gluten intolerance: are people who complain of gluten

2/10/2016

1

Gluten Intolerance: Madness, Myth, Medicine or Mystery?

Lunch and Learn

Em M. Pijl‐Zieber PhD, RN

Faculty of Health Sciences

University of Lethbridge

Some Questions We Will Explore

• What is with the gluten‐free fad?

• Are people who complain of gluten intolerance or gluten sensitivity—without having celiac disease—hypochondriacs or attention‐seekers?

• Do some people who do not have celiac disease react negatively to ingested gluten?

• Is gluten‐free just another passing fad upon which the food industry is capitalizing?

When Did All This Craze Start? What Is Gluten?

• Gluten is found in grains such as wheat, barley, rye, and a cross between wheat and rye called triticale

• Gluten is a complex protein formed of two protein structures: gliadin and glutenin, connected by disulfide bridge

• Gluten is the magical protein responsible for the capability for bread dough to rise and contain carbon dioxide

What Is Gluten? What Is This Gluten‐Free “Fad”?

• According to Agriculture and Agri‐Food Canada (2013):• "Gluten free" is the fastest growing food intolerance category

• Celiac disease is recognized as one of the most common chronic diseases world‐wide (Health Canada 2008), affecting an estimated 1% (1/133) of Canadians, with less than 10% of people with celiac disease having been diagnosed.

2/10/2016

2

What Is This Gluten‐Free “Fad”?

• According to Agriculture and Agri‐Food Canada (2013):• Almost one third of Canadians (10 million) are looking for gluten‐free products

(Canadian Celiac Association, 2013)

What Is This Gluten‐Free “Fad”?

• According to Agriculture and Agri‐Food Canada (2013):• Reasons for a gluten free diet:

(Hartman Group, 2013)

What Clinicians Have Known

• Narrow spectrum of gluten disorders:• Celiac disease (1%)

• Wheat allergy (<1%)

• Wider range of intestinal diseases:• Irritable bowel disease

• Colitis

• Crohn’s disease

(Volta, Caio et al., 2015)

98% of people are “normal” and unaffected by gluten or wheat

Unrelated, but possibly influenced to some degree, by diet (not gluten)

What Clinicians Are Seeing

• A set of symptoms that in many ways looks like:• Irritable bowel syndrome

• Celiac disease

• A set of symptoms that may also be:• Neurological – “brain fog”, fibromyalgia, ataxia

• Not limited to the intestines – extraintestinal symptoms

…All in the absence of what we consider celiac disease, namely• Negative blood test, and/or

• Negative histology (intestinal biopsy)

What Is Celiac Disease?

• Celiac disease is an immune reaction to eating gluten, a protein found in wheat, barley and rye.

• Eating gluten triggers an immune response in the small intestine. This reaction produces inflammation that damages the small intestine's lining and prevents absorption of some nutrients (malabsorption).

• The intestinal damage can cause weight loss, bloating and sometimes diarrhea. Eventually, the brain, nervous system, bones, liver and other organs can be deprived of vital nourishment.

• A multi‐system autoimmune disorder, the manifestations (over 200 possible symptoms) of which respond to a strict gluten free diet


2/10/2016

3


• Genetic, environmental, and immunologic components

GENETIC ENVIRONMENTAL

IMMUNOLOGICAL


• Testing for celiac disease:• Blood test (screening)—tTG (measure of serum IgA)

• 90% accurate

• Some people are IgA deficient, resulting in a false negative

• Some physicians do not correctly use the test – should be a gateway to biopsy; fail to consider the patient’s presentation

• Upper endoscopy and intestinal biopsy (diagnostic)—villous atrophy • Very accurate…if the affected part of the small intestine is biopsied – patchy versus “PVC pipe”

• HLA DQ2 and HLA DQ8 – genetic test; 40% of North Americans will have the gene but only 0.5‐1.0% will develop celiac disease

(Armstrong, Don‐Wauchope, & Verdu, 2011)


• Based on this understanding of known wheat or gluten disorders, patients are classified as:

Celiac1% of population

Wheat Allergy.3% of population

Normal98.7% of population (EVERYBODY ELSE)




Wheat Allergy.3% of population

Normal98.7% of population (EVERYBODY ELSE)

2/10/2016

4




Normal99% of population (EVERYBODY ELSE)

Does Non Celiac Gluten Sensitivity Exist?

• Scientific findings have had conflicting results

• Studies are compromised by:• No set definition of NCGS – wide range of symptoms, experiences

• Patients self‐identify as NCGS and are thus enrolled in the study

• There are no biomarkers of NCGS – what are we measuring in these studies? More self‐report?

• What is the agent of harm: Gluten? Wheat? FODMAPs?

• Pathological mechanism is not understood

• Multiple food sensitivities are often reported (confounding)

• Symptoms are similar, even identical, to celiac disease, and the severity of damage in the bowel (if any) does not correlate well to severity of symptoms

Di Sabatino and Corazza, 2012; Lebwohl and Leffler 2015


Anecdotes

Biesiekierski & Iven, 2015Elli et al, 2015Fasano, 2014Hadjivassiliou et al, 2006Isasi et al, 2014Kheder et al, 2012Khwaja et al, 2015Lionetti, Leonardi et al., 2015Tonutti & Bizzaro, 2014Vandenplas, Benninga et al., 2015Volta et al, 2013

Aziz et al, 2015Bonciolini et al, 2015? Brottveit et al, 2012Hadjivassiliou et al, 2010? Hollon et al, 2015Ihara et al, 2006

Kabbani et al, 2014Marietta & Murray, 2012Sbarbati et al, 2003 Sapone et al, 2010; 2011Vazquez‐Roque et al., 2013

Molina‐Infante, Santolaria et al., 2015Biesiekierski, Newnham et al., 2011Biesiekierski, Peters et al., 2013Di Sabatino, Volta et al., 2015Peters, Biesiekierski et al., 2014Shahbazkhani, Sadeghi et al., 2015

Gaesser and Angadi, 2015; Sapone, Bai, et al., 2012


Your tTG test is negative. Go home and have a

doughnut!

Yikes. Am I a hypochondriac? Am I imagining my symptoms?


Your tTG test is negative, but I am intrigued by your experience and

symptoms. I’m going to look into this for you.

Thank goodness she believes me. I thought I was going nuts.

2/10/2016

5


• One theory: Gluten cannot be processed by humans• “Wheat Belly” vilifies wheat as unfit for human consumption

• Gluten is vilified around every corner these days and blamed for many disorders

• Most people can tolerate gluten and wheat well, as we have evolved eating gluten‐containing grains

The Paleo Babe


• Another theory: Wheat itself has changed, or how it’s used• Novel variants of wheat that are known to contain high amount of toxic gluten peptides potentially harmful to the integrity of the enteric mucosa?• Celiac‐triggering gluten proteins are expressed to higher levels in modern cereals while non‐triggering proteins are expressed less.

• Sophisticated hybridization techniques have been used to produce new strains of modern wheat, the most high‐yielding of which have since made their way into human foods in the absence of animal or human safety testing.

• Mechanization of farming and the growing industrial use of pesticides?

• Overall reduced time of dough fermentation resulting in a higher content of toxic gluten fractions in bakery products?

(de Lorgeril & Salen, 2014; Fardet, 2015; Volta, Caio et al., 2015)


• Theory:Media has fanned the flames of gluten sensitivity• Increasing awareness among non‐medical people

• Increasing awareness among clinicians

• Increased market for gluten free products (although often with high rates of cross contamination that make many food items unsafe for people with celiac disease)

(Volta, Caio, Stanghellini, & De Giorgio, 2014)

GLUTEN FREE“(no hidden ingredients)”But……

• A theory with promise: Based on the fact that the degree of intestinal damage and the severity of a person’s symptoms are poorly correlated, Dr. Fasano proposes this view:

GLUTEN SENSITIVITY + AUTOIMMUNE = CELIAC DISEASE

GLUTENSENSITIVITY

AUTOIMMUNE

GLUTENSENSITIVITY


AUTOIMMUNEGLUTEN

SENSITIVITY + =


• An emerging theory: “Leaky gut” (don’t laugh) • Damaged to small intestine, in this case by the presence of gluten

• Changes of the gut microbiota might favor the inflammatory response to gluten

• Zonulin has an increased expression in patients with celiac disease; might this also be a factor in NCGS?

• Gliadin has been shown to activate zonulin signaling (to open gap junctions) irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules

• Data is conflicting regarding small intestine permeability, however.

(Drago, El Asmar, et al, 2006; Fasano, Not, et al., 2000; Lammers, Lu, et al, 2008; Volta, Caio et al. 2015)


• Theory: A mixed bag of potential mechanisms • Overlapping condition with functional bowel disorders (IBS)

• Overlapping condition with other food hypersensitivities • Other wheat components

• FODMAPS

• Unique immunology, different from celiac disease • Similarities: Gluten causes inflammation, altered gut microbiome, T cells (in animal models)

(Ejsing‐Duun et al., 2008; Hansen et al., 2006; Larsen et al., 2014; Palova‐Jelinkova et al., 2013; Volta et al, 2015)

2/10/2016

6

In The Real World….Some Questions

• This gray zone of NCGS: Does it help or hinder the plight of “true” celiacs?

• Should a non‐celiac be able to go to a restaurant and say “I’m celiac. My meal needs special care to ensure no cross‐contamination occurs while being prepared.”

• Why are we so addicted to biomarkers to validate people’s experiences?

• How can health professionals validate patients’ experiences in the absence of biomarkers?

• Does it matter if the patient has NCGS or if it’s just a placebo effect?

Future Research

• What is the natural history of NCGS?

• Serological biomarkers for NCGS

• How do the symptoms and quality of life compare between patients with CD and NCGS?

• Are there long term complications associated with NCGS, as there may be in CD?

In Conclusion…

Lebwohl & Leffler (2015). Exploring the strange new world of non‐celiac gluten

sensitivity. Clinical Gastroenterology and Hepatology, 13(9), 1613‐1615.

Questions?

References

Armstrong, D., Don‐Wauchope, A. C., & Verdu, E. F. (2011). Testing for gluten‐related disorders in clinical practice: The role of serology in managing the spectrum of gluten sensitivity. Canadian Journal of Gastroenterology, 25(4), 193‐197.

Aziz, I., Branchi, F., Pearson, K., Priest, J., & Sanders, D. S. (2015). A study evaluating the bidirectional relationship between inflammatory bowel disease and self‐reported non‐celiac gluten sensitivity. Inflammatory Bowel Diseases, 21(4), 847‐853. doi:10.1097/MIB.0000000000000335

Aziz, I., Hadjivassiliou, M., & Sanders, D. S. (2014). Self‐reported gluten sensitivity: An international concept in need of consensus? Am J Gastroenterol, 109(9), 1498‐1499. doi:10.1038/ajg.2014.205

Aziz, I., & Sanders, D. S. (2012). Emerging concepts: From coeliac disease to non‐coeliac gluten sensitivity. Proceedings of the Nutrition Society, 71(4), 576‐580. doi:10.1017/S002966511200081X

Biesiekierski, J. R., & Iven, J. (2015). Non‐coeliac gluten sensitivity: Piecing the puzzle together. United European Gastroenterology Journal, 3(2), 160‐165. doi:10.1177/2050640615578388

Biesiekierski, J. R., Muir, J. G., & Gibson, P. R. (2013). Is gluten a cause of gastrointestinal symptoms in people without celiac disease? Current Allergy and Asthma Reports, 13(6), 631‐638. doi:10.1007/s11882‐013‐0386‐4

Biesiekierski, J. R., Peters, S. L., Newnham, E. D., Rosella, O., Muir, J. G., & Gibson, P. R. (2013). No effects of gluten in patients with self‐reported non‐celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short‐chain carbohydrates. Gastroenterology, 145(2), 320‐328.e321‐323.

References

Bonciolini, V., Bianchi, B., Del Bianco, E., Verdelli, A., & Caproni, M. (2015). Cutaneous manifestations of non‐celiac gluten sensitivity: Clinical histological and immunopathological features. Nutrients, 7(9), 7798‐7805 7798p. doi:10.3390/nu7095368

Brottveit, M., Vandvik, P. O., Wojniusz, S., Løvik, A., Lundin, K. E. A., & Boye, B. (2012). Absence of somatization in non‐coeliac gluten sensitivity. Scandinavian Journal of Gastroenterology, 47(7), 770‐777. doi:10.3109/00365521.2012.679685

Catassi, C. (2015). Gluten sensitivity. Annals of Nutrition & Metabolism, 67 Suppl 2, 16‐26. doi:10.1159/000440990

Catassi, C., Bai, J. C., Bonaz, B., Bouma, G., Calabro, A., Carroccio, A., . . . Fasano, A. (2013). Non‐celiac gluten sensitivity: The new frontier of gluten related disorders. Nutrients, 5(10), 3839‐3853. doi:10.3390/nu5103839

Catassi, C., Elli, L., Bonaz, B., Bouma, G., Carroccio, A., Castillejo, G., . . . Fasano, A. (2015). Diagnosis of non‐celiac gluten sensitivity (NCGS): The Salerno experts' criteria. Nutrients, 7(6), 4966‐4977. doi:10.3390/nu7064966

Di Sabatino, A., Volta, U., Salvatore, C., Biancheri, P., Caio, G., De Giorgio, R., . . . Corazza, G. R. (2015). Small amounts of gluten in subjects with suspected nonceliac gluten sensitivity: A randomized, double‐blind, placebo‐controlled, cross‐over trial. Clinical Gastroenterology and Hepatology. doi:10.1016/j.cgh.2015.01.029

Ejsing‐Duun, M., Josephsen, J., Aasted, B., Buschard, K., & Hansen, A. K. (2008). Dietary gluten reduces the number of intestinal regulatory T cells in mice. Scandinavian Journal of Immunology, 67(6), 553‐559. doi:10.1111/j.1365‐3083.2008.02104.x

2/10/2016

7

References

Elli, L., Branchi, F., Tomba, C., Villalta, D., Norsa, L., Ferretti, F., . . . Bardella, M. T. (2015). Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non‐celiac gluten sensitivity. World Journal of Gastroenterology, 21(23), 7110‐7119. doi:10.3748/wjg.v21.i23.7110

Elli, L., Roncoroni, L., & Bardella, M. T. (2015). Non‐celiac gluten sensitivity: Time for sifting the grain. World Journal of Gastroenterology, 21(27), 8221‐8226. doi:10.3748/wjg.v21.i27.8221

Fasano, A. (2014). A Clinical Guide to Gluten‐Related Disorders. Philadelphia Wolters Kluwer/Lippincott Williams & Wilkins.

Fasano, A., Sapone, A., Zevallos, V., & Schuppan, D. (2015). Nonceliac gluten sensitivity. Gastroenterology(0). doi:http://dx.doi.org/10.1053/j.gastro.2014.12.049

Guandalini, S., & Polanco, I. (2015). Nonceliac gluten sensitivity or wheat intolerance syndrome? The Journal of Pediatrics, 166(4), 805‐811. doi:10.1016/j.jpeds.2014.12.039

Hadjivassiliou, M., Grünewald, R. A., Kandler, R. H., Chattopadhyay, A. K., Jarratt, J. A., Sanders, D. S., . . . Davies‐Jones, G. A. B. (2006). Neuropathy associated with gluten sensitivity. Journal of Neurology, Neurosurgery & Psychiatry, 77(11), 1262‐1266.

Hadjivassiliou, M., Rao, D. G., Wharton, S. B., Sanders, D. S., Grünewald, R. A., & Davies‐Jones, A. G. B. (2010). Sensory ganglionopathy due to gluten sensitivity. Neurology, 75(11), 1003‐1008. doi:10.1212/WNL.0b013e3181f25ee0

Hadjivassiliou, M., Sanders, D. S., Grünewald, R. A., Woodroofe, N., Boscolo, S., & Aeschlimann, D. (2010). Gluten sensitivity: From gut to brain. The Lancet Neurology, 9(3), 318‐330. doi:10.1016/S1474‐4422(09)70290‐X

References

Hansen, A. K., Ling, F., Kaas, A., Funda, D. P., Farlov, H., & Buschard, K. (2006). Diabetes preventive gluten‐free diet decreases the number of caecal bacteria in non‐obese diabetic mice. Diabetes/Metabolism Research & Reviews, 22(3), 220‐225 226p.

Hollon, J., Puppa, E. L., Greenwald, B., Goldberg, E., Guerrerio, A., & Fasano, A. (2015). Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non‐celiac gluten sensitivity. Nutrients, 7(3), 1565‐1576. doi:10.3390/nu7031565

Ihara, M., Makino, F., Sawada, H., Mezaki, T., Mizutani, K., Nakase, H., . . . Shimohama, S. (2006). Gluten sensitivity in Japanese patients with adult‐onset cerebellar ataxia. Internal Medicine, 45(3), 135‐140.

Isasi, C., Colmenero, I., Casco, F., Tejerina, E., Fernandez, N., Serrano‐Vela, J. I., . . . Villa, L. F. (2014). Fibromyalgia and non‐celiac gluten sensitivity: A description with remission of fibromyalgia. Rheumatology International, 34(4). doi:10.1007/s00296‐014‐2990‐6

Isasi, C., Tejerina, E., Fernandez‐Puga, N., & Serrano‐Vela, J. I. (2014). Fibromyalgia and chronic fatigue syndrome caused by non‐celiac gluten sensitivity. Reumatologia Clinica.

Kabbani, T. A., Vanga, R. R., Leffler, D. A., Villafuerte‐Galvez, J., Pallav, K., Hansen, J., . . . Kelly, C. P. (2014). Celiac disease or non‐celiac gluten sensitivity? An approach to clinical differential diagnosis. Am J Gastroenterol, 109, 741–746.

Kheder, A., Currie, S., Romanowski, C., & Hadjivassiliou, M. (2012). Progressive ataxia with palatal tremor due to gluten sensitivity. Movement Disorders, 27(1), 62‐63. doi:10.1002/mds.23987

References

Khwaja, G. A., Bohra, V., Duggal, A., Ghuge, V. V., & Chaudhary, N. (2015). Gluten sensitivity ‐ A potentially reversible cause of progressive cerebellar ataxia and myoclonus ‐ A case report. Journal of Clinical & Diagnostic Research, 9(11), 7‐8. doi:10.7860/JCDR/2015/13299.6743

Larsen, J., Dall, M., Antvorskov, J. C., Weile, C., Engkilde, K., Josefsen, K., & Buschard, K. (2014). Dietary gluten increases natural killer cell cytotoxicity and cytokine secretion. European Journal of Immunology, 44(10), 3056‐3067. doi:10.1002/eji.201344264

Lionetti, E., Leonardi, S., Franzonello, C., Mancardi, M., Ruggieri, M., & Catassi, C. (2015). Gluten psychosis: Confirmation of a new clinical entity. Nutrients, 7(7), 5532‐5539. doi:10.3390/nu7075235

Marietta, E., & Murray, J. (2012). Animal models to study gluten sensitivity. Seminars in Immunopathology, 34(4), 497‐511. doi:10.1007/s00281‐012‐0315‐y

Palova‐Jelinkova, L., Danova, K., Drasarova, H., Dvorak, M., Funda, D. P., Fundova, P., . . . Tuckova, L. (2013). Pepsin digest of wheat gliadin fraction increases production of IL‐1beta via TLR4/MyD88/TRIF/MAPK/NF‐B signaling pathway and an NLRP3 inflammasome activation. PLoS One, 8(4), e62426.

Peters, S. L., Biesiekierski, J. R., Yelland, G. W., Muir, J. G., & Gibson, P. R. (2014). Randomised clinical trial: Gluten may cause depression in subjects with non‐coeliac gluten sensitivity ‐ An exploratory clinical study. Alimentary Pharmacology & Therapeutics, 39(10), 1104‐1112. doi:10.1111/apt.12730

References

Sapone, A., Lammers, K. M., Casolaro, V., Cammarota, M., Giuliano, M. T., De Rosa, M., . . . Fasano, A. (2011). Divergence of gut permeability and mucosal immune gene expression in two gluten‐associated conditions: celiac disease and gluten sensitivity. BMC Medicine, 9, 23‐23. doi:10.1186/1741‐7015‐9‐23

Sapone, A., Lammers, K. M., Mazzarella, G., Mikhailenko, I., Cartenì, M., Casolaro, V., & Fasano, A. (2010). Differential mucosal IL‐17 expression in two gliadin‐induced disorders: Gluten sensitivity and the autoimmune enteropathy celiac disease. International Archives of Allergy & Immunology, 152(1), 75‐80. doi:10.1159/000260087

Sapone, A., Serena, G., Lammers, K., Patturelli, M., D'Urso, R., Vastarella, A., . . . De Magistris, L. (2014). LBA.02.1 Expression of FOXP3 isoforms in gluten related disorders. Digestive and Liver Disease, 46(Supplement 2), S142. doi:10.1016/S1590‐8658(14)60418‐7

Sbarbati, A., Valletta, E., Bertini, M., Cipolli, M., Morroni, M., Pinelli, L., & Tatò, L. (2003). Gluten sensitivity and 'normal' histology: Is the intestinal mucosa really normal? Digestive and Liver Disease, 35(11), 768‐773.

Shahbazkhani, B., Sadeghi, A., Malekzadeh, R., Khatavi, F., Etemadi, M., Kalantri, E., . . . Rostami, K. (2015). Non‐celiac gluten sensitivity has narrowed the spectrum of irritable bowel syndrome: A double‐blind randomized placebo‐controlled trial. Nutrients, 7(6), 4542‐4554. doi:10.3390/nu7064542

Tonutti, E., & Bizzaro, N. (2014). Diagnosis and classification of celiac disease and gluten sensitivity. Autoimmunity Reviews, 13(4–5), 472‐476. doi:http://dx.doi.org/10.1016/j.autrev.2014.01.043

References

Tovoli, F., Giampaolo, L., Caio, G., Monti, M., Piscaglia, M., Frisoni, M., . . . Volta, U. (2013). Fibromyalgia and coeliac disease: A media hype or an emerging clinical problem? Clinical & Experimental Rheumatology, 31(6 Suppl 79), S50‐S52.

Tovoli, F., Masi, C., Guidetti, E., Negrini, G., Paterini, P., & Bolondi, L. (2015). Clinical and diagnostic aspects of gluten related disorders. World Journal Of Clinical Cases, 3(3), 275‐284. doi:10.12998/wjcc.v3.i3.275

Vandenplas, Y., Benninga, M., Broekaert, I., Falconer, J., Gottrand, F., Guarino, A., . . . Wilschanski, M. (2015). Functional gastro‐intestinal disorder algorithms focus on early recognition, parental reassurance and nutritional strategies. Acta Paediatrica, n/a‐n/a. doi:10.1111/apa.13270

Vazquez‐Roque, M. I., Camilleri, M., Smyrk, T., Murray, J. A., Marietta, E., O'Neill, J., . . . Zinsmeister, A. R. (2013). A controlled trial of gluten‐free diet in patients with irritable bowel syndrome‐diarrhea: effects on bowel frequency and intestinal function. Gastroenterology, 144(5), 903‐911.e903.

Volta, U., Caio, G., De Giorgio, R., Henriksen, C., Skodje, G., & Lundin, K. E. (2015). Non‐celiac gluten sensitivity: A work‐in‐progress entity in the spectrum of wheat‐related disorders. Best Practice & Research in Clinical Gastroenterology, 29(3), 477‐491. doi:10.1016/j.bpg.2015.04.006

Volta, U., Caio, G., Stanghellini, V., & De Giorgio, R. (2014). The changing clinical profile of celiac disease: a 15‐year experience (1998‐2012) in an Italian referral center. BMC Gastroenterology, 14, 194.

References

Volta, U., Caio, G., Tovoli, F., & De Giorgio, R. (2013). Non‐celiac gluten sensitivity: Questions still to be answered despite increasing awareness. Cellular & Molecular Immunology, 10(5), 383‐392. doi:10.1038/cmi.2013.28

Volta, U., & De Giorgio, R. (2010). Gluten sensitivity: an emerging issue behind neurological impairment? The Lancet Neurology, 9(3), 233‐235. doi:10.1016/S1474‐4422(09)70357‐6

Volta, U., & De Giorgio, R. (2012). New understanding of gluten sensitivity. Nature Reviews | Gastroenterology & Hepatology, 9(5), 295‐299. doi:10.1038/nrgastro.2012.15

Volta, U., Tovoli, F., Cicola, R., Parisi, C., Fabbri, A., Piscaglia, M., . . . Caio, G. (2012). Serological tests in gluten sensitivity (nonceliac gluten intolerance). Journal of Clinical Gastroenterology, 46(8), 680‐685. doi:10.1097/MCG.0b013e3182372541

gluten intolerance: are people who complain of gluten

Documents