this planet eat it––lots of it.  These children need to learn how to handle the fact that for the rest of their lives, they’ll be surrounded by people eating gluten.  If that makes them feel bad, sad, or mad, that’s okay.  What better place to learn to deal with those unpleasant emotions than in the loving environment of their own home?  They may be more tempted to cheat because the food is in their home and others are eating it; again, there may be no better place to deal with temptation and learn to resist it than in the loving environment of their own home.

The compromise: In no way am I advocating someone waving a Krispy Kreme donut in your face singing, “Nah-nee-nah-nee-nah-nee…you can’t eat this” in an effort to build character.  With the excellent gluten-free products available today, it’s easier than ever to compromise by eating relatively gluten-free.  Try to buy salad dressings, condiments, spices, and other foods and ingredients that are gluten-free when you can.  For foods like pasta, bread, and pizza, you can make two varieties, one of which of course is gluten-free and prepared carefully to avoid contamination.

Cost aside, I don’t see any reason to bake “regular” cookies and baked goods anymore.  The gluten-free mixes are so incredible that my kids and their friends prefer them to “the real deal.”  They’re easy enough that the kids can make them themselves, and it’s a psychological upper for my gluten-free son when his sister and friends can’t get enough of “his kind” of cookies.

You’ll probably find that because it’s easier to make one meal than two, you’ll gravitate toward gluten-free menus.  With good menu planning, and a kitchen well-stocked with gluten-free condiments and ingredients, it’s likely that your entire family will inadvertently become mostly gluten-free without realizing it, and without the resentment that might have developed if the issue had been forced.

If your family does end up mostly gluten-free, or if you eliminate gluten completely, remember that anyone who is going to be tested for celiac disease (and all family members should be) must be eating gluten for at least several weeks prior to doing any tests for celiac disease.

Celiac.com 05/10/2004 - Identical twins enter life from the same womb sharing the same genetic code, the same family, the same home, largely experiencing the same environment as they develop from infancy through childhood and mature into adults. When celiac disease strikes one identical twin, the odds are the other twin also has celiac disease. Twin studies lead to the conclusion that celiac disease is strongly linked to genetic factors. Yet one identical twin may develop celiac disease while the other twin may remain completely free of celiac disease for decades if not for a lifetime.

One study looked at 20 pairs of identical twins and 27 pairs of fraternal twins where at least one twin of the pair was known to have celiac disease. In 75% of the pairs of identical twins, both twins had celiac disease. In contrast, in only 11% of the pairs of fraternal twins did both twins have celiac disease. However, in 25% of the 20 identical twin pairs studied, one twin of the pair did not have celiac disease¹. In another study which followed 5 pairs of female identical twins for 11-23 years (at least one twin of the pair having celiac disease or dermatitis herpetiformis), it was found that two of the twins who began the study with neither celiac disease or dermatitis herpetiformis remained free of the disease throughout the study². In other words, something beyond genetics, some environmental factor, seems to be responsible for the onset of celiac disease. Exactly what is it that makes one twin intolerant to gluten and not the other?

Looking for Answers

To find an answer, one might start by asking when do signs of an intolerance to gluten first begin to emerge? A recent study in the UK looked at a screened sample of 5,470 children aged 7 years old and found 54 who tested positive for both tTG antibodies and IgA-EMA (tissue transglutaminase and antiendomysial antibodies) indicating celiac disease is likely present. This 1% prevalence in children is comparable to the 1% prevalence of celiac disease in adults in the UK. Since the prevalence of celiac disease is not greater in adults, this suggests that the onset of celiac disease begins in early childhood, even in cases where celiac disease is not diagnosed until later in adulthood. The authors of this study concluded, “The search for the trigger resulting in the breakdown of immune tolerance to gluten therefore needs to focus on infancy and intrauterine life³.”

Breast-Feeding

Breast-feeding has long been thought to delay or reduce the risk of developing celiac disease in children. This effect has been attributed to a number of potentially protective milk components and antibodies passed from the mother. Studies relying on questionnaires have found that the onset of celiac disease in children is significantly delayed if gluten is introduced into the diet while the child is still being breast-fed^4-7. The effect of epidermal growth factor (EGF), a component of breast milk, was studied in newborn rats. Interferon-gamma and gliadin, a gluten protein, were administered to rat pups to induce gluten enteropathy. Celiac disease-like villus atrophy was found in rat pups fed an artificial milk diet without EGF but not in breast-fed pups or pups supplemented with EGF⁸. Recent research shows that breast milk also passes bacterial flora from mother to newborn⁹. Growth factors found in human milk have been shown to aid in establishing predominant species of commensal bacteria in the gut of breast-fed infants¹⁰. The makeup of microflora which colonize the gut in early infancy is dependant on many factors, including whether babies are bottle-fed or exclusively breast-fed, whether or not delivered by caesarean section, on treatment in neonatal intensive care units, hygienic conditions, and antimicrobial procedures. Initially, it is the maternal microflora that is the source of bacteria for the newborn gut. A diet of breast milk induces the development of a flora rich in Bifidobacterium in full-term infants¹¹. The possibility that these microflora play critical symbiotic roles in the development of the intestine and its immunological functions has not yet been considered as a factor in the onset of celiac disease.

The Beneficial Roles of Gut Bacteria

Over 500 species of bacteria may be present in the human gut in concentrations of between 100 billion to 1 trillion microbes per gram adding up to about 95% of the total number of cells in the human body^12,13. For many years it has been known that gut bacteria play an important and beneficial role in one’s health. Extraordinary new findings on how commensal microflora participate in early gut development and in the development of the immune system have been uncovered by recent research. Here is sampling of some of these discoveries:

A study of 64 healthy formula and breast-fed infants, aged 0-6 months, examined fecal samples for intestinal colonization of Bacteriodes fragilis, Bifidobacterium-like, and Lactobacillus-like bacteria, and compared these results with counts of IgA, IgM, and IgG antibody-secreting cells in blood fluids drawn from the infants. The result was that infants colonized with B. fragilis at one month of age had significantly higher counts of IgA- and IgM-secreting cells at the age of two months than infants not colonized with B. fragilis. It was concluded that colonization timing and the type of bacteria colonizing the gut of newborns may influence the maturation of the naive immune system¹⁴.

Bacteriodes thetaiotaomicron, a species abundant in the guts of humans and mice, has been the focus of much research, chosen because of its predominance in the microflora and ability to be genetically manipulated. Studies of this microbe introduced into the developing guts of gnotobiotic (germ-free) laboratory mice have found B. thetaiotaomicron seems to communicate with host cells in the intestine, altering and influencing gut development and function.

One study has shown gene activity in the host is affected by B. thetaiotaomicron colonization. Using sophisticated DNA microarray devices, a comparison of gene expression of some 25,000 mouse genes was made between germ-free and B. thetaiotaomicron colonized mice. The activity of 118 genes was found to be increased or reduced by colonization. These genes are involved in several important intestinal functions, including nutrient absorption, intestinal permeability, toxin neutralization, intestinal blood vessel development, and postnatal gut maturation suggesting that these functions should be examined further in future studies¹⁵.

An influence on fructose production in the gut by B. thetaiotaomicron was the first finding uncovered by researchers. Pre-weaned mice produce fructose sugar on the surface of cells lining the intestine providing a food source helping to establish commensal bacteria. B. thetaiotaomicron colonizing the gut of germ-free mice causes intestinal cells to continue fructose production after weaning. If B. thetaiotaomicron is not present after weaning, fructose synthesis stops. B. thetaiotaomicron actually senses when its supply of fructose is low and instructs the host to produce more fructose in response¹⁶.

Gene activity findings led researchers to look at the development of the intricate network of intestinal blood vessels in mice raised germ-free and in mice raised colonized with B. thetaiotaomicron or normal gut flora. When the mice reached adulthood, capillary development in the intestines was examined. Capillary development in mice colonized with B. thetaiotaomicron or normal flora was normal and complex, but capillary development in the germ-free mice was immature and arrested. Further, it was, found for blood vessel development to occur, these microbes must interact with Paneth cells (epithelial cells located at the base of the “crypts” in the small intestine)¹⁷.

The relationship of B. thetaiotaomicron with Paneth cells was further studied. It was discovered that Paneth cells produce a protein called angiogenin 4 or Ang4 and that Paneth cells are induced to express Ang4 by B. thetaiotaomicron. Ang4 and other angiogenins were found to exhibit bactericidal and fungicidal activities against certain known pathogens. It appears that B. thetaiotaomicron and other commensal microbes, which are themselves resistant to Ang4, take part in shaping the microbial ecology of the gut and innate immunity¹⁸.

Another study found a relationship between commensal bacteria and the development of gut-associated lymphoid tissue (GALT) in rabbits. GALT consists of lymphocytes and organized tissues called Peyer’s patches and mesenteric lymph nodes (MLNs) located within the intestinal mucosa, which are involved in the induction of immunity and tolerance. During the first few months after birth, newborn animals and humans rely on antibodies passed maternally to fend off infections until the immune system can mature. After those first few months, a diversification of antibody repertoire normally takes place within the GALT. When, shortly after birth, the appendices of rabbits are tied-off and isolated to prevent colonization by microflora, GALT development within the appendices is arrested. Rabbit pups delivered sterilely, isolated and hand-reared on a sterile diet exhibited underdeveloped GALT and antibody repertoires. In further experimentation, a number of different bacteria species were introduced into surgically-rendered, germ-free appendices of rabbits. No bacteria species alone promoted GALT development. However, the combination of Bacteroides fragilis and Bacillus subtilis consistently resulted in the development of GALT and antibody repertoire. The conclusion is that specific combinations of microflora are required for GALT development^19,20.

In other research, the composition of commensal flora in rats was shown to alter intestinal permeability. Colonization with Escherichia coli, Klebsiella pneumoniae, and Streptococcus viridans significantly increased colonic wall permeability while colonization with the common probiotic strain, Lactobacillus brevis, significantly reduced permeability of the colon wall. Bacteroides fragilis induced only a slight permeability reduction²¹.

Gut pathogens in combination with stimulation by cytokines such as TNF-alpha (tumor necrosis factor) can cause cells of the intestinal epithelium to respond by releasing proinflammatory cytokines like interleukin-8 (IL-8). A study found that probiotic strains, Bifidobacterium longum and Lactobacillus bulgaricus, can suppress IL-8 secretion in intestinal epithelia when stimulated by proinflammatory cytokines. Hence, some probiotic strains of bacteria may be able to down-regulate inflammation in the gut²².

Other beneficial functions of microflora include the fermentation and removal of non-digestible dietary residue and the mucus residue produced by the epithelia; the derivation of energy as short-chain fatty acids by fermentation of carbohydrates in the colon; the production of vitamins, particularly those of the B group and vitamin K; the absorption of minerals and ions including calcium, magnesium and iron; and the formation of a protective functional barrier against pathogens^23,24.

A Role for Bacteria in Celiac Disease?

As can been seen, commensal microflora play a myriad of complex, diverse and important roles in normal health and development. Much remains to be investigated, and new roles and functions microflora play are waiting to be discovered. The possibility that commensal bacteria are involved in the pathogenesis of celiac disease cannot be overlooked. Certainly, differences in the mix of microflora could account for why one identical twin may develop celiac disease while the other does not. Could the mix of commensal bacteria in newborn infants set the stage for the development of celiac disease? Could the onset of celiac disease be triggered by an event such as illness, use of antibiotics, stress, or pregnancy which alters the mix of microflora opening the door to a pathogenic interaction with gluten? One recent study has already found an association between antibiotic use and the development of Crohn’s disease²⁵.

Over the course of the last few years, much new understanding of the pathogenesis of celiac disease has come to light, but a fundamental question remains unanswered: Why does the immune system fail to tolerate gluten in some people? A possible mechanism involving one or more unidentified species of commensal bacteria possibly explaining why tolerance to gluten fails will be proposed and discussed here.

Tolerance and Immunity

The subject of tolerance and immunity is involved and complex, and science remains far from fully comprehending its workings. At heart, is how the immune system decides to react when an antigen is first presented to a naive T cell. The response of the immune system to an antigen is mediated and regulated by cell secretions of numerous proteins called “cytokines” sensed by a multitude of receptors on the various specialized cells of the immune system. Structural components of pathogens are also sensed by immune cell receptors called “Toll-like receptors”. Antigens may be any substance foreign to the body and may or may not actually be harmful. They could be components of food, or could be components of either friendly or pathogenic organisms.

In celiac disease, the antigens are those gluten peptides which survive the process of digestion. In the current understanding of celiac disease, these peptides are transported across the mucosal epithelium as polypeptides. In mainly the subepithelial region, gluten peptides undergo a process called deamidation by an enzyme called tissue transglutaminase (tTG). A peptide is a chain of amino acids. Deamidation is a process that converts glutamine amino acid components of a gluten peptide into glutamic acid components. In the lamina propria region of the intestines, deamidated gluten peptides are taken up by antigen presenting cells called dendritic cells and presented by HLA-DQ2 or -DQ8 molecules on the surface of dendritic cells to receptors of gluten-sensitive naive CD4+ T cells (Note celiac disease here refers to a “cluster of differentiation” number, a numbering system for the cell-surface molecules which identify T cell type). Activated CD4+ T cells then differentiate and proliferate. Some T cells interact with B cells which, in turn, then differentiate into plasma cells producing antigliadin, antiendomysial and anti-tTG antibodies. Other T cells become natural killer or cytotoxic T cells, secreting cytokines which cause inflammation and damage to the enterocytes in the epithelium. Connective tissue cells called “fibroblasts” increase their output of matrix metalloproteinase enzymes which may play an active role in villus atrophy. Intraepithelial lymphocytes also increase, but their role is not clear^26-29.

Human leukocyte antigen (HLA) genes encode the class II molecules DQ2 and DQ8, the key genetic risk factors in celiac disease. The HLA system is the human version of the major histocompatibility complex (MHC). HLA class II molecules are expressed on the surface of antigen presenting cells such as dendritic cells. Virtually all celiac disease patients carry DQ2 or DQ8, but carrying DQ2 or DQ8 alone does not confer celiac disease. DQ2 and DQ8 molecules may be encoded by several different haplotypes. Haplotypes are combinations of alternative genes for the same trait (alleles) occupying different locations on a chromosome which tend to be inherited as a group. These DQ2 and DQ8 molecules play a central role in the pathogenesis of celiac disease. The function of HLA class II molecules is to bind peptide antigens and present them to CD4+ T-cell receptors. The pattern of amino acids in the makeup of the chain that forms the peptide antigen is called an epitope, and that pattern is crucial to the binding between HLA molecule and peptide. It is the misfortune of celiac disease patients that epitopes of deamidated gluten peptides just happen to match up and firmly anchor into the binding grooves of DQ2 and DQ8 molecules. This strong binding results in the activation of CD4+ T cells and the subsequent processes which damage the intestinal epithelia. But why is it that CD4+ T cells are not activated in everyone who possesses the appropriate HLA-DQ2 and -DQ8 haplotypes? The question arises again. Why is one identical twin tolerant to gluten and not the other?^26-30

Dendritic Cells

Whether an outcome of tolerance or intolerance results when a dendritic cell presents an antigen to a naive T cell depends on many factors. A dendritic cell is a special type of white blood cell (leukocyte) which circulates throughout the body looking to acquire antigens. Dendritic cells engulf and internalize antigens through a process called endocytosis. In receptor-mediated endocytosis, dendritic cells express a variety of surface receptors to capture protein antigens. In macropinocytosis, dendritic cells surround and “drink up” soluble antigens. In phagocytosis, dendritic cells engulf pathogenic bacteria, viruses, fungi, dead or infected cells, or their products. After digestion and processing, the antigens are bound to HLA (or MHC) molecules and expressed on the surface of dendritic cells for presentation to T cells. Antigen presentation occurs after dendritic cells migrate to the lymph nodes which are rich with T cells. T cell activation also requires secondary stimulation by costimulatory molecules expressed on the dendritic cell surface. Dendritic cells have three stages in their life cycle: Precursor, immature and mature. Precursor dendritic cells arise from the bone marrow. Subsets of precursor dendritic cells have been identified that grow and differ with regard to observable characteristics (phenotype), function and anatomical location. Studies have linked dendritic cell subsets with particular functions such as T cell differentiation or tolerance induction. Immature dendritic cells spread throughout tissues seeking antigens. Dendritic cells enter the mature stage when they reach the lymph nodes after antigen capture and having become primed and ready to activate T cells with antigens and costimulatory molecules. The processing of antigens produces roughly 100,000 to 300,000 peptide-laden HLA molecules on the dendritic cell surface, most peptides represented by about 100 copies. A single mature dendritic cell is capable of stimulating 100–3,000 T cells^31-34.

Immature dendritic cells are capable of phagocytosis of bacteria. Dendritic cell phagocytosis of Salmonella and Borrelia burgdorferi has been observed and studied. Immature dendritic cells roaming the lamina propria below the epithelial cells of the intestine not only capture bacteria which invade and cross the epithelial barrier, but have been observed reaching through the tight junctions between epithelial cells with their dendrite arms to directly sample non-invasive bacteria in the gut lumen and mucosa tissues outside the epithelium^34-37.

Immature dendritic cells express a variety of surface receptors which when stimulated cause dendritic cells to mature and respond in specific ways which can result in tolerance or immune activity. These receptors include Toll-like receptors (TLR), cytokine receptors, TNF (tumor necrosis factor) receptor, immunoglobulin (antibody) receptors, and sensors for cell death. TNF and other cykotine inflammatory mediators signal infections. In particular, interleukin-1 (IL-1) can prevent oral tolerance in mice by altering the response of normally tolerogenic dendritic cells into an active immune response^32,34.

Toll-like receptors are known as pattern recognition receptors which identify structural components found only on the surface of bacteria and other pathogens. These components are referred to as pathogen-associated molecular patterns (PAMPs). At least 10 types of TLR have been identified in humans and given the designations, TLR1-TLR10. Examples of PAMP include microbial carbohydrates like the toxin lipopolysaccharides (LPS), flagellin, products from bacterial cell walls, bacterial RNA and DNA. Signaling through different TLR evokes distinct biological responses. TLR expressed differently by different dendritic cell subsets may determine the manner in which dendritic cell subsets respond to particular microbial structures^34,39.

Mature dendritic cells can produce cytokines while activating CD4+ T cells which may influence T cell differentiation and function. Activated T cells divide and proliferate and differentiate into a variety of types. Tolerance and immunity induction are influenced most by differentiation into type 1 and type 2 helper T cells (Th1 and Th2) and regulatory T cells. The type of cytokines produced by the T cells determine their classification. Th2 responses favor tolerance. Th1 responses favor immunity and inflammation. Regulatory T cells suppress immune responses. IL-10 produced by dendritic cells appears to contribute to Th2 and regulatory T cell responses. Dendritic cell production of IL-12, IL-18, and IL-23 contribute to a Th1 response^34,40.

Why Does Tolerance to Gluten Fail?

Okay. So why does the immune system fail to tolerate gluten in celiac disease? The immune system receives and responds to all kinds of signals from a pathogen, but how can a simple gluten peptide turn this complex immune machinery into a force against itself? Thinking about this leads to a very provocative question:

What if instead of responding to gluten peptides alone, the immune system responds to a pathogenic gut bacteria which routinely ingests gluten peptides?

A 33 amino acid gluten peptide has been identified as the primary initiator of the inflammatory response in celiac disease. This peptide contains a number of amino acid sequences which correspond to epitopes known to activate T cells and initiate celiac disease response. In particular, this 33-mer peptide was identified because it remained intact in the residue of a solution of gliadin mixed with gastric and pancreatic enzymes. This demonstrates some gluten peptides are difficult to breakdown by normal digestive processes. Another experiment identified a 17 amino acid gluten peptide which also contained epitopes associated with celiac disease^41,42.

Bacteria do not ingest nutrients in the normal sense. Nutrients are transported across cell membranes via several different mechanisms. Transported nutrients are necessarily limited in size. Nutrients are broken down externally by enzymes and by processes such as fermentation, an oxidation process resulting from acids produced by bacteria. Growth factors consisting of purines, pyrimidines, vitamins and amino acids are required by some bacteria in order to grow. Other bacteria are able to synthesize these essential growth factors. Researchers have found that some bacteria can transport and internalize amino acids in the form of peptides. Studies so far have found peptides up to 18 amino acids in length can be internalized by bacteria^43-46.

Epitopes of gluten peptides deamidated by tissue transglutaminase (tTG) are believed central to celiac disease pathogenesis. However, a study of gluten response in children with celiac disease found that T cells can respond to native gluten peptides independent of deamidation⁴⁷. Celiac disease may begin its course without deamidation. As the disease progresses, inflammation may cause an increase in expression of tTG. An increase in tTG expression has been shown during wound healing, in liver injury, and in response to an inflammatory stimulus by lipopolysaccharide^48-50. Through a process called epitope spreading and with the increase in tTG expression, deamidation of gluten peptides is more likely to occur and T cell response to deamidated gluten peptides likely develops. tTG is expressed in the epithelial brush border and extracellularly in the subepithelial region²⁶ (The brush border is composed of the microvilli found on each individual epithelial cell).

In the course of evolution of bacteria in the gut, it would seem highly plausible that at least one or more bacteria species have evolved and adapted in some way to transport, internalize and utilize gluten peptides as a source of amino acids. Since tTG is expressed in the epithelial brush border, deamidated gluten peptides are available to such bacteria (though in the early stage of celiac disease deamidation may not be required). If these bacteria colonize the gut and exhibit some pathogenic characteristic, such as expressing lipopolysaccharide, dendritic cells may be signaled to reach through the epithelial barrier into the lumen to sample and phagocytize the bacteria. When this bacteria is digested and processed by the dendritic cells, the antigens bound to HLA molecules and expressed on the dendritic cell surface are likely to include the difficult to breakdown, intact gluten peptides that have been internalized by the bacteria. As far as the immune system is concerned, these gluten peptides are indistinguishable from the other bacterial peptides bound to HLA molecules expressed on the dendritic cell surface. When these gluten peptide antigens are bound to HLA-DQ2 or -DQ8 molecules and presented to CD4+ T cells, the T cells simultaneously receive all the signals telling them that the gluten peptide is an antigen from a pathogenic bacteria. The result is that the immune system responds to the presence of gluten as though pathogenic bacteria were present. Such gluten-ingesting bacteria may be the missing link in the pathogenesis of Celiac Disease.

If these bacteria exist, there is now a clear explanation as to why one identical twin may develop celiac disease and not the other. Of course, the presence of such a bacteria in the gut of one twin and not the other would fully explain the discordance. It is also possible that such a bacteria may exist in both twins, but is kept under control by the mix of commensal bacteria colonizing the gut of one twin. Some disturbance to this mix, such as an infection or use of antibiotics, might provide an opportunity for this gluten-ingesting bacteria to colonize and proliferate to a level where its pathogenic properties, such as production of endotoxins, are sensed by the immune system initiating the onset of celiac disease. The existence of such bacteria could also explain why there may be varying degrees of gluten sensitivity, even in individuals without DQ2 and DQ8 molecules.

The possibility that these gluten-ingesting bacteria may exist raises another intriguing question: If these gluten-ingesting bacteria are controlled or eliminated from the gut, could tolerance to gluten be restored? There could be a very real possibility that celiac disease might be cured by eliminating these bacteria. After all, peptic ulcers can be cured by eliminating Helicobacter pylori.

The Future

So where should research go from here? The most obvious path would be first to try to find and identify any gut bacteria that has gluten peptides present within its cell membranes. From there, the possible link to celiac disease could be studied. Additionally, it would be quite valuable to initiate a large long-term study of the makeup of commensal bacteria in identical twins beginning at birth via fecal samples. By comparing the differences in microflora and the onset and discordance of diseases in identical twins over many years, the relationships of specific species of bacteria to specific diseases, including celiac disease, could be established. And if it proves to be true that gluten-ingesting bacteria cause celiac disease, a similar mechanism involving bacteria and peptides from other proteins may be the root cause for many other autoimmune diseases. A whole class of autoimmune diseases might be cured by eliminating specific species of bacteria.

Roy Jamron holds degrees in physics and engineering from the University of Michigan and the University of California at Davis and actively pursues and investigates research on celiac disease and related disorders.

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